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• Evid Based Complement Alternat Med
• v.2016; 2016

Therapeutics Role of Azadirachta indica (Neem) and Their Active Constituents in Diseases Prevention and Treatment

Mohammad a. alzohairy.

Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, P.O. Box 6699, Buraidah, Saudi Arabia

Neem ( Azadirachta indica ) is a member of the Meliaceae family and its role as health-promoting effect is attributed because it is rich source of antioxidant. It has been widely used in Chinese, Ayurvedic, and Unani medicines worldwide especially in Indian Subcontinent in the treatment and prevention of various diseases. Earlier finding confirmed that neem and its constituents play role in the scavenging of free radical generation and prevention of disease pathogenesis. The studies based on animal model established that neem and its chief constituents play pivotal role in anticancer management through the modulation of various molecular pathways including p53, pTEN, NF- κ B, PI3K/Akt, Bcl-2, and VEGF. It is considered as safe medicinal plants and modulates the numerous biological processes without any adverse effect. In this review, I summarize the role of Azadirachta indica in the prevention and treatment of diseases via the regulation of various biological and physiological pathways.

1. Introduction

The plant product or natural products show an important role in diseases prevention and treatment through the enhancement of antioxidant activity, inhibition of bacterial growth, and modulation of genetic pathways. The therapeutics role of number of plants in diseases management is still being enthusiastically researched due to their less side effect and affordable properties. It has been accepted that drugs based on allopathy are expensive and also exhibit toxic effect on normal tissues and on various biological activities. It is a largely accepted fact that numerous pharmacologically active drugs are derived from natural resources including medicinal plants [ 1 , 2 ]. Various religious documents such as Bible and Quran also supported the herbs role in health care and prevention. Islamic perspective also confirms the herbs role in diseases management and Prophet Mohammed (PBUH) recommended various plants/fruits in the diseases cure [ 3 ]. Neem ingredients are applied in Ayurveda, Unani, Homeopathy, and modern medicine for the treatment of many infectious, metabolic, or cancer diseases [ 4 , 5 ]. Different types of preparation based on plants or their constituents are very popular in many countries in diseases management. In this vista, neem ( Azadirachta indica ), a member of the Meliaceae family, commonly found in India, Pakistan, Bangladesh, and Nepal, has therapeutics implication in diseases cure and formulation based on the fact that neem is also used to treat various diseases. Azadirachta indica has complex of various constituents including nimbin, nimbidin, nimbolide, and limonoids and such types of ingredients play role in diseases management through modulation of various genetic pathways and other activities. Quercetin and ß-sitosterol were first polyphenolic flavonoids purified from fresh leaves of neem and were known to have antifungal and antibacterial activities [ 6 ]. Numerous biological and pharmacological activities have been reported including antibacterial [ 7 ], antifungal [ 8 ], and anti-inflammatory. Earlier investigators have confirmed their role as anti-inflammatory, antiarthritic, antipyretic, hypoglycemic, antigastric ulcer, antifungal, antibacterial, and antitumour activities [ 9 – 12 ] and a review summarized the various therapeutics role of neem [ 13 ]. This review summarizes the role of neem and its active ingredients in the diseases prevention and treatment through the modulation of various biological pathways.

2. Botanical Description of Neem

Neem tree belongs to the family Meliaceae which is found in abundance in tropical and semitropical regions like India, Bangladesh, Pakistan, and Nepal. It is a fast-growing tree with 20–23 m tall and trunk is straight and has a diameter around 4-5 ft. The leaves are compound, imparipinnate, with each comprising 5–15 leaflets. Its fruits are green drupes which turn golden yellow on ripening in the months of June–August. Taxonomic position of Azadirachta indica (neem) is classified in Table 1 [ 14 ].

Taxonomic position of Azadirachtaindica (neem).

3. Active Compounds of Azadirachta indica L. (Neem)

Azadirachta indica L. (neem) shows therapeutics role in health management due to rich source of various types of ingredients. The most important active constituent is azadirachtin and the others are nimbolinin, nimbin, nimbidin, nimbidol, sodium nimbinate, gedunin, salannin, and quercetin. Leaves contain ingredients such as nimbin, nimbanene, 6-desacetylnimbinene, nimbandiol, nimbolide, ascorbic acid, n-hexacosanol and amino acid, 7-desacetyl-7-benzoylazadiradione, 7-desacetyl-7-benzoylgedunin, 17-hydroxyazadiradione, and nimbiol [ 15 – 17 ]. Quercetin and ß-sitosterol, polyphenolic flavonoids, were purified from neem fresh leaves and were known to have antibacterial and antifungal properties [ 6 ] and seeds hold valuable constituents including gedunin and azadirachtin.

4. Mechanism of Action of Active Compounds

Neem ( Azadirachta indica ), a member of the Meliaceae family, has therapeutics implication in the diseases prevention and treatment. But the exact molecular mechanism in the prevention of pathogenesis is not understood entirely. It is considered that Azadirachta indica shows therapeutic role due to the rich source of antioxidant and other valuable active compounds such as azadirachtin, nimbolinin, nimbin, nimbidin, nimbidol, salannin, and quercetin.

Possible mechanism of action of Azadirachta indica is presented as follows.

Neem ( Azadirachta indica ) plants parts shows antimicrobial role through inhibitory effect on microbial growth/potentiality of cell wall breakdown. Azadirachtin, a complex tetranortriterpenoid limonoid present in seeds, is the key constituent responsible for both antifeedant and toxic effects in insects [ 18 ]. Results suggest that the ethanol extract of neem leaves showed in vitro antibacterial activity against both Staphylococcus aureus and MRSA with greatest zones of inhibition noted at 100% concentration [ 19 ].

• Neem plays role as free radical scavenging properties due to rich source of antioxidant. Azadirachtin and nimbolide showed concentration-dependent antiradical scavenging activity and reductive potential in the following order: nimbolide > azadirachtin > ascorbate [ 20 ].
• Neem ingredient shows effective role in the management of cancer through the regulation of cell signaling pathways. Neem modulates the activity of various tumour suppressor genes (e.g., p53, pTEN), angiogenesis (VEGF), transcription factors (e.g., NF- κ B), and apoptosis (e.g., bcl2, bax).
• Neem also plays role as anti-inflammatory via regulation of proinflammatory enzyme activities including cyclooxygenase (COX), and lipoxygenase (LOX) enzyme.

5. Therapeutic Implications of Neem and Its Various Ingredients in Health Management

Active constitutes play role in the diseases cure via activation of antioxidative enzyme, rupture the cell wall of bacteria and play role as chemopreventive through the regulation of cellular pathways. Pharmacological activities of neem are discussed in detail ( Figure 1 ).

Pharmacological activities of Azadirachta indica L. neem in diseases management through the modulation of various activities.

5.1. Antioxidant Activity

Free radical or reactive oxygen species are one of the main culprits in the genesis of various diseases. However, neutralization of free radical activity is one of the important steps in the diseases prevention. Antioxidants stabilize/deactivate free radicals, often before they attack targets in biological cells [ 21 ] and also play role in the activation of antioxidative enzyme that plays role in the control of damage caused by free radicals/reactive oxygen species. Medicinal plants have been reported to have antioxidant activity [ 22 ]. Plants fruits, seeds, oil, leaves, bark, and roots show an important role in diseases prevention due to the rich source of antioxidant.

Leaf and bark extracts of A. indica have been studied for their antioxidant activity and results of the study clearly indicated that all the tested leaf and bark extracts/fractions of neem grown in the foothills have significant antioxidant properties [ 23 ]. Another important study was performed based on leaves, fruits, flowers, and stem bark extracts from the Siamese neem tree to assess the antioxidant activity and results suggest that extracts from leaf, flower, and stem bark have strong antioxidant potential [ 24 ].

A valuable study was carried out to evaluate in vitro antioxidant activity in different crude extracts of the leaves of Azadirachta indica (neem) and antioxidant capacity of different crude extracts was as follows: chloroform > butanol > ethyl acetate extract > hexane extract > methanol extract. Result of the current finding suggested that the chloroform crude extracts of neem could be used as a natural antioxidant [ 20 ].

Other results revealed that azadirachtin and nimbolide showed concentration-dependent antiradical scavenging activity and reductive potential in the following order: nimbolide > azadirachtin > ascorbate. Furthermore, administration of azadirachtin and nimbolide inhibited the development of DMBA-induced HBP carcinomas through prevention of procarcinogen activation and oxidative DNA damage and upregulation of antioxidant and carcinogen detoxification enzymes [ 25 ]. Experimentation was made to evaluate the antioxidant activity of the flowers and seed oil of neem plant Azadirachta indica A. Juss. and results revealed that ethanolic extract of flowers and seed oil at 200  μ g/mL produced the highest free radical scavenging activity with 64.17 ± 0.02% and 66.34 ± 0.06%, respectively [ 26 ].

The results of the study revealed that root bark extract exhibited higher free radical scavenging effect with 50% scavenging activity at 27.3  μ g/mL and total antioxidant activity of this extract was found to be 0.58 mM of standard ascorbic acid [ 27 ]. Other results of study concluded that tested leaf and bark extracts/fractions of neem grown in the foothills (subtropical region) have significant antioxidant properties [ 23 ].

Leaves, fruits, flowers, and stem bark extracts from the Siamese neem tree were evaluated for antioxidant and results of the study showed that leaf aqueous extract and flower and stem bark ethanol extracts showed higher free radical scavenging effect with 50% scavenging activity at 26.5, 27.9, and 30.6 microg/mL, respectively. Furthermore, total antioxidant activity of extracts was found to be 0.959, 0.988, and 1.064 mM of standard trolox, respectively [ 28 ].

5.2. Anticancerous Activity

Cancer is multifactorial disease and major health problem worldwide. The alteration of molecular/genetic pathways plays role in the development and progression of cancer. The treatment module based on allopathic is effective on one side but also shows adverse effect on the normal cell. Earlier studies reported that plants and their constituents show inhibitory effects on the growth of malignant cells via modulation of cellular proliferation, apoptosis, tumour suppressor gene, and various other molecular pathways [ 29 ]. Neem contains flavanoids and various other ingredients that play an important role in inhibition of cancer development ( Figure 2 ). Large number of epidemiological studies proposes that high flavonoid intake may be correlated with a decreased risk of cancer [ 30 ].

Anticancerous activities of Azadirachta indica L. neem through the modulation of various cell signaling pathways.

Neem oil holds various neem limonoids which prevents mutagenic effects of 7,12-dimethylbenz(a)anthracene [ 31 ]. A study was performed to investigate the cytotoxic effects of nimbolide found in leaves and flowers on human choriocarcinoma (BeWo) cells and results showed that treatment with nimbolide resulted in dose- and time-dependent inhibition of growth of BeWo cells with IC 50 values of 2.01 and 1.19  μ M for 7 and 24 h, respectively [ 32 ]. A study was made to assess the chemopreventive potential of the limonoids, azadirachtin, and nimbolide and results showed that azadirachtin and nimbolide inhibited the development of DMBA-induced HBP carcinomas through influencing multiple mechanisms such as prevention of procarcinogen activation and oxidative DNA damage, upregulation of antioxidant and carcinogen detoxification enzymes, and inhibition of tumour invasion and angiogenesis [ 25 ].

Azadirachta indica and their active compounds play pivotal role in the prevention of cancer development and progression. The exact molecular mechanism in this vista is not understood fully. Based on experimentation, it was considered that neem and its ingredients play role in the modulation of various cell signaling pathways. Azadirachta indica hold various ingredients and theses constituents activate the tumour suppressor genes and inactivate the activity of several genes involved in the cancer development and progression such as VEGF, NF- κ B, and PI3K/Akt. Neem has been reported to be a good activator of tumour suppressor gene and inhibitor of VEGF and phosphoinositol PI3K/Akt pathways. It also activates apoptosis, suppression of NF- κ B signaling, and cyclooxygenase pathway.

Neem and its constituents play role in the prevention of malignancies through the modulation of molecular pathways which are described below.

5.2.1. Effect of Neem and Its Constituents on Tumour Suppressor Genes

p53 is an important tumour suppressor gene and it plays role in the inhibition of the proliferation of abnormal cells, in that way inhibiting the development and progression of cancer. A study confirmed that ethanolic fraction of neem leaf (EFNL) treatment effectively upregulated the proapoptotic genes and proteins including p53, Bcl-2-associated X protein (Bax), Bcl-2-associated death promoter protein (Bad) caspases, phosphatase and tensin homolog gene (pTEN), and c-Jun N-terminal kinase (JNK) [ 33 ]. A finding showed that ethanolic neem leaf extract enhanced the expression of proapoptotic genes, such as caspase-8 and caspase-3, and suppressed the expression of Bcl-2 and mutant p53 in the 7,12-dimethylbenz(a)anthracene-induced cancer cells [ 34 , 35 ].

Nimbolide, a tetranortriterpenoid limonoid, is one of the important contributors to the cytotoxicity of neem extracts [ 36 ]. Nimbolide downregulated cell survival proteins, including I-FLICE, cIAP-1, cIAP-2, Bcl-2, Bcl-xL, survivin, and X-linked inhibitor of apoptosis protein, and upregulated the proapoptotic proteins p53 and Bax [ 37 ].

pTEN activity is commonly lost via mutations, deletions, or promoter methylation silencing in various types of primary and metastatic cancers [ 38 , 39 ]. Inactivation of pTEN has been noticed in various types of tumour. A study confirmed that ethanolic fraction of neem leaf treatment significantly increased the expression of pTEN, which could inhibit mammary tumourigenesis through its inhibitory effect on Akt [ 33 ].

5.2.2. Effect of Neem and Its Constituents on Apoptosis

bcl2 and bax play an important role in the regulation of apoptotic process. Any alteration in bcl2 and bax causes the development and progression of tumours [ 40 ]. Altered expression of such genes has been noticed in many tumours. A study was performed to investigate the effect of extract in an in vivo 4T1 breast cancer model in mice and results confirmed that CN 250 and CN 500 groups had a higher incidence of apoptosis compared with the cancer controls [ 41 ]. Another study reported that extract has been shown to cause cell death of prostate cancer cells (PC-3) via inducing apoptosis [ 42 ].

A study finding revealed that leaf extract downregulated Bcl-2 expression and upregulated Bim, caspase-8, and caspase-3 expression in the buccal pouch indicating that it has apoptosis inducing effects in the target organ [ 35 ] and study results confirmed that leaf extract induced a dose-dependent reduction in chronic lymphocytic leukemia (CLL) cell viability with significant apoptosis observed at 0.06% (w/v) by 24 h [ 43 ]. Isolated compound and chief constituents from neem show a range of activities affecting multiple targets and also play role in the induction of apoptotic cell death in cancer [ 44 , 45 ].

5.2.3. Effect of Neem and Its Constituents on Angiogenesis

Angiogenesis is complex process that supplies blood to the tissue and that is essential for growth and metastasis of tumour. Angiogenesis is regulated by activators as well as inhibitors. The development of antiangiogenic agents to block new blood vessel growth is crucial step in the inhibition/prevention of tumour growth. Medicinal plants and their ingredients play role in prevention of tumour growth due to their antiangiogenic activity.

An important study revealed that ethanolic fraction of neem leaf (EFNL) treatment effectively inhibited the expression of proangiogenic genes, vascular endothelial growth factor A, and angiopoietin, indicating the antiangiogenic potential of EFNL. Furthermore, inhibition of angiogenesis by ethanolic fraction of neem leaf (EFNL) could be a reason for reduction in mammary tumour volume and for blocked development of new tumours as observed in current studies [ 33 ]. Another study was performed to evaluate the antiangiogenic activity of extract of leaves in human umbilical vein endothelial cells (HUVECs) and results showed treatment of HUVECs with EENL inhibited VEGF induced angiogenic response in vitro and in vivo and also EENL suppressed the in vitro proliferation, invasion, and migration of HUVECs [ 46 ]. A study was made on zebra fish embryos via treatment of various concentrations of water soluble fractions of crude methanolic extract of neem root, imatinib (standard), and control and results of the study concluded that water soluble fractions of methanolic extract of neem root were found to have the ability to inhibit angiogenesis [ 47 ].

5.2.4. Effect of Neem on Oncogene

An oncogene is a mutated gene that plays significant role in the development and progression of tumours. Experiment was performed to investigate effect of leaf extract on c-Myc oncogene expression in 4T1 breast cancer BALB/c mice and results revealed that 500 mg/kg neem leaf extract (C500) group showed significant suppression of c-Myc oncogene expression as compared to the cancer control group [ 48 ].

5.2.5. Effect of Neem on PI3K/Akt Pathways

PI3K/Akt pathways show pivotal effect in the promotion of tumour. However, inhibition of PI3K/Akt pathways is one of the important steps towards regulation of tumour development. Effect of leaf extract on PI3K/Akt and apoptotic pathway in prostate cancer cell lines (PC-3 and LNCaP) was investigated and results suggested that effect of leaf extract induces apoptosis and inhibits cell proliferation through inhibiting PI3K/Akt pathway in both PC-3 and LNCaP cells [ 49 ].

Another study was performed to evaluate the molecular mechanisms involved in the induction of apoptosis and antiproliferative activity exerted by leaf extract on the human breast cancer cell lines and results confirmed that extract treated cells significantly decreased the protein expression such as IGF signaling molecules IGF-1R, Ras, Raf, p-Erk, p-Akt, and cyclin D1  [ 50 ].

Another study was carried out to evaluate the effects of nimbolide on apoptosis and insulin-like growth factor (IGF) signaling molecules in androgen-independent prostate cancer (PC-3) cells line and results of the study suggested that nimbolide acts as a potent anticancer agent by inducing apoptosis and inhibiting cell proliferation via PI3K/Akt pathway in PC-3 cells [ 51 ].

5.2.6. Effect of Neem on NF- κ B Factor

The NF- κ B transcription factor plays a major role in cancer and related diseases [ 52 ]. However, the inhibition of NF- κ B action is a vital step in the prevention of cancer development and progression. An important study was performed to investigate the efficacy of bioactive phytochemicals in inhibiting radiotherapy- (RT-) induced NF- κ B activity, signaling, and NF- κ B-dependent regulation of cell death and results showed that curcumin, leaf extract, and black raspberry extract (RSE) significantly inhibited both constitutive and RT-induced NF- κ B [ 53 ] and other important study results demonstrate that nimbolide, a neem derived tetranortriterpenoid, concurrently abrogates canonical NF- κ B and Wnt signaling and induces intrinsic apoptosis in human hepatocarcinoma (HepG2) cells [ 54 ].

6. Effect of Neem as Anti-Inflammatory

Plants or their isolated derivatives are in the practice to treat/act as anti-inflammatory agents. A study result has confirmed that extract of A. indica leaves at a dose of 200 mg/kg, p.o., showed significant anti-inflammatory activity in cotton pellet granuloma assay in rats [ 55 ]. Other study results revealed that neem leaf extract showed significant anti-inflammatory effect but it is less efficacious than that of dexamethasone [ 56 ] and study results suggest that nimbidin suppresses the functions of macrophages and neutrophils relevant to inflammation [ 57 ].

Earlier finding showed immunomodulator and anti-inflammatory effect of bark and leave extracts and antipyretic and anti-inflammatory activities of oil seeds [ 58 , 59 ]. Experimentation was made to evaluate the analgesic activity of neem seed oil on albino rats and results of the study showed that neem seed oil showed significant analgesic effect in the dose of 1 and 2 mL/kg and oil has dose-dependent analgesic activity [ 60 ].

Another study was made to investigate the anti-inflammatory effect of neem seed oil (NSO) on albino rats using carrageenan-induced hind paw edema and results revealed that NSO showed increased inhibition of paw edema with the progressive increase in dose from 0.25 mL to 2 mL/kg body weight. At the dose of 2 mL/kg body weight, NSO showed maximum (53.14%) inhibition of edema at 4th hour of carrageenan injection [ 61 ].

Results of the study concluded that the treated animals with 100 mg kg −1 dose of carbon tetrachloride extract (CTCE) of Azadirachta indica fruit skin and isolated ingredient azadiradione showed significant antinociceptive and anti-inflammatory activities [ 62 ].

7. Hepatoprotective Effect

Medicinal plants and their ingredients play a pivotal role as hepatoprotective without any adverse complications. A study was performed to investigate the hepatoprotective role of azadirachtin-A in carbon tetrachloride (CCl 4 ) induced hepatotoxicity in rats and histology and ultrastructure results confirmed that pretreatment with azadirachtin-A dose-dependently reduced hepatocellular necrosis [ 63 ]. Furthermore results of the study show that pretreatment with azadirachtin-A at the higher dose levels moderately restores the rat liver to normal [ 63 ].

Another study was carried out to evaluate the protective effect of active constituent of neem such as nimbolide against carbon tetrachloride (CCl 4 ) induced liver toxicity in rats and results suggest that nimbolide possesses hepatoprotective effect against CCl 4 induced liver damage with efficiency similar to that of silymarin standard [ 64 ] and another study finding revealed that leaf extract was found to have protection against paracetamol-induced liver necrosis in rats [ 65 ].

A study assesses the hepatoprotective activity of Azadirachta indica (AI) leaf extract on antitubercular drugs-induced hepatotoxicity and results confirmed aqueous leaf extract significantly prevented changes in the serum levels of bilirubin, protein, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase and significantly prevented the histological changes as compared to the group receiving antitubercular drugs [ 66 ]. Additionally, other results showed that ethanolic and aqueous leaf extracts of A. indica exhibited moderate activity over carbon tetrachloride treated animals [ 67 ]. Hepatoprotective effect of methanolic and aqueous extracts of Azadirachta indica leaves was evaluated in rats and study result established that the plant has good potential to act as hepatoprotective agent [ 68 ].

An experiment was made to investigate the protective effect of neem extract on ethanol-induced gastric mucosal lesions in rats and results showed that pretreatment with neem extract showed protection against ethanol-induced gastric mucosal damage [ 69 ].

8. Wound Healing Effect

Numerous plants/their constituents play an important role in the wound healing effect. A study was made to evaluate the wound healing activity of the extracts of leaves of A. indica and T. cordifolia using excision and incision wound models in Sprague Dawley rats and results revealed that extract of both plants significantly promoted the wound healing activity in both excision and incision wound models [ 70 ]. Furthermore, in incision wound, tensile strength of the healing tissue of both plants treated groups was found to be significantly higher as compared to the control group [ 69 ]. Other results showed that leave extracts of Azadirachta indica promote wound healing activity through increased inflammatory response and neovascularization [ 71 ].

9. Antidiabetic Activity

A study was undertaken to evaluate the 70% alcoholic neem root bark extract (NRE) in diabetes and results showed that neem root bark extract showed statistically significant results in 800 mg/kg dose [ 72 ]. Another experiment was performed to examine the pharmacological hypoglycemic action of Azadirachta indica in diabetic rats and results showed that in a glucose tolerance test with neem extract 250 mg/kg demonstrated glucose levels were significantly less as compared to the control group and Azadirachta indica significantly reduce glucose levels at 15th day in diabetic rats [ 73 ].

Studies using in vivo diabetic murine model, A. indica , and B. spectabilis chloroform, methanolic, and aqueous extracts were investigated and results showed that A. indica chloroform extract and B. spectabilis aqueous, methanolic extracts showed a good oral glucose tolerance and significantly reduced the intestinal glucosidase activity [ 74 ]. Another important study suggested that leaves extracts of Azadirachta indica and Andrographis paniculata have significant antidiabetic activity and could be a potential source for treatment of diabetes mellitus [ 75 ].

10. Antimicrobial Effect

Neem and its ingredients play role in the inhibition of growth of numerous microbes such as viruses, bacteria, and pathogenic fungi. The role of neem in the prevention of microbial growth is described individually as follows.

10.1. Antibacterial Activity

A study was performed to evaluate antimicrobial efficacy of herbal alternatives as endodontic irrigants and compared with the standard irrigant sodium hypochlorite and finding confirmed that leaf extracts and grape seed extracts showed zones of inhibition suggesting that they had antimicrobial properties [ 76 ]. Furthermore, leaf extracts showed significantly greater zones of inhibition than 3% sodium hypochlorite [ 76 ].

The antibacterial activity of guava and neem extracts against 21 strains of foodborne pathogens was evaluated and result of the study suggested that guava and neem extracts possess compounds containing antibacterial properties that can potentially be useful to control foodborne pathogens and spoilage organisms [ 77 ].

Another experiment was made to evaluate the antibacterial activity of the bark, leaf, seed, and fruit extracts of Azadirachta indica (neem) on bacteria isolated from adult mouth and results revealed that bark and leaf extracts showed antibacterial activity against all the test bacteria used [ 78 ]. Furthermore, seed and fruit extracts showed antibacterial activity only at higher concentrations [ 78 ].

10.2. Antiviral Activity

Results showed that neem bark (NBE) extract significantly blocked HSV-1 entry into cells at concentrations ranging from 50 to 100  μ g/mL [ 78 ]. Furthermore, blocking activity of NBE was noticed when the extract was preincubated with the virus but not with the target cells suggesting a direct anti-HSV-1 property of the neem bark [ 79 ].

Leaves extract of neem ( Azadirachta indica A. Juss.) (NCL-11) has shown virucidal activity against coxsackievirus virus B-4 as suggested via virus inactivation and yield reduction assay besides interfering at an early event of its replication cycle [ 80 ].

10.3. Antifungal Activity

Experiment was made to evaluate the efficacy of various extracts of neem leaf on seed borne fungi Aspergillus and Rhizopus and results confirmed that growth of both the fungal species was significantly inhibited and controlled with both alcoholic and water extract. Furthermore, alcoholic extract of neem leaf was most effective as compared to aqueous extract for retarding the growth of both fungal species [ 81 ]. Another finding showed the antimicrobial role of aqueous extracts of neem cake in the inhibition of spore germination against three sporulating fungi such as C. lunata , H. pennisetti , and C. gloeosporioides f. sp. mangiferae [ 82 ] and results of the study revealed that methanol and ethanol extract of Azadirachta indica showed growth inhibition against Aspergillus flavus , Alternaria solani , and Cladosporium [ 83 ].

Aqueous extracts of various parts of neem such as neem oil and its chief principles have antifungal activities and have been reported by earlier investigators [ 84 – 86 ]. A study was undertaken to examine the antifungal activity of Azadirachta indica L. against Alternaria solani Sorauer and results confirmed that ethyl acetate fraction was found most effective in retarding fungal growth with MIC of 0.19 mg and this fraction was also effective than fungicide (metalaxyl + mancozeb) as the fungicide has MIC of 0.78 mg [ 87 ].

10.4. Antimalarial Activity

Experiment was made to evaluate the antimalarial activity of extracts using Plasmodium berghei infected albino mice and results revealed that neem leaf and stem bark extracts reduced the level of parasitemia in infected mice by about 51–80% and 56–87%, respectively, [ 88 ] and other studies showed that azadirachtin and other limonoids available in neem extracts are active on malaria vectors [ 89 – 91 ].

Another finding based on crude acetone/water (50/50) extract of leaves (IRAB) was performed to evaluate the activity against the asexual and the sexual forms of the malaria parasite, Plasmodium falciparum , in vitro and results showed that, in separate 72-hour cultures of both asexual parasites and mature gametocytes treated with IRAB (0.5 microg/mL), parasite numbers were less than 50% of the numbers in control cultures, which had 8.0% and 8.5% parasitemia, respectively [ 92 ].

11. Role of Neem in Dentistry

A study was made to assess the efficacy of neem based on mouth rinse regarding its antigingivitis effect and study confirmed that A. indica mouth rinse is equally effective in reducing periodontal indices as chlorhexidine [ 93 ].

Another study was carried out to evaluate the antimicrobial properties of organic extracts of neem against three bacterial strains causing dental caries and results showed that petroleum ether and chloroform extract showed strong antimicrobial activity against S. mutans . Chloroform extract showed strong activity against Streptococcus salivarius and third strain Fusobacterium nucleatum was highly sensitive to both ethanol and water extract [ 94 ]. Earlier finding confirmed that dried chewing sticks of neem showed maximum antibacterial activity against S. mutans as compared to S. salivarius , S. mitis , and S. sanguis [ 95 ].

12. Antinephrotoxicity Effect

An experiment was made to investigate the effects of methanolic leaves extract of Azadirachta indica (MLEN) on cisplatin- (CP-) induced nephrotoxicity and oxidative stress in rats and results confirmed that extract effectively rescues the kidney from CP-mediated oxidative damage [ 90 ]. Furthermore, PCR results for caspase-3 and caspase-9 and Bax genes showed downregulation in MLEN treated groups [ 96 ].

13. Neuroprotective Effects

A study was performed to investigate the neuroprotective effects of Azadirachta indica leaves against cisplatin- (CP-) induced neurotoxicity and results showed that morphological findings of neem before and after CP injection implied a well-preserved brain tissue. No changes, in biochemical parameters, were observed with neem treated groups [ 97 ].

14. Immunomodulatory and Growth Promoting Effect

Experiment was performed to investigate growth promoting and immunomodulatory effects of neem leaves infusion on broiler chicks and results showed that neem infusion successfully improved antibody titre, growth performance, and gross return at the level of 50 mL/liter of fresh drinking water [ 98 ].

Another study investigated the effects of feeding of powdered dry leaves of A. indica (AI) on humoral and cell mediated immune responses, in broilers and results showed that AI (2 g/kg) treatment significantly enhanced the antibody titres against new castle disease virus (NCDV) antigen [ 99 ].

15. Safety, Toxicities, and LD 50 Values of Neem

The measurement of toxicities of natural compound is crucial before their application in health management. Various studies based on animal model and clinical trials confirmed the neem is safe at certain dose and on the other side neem and its ingredients showed toxic/adverse effect.

Several studies reported, in children, neem oil poisoning causing vomiting, hepatic toxicity, metabolic acidosis, and encephalopathy [ 100 – 102 ] and another study based on rat model showed that administration of leaf sap caused an antianxiety effect at low doses, whereas high doses did not show such types of effect [ 103 ]. An important study based on rats model showed that azadirachtin did not show toxicity even at 5 g/kg bw [ 104 ]. A study based on rabbit was performed to check the toxicological analysis and results of the study showed there was progressive increase in body weight in both the test and control animals, and during the entire duration of the administration of the neem extract, there was no observed sign of toxicity in both groups [ 105 ].

A study result showed that, in the acute toxicity test, the LD 50 values of neem oil were found to be 31.95 g/kg [ 106 ]. Another study was performed to evaluate the toxicity in chicken and finding showed that acute toxicity study of neem leaf aqueous extract revealed an intraperitoneal LD 50 of 4800 mg/kg, and clinical signs were dose dependent [ 107 ].

A study reported that lethal median doses (LD 50 ) recorded for neem leaf and stem bark extracts were 31.62 and 489.90 mg/kg body weight, respectively [ 108 ]. The LD 50 of water extract of A. indica leaves and seeds were 6.2, 9.4 mL kg −1 , respectively [ 109 ]. Lethal dose values were calculated with probit analysis and LD 50 and LD 90 values were found to be 8.4 and 169.8  µ g/fly of neem extract, respectively [ 110 ]. A test for acute oral toxicity in mice revealed that LD 50 value of approximately 13 g/kg body weight [ 111 ].

16. Clinical Studies Based on Neem

Various clinical trials based studies confirmed that herbal products or derivatives from the natural products play vital role in diseases prevention and treatment. A very few studies on active compounds such as nimbidin were made to check the efficacy in the health management. An important study was made based on human subjects to investigate the role of neem bark extract as antisecretory and antiulcer effects in human subjects. Administration of lyophilised powder of the extract for 10 days at the dose of 30 mg twice daily showed significant decrease (77%) of gastric acid secretion. The bark extract at the dose of 30–60 mg twice daily for 10 weeks almost completely healed the duodenal ulcers and one case of esophageal ulcer and one case of gastric ulcer healed completely when administrated at the dose of 30 mg twice daily for 6 weeks [ 9 ].

A double blind clinical drug trial study was performed to check the efficacy of drug made up of aqueous extract of neem leaves in 50 cases of uncomplicated psoriasis taking conventional coal tar regime and results revealed that patients taking drug in addition to coal tar had shown a quicker and better response in comparison to placebo group [ 112 ]. A clinical study of six weeks was made to check the efficacy of neem extract dental gel with chlorhexidine gluconate (0.2% w/v) mouthwash as positive control and results of the study showed that the dental gel containing neem extract has significantly reduced the plaque index and bacterial count compared to that of the control group [ 113 ]. A study showed that, in ulcer healing tests, nimbidin significantly enhanced the healing process in acetic acid induced chronic gastric lesions in albino rats and dogs [ 114 ].

17. Conclusion

Popularity of natural products or their derivatives role in diseases cure and prevention is increasing worldwide due to less side effect properties. Neem and its ingredients have therapeutics implication and have been traditionally used worldwide especially in Indian Subcontinent since ancient time. Clinical based studies confirmed that neem plays pivotal role in prevention of various diseases. The role of active ingredients as chemopreventive effect has been noticed in various tumour via modulation of numerous cell signaling pathways. The detailed study should be made based on animal to know the exact mechanism of action in the diseases management.

Conflict of Interests

The author declares that there is no conflict of interests regarding the publication of this paper.

The Neem Patent Case

Contributor.

Neem Patent: Protecting the Traditional Knowledge of India

India i.e., ‘Bharat', is a country, “which has been nurturing a tradition of civilization over a period of about 5,000 years. India's ancient scriptures consist of the four Veda, 108 Upanishads, 2 epics, Bhagavad-Gita, Brahma sutras, eighteen Puranas, Manu smriti, Kautilya Shastra and smritis.” One of the most complicated issues in India is to protect the Traditional Knowledge which is possessed by the people as inheritance from their ancestors, but is not protected since it doesn't contain any inventive character. This knowledge is called ‘Sacred Intangible Traditional Knowledge', and the three key articulations that must be characterized to define the terms “Sacred”, “intangible” and “Traditional Knowledge” are as follow. Sacred is mainly used to refer to the expressions of Traditional Knowledge that relates to spiritual beliefs or traditions or something religious. Intangible “which simply means incorporeal, when applied to property, would include intellectual property.”

Traditional Knowledge “is a living body of knowledge that is developed, sustained and passed on from generation to generation within a community, often forming part of its cultural or spiritual identity.” One of the most important factors is that Traditional Knowledge has some ancient roots, and is mostly orally passed from one person to another.

Traditional Knowledge Protection

Traditional Knowledge is not protected under the existing Indian Patent Act, 1970 because Traditional Knowledge in itself is not considered as an innovation as stated under Section 3(p) of Indian Patents Act, 1970, thus not considered as invention and hence, cannot be patented. Section 25 and Section 64 of the Indian Patent Act, 1970 1 , provides certain grounds for revoking patent applications for protecting Traditional Knowledge. The Copyright Act, 1957 2 of India also doesn't specifically provide for the protection of traditional culture, artistic work or folklore but Section 31A provides for protection of unpublished Indian work. However, Copyrights Act requires certain criteria to be fulfilled and protection is for limited time period.

Biopiracy is not a legal concept but termed as a socio-political device where indigenous people, their Traditional knowledge and also their biological resources are illegally used by the companies or researchers who from this knowledge later claim the IP Rights over the products which have been gotten from the knowledge of those resources. Biopiracy by its name suggests that there is piracy of various biosphere elements which includes micro-organisms, plants, animals etc. In 2000, Council of Scientific & Industrial Research (CSIR) study found that 80% of the total medicinal patents made by US and UK were from seven medicinal plants of Indian origin. In 2003, there were around 15000 patents made by US and UK from the Indian origin medicinal plants and later in 2005 the patents increased to 35000 which shows the interest of developed countries in the knowledge of developing countries. In addition to this, the patent examiner who comes for inspection is from developed countries and not from the developing countries which gives the former a free hand to steal and use traditional medical knowledge.

Biopiracy is inherently an act of appropriation of traditional knowledge by individuals and corporations for commercial gain but there are existing difficulties in protecting such knowledge that allow attempts and possibilities at appropriation. Such difficulties include:

• Collective Resource : The exclusive rights conferred by Intellectual Property Rights are usually given to the individual ownership of knowledge but traditional knowledge protection is usually provided to a community at large.
• Criteria of novelty in IPR : : Most traditional knowledge is not based on scientific methods of assessment and evolves organically with the help of communities as a response to new challenges and needs. The evolution of such knowledge across generations means that the novelty or innovative factor is non-existent. Thus, such knowledge often fails to meet the criteria of novelty required for IPR patents.
• Limited Protection under IPR : Traditional knowledge requires protection for an indefinite period simply because it is associated with the living practices of an indigenous population. These practices may also be vulnerable to appropriation. The Indian Patents Act does not allow for evergreening of patents.
• Problem of Benefit -Sharing : When it comes to sharing monetary and other benefits after commercialization of a traditional practice through a legal procedure, it is sometimes difficult to identify the beneficiary. For instance, in the mid-1990s, scientists at the Tropical Botanic Garden and Research Institute (TBGRI) developed and patented a drug called “Jeevani”. Although TBGRI ended up signing a benefit-sharing agreement with a trust with members from the Kani tribe, not all Kani people agree with the arrangement claiming traditional rights on beneficial properties of the herb.
• Lack of adequate documentation : Traditional knowledge is usually a product of learning through experience and oral traditions passed over centuries. It may have been generated, transmitted, and strengthened through rituals, songs, oral history, human interactions, ceremonies, languages, experiences and practices. These traditions are often inaccessible to the patentee or the concerned authority due to the lack of formal documentation.

Over the years, there have been several national and international policies/conventions to secure the rights of source countries as well as indigenous populations over traditional knowledge. At the national level in India, one such intervention is the Traditional Knowledge Digital Library which was created to overcome the problem of documentation and availability of information about traditional knowledge in the public domain.

The Neem Dispute

The neem tree (Azadirachta indica) originates from the Indian subcontinent and now grows in the dry regions of more than 50 tropical countries around the world. The neem tree has multiple uses. It is mentioned in Indian texts written over 2000 years ago and has been used for centuries by local communities in agriculture as an insect and pest repellent, in human and veterinary medicine, toiletries and cosmetics. It is also venerated in the culture, religions and literature of the region. The neem tree, is known in Sanskrit as “ sarva-roga nivarini ”. It is also seen as a prominent resource in the country.

Even though first report on pesticide property of neem was reported in India in 1928, only after 30 years later systematic research work on neem was initiated. The past five decades witnessed intensive investigation and upward trend to scientific interest in neem and its diverse properties, resulting in large number of research publications, books and conferences at national and international levels. Since the 1980s, many neem related process and products have been patented in Japan, USA and European countries.

Brief Background of the case

The patent for Neem was first filed by W.R. Grace and the Department of Agriculture, USA in European Patent Office. The said patent was deemed to be a method of controlling fungi on plants comprising of contacting the fungi with a Neem oil formulation. A legal opposition was filed by India against the grant of the patent. The legal opposition to this patent was lodged by the New Delhi-based Research Foundation for Science, Technology and Ecology (RFSTE), in cooperation with the International Federation of Organic Agriculture Movements (IFOAM) and Magda Aelvoet, former green Member of the European Parliament (MEP).

A tree legendary to India, from its roots to its spreading crown, the Neem tree contains a number of potent compounds, notably a chemical found in its seeds named azadirachtin. It is used as an astringent in so many fields. The barks, leaves, flowers, seeds of neem tree are used to treat a variety of diseases ranging from leprosy to diabetes, skin disorders and ulcers. Neem twigs are used as antiseptic tooth brushes since time immemorial. The opponents' submitted evidence of ancient Indian ayurvedic texts that have described the hydrophobic extracts of neem seeds were known and used for centuries in India, both in curing dermatological diseases in humans and in protecting agricultural plants form fungal infections. The EPO identified the lack of novelty, inventive step and possibly form a relevant prior art and revoked the patent. Apart from this, several US patents were recently taken out Neem-based emulsions and solutions.

Grace Patent under the US Laws

Under the US laws related to Patents, the Grace patent appears to be an unexceptional example of American discovery, innovation and commercialization. The laws provide that the purification or any type of modification of a naturally occurring compound can result in the grant of a patent. As far as the Grace patent is concerned, it appears to satisfy 35 sections of the US Code 3 . Sections 101, 102 and 103 provide the requirements for the grant: (1) has some practical usefulness, (2) is novel in relation to the “prior art” 4 , (3) is not obvious from the “prior art” to a person of ordinary skill in the art at the time the invention was made, and (4) provides a description that is adequate to enable a knowledgeable person to practice the invention in the best mode. The fact that the invention is “obvious” to the Indian farmers does not defeat the purpose of the patentability in the United States. According to section 102(a) and (b), foreign knowledge can only defeat a U.S. patent's novelty claim if that foreign knowledge appeared in a printed publication before the invention or application by the U.S. applicant.

Analysis of the decision

Since the grant of the patent, Dr. Shiva, one of the activists in India, along with the International Federation of Organic Agriculture Movement and the Green Party in European Parliament, had been opposing it. Later, in 2000, the European Patent Office revoked the patent but the victory was short-lived as the revocation was followed by an appeal. Amidst the proceedings of the appeal, the opposers gave them evidence of farmers using this knowledge for a long time and also gave them information about the two scientists who had conducted research on neem before the patent had been granted.

The European Patent Office in Munich in 2005 dismissed an appeal against revoking a patent granted by it for the preparation of a fungicide derived from the seeds of the neem tree. The dispute was a long way to give confidence to the traditional users. Dr. Shiva, one of the three parties opposing the patent stated “It was pure and simple piracy. The oil from neem has been used traditionally by farmers to prevent fungus. It was neither a novel idea nor was it invented. It is the major victory that the appeal has been dismissed.”

Post-dispute

In India, after the neem patent controversy, the need to protect the traditional knowledge of India has gained importance. India has taken an initiative through TKDL (Traditional Knowledge Digital Library), which helps the examiners of Patent Offices to search for any information regarding substance or practice while granting patents and they can dismiss the grant of patent, if the substance or practice is already there in the TKDL list as Indian traditional knowledge.

The neem tree controversy is composed of a number of different facets. On an instinctive level, many Indians simply distrust any action taken by multinational companies. With their history of colonial exploitation and recent large-scale industrial accidents, Indians tend to see multinational companies as the enemy of Indian freedom. Moreover, many Indians are angry at the fact that the multinational companies seem continually to reap tremendous economic benefits from India, while the country as a whole remains very poor. Activist organizations, throughout the dispute, expressed outrage that Grace can use knowledge that is so commonplace in India to achieve million-dollar international profits. This fact only serves to intensify the sense that the international intellectual property regimes are rigged against developing countries such as India. The United States-and Western countries generally-must realize that while developing countries continue to perceive the distribution of economic benefits of intellectual property protections as skewed, there will be resistance to sharing biological resources. To make developing countries willing partners in exploiting the promise of biodiversity, the international community should consider devices for sharing benefits. If individuals or communities in developing nations feel that their knowledge is consistently being “ripped off,” they are unlikely to reciprocate enforcement of intellectual property laws . Therefore, the community must explicitly address the philosophical differences over the issue of patenting life, as this debate is likely to continue in new forms.

1 Act no. 39 of 1970.

2 Act no. 17 of 1957.

3 U.S.C. d 101, 102 and 103.

4 Prior art is any evidence that your invention is already known.

The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.

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Neem: Traditional Knowledge from Ayurveda

• First Online: 20 October 2019

Cite this chapter

• S. N. Venugopalan Nair 5 ,
• Naveen Shilpa 5 ,
• Thomas Vargheese 5 &
• I. F. Tabassum 5  

Part of the book series: Compendium of Plant Genomes ((CPG))

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Ancient Indian medical literature is said to be one of the world’s most well-documented and incomparable evidences of the extreme wealth of Indian knowledge systems which dates back between 1500 BCE and 1900 CE. Detailed theoretical foundations and resources from Ayurveda, Unani, Siddha, and Tibetan medicine on medicinal plants, disease diagnosis, and treatment methods have long existed with considerable documented evidences. While on the other hand, undocumented knowledge is widely practised by hundreds of tribal communities across India and is often regarded as folk medical knowledge. Surpassing 6500 well-documented medicinal plants, India holds a treasure house of knowledge in this regard and Neem is one of the most important medicinal plant being widely used by all medicinal systems. This chapter aims to capture the essence of traditional knowledge on Neem, as documented in Ayurveda with detailed references. Various examples with detailed citations and descriptions, translated from ancient Acharyas such as Charaka , Susrutha, and Vaghbata have been covered. Vernacular names and Sanskrit synonyms of Neem along with its descriptive meaning illustrates the importance and popularity of Neem at a wider scale. The sheer depth of Indian Knowledge Systems is demonstrated with Sanskrit slokas and its approximate English meaning with the explanation on the use of various parts of the Neem as well as simple and compound medicinal formulations. Highly informative data sources and bibliography with supportive evidences authentic in nature have also been provided for further referencing.

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Acknowledgements

We thank Dr. P. M. Unnikrishnan and Dr. Subramanya Kumar K. for their valuable inputs and encouragements.

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Chittaranjan Kole

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Venugopalan Nair, S.N., Shilpa, N., Vargheese, T., Tabassum, I.F. (2019). Neem: Traditional Knowledge from Ayurveda. In: Gowda, M., Sheetal, A., Kole, C. (eds) The Neem Genome. Compendium of Plant Genomes. Springer, Cham. https://doi.org/10.1007/978-3-030-16122-4_1

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A Tree for Solving Global Problems

The neem tree, one of the most promising of all plants, may eventually benefit every person on the planet. Probably no other plant yields as many varied products or has as many exploitable by-products. Indeed, as foreseen by some scientists, this tree may usher in a new era in pest control; provide millions with inexpensive medicines; cut the rate of population growth; and perhaps even reduce erosion, deforestation, and the excessive temperature of an overheated globe.

On the other hand, although the enthusiasm may be justified, it is largely founded on exploratory investigations and empirical and anecdotal evidence. The purpose of this book is to marshal the various facts about this little-known species, to help illuminate its future promise, and to speed realization of its potential.

• Biology and Life Sciences — Animals, Plants and Other Organisms

Suggested Citation

National Research Council. 1992. Neem: A Tree for Solving Global Problems . Washington, DC: The National Academies Press. https://doi.org/10.17226/1924. Import this citation to: Bibtex EndNote Reference Manager

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Types of Publications

Patent on Neem

The neem tree (Azadirachta indica) originates from the Indian subcontinent and now grows in the dry regions of more than 50 tropical countries around the world. The neem tree has multiple uses. It is mentioned in Indian texts written over 2000 years ago and has been used for centuries by local communities in agriculture as an insect and pest repellent, in human and veterinary medicine, toiletries and cosmetics. It is also venerated in the culture, religions and literature of the region.

Even though first report on pesticide property of neem was reported in India in 1928, only after 30 years later systematic research work on neem was initiated. The past five decades witnessed intensive investigation and upward trend to scientific interest in neem and its diverse properties, resulting in large number of research publications, books and conferences at national and international levels. It led to isolation and identification of hundreds of the active compounds, from various parts with pesticidal, nematicidal, fungicidal, bactericidal, anti inflammatory, anti-tumor and other properties and found its applications in pesticide, medical, healthcare and cosmetic industry all over the world.

Since the 1980s, many neem related process and products have been patented in Japan, USA and European countries. The first US patent was obtained by Terumo Corporation in 1983 for its therapeutic preparation from neem bark. In 1985 Robert Larson from (USDA) obtained a patent for his preparation of neem seed extract and the Environmental Protection Agency approved this product for use in US market. In 1988 Robert Larson sold the patent on an extraction process to the US Company W.R. Grace (presently Certis). Having gathered their patents and clearance from the EPA, four years later, Grace commercialized its product by setting up manufacturing plant in collaboration with P.J. Margo Pvt. Ltd in India and continued to file patents from their own research in USA and other parts of world. Aside from Grace, neem based pesticides were also marketed by another company, AgriDyne Technologies Inc., USA, the market competition between the two companies was intense. In 1994, Grace accused AgriDyne a non-exclusive royalty-bearing license. During this period in India large number of companies also developed stabilized neem products and made them available commercially. The number of patents filed in this period were limited and geographically confined to few countries.

The challenge to a neem based patent held by W.R. Grace & Co. has returned many of intellectual property related issues controversies to center-stage globally.

These two cases not only created a global awareness on neem and its properties but also raised issues on biopiracy, need for documentation of traditional knowledge, equitable sharing of gains from traditional knowledge and harmonization of patent rule. Success of revocation of European patent illustrates the requirement of systematic documentation of knowledge whether traditional or scientific. Further these cases demonstrate the potential of IPR in creating awareness, enthusiasm in scientists, entrepreneurs, organizations and society and increased investments in research and development of products which compete in the market place. This is evident from upward trend of patents filed globally on neem from 1994 – 96 onwards – intense patent debate period and commercial product available in markets from neem.

Largest number of patents is in USA (54) followed by Japan (35), Australia (23), India (14). In India additionally more than 53 patent applications are pending for either gazette notification or opposition since 1995. If granted India will have the largest number of patents in neem. This itself illustrates that IPR does not stifle creativity and innovation but creates challenges and opportunities to over come the existing patents barriers by innovation and invention. There is also an increasing trend of filing application through PCT.

An analysis of type of patents suggests that majority of them are for crop protection applications (63%), followed by health care (13%), industrial (5%), veterinary care (5%), cosmetics (6%) and others (8%). This trend is also shown in country wise granted patents. For example in US out of 54 patents granted 31 were for crop protection rest for healthcare, cosmetics, industrial and veterinary applications. Organization wise patents ownership indicates largest number owned by Certis – W.R. Grace (49) followed by Rohm & Haas (36), CSIR-India (14), Trifolio (9), Bayer (8) and EID Parry (6).

The neem tree has been recognized the world over as a commercial opportunity. This is a welcome sign – but the bio-diversity prospects of this tree cannot be a free access to the entire world. It is now utterly urgent that the genetic fingerprints of our traditional wealth like neem are properly documented. The Neem Foundation has repeatedly pointed out that an immensely potential plant like neem should not be just left unrecognized and unprotected.

Granting neem the status of National Tree would send out the right signals to the world. This one move will help convert a national resource into a national asset.

The Tea Tree of Australia, Gingko Biloba of China, Ginseng of Korea, Guarana of the Amazon and Aloe Vera of Mexico are huge money-spinners in the booming alternate therapy market place of the West. Neem of India can emerge as the biggest player of them all – if India wakes up in time, takes charge and leads by farming policies and encouraging its use in its farmlands and public health programs.

A small country like Korea could successfully globalize its national treasure GINSENG – with an integrated approach, active research and development and positive promotion. It is a hallmark of the success of Korean farmers and Governmental efforts. India must draw lessons from this example.

In early 90s, the European Patent Office granted patents to the US Department of Agriculture and Multinational Agricultural Corporation (W.R. Grace of USA)

The patent was rejected on the basis that products derived from genetic resources (like peanut oil, sugarcane, corn, etc.) can not be patented. There were about 50 companies that tried to get patents on Neem Products and about 70 patents were rejected. This dropped interest of Neem Oil by multinational mega corporations in the agricultural area.

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Assessing the Impact of Neem on Fall Armyworm Damage to Maize Crops: A Field-Based Study in Nabdam District, UER, Ghana

This paper examines the effectiveness of neem as a biopesticide (using both oil and seed cake) obtained from the neem tree (Azadirachta indica) for controlling fall armyworm infestations in maize crops in Nabdam District, Upper East Region, Ghana. In July 2018, a demonstration maize field plot, with the monitoring of fall armyworm damage carried out before and after neem treatments. After two weeks, no fall army worms were seen in the section treated with neem oil spray, while they were found in the neem cake and control sections. In September 2018, maize yields were weighed. Although heavy rains affected the yield, a slightly greater yield was seen in the neem-oil sprayed section. The results of this field application of neem biopesticides is also considered in terms of practicality, effectiveness, cost, and environmental and health issues. The paper concludes with a discussion of the importance of farmer education for effective fall army worm monitoring and neem biopesticide use. ...

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Ogechi Umeh

Efficacy of neem bio-pesticide and synthetic insecticides against control of fall armyworm (Spodoptera frugiperda) in Maize

trymore kamunhukamwe

Fall Armyworm (FAW), Spodoptera frugiperda, is prevalent in Zimbabwe, causing significant damage to maize and yield losses. Three synthetic insecticides (Nemesis, Ecoterex and Lamda-cyhalothrin) belonging to different chemical groups and neem bio-pesticide (Neem Leaf Extract) were tested for their efficacy against FAW under laboratory and field conditions. The aim of the study was to assess the effect of neem bio-pesticide and synthetic insecticides on the population of FAW larvae, level of leaf damage and maize grain yield in comparison with untreated control plants. In laboratory experiment, neem biopesticide and the three synthetic insecticides resulted in significantly higher FAW larval mortality (p < 0.05) at 24, 48 and 72 hours after application of treatments as compared with the untreated plants. Neem bio-pesticide and the synthetic insecticides caused highest percentage of larval mortality (> 90%) at 72 hours after treatment application. In the field, both bio-pesticide and synthetic insecticides resulted in significantly higher efficacy (p < 0.05) against fall armyworm larvae, reduced the level of leaf damage and increased maize grain yield as compared to the untreated control plants. The untreated maize plants were found to be extensively damaged by FAW as compared to those treated with insecticides and neem bio-pesticide. The highest efficacy was recorded on plants treated with Nemesis, followed by Neem Leaf Extract, Ecoterex and lastly Lamda-cyhalothrin, respectively. The neem bio-pesticide and synthetic insecticides which were used in this study showed high efficacy against FAW larvae and can be recommended to be used as components for integrated pest management (IPM) plans for FAW under smallholder farmer conditions in Zimbabwe and the rest of Africa.

Asian Journal of Biological and Life Sciences

Emmanuel Okrikata

Azadirachta indica (A) Juss which is commonly called Neem was introduced to Nigeria from Ghana, and was first grown from the seeds in Maiduguri, in the then Bornu province (Now Borno State), Nigeria in 1928. Aside its medicinal importance, neem products have great pesticidal and most especially insecticidal potential. Various neem formulations such as oil, seed kernel powder and, leaf and seed kernel extracts have been experimented for the control of different insect pests with appreciable success thereby bringing to the fore the potential of neem in insect pest management. However, for these research findings to be propagated and accepted by our low-resource/grass-root farmers, who happens to be the backbone of Nigerian Agriculture, the researches need to be holistic; hence the following aspects which so far have not received serious attention are recommended for further investigation in Nigeria. These aspects include; on farm trials, cost benefit analysis of neem based pesticides, evaluation of the potential of neem products to act as synergists/to be synergized particularly by other botanicals, determination of neem trees with better insecticidal properties; environmental impact, phytotoxicity, pest resurgence and pest resistance assessments of neem based pesticides

Paul Simfukwe

Salako Samuel

IOSR Journals

Experiment was carried out in August, 2019, at the teaching and research plot of Department of Crop Production Technology, Federal Polytechnic, Bali; to determine the efficacy of neem products for control of field insect pests of white beans (kanannado). Sixty-four (64) beds measuring 3 m x 3 m were raised on a plot measuring 54 m x 15 m, which comprised of four replicates of 16 beds each. Individual bed contained nine (9) stands of cowpea plant spaced 1m apart. Treatments applied were extracts from neem leaf, neem bark and neem seed oil. Randomized Complete Block Design (RCBD) was adopted for the application of the treatments. Parameters assessed include ten pods weight, ten seed weight and total weight of pods per bed. Data collected were analysed using two-way analysis of variance (ANOVA) with the help of "R" statistical package. Means were separated using least significant differences (LSD) at 5% level of significance.

Journal of entomology and zoology studies

Illahi Bux Bhatti

Sugar beet Armyworm is an important pest of vegetables and other crops throughout the world. Field experiments were conducted to evaluate efficacy of neem oil spray in comparison to pesticide on sugar beet armyworm Spodoptera exigua during 2006-07 and 2007-08 at PARC-NSTHRI farm, Thatta. The armyworm infestation data indicated that minimum average population of armyworm was (1.43 and 0.88) in T-3 followed by (1.65 and 1.07), (1.77 and 1.04) and (1.81 and 1.58) in T-5, T-2 and T-4 respectively as compared control plot (3.64 and 3.58) during 2006-07 and 2007-08. However, from the results of yield, it was observed that T-5 produced significantly higher yield (116.940 and 115.205 t ha) followed by T-3 (115.078 and 112.675 t ha), T-4 (113.666 and 112.687 t ha) and T-2 (110.315 and 110.658 t ha) as compared control plot (68.280 and 68.500 during the year 2006-07 and 2007-08 respectively. Furthermore, the result of sugar content % showed no significant different among treatments. However, ...

Egyptian Journal of Agronematology

Fall armyworm infestation poses a serious threat to the food security and livelihoods of smallholder maize farmers in Ghana. The most sustainable management approach is Integrated Pest Management. Entomopathogenic nematodes have the potential for inclusion in IPM to manage crop insect pests. The study aimed at finding a sustainable option to manage fall armyworms in maize. Maize plant rhizosphere soils were sampled from maize farms in 2019 for entomopathogenic nematodes. On an acre maize farm, 10 core soil samples were collected using soil augur at &lt;20 cm soil depth and composited weighing 0.5 kg. Each composite soil sample was supplied with five 5 instar stage fall armyworm larvae and incubated (25°C; 85% RH) in a dark room. After 4 days, the fall armyworm larvae cadavers were removed from the soil for culturing and collection of infective entomopathogenic nematodes using modified White traps. A partitioned plant house accommodated each of three treatments: (T1) Supa ataka (Emam...

Patrick Beseh

The invasive fall armyworm (FAW) is threatening maize production and the livelihoods of millions of smallholder farmers in the newly invaded areas in Africa and Asia. To control this new key pest and to overcome health, environmental, and resistance problems related to the indiscriminate use of insecticides, effective and sustainable alternative pest control approaches are needed. Here, we report on field trials that tested maltodextrin, neem-based products, ash, and soil, as well as the locally produced alata samina soap, in the Upper West and Greater Accra regions, Ghana. Significant reductions of larval numbers and crop damage, together with increased yields, were mostly achieved by applying the insecticide emamectin benzoate, which was considered the positive control in this set of trials. However, high efficiency and cost–benefit ratios were also achieved with two neem-based products. Maltodextrin was only efficient at one of the two sites, with a clear dose-dependent effect, w...

Crop Protection

Hamadttu Elshafie

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A case study of the assistive technology network in Sierra Leone before and after a targeted systems-level investment

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Many people with disabilities in low-income settings, such as Sierra Leone, do not have access to the assistive technology (AT) they need, yet research to measure and address this issue remains limited. This paper presents a case study of the Assistive Technology 2030 (AT2030) funded Country Investment project in Sierra Leone. The research explored the nature and strength of the AT stakeholder network in Sierra Leone over the course of one year, presenting a snapshot of the network before and after a targeted systems level investment.

Mixed-method surveys were distributed via the Qualtrics software twice, in December 2021 and September 2022 to n=20 and n=16 participants (respectively). Qualitative data was analyzed thematically, while quantitative data was analyzed with the NodeXL software and MS Excel to generate descriptive statistics, visualizations, and specific metrics related to indegree, betweenness and closeness centrality of organizations grouped by type.

Findings suggest the one-year intervention did stimulate change within the AT network in Sierra Leone, increasing the number of connections within the AT network and strengthening existing relationships within the network. Findings are also consistent with existing data suggesting cost is a key barrier to AT access for both organizations providing AT and people with disabilities to obtain AT.

While this paper is the first to demonstrate that a targeted investment in AT systems and policies at the national level can have a resulting impact on the nature and strength of the AT, it only measures outcomes at one-year after investment. Further longitudinal impact evaluation would be desirable. Nonetheless, the results support the potential for systemic investments which leverage inter-organizational relationships and prioritize financial accessibility of AT, as one means of contributing towards increased access to AT for all, particularly in low-income settings.

Assistive technology (AT) is an umbrella term which broadly encompasses assistive products (AP) and the related services which improves function and enhances the user’s participation in all areas of life. 1 Assistive products are “any external products (including devices, equipment, instruments and software) […] with the primary purpose to maintain or improve an individual’s functioning and independence and/or well-being, or to prevent impairments and secondary health conditions”. 2

Recently, awareness for the urgent need to improve access to Assistive Technology has expanded, as 2022 global population statistics highlights one in three people, or 2.5 billion people, requires at least one assistive product. 1 The demand for AT is projected to increase to 3.5 billion people by 2050, yet 90% of them lack access to the products and services they need. 1 , 3 A systemic approach which adequately measures outcomes and impact is urgently required to stimulate evidence-based policies and systems which support universal access to AT. 1 , 4 , 5 However, a systemic approach first necessitates baseline understandings of the existing system, inclusive of sociopolitical context and the key stakeholders working within that context.

Assistive technology is necessary for people with disabilities to engage in activities of daily living, such as personal care or employment, and social engagement. 6 Moreover, people with disabilities also require AT to enact their basic human rights, as outlined in the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD). 7 Unfortunately, many people do not have access to the AT they require, an inequity which is perpetuated within low-income settings. 8 Despite this growing disparity and a well-documented association between poverty and disability, 9 research gaps remain related to AT within low-income settings in the global South. 10

In Sierra Leone, the national prevalence of disability is estimated to be 1.3%, according to the most recent population and housing census data. 11 , 12 This is unusually low, as compared to the 16% global prevalence (World Health Organization, 2022). National stakeholders within the AT network argue this statistic does not adequately represent the true scope of disability in Sierra Leone. 10 Their stance is supported by survey data from the Rapid Assistive Technology Assessment (rATA) across a subset of the population in Freetown, which indicated a dramatically different picture: a 24.9% prevalence of self-reported disability on the basis of the Washington Group Questions (20.6% reported as having “some difficulty”, while 4.3% rated “a lot of difficulty” or above), predominantly mobility and vision related disabilities. 13 The rATA also highlighted 62.5% of older people surveyed indicated having a disability, while the incidence of disability among females was nearly 2% higher than in males. 13

Despite the 2011 Sierra Leone Disability Act being implemented, access to AT in Sierra Leone remains poor. 13 The rATA suggests only 14.9% of those with disabilities in Freetown have the assistive products they require, an alarming rate which also fails to consider people with disabilities not surveyed in rural Sierra Leone where access to such services is likely lower. 13 Meanwhile, it is estimated over half of the population of Sierra Leone lives in poverty, with 13% in extreme poverty. 14 As affordability ranks as the top barrier for AT access, poverty further perpetuates the challenges of people with disabilities within this subset of the population to access necessary AT. 13 Within the context of low-resource settings it is therefore imperative that those resources which are allocated to provide assistive products are used in the most optimal manner, and that different stakeholders work together to co-construct a systemic approach which can identify and prioritise those most in need.

This paper presents a dataset collected in tandem with an Assistive Technology 2030 (AT2030) funded Country Investment project in Sierra Leone in collaboration with Clinton Health Access Initiative (CHAI). The study aimed to explore the nature and strength of the assistive technology stakeholder network in Sierra Leone over the course of one year through a mixed methods survey methodology. We provide a systemic snapshot of the AT network in Sierra Leone, highlighting what assistive products are available, who provides and receives them, and how. We also present a relational analysis of the existing AT network, inclusive of the organizations working within areas of AT and their degrees of connectivity and collaboration amongst one another. We hope that such data can strengthen the provision of AT in Sierra Leone through identifying assistive product availability, procurement, and provision, as well as the nature of the relationships between (the relationality ) of the AT network. We also sought to provide an overview of any possible changes to the network over the course of a one-year investment by AT2030.

This study used a mixed methods survey approach, facilitated by Qualtrics online survey software. Surveys were collaboratively developed and distributed at the two time periods in December 2021 and September 2022 (herein respectively described as Baseline=T1 and Follow Up= T2).

Intervention

This paper presents the Sierra Leone country project built within a larger, targeted investment in assistive technology systems development in four African countries,by AT2030, a project led by the Global Disability Innovation Hub and funded by UK Aid. The four in-country projects were administered by Clinton Health Access Initiative (CHAI) in partnership with local government ministries and agencies. As part of this investment, CHAI and its partners convened a Technical Working Group which brought together key stakeholders in the assistive technology field. Over the course of one year, the Technical Working Group had an overarching goal to develop and strengthen key assistive technology related policies in each of the four countries. The data in this study on the AT network in Sierra Leone was collected at the outset and following completion of the AT2030 investment, by researchers who were not part of the investment process, thus allowing for third-party evaluation. To maintain objectivity, neither CHAI nor the funder were responsible for the design, data collection, analysis or reporting of results, but this paper has benefited from a programmatic perspective provided by CHIA.

Participants

Participants included members of relevant ministries involved in assistive technology leadership and/or delivery, and staff representing relevant non-profit organizations (both international and local), service providers and organizations for persons with disabilities. Participants were asked to respond on behalf of their organization. All prospective participants were identified by the researchers and local project partners, including those coordinating the investment identified above, and added to a distribution list on Qualtrics, which only contained pertinent identifying information such as name, organization, and email. Over the course of the study, n=20 (T1) and n=16 (T2) participants consented to and completed surveys. While the relatively small sample size may inherently restrict the generalizability of this study, the sample size is reflective of the size of the assistive technology network in Sierra Leone, which we aimed to explore.

Data collection

The survey was emailed to the distribution list at two time points: December 2021 (T1) and September 2022 (T2). Two reminder emails were sent out via Qualtrics at two-week intervals following each time point, to participants who had not yet completed the surveys as a means to stimulate participant retention. The T1 and T2 surveys were identical, however the T2 survey utilized display logic functionalities such as conditional skipping to prevent retained respondents from completing redundant questions such as demographic information. If a participant completed the survey for the first time during the T2 period, they received the survey in its entirety without conditional skipping.

Survey content

Survey questions aimed to capture what AT is available, how it is being provided, who is receiving it and how. Questions also consisted of demographic information and qualitative prompts to identify participants’ roles within the AT network and critical challenges experienced in enacting their roles, as well as the nature and strength of relationships between stakeholders. Additional data was collected on participatory engagement in policy development, knowledge of assistive technology, and capacity for leadership which will be published separately.

Using the methodology reported by Smith and colleagues, 15 the WHO priority assistive products list was provided for respondents to select the products and associated services their organization provides. Additionally, the survey requested respondents to select from a list of organizations, which ones they were aware of as working within AT areas in Sierra Leone, followed by a subsequent 5-point Likert scale (1-5, 1= no relationship, 5= collaboration) to indicate which organizations they had working relationships with and to what extent. In attempts to maximize response rates and maintain participant retention, two reminder emails were sent to participants for T1 and T2; however, challenges encountered were participant drop-out from T1 to T2.

Data analysis

Data was reviewed across the two time periods and descriptive statistics (counts and means) were calculated for all variables using MS Excel software. Qualitative data employed content analysis of the text responses from each open-ended survey question, with a particular emphasis on themes which represented commonalities or a lack of representation across all stakeholders. Network data was analyzed using the NodeXL software and MS Excel to generate visualizations, and specific metrics related to indegree, betweenness and closeness centrality of organizations grouped by organization type. Indegree represents the total number of incoming connections per organization, while weighted indegree represents the sum of weights (strength) of each connection. Closeness centrality represents the relationship of the organization to the centre of the network (lower scores indicate greater centrality). To accommodate for different response rates at baseline and follow up, indegree was calculated as a proportion of incoming connections out of the total respondents (n) for that time point. Weighted indegree was calculated as a proportion of the sum of weights of incoming connections divided by the total possible weighting for the respondents for that time point (i.e. n*5). Statistical comparisons for overall network metrics across T1 and T2 were calculated using a paired t-test in SPSS v.28. While means are also reported by organization type as a subsample of the overall data, no statistical tests were carried out due to small subsample sizes.

The study received ethical approval from Maynooth University and the Sierra Leone Ethics and Scientific Review Committee. Each survey contained a mandatory informed consent section which required completion prior to respondents accessing the survey questions. Respondents were not required to answer any specific questions and were not coerced to participate. All respondents received a unique identification code to preserve anonymity, and any identifying information was removed prior to data analysis.

A total of 27 participants from 24 organizations participated in the surveys across both baseline and follow-up time points (T1 n=20 and T2 n= 16). Nine individuals and 11 organizations were retained across both T1 and T2 surveys. The majority of participants represented International non-governmental organizations (n=9), followed by Organizations of Persons with Disabilities (n=8), Government Ministry (n=4), Service Delivery organisations (n=4) and Academic Institutions (n=2).

Additionally, the respondents were requested to identify multiple areas of AT that their organizations were aligned with. Advocacy ranked as the top selection (24.5%), followed by direct service provision (14.9%), human resources and capacity building (14.9%), policy or systems development (13.8%), product selection and/or procurement (13.8%), data and information systems (11.7%), and financing (6.4%).

Assistive Products in Sierra Leone

Participants were asked to select from the APL which products and/or product services they provide. Manual wheelchairs, crutches, canes, lower limb prosthetics and orthopaedic footwear were the most selected across both time points. Table 1 lists summarises the types of assistive products and services provided in Sierra Leone, and the number of organisations providing each product and/or service across all 50 APL products.

*Other assistive product offered but not on the Assistive Product List **Assistive product not provided, only service related to the prescription, servicing and maintenance, and customization of that Assistive product

Respondents indicated that the products they provide were most commonly procured by their organizations through purchase (38.7%), followed by donation (29%), building products themselves (22.6%) or other (9.7%), which was explicated as recycling used products.

Providers of Assistive Products in Sierra Leone

Participants were asked to indicate whether their organization provided assistive products and/or related services. The findings highlighted 38.3% of stakeholders directly provided AT and 40.4% directly provided AT related services to beneficiaries, while only 21.3% indicated they do not provide AT or AT related services at all.

More specifically, respondents who did indicate providing products and/or services indicated they provided the following services: provision of locally made assistive products, repairs and maintenance of assistive products, education and training of users on the utility of assistive products, referrals of people with disabilities to service providers, prosthetic and orthotics, accessibility assessments, and rehabilitation service provision. Participants whom do not directly provide AT or AT related services indicated their work falls within AT advocacy, fundraising, procurement, policy, and research.

When asked about the challenges they experienced procuring and distributing these products to beneficiaries, qualitative data indicated difficulty sourcing materials, challenges obtaining products due to poor infrastructure, poor quality standards and/or customizability of products, and low technical and managerial support as common barriers. High product and material costs and inadequate funds from both the organizations and beneficiaries was the most commonly cited challenge.

Beneficiaries of Assistive Products in Sierra Leone

When probed on the number of clients they served each month, respondents indicated the range of beneficiaries spanned from as little as 10 per month to upwards of 1000, while one respondent noted there was no fixed number as they serve at the national level. Respondents noted that their beneficiaries were predominantly people with mobility related disabilities or functional limitations (21.4%), closely followed by people with vision disabilities (17.9%), communication disabilities (15.4%) and hearing disabilities (13.1%).

Participants emphasized children and adolescents were the highest populations served, with an equal representation among the ages of 5-12 (23.7%) and 13-18 (23.7%). Adults aged 20-50 years (21%) closely followed, while children under 4 (15.8%) and adults over 50 years of age (15.8%) are equally less represented as beneficiaries of assistive products and services in Sierra Leone.

Respondents whose organizations provide assistive products indicated that their beneficiaries most commonly received APs free of cost (63.2%), followed by client payment (26.3%) and a fixed cost structure (10.5%).

Network Analysis

Respondents were asked to indicate which organizations in the AT network they were aware of, and subsequently to rate the strength of their relationship with the organizations they indicated an awareness of. The degree of relationality among these stakeholders involved in the assistive technology network was then analyzed across the two time points and organizational relationships were visualized using the NodeXL software, presented in Figure 1 and Figure 2 . The colored nodes in the figures depict the various sub-types of organizations, while the lines between the nodes represent their relationships, with thicker lines indicating stronger relationships. The red nodes represent government ministries and agencies, the green represent service delivery organizations, blue represents organization of persons with disabilities, black represents NGOs and yellow represents academic institutions.

Overall, this representation depicts a relatively centralized network with a higher degree of connections between organizations. Furthermore, ministries and government agencies appear towards the centre of the network, indicating a relatively greater role in connecting organizations to one another, however it is noteworthy that these are not the most central organizations in the network.

Table 2 provides quantitative data which demonstrates the overall number and strength of interconnections among the organizations within the assistive technology network in Sierra Leone. Indegree is the number of identified inward connections, or the number of other organizations who identified a connection with that organization. Indegree data are presented as a mean value per organization type to preserve anonymity. The data visualized in Table 2 significantly increased over one year from baseline to follow up, while the relative centrality of organizations did not change, at least over the one-year time period of this study.

SD – standard deviation, NGO – non-governmental organization *Differs significantly from baseline at p<0.01 (two-tailed)

Overall, there was a statistically significant increase in indegree scores between the two timepoints suggesting a higher level of connection among AT organizations in Sierra Leone following the 1-year investment. This suggests those organizations built more relationships and expanded their reach within the AT network. As relationship strength was measured on a 5-point scale (no awareness, awareness, communication, cooperation, collaboration), we can interpret increases in weighted indegree to suggest greater inter-organizational working between members of the network (please refer to Table 2 ).

These findings suggest the one-year intervention did indeed stimulate change within the AT network in Sierra Leone, increasing the number connections within the AT network, and strengthening existing relationships within the network.

The most common assistive products available in Sierra Leone were indicated to be manual wheelchairs, crutches, canes, lower limb prosthetics and orthopaedic footwear. This aligns with our participants ranking mobility related disabilities or functional limitations as the most common reason for beneficiary referral, as well as the rATA data 13 ). The global report on AT notes “the type, complexity, magnitude and duration of a humanitarian crisis impacts the need for and supply of assistive technology”. 1 When we factor in the sociopolitical context of Sierra Leone and its history of civil war, and the population requiring these products due to political violence, such as lower limb amputations, it is also not surprising that mobility related products are so widely available due to population need. Moreover, as many low-income settings procure their products through donations, often from abroad, these items are probable to be in high circulation in relation to the high global prevalence of mobility related disabilities, likely shaping what products donors perceive as being most relevant. 1

Interestingly, data from the rATA shows the people with disabilities who did have AP, most often obtained their product(s) through purchase, despite cost being the most significant barrier to access. 13 As such, these APs were often purchased through informal and unregulated providers who offer lower costs, such as market vendors. 16 In comparison, our findings demonstrated AT stakeholders providing AP did so predominantly at no-cost. This discrepancy could suggest those who need AT most are not aware of the regulated providers who offer free AP and/or AP services in Sierra Leone, or they simply cannot access them due to infrastructural barriers, or not having AT needed to navigate their environment in the first place. For example, our data highlighted only two organizations offering spectacles, yet the rATA indicated spectacles as being the most common AP obtained by people with disabilities sampled in Sierra Leone. This further supports our interpretation that access to free APs is limited if only a small subset of regulated providers are offering them, leading to an increased reliance on people with disabilities procuring APs from informal and unregulated providers in Sierra Leone. An interconnected and coherent national AT network could offer a way forward, should collaborative relationships among AT stakeholders continue to forge and their collective resources, contacts and beneficiaries were to be cross-pollinated for the advancement of beneficiary access.

As technology and what constitutes as AT continues to advance, juxtaposed with the prevalence of disability increasing, there is a risk that the gap in access to AT will continue to rise. 17 It is therefore paramount that the goal of improving AT related outcomes, such as improved access to AT for all, is first warranted by the measurement of such outcomes. 4 This paper has attempted to provide a systemic snapshot of the AT network in Sierra Leone, highlighting key information such as what assistive products are presently available, who provides them, who receives them (and how), and the relational cohesion of the network itself.

This paper is the first to demonstrate that a targeted investment in assistive technology systems and policies at the national level can have a resulting impact on the nature and strength of the assistive technology ecosystem relationships. It is therefore recommended as an intervention to engage stakeholders within the assistive technology space, in particular policy makers who have power to formulate AP related policy and access. However, this work is limited in scope as it only provides a reassessment of outcomes following the one-year investment, and does provide a more longitudinal evaluation of the impact of that investment in the longer term.

Future research is recommended to replicate the work done to date to evaluate whether there is an improvement in access to assistive technologies over a longer period of time as a result of targeted policy and systems change, as well as larger impacts on policy formulation for AP access. For example, attention to data collection of which types and categories of AP are being manufactured locally can inform policy formation to encourage continuity of local manufacturing, while improving access to AP. Moreover, further studies to investigate factors influencing limited uptake of free AP by persons with disabilities, as explicated above and discovered in this study, are recommended.

CONCLUSIONS

Cohesive AT networks are particularly important in low-income settings such as Sierra Leone, where the intersection of poverty and disability disproportionately reduces people with disabilities’ access to the AT they need. Power and colleagues 18 have proposed the Assistive Technology Embedded Systems Thinking (ATEST) Model as a way of conceptualising the embedded relationships between individual-community- system-country-world influences on assistive technology provision. This paper suggests that even where resources are scarce and systemic relationships are uneven, an internationally-funded investment, which embraces the participation of country-level stakeholders and service providing organisations can result in enhanced inter-organisational working, which in turn has the potential to use existing resources more optimally, allowing greater access to services for individuals most in need.

The findings of this paper demonstrate an increase in organizational collaboration can strengthen assistive technology networks, however key barriers to access remain cost for both organizations providing AT and people with disabilities to obtain AT. Future work should use systemic approaches to leverage organizational relationality and prioritize financial accessibility of AT within systemic approaches to AT policy and practice, to leverage existing resources (particularly no-cost AT) and advance towards the ultimate goal of increased access to AT for all.

Ethics Statement

Ethical approval for the study was granted by Maynooth University and the Sierra Leone Ethics and Scientific Review Committee. The study involved human participants but was not a clinical trial. All participants provided informed consent freely and were aware they could withdraw from the study at any time.

Data Availability

All data generated or analysed during this study are included in this article.

This work was funded by the Assistive Technology 2030 project, funded by the United Kingdom Foreign Commonwealth Development Office (FCDO; UK Aid) and administered by the Global Disability Innovation Hub.

Authorship Contributions

Stephanie Huff led the manuscript preparation and contributed to data analysis. Emma M. Smith led the research design, data collection, analysis and contributed to manuscript preparation. Finally, Malcolm MacLachlan contributed to research design, analysis, manuscript review, and supervision. All authors read and approved the final manuscript.

Disclosure of interest

The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests.

Correspondence to:

Emma M. Smith Maynooth University Maynooth, Co. Kildare Ireland [email protected]

Submitted : February 27, 2024 BST

Accepted : June 26, 2024 BST