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There has been astronomical increase in the costs of chemical fertilizers, agrochemicals, animal feeds and synthetic drugs in the developing countries, with an increasing indebtedness and acute poverty. This situation exerts enormous pressure to explore local resources, handy to combat these deficits and improve quality of life of the people. One of such available resources with great potentials in the 21st century is the neem (Azadirachta indica A. Juss) tree. Neem belongs to the family Meliaceae. It is the most versatile, multifarious trees of tropics, with immense potentials. It possesses maximum useful non-wood products such as leaves, bark, flowers, fruits, seeds, gum, oil and neem cake than any other tree species. Biologically neem has numerous bioactive ingredients with diverse applications. These bioactive ingredients are known to have antiallergenic, antidermatic, antifeedent, antiviral, antifungal, anti-inflammatory, antipyorrhoeic, antiscabic, insecticidal, larvicidal, anti-implantation, nematicidal, spermatocidal and other biological activities. This review is an attempt to assemble all the major research findings in neem which is of direct relevance to environment, industry, medicine and agriculture.
INTRODUCTION
The neem is a tropical evergreen tree native to Indian sub-continent (Roxburgh, 1874). It has been used in Ayurvedic medicine for more than 4000 years due to its medicinal properties. Most of the plant parts such as fruits, seeds, leaves, bark and roots contain compounds with proven antiseptic, antiviral, antipyretic, anti-inflammatory, antiulcer and antifungal uses. It has great potential in the fields of pest management, environment protection and medicine. Neem is a natural source of eco-friendly insecticides, pesticides and agrochemicals (Brahmachari, 2004). Neem is considered to be a part of India’s genetic diversity (Sateesh, 1998). It is the most researched tree in the world and is said to be the most promising tree of 21st century. The tree has adaptability to a wide range of climatic, topographic and edaphic factors. It thrives well in dry, stony shallow soils and even on soils having hard clay pan, at a shallow depth. Neem tree requires little water and plenty of sunlight (Sateesh, 1998). The tree grows naturally in areas where the rainfall is in the range of 450 to 1200 mm. However, it has been introduced successfully even in areas where the rainfall is as low as 150 to 250 mm. Neem grows on altitudes up to 1500 m (Jattan et al., 1995; Chari, 1996). It can grow well in wide temperature range of 0 to 49°C (Hegde, 1995). It cannot withstand water-logged areas and poorly drained soils. The pH range for the growth of neem tree lies in between 4 to 10. Neem trees have the ability to neutralize acidic soils by a unique property of calcium mining (Hegde, 1995).
Biologically active principles isolated from different parts of the plant include: azadirachtin, meliacin, gedunin, salanin, nimbin, valassin and many other derivatives of these principles. Meliacin forms the bitter principles of neem seed oil; the seed also contain tignic acid (5-methyl-2-butanic acid) responsible for the distincitive odour of the oil (Schmutterer, 1990; Uko and Kamalu, 2001; Lale, 2002). These compounds belong to natural products called triterpenoids (Limonoids). The active principles are slightly hydrophilic, but freely lipophilic and highly soluble in organic solvents like, hydrocarbon, alcohols, ketones and esters (Schmutterer and Singh, 1995). Therefore, this review will focus on the relevance of neem and its products in agriculture, industry, biomedicine and environment.
ORIGIN AND DISTRIBUTION OF NEEM
Two species of Azadirachta have been reported, Azadirachta indica A. Juss-native to Indian subcontinent and Azadirachta excelsa Kack. confined to Philippines and Indonesia (Jattan et al., 1995; Hegde, 1995). The former grows as a wild tree in India, Bangladesh, Burma, Pakistan, Sri Lanka, Malaysia, Thailand and Indonesia. Presently neem trees can be seen growing successfully in about 72 countries worldwide, in Asia, Africa, Australia, North, Central and South America (Ahmed et al., 1989; Sidhu, 1995; Sateesh, 1998; Fathima, 2004).
There are an estimated 25 million trees growing all over India (Rembold, 1996), of which 5.5% are found in Karnataka and it is in the third place next to Uttar Pradesh (55.7%) and Tamilnadu (17.8%) occupying the first two places respectively. The other states of India where neem tree is found growing includes Andhra Pradesh, Assam, Bihar, Delhi, Gujarat, Haryana, Himachal Pradesh, Kerala, Madhya Pradesh, Maharashtra, Meghalaya, Orissa, Punjab, Rajasthan, West Bengal along with Andaman and Nicobar Islands, the Union territory (Sindhuveerendra, 1995; Chakraborthy and Konger, 1995; Bahuguna, 1997; Fathima, 2004). India stands first in neem seed production and about 442,300 tons of seeds are produced annually yielding 88,400 tons of neem oil and 353,800 tons of neem cake.
TAXONOMICAL CLASSIFICATION OF NEEM
Neem is a member of the Mahogany family. It has similar properties to its close relative, Melia azederach. The word Azadirachta is derived from the Persian azaddhirakt (meaning 'noble tree’). The taxonomic positions of neem are as follows:
Order: Rutales
Suborder: Rutinae
Family: Meliaceae
Subfamily: Melioideae
Tribe - Melieae
Genus: Azadirachta
Specie: Indica
Latin: Azadirachta indica
Indian: Holy tree, Indian lilac tree
Hindi: Neem, Nim
Sanskrit: Nimba
Hausa: Dogon yaro
Igbo: Ogwu akuma
BOTANICAL DESCRIPTION OF NEEM
It is a hardy, fast-growing evergreen tree with a straight trunk, long spreading branches and moderately thick, rough, longitudinally fissured bark. Mature trees attain a height of 7-15 m (23-50 feet) (Ogbuewu, 2008). The tree starts producing the yellowish ellipsoidal drupes (fruits) in about 4 years, becomes fully productive in 10 years and may live for more than 200 years. The leaves are compound, imparipinnate, comprising up to 15 leaflets arranged in alternate pairs with terminal leaflets (Ogbuewu, 2008). The leaflets are narrow, lanceolate, up to 6 cm long. The flowers are abundant, sweet-smelling white panicles in the leaf axils. Seed propagation in nurseries followed by direct planting in the field is the accepted method to produce plantation stands (Ogbuewu, 2008). The one seed neem fruit is yellow when ripe and is about one inch long (Ogbuewu, 2008). Neem flowers mature from May to August (Koul et al., 2006) in India.
CHEMISTRY OF NEEM
Major chemical constituents of neem are Terpenes and Limonoids. The major active components in the Limonoids are azadirachtin, 3-deacetyl-3- cinnamoylazadirachtin, I-tigloyl-3-acetyl-II-methoxyazadirachtin, 22, 23-dihydro-23β-methoxyazadirachtin, nimbanal, 3-tigloylazadirachtol, 3-acetyl-salannoV nimbidioV margocin, margocinin, margocilin and others (Ogbuewu, 2008). Terpenoids are isoazadirolide, 6 nimbocinolide, nimbonone, nibonolone, methylgrevillate and Margosinone. Neem increases the production of Glutathione-s-transferase, thus improving the ability of the liver to detoxify itself of chemical contamination.
NEEM AND ENVIRONMENTAL PROTECTION
Afforestation: The large scale plantation of neem trees help to combat desertification, deforestation, soil erosion and to reduce excessive global warming (Sateesh, 1998). Neem has high rate of photosynthesis and liberates more oxygen than many other tree species, thus purifying the atmosphere (Nigam et al., 1994). Neem products have water purifying activity. Neem leaf powder could be used as biosorbent for the removal of dyes like Congo red from water (Bhattacharyya and Sharma, 2004). The temperature under the neem has been found to be ~10°C less than the surrounding temperature, during hot summer months in the northern parts of India. In agro-forestry, neem product benefits extended to providing shade, firewood, timber, wind breaks, shelter belt and check against desertification in the semi-arid zone of northern Nigeria.
Neem has the ability to re-sprout after cutting and to re-grow its canopy after pollarding. Thus it is highly suited for pole production. In Saudi Arabia neem plantation when full grown is expected to provide shade to about two million pilgrims (Ahmed et al., 1989). In Nigeria, neem forms about 90% of the trees in the forestry plantations established in the 12 states within the savanna zone under the afforestation programme, Nigeria inclusive (Nwokeabia, 1994). In Chad, neem constitutes about 17% of the tree cover (Ohabuike, 1995). Neem plantations have been used for halting the spread of Sahara desert in the countries from Somalia to Mauritania.
PEST MANAGEMENT PROSPECTS
The dependency on synthetic chemicals during early and middle twentieth century has prompted the large scale synthesis of newer chemicals (pesticides). Many a times, the side effects of the synthetic pesticides are more serious than problems themselves. They are also known to cause health problems in farmers of both developed and developing countries. According to World Health Organization estimation, annually 220,000 deaths occur due to acute poisoning caused by synthetic pesticides (Sateesh, 1998).
Neem based pesticides are found to be much safer in this regard. Today, neem has gained importance internationally as all communities have inclined towards green technology. Neem products have no ill effects on humans and animals and have no residual effect on agricultural produce. This makes neem the best, reliable substitute to hazardous pesticides. The demand for chemical pesticides will be reduced by large scale use of neem based pesticides that will in turn reduce the load of synthetic chemicals in environment.
Today, modern societies, finding themselves confounded in the web of their creation, are willing to revert to nature for remedies and neem tree provides a promising means in this matter. Neem wood is durable and termite resistant and thus used as mulch materials. The pesticidal activity of neem span a wide spectrum, having repellent, phagodeterrent (antifeedant), insect growth regulatory (IGR), anti-ovipositional, fecundity and fitness reducing properties on insects. Schmutterer and Singh (1995) listed 413 insect pest species sensitive to neem products. These principles act as ecdysteroid analogues, which affect corpus cardiacum and block reproductive and growth processes in most insects causing sterility in females and degenerative changes in male testis due to disturbance in insect metabolism. Formulations like: Margosan O(R), Neemix (™), Azatin(R), NIM-20 and NIM-76, gave negative result with respect to toxicity effect on mammals (Schmutterer, 1990; Govindachari et al., 2000). Hence, Neemix (™), was registered for use on vegetables in US for its inherent safety. In most tests, neem products performed equally or sometimes better than synthetics like Pirimiphos-methyl (Actellic 25 EC), Permethrin and Lindane (γBHC) (Ogunwolu and Oddunlami, 1996; Lale and Mustapha, 2000). Furthermore, the oriental yellow scale insects Aonidiela orientalis threatens survival of this Jewel in the savanna (Mahmood, 1995), through necrosis, chlorosis and scorching of the whole foliage, as they inject toxic metabolites into the foliage.
Neem based pesticides are easy to prepare, cheap and highly effective and thus constitute an important source of pesticide for economically poor third world country farmers (Brahmachari, 2004). Neem bio-pesticides are systemic in nature and provide long term protection to plants against pests. Pollinator insects, bees and other useful organisms are not affected by neem based pesticides (Tanzubil, 1996).
Organic fertilizer prospects: Neem cake is a cheap and useful fertilizer. The plant debris is potential source of organic manure (Brahmachari, 2004). Neem cake coated with urea has been produced, which when used increases nitrogen assimilation compared to untreated urea. Neem leaves could be used as a source for the preparation of vermi-compost having both fertilizer and pesticidal potential (Gajalakshmi and Abbasi, 2004).
Biological Nitrogen Fixation (BNF) maintains soil nitrogen (N) fertility. Non-symbiotic micro organisms like photosynthetic bacteria and Blue Green Algae (BGA) enhance this process. It is also known to increase soil fertility and water holding capacity. In field experiments neem cake stimulate algal growth by suppressing the grazers particularly Ostracods (class: Crustacea). BGA biomass tripled and N-fixation activity increases by 10 fold (Grant et al., 1983). The underlying mechanism is acute toxic effect rather than anti-feedant on the Ostracods. Admixing neem cake with urea fertilizer improves efficiency of fertilizer utilization in crop production by gradual release of nitrogen to crops (Ketkar, 1983). In tomato fields, neem cake significantly reduce root-knot nematode index to zero, with improved growth of tomatoes. The cake inhibited larval emergence and egg hatching. Finally these effects of neem enable exploitation by Nigerian, Indians and other Asians.
NEEM AND AGRICULTURE
Animal feeds: The livestock industry in developing countries has been plagued by numerous problems, which include scarce feed ingredients that are in strict competition with man’s dietary need. The high cost of conventional feedstuff has already sent a lot of livestock farmers out of business, thus leading to reduction in overall animal protein production and availability for humans dietary’s need. The provision of feed alone has been reported to account for 60-80% of total cost of livestock production in developing countriesalone (Igboeli, 2000; Esonu, 2006). In view of this, there is increased interest by livestock farmers on the search for non conventional feed ingredients of comparable quality that are believed to be cheaper such as leaf and seed meals of ethnomedicinal plants (Okoli et al., 2001,2002).
In an effort to develop new feedstuff for animal rearing, a number of researchers in recent times has investigated the proximate composition of neem seed cake (Bawa et al., 2006; Uko and Kamalu, 2001) and leaf meal (Oforjindu, 2006; Esonu et al., 2005, 2006; Ogbuewuet al., 2010a, b) and its use as feedstuff in poultry (Esonu et al., 2005; Oforjindu, 2006; Uko and Kamalu, 2007) and rabbits (Sokunbi and Egbunike, 2000a; Ogbuewu, 2008). Result of proximate analysis of neem showed that neem leaf meal had of 92.42% dry matter, 7.58% moisture, 20.68% crude protein, 16.60% crude fibre, 4.13% ether extract, 7.10% ash and 43.91% nitrogen free extract (Esonu et al., 2005; Oforjindu, 2006; Ogbuewu, 2008).
Neem cake has also been very widely used as animal feed (Bawa et al., 2006; Uko and 2007). Despite the bitter components, livestock consume diets containing varied percentage of neem cake. Alkali treatment of neem cake with caustic soda yields palatable product, by removing the toxicant triterpenoids (Devakumar and Dev, 1993). Nagalakshmi et al. (1996) and Verma et al. (1998) reported beneficial effect of alkali treated (10-20 g NaOH) neem kernel cake incorporated into poultry feeds. It resulted to an increased feeding value and protein utilization with spectacular growth. However, no significant difference was observed among the different dietary groups in feed intake, egg production, egg quality, fertility, hatchability and chick weight (Nagalakshmi et al., 1996; Verma et al. 1998).
Neem oil and de-oiled neem seed cake are used as animal feed. Neem oil which is rich in long chain fatty acids is used in poultry feed. Deoiled neem seed cake is rich in essential amino acids, crude proteins, fiber contents, sulphur and nitrogen (Uko and Kamalu, 2007).
Eco-friendly agrochemicals: Approximately one third of world’s agricultural food stuffs get destroyed by more than 20,000 species of field and storage pests and diseases (McEwen, 1978). To prevent this loss, large amounts of synthetic pesticides are applied, out of which only 0.1% reaches the target pests and more than 99% contaminates the ecosystem (Sateesh, 1998). In addition, synthetic agrochemical usage has resulted in development of resistant pests and pathogens. Cost-effective, non toxic, biodegradable, eco-friendly and botanical soft-agro chemicals are the need of present day agriculture as an alternative to hazardous and recalcitrant synthetic chemicals (Sateesh, 1998). Neem tops the list of 2,400 plant species that are reported to have antimicrobial properties and is regarded as the most reliable source of eco-friendly agrochemical property. Neem is also used as a bio-control agent to control many plant diseases (Kak, 2000). The insecticides from neem are non-phytotoxic with good shelf life and effective against a wide range of insects and pests.
Neem products are effective against more than 350 species of arthropods, 12 species of nematodes, 15 species of fungi, 4 strains of viruses, 2 species of snails and 1 crustacean species (Saxena et al., 1989; Nigam et al., 1994; Singh and Raheja, 1996; Mehta, 1997). Two tetracyclic triterpenoids - meliantetyraolenone and odoratone isolated from neem exhibited insecticidal activity against Anopheles stephensi (Siddiqui et al., 2003). Over 195 species of insects are affected by neem extracts and insects that have become resistant to synthetic pesticides are also controlled with these extracts. The apprehension that large-scale use of neem based insecticides may lead to resistance among pests, as being observed with synthetic pesticides, has not been proved correct. This is because the neem based insecticides have relatively weak contact effect in insects and also they have unique mode of action on insect’s life cycle and physiology.
Today, many neem bio-pesticides are now in market world over (Khanna, 1992; Brahmachari, 2004). Commercially available neem formulations like Achook (0.15% E.C.), Bioneem (0.03% E.C.), Nimbicidine (0.03% E.C.) and Neemark (0.03% E.C.) showed antifungal activity against pathogenic fungi viz., Fusarium oxysporum, Alternaria solani, Curvularia lunata, Helminthosporium sp. and Sclerotium rolfsii (Bhonde et al., 1999).
NEEM AND BIO-MEDICINE
Ethnoveterinary usage: In third world countries, neem has been used for centuries to provide health cover to human and livestock in various forms. In poultry, the bark is used to treat wounds, diarrhoea, ticks and lice (Ogbuewu, 2008). In the poultry industry, aflatoxicosis caused by Aspergillus flavus which originates from contaminated poultry feed is prevented using neem leaves. Neem leaf extract inhibits the production of aflatoxin by Aspergillus parasiticus (Allameh et al., 2002) and Patulin production by Penicillium expansum(Mossini et al., 2004). The processed neem cake has wormicidal activity and can be used as an excellent poultry feed. The leaves are used to treat abscesses and also applied after castration (Ogbuewu, 2008). They are also effective against bleeding, udder infections, fever, foot rot and lice in ruminants. Neem leaf has anti-hyperglycaemic and hypocholesmic effects in rabbits (Sokunbi and Egbunike, 2000b;Ogbuewu et al., 2010a, b) and poultry (Oforjindu, 2006; Esonu et al., 2006).The seeds are used for the treatment of ticks in ruminants and the bark, seeds, leaves and roots are used as an insect repellent.
All parts of the plant, as well as the gum and oil, are effective against worms, wounds in the mouth, glossitis, E. coli, bacillosis, swelling of the liver, jaundice, bloody dysentery and intestinal wounds (Ketkar and Ketkar, 1995). They are also used for constipation, indigestion, respiratory and throat disorders, asthma, pleuropneumonia and swelling of the mucous membranes in the respiratory tract and lungs. They are also used in skin disorders including ringworm, alopecia, eczema, urticaria, scabies, ticks and lice. Other minor indications include metritis, orchitis and tetanus, rinderpest, rheumatism, stoppage of urination, swelling of the kidney, mastitis, otitis and abscess in the ear (Ogbuewu, 2008). Alcohol and aqueous extracts of flowers of neem exhibits lethal effect against cattle filarial parasite Setaria cervi (Mishra et al., 2005). Livestock insects such as maggots, horn flies, blow flies and biting flies are controlled traditionally using neem.
Neem and ethnomedicinal uses: In West Africa, India, Burma, etc., both aqueous and alcohol extracts of bark and leaves of neem are effective anti malaria agents, particularly on chloroquine resistant strains (Badam et al., 1987; Udeinya et al., 2008). One active component, gedunin gave significant control as effective as quinine on malaria (Khalid et al., 1989; Subapriya and Nagini, 2005). The mechanism is possibly redox status of red blood cells (RBC) on parasite. The plasmodial parasite generates oxidant, while neem extracts reduced the oxidized cells to destroy the malaria parasite.
Furthermore, neem barks and leaves posses strong antiseptic property warranting use as active ingredient in tooth paste in India and Germany. While aqueous extract of leaves exhibit laxative potentials by increased bowel movement (Uko et al., 1995), over dose could however produce severe abdominal cramps or rectal prolapse. Kloos and McCullough (1987) reported potency of neem seed oil on snail fever (Schistosomiasis) with the active principle being mulluscicidal, ovicidal and cercariacidal. Several herbalists opined that neem products have broad spectral chemotherapeutic effect on the Flat, Tape and Round worms (Devakumar et al., 1985). Dental gel containing neem leaf extract reduces the oral plaque index and bacterial count (Pai et al., 2004).
Neem is used to treat malarial fever in ayurvedic medicine system. Neem oil treated mosquito nets and mosquito-repellent tablets are now available in the North-east India. Gedunin (a Limonoids) obtained from neem has activity similar to quinine against malarial pathogen. The neem liminoids (Azadirachtin, salannin, deacetylgedunin) exhibited high larvicidal, pupicidal and anti-ovipositional bioactivity against malaria vector - Anopheles stephensi. Tablet suspension of the bark and leaf of neem showed moderate effect against malarial pathogen, Plasmodium sp. (Isah et al., 2003). Methanolic extract fraction of neem leaves when tried against Coxsackie B group viruses, produced in vitro antiviral and virucidal effect (Badam et al., 1999). Anticarcinogenic activity of neem leaf extract was observed in murine system (Dasgupta et al., 2004).
Injection of neem leaf preparation to tumor in mice reduced tumour growth, exhibiting anti-carcinogenic activity (Baral and Chattopadhyay, 2004). Induction of apoptosis in rat oocytes was seen when treated with neem leaf extract (Chaube et al., 2006). Buccal pouch carcinogenesis in hamsters was inhibited by ethanolic leaf extract of neem (Subapriya et al., 2005). Good antioxidant activity was observed with neem leaf aqueous extract; flower and stem bark ethanolic extracts. Neem bark extract had potential of controlling gastric hyper-secretion and gastro-esophageal and gastro-duodenal ulcers (Bandyopadhyayk et al., 2004). Acetone-water neem leaf extract showed antiretroviral activity through inhibition of cytoadhesion. The extract increased haemoglobin concentration, mean CD4+ cell count and erythrocyte sedimentation rate in HIV/AIDS patients (Udeinya et al., 2004). Enhancement of antibody production and cellular mediated response by neem components helps in the treatment of AIDS.
NEEM AND REPRODUCTION
The neem seed oil, leaf extracts and NIM-76 act as powerful spermicide and significantly inhibited spermatogenesis, decreased sperm motility, count and cessation of fertility. These conditions were reversed by the withdrawal of neem products 4-6 weeks later (Sadre et al., 1983). Ogbuewu et al. (2009) reported no significant reduction in libido of rabbit bucks fed graded levels of neem leaf meal based diets. Furthermore, neem seed oil possesses anti-implantation and abortifacient properties. Sinha et al. (1984) found spermatozoa of human and Rhesus monkey were immotile and die within 30 min of contact with NSO in an intravaginal dose of 1.0 mL. Vaginal biopsy revealed no side effect, while radio-isotope studies indicate non-absorption in the vagina and non anti-ovulatory (Sinha et al., 1984). These findings enabled neem oil formulation ‘sensal’ use in India as powerful contraceptive.
Ogbuewu et al. (2009) and Mohan et al. (1997) reported significant reduction in semen volume, sperm count, higher incidence of morphological abnormalities of spermatozoa, fertilizing ability of rabbit bucks fed neem leaf meal based diets and hatchability of eggs on birds fed neem kernel cakes. The contraceptive property of neem oil has been reported (Upadhyay et al., 1994). Neem leaf extract has spermatotoxic effect (Ogbuewu et al., 2009). The leaf extracts of neem showed 100% immobilization and mortality of human spermatozoa at a 3 mg dose within 20 seconds (Khan and Awasthy, 2003; Khillare and Shrivastav, 2003). A new vaginal contraceptive, NIM- 76 was developed from neem oil having antimicrobial activity against Escherichia coli, Klebsiella pneumoniae and Candida albicans (Ram et al., 2002). Treatment of mice with neem leaf extract (aqueous) caused adverse effects on sperm motility, acrosomal morphology and number of spermatozoa (Mishra and Singh, 2005). Neem seed extracts inhibited folliculogenesis in albino rats. Neem extracts could thus be used as bio-rodenticides instead of toxic synthetic rodenticides that are pollutants (Roop et al., 2005).
NEEM AND SERUM METABOLITES
Administration of 5 g of aqueous leaf extract or an equivalent amount of dried leaf significantly reduced the insulin dosage by 30 - 50%, without a significant effect on the blood glucose levels (Khosla et al., 2000; Gupta et al., 2008). Aqueous extract of neem root and leaves reduced blood sugar level in rats exhibiting antidiabetic activity (Halim, 2003). In a study with rabbits and guinea pigs, it was reported that administration of the leaf extract of Azadirachta indica induced a potent and dose-dependent hypotension in rabbits (5-200 mg kg-1, IP) and guinea pigs (5-40 mg kg-1). The extract also exhibited anti-carrhythmic activity (40 mg kg-1 IV) against ouabain-induced dysrhythmia in rabbits. The mechanism of action may be explained an effect on vascular smooth muscle, giving rise to vasodilatation.
The neem leaf extract provided a hepatoprotective effect against paracetamol-induced hepatic cell damage in rats, findings supported by histopathological studies (Gupta et al., 2008). Both the neem leaf extract and seed oil produced a hypoglycaemic effect in normal as well as diabetic rabbits, comparable to that of glibenclamide. The effect was more pronounced in the diabetic animals. Pretreatment withIndica leaf extract or seed oil, given two weeks prior to alloxan, partially prevented the rise in blood glucose levels as compared to control diabetic animals (Gupta et al., 2008).
Administration of aqueous extract of neem along with DOCA salt prevented the development of hypertension in rats (Obiefuna and Young, 2005). Administration of the mature leaf extract decreased serum cholesterol significantly without changing serum protein, blood urea and uric acid levels in rats (Chattopadhyay et al., 2000; Ogbuewu et al., 2010a, b).
Neem and anti-microbial activity: Several active principles from neem have demonstrated high efficacy, against most pathogens. As fungicides, over 14 common fungi species are sensitive to neem preparations (Khan and Wassilew, 1987) they include the generaTrichophyton (athletes foot), Epidermophyton (ringworm of skin and nails), Microsporum (ringworm of skin and hair) and Candida(thrush). SaiRam et al. (1997) reported protection against systemic candidiasis (Candida albican) by NIM-76. The mechanism is simply antifungal and immunomodulatory. In Aspergillus flavus, neem leaf extract fail to inhibit growth, but reduce formation of aflatoxin by blocking polyketides production, which is commonly converted to toxins. Several diseases including Cercospora, Anthracnose, Downy mildew and Sigatoka are under investigation to establish efficacy of neem products as plant fungicides. As antibiotics, pathogenic bacteria like Staphylococcus aureus, Salmonella typhi are significantly suppressed by NSO. Trials with NIM-76 significantly suppressed E. coli and K. pneumoniea, which hitherto were insensitive to whole NSO (Ram et al., 2002). As antiviral agents, experiment with Small pox, Chicken pox and Fowl pox viruses show biological efficacy of neem extracts. Crude neem extracts adsorbed the viruses by blocking entry into uninfected cells. NIM-76 suppressed Polio virus replications and inhibited DNA polymerase of Herpes virus with no potency once infection is established in vivo (Rao et al., 1989). Therefore neem can be used against phytopathogenic fungi as a means of biological control (Jatav and Mathur, 2005).
Neem leaf and seed extracts exhibited antidermatophytic activity against dermatophytes viz., Trichophyton ruberum, Mentagrophytes,Trichophyton violaceum, Microsporum nanum and Epidermophyton flocosum under in vitro conditions (Natarajan et al., 2002). Neem seed oil showed bactericidal activity against 14 strains of pathogenic bacteria (Baswa et al., 2001). Crude aqueous and solvent extracts of neem were tried against 20 strains of pathogenic bacteria wherein crude extract produced better results (Srinivasan et al., 2001). Neem leaf extracts are antimutagenic. The ethanolic extract of neem leaves exhibited strong antimutagenic activity in Channa punctatus, a fresh water fish model (Farah et al., 2006).
INDUSTRIAL USES
In 2002, at the World neem conference, idea of promoting neem as an “Industrial Plant” was put forward (Kumar, 2003). Several industries including pharmaceuticals, cosmetics and textile industries use neem oil (Jattan et al., 1995). Many such neem-based commercial preparations are currently available (Khanna, 1992). In India neem is highly exploited by many Ayurvedic drug industries. Neem oil and powdered neem leaves are employed in various cosmetic preparations such as face creams, nail polish, nail oils, shampoos, conditioners (Jattan et al., 1995). A new shampoo, based on seed extract of neem was highly effective, more than permethrin-based product, against head lice under in vitro conditions (Heukelbach et al., 2006). Neem cake a by-product of neem oil industry is used as livestock feed, fertilizer and natural pesticide. Neem oil is commonly used in soap production. Medicated neem soaps are gaining popularity.
Neem based toothpaste is widely used in India and European countries. Neem is a source for many oral-hygiene preparations and dental care products. Neem bark yields gum and tannins which are used in tanning, dyeing etc. Neem seed pulp is used as a rich source of carbohydrate in fermentation industries and for methane gas production. Cultivation of neem and processing of neem products provides employment and income generation opportunities. Collection of neem seeds to be supplied to the industries provides important means of supplementary employment and income for the poor households, especially the rural women. India stands first in neem production and about 540,000 tons of seeds are produced annually yielding 107,000 tons of neem oil and 425,000 tons of neem cake. The amount of azadirachtin available is estimated to be about 1600 tons per annum, providing enormous amount of raw material for pesticide industry. In the product sector, annual estimated turnover is about Rs. 1000-1200 crores. Small scale industries have a major role to play in harnessing the potential. Therefore, in India it is the time to take right steps in promoting neem, both for the benefit of farmers and industries (Kumar, 2003).
NEEM AND PATENCY
During the past five decades intensive investigations on the diverse properties of neem have been carried out. As a result large numbers of research publications and books have been published. Many conferences have been conducted at national and international level. Hundreds of active compounds that are isolated from various parts of neem find their applications in pesticide, medicine, health care and cosmetic industry all over the world. World over the neem tree has been recognized as a commercial opportunity.
Many neem related processes and products have been patented in Japan, USA and European countries, since 1980s. In 1983, Temuro Corporation obtained the first US patent for its therapeutic preparation from neem bark. USA with 54 patents on neem and neem based products stands first followed by Japan (McEwen, 1978), Australia (Chakraborthy and Konger, 1995) and India (Fathima, 2004). Since 1995, more than 53 patent applications are pending in India for either gazette notification or opposition. Hopefully, if all these patents are granted India will have the largest number of patents in neem. Majority of patents that have been granted are for crop protection application (63%) followed by health care (13%), industrial (5%), veterinary care (5%), cosmetics (6%) and others (8%). Organization wise, largest number of patents are owned by Certis-W.R. Grace followed by Rohm and Haas (Kak, 2000), CSIR-India (Fathima, 2004), Trifolio (Jattan et al., 1995), Bayer (Chari, 1996) and EID Parry (Brahmachari, 2004).
CONCLUSION
Owing to its versatile characteristics neem is rightly called the village pharmacy. National Research Council, Washington, USA considers the neem, one of the most promising of all plants and the fact is that it may eventually benefit every person on this planet. Probably no other plant yields as many strange and varied products or has as many exploitable by-products. However, most of these findings on neem and its products are not patented, despite being potentially valuable, cost effective, reduces incidence of pests and parasite resistance with increase in agricultural production, environmental protection and health care services for humans and livestock. It is inferred from the above that neem plant is indeed a jewel globally. In line with these adequate benefits, researches on neem must be directed at identification and quantification of the active principles and patenting of findings thereby making these findings readily accessible to mankind for adoption.
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Traduction - espagnol La Creciente Importancia del Nim (Azadirachta indica A. Juss) en la Agricultura, Industria, Medicina y Medio Ambiente: Un Análisis
En los países en vías de desarrollo el costo de fertilizantes químicos, agroquímicos, alimentos para animales y medicamentos sintéticos ha aumentando exponencialmente, dejando un endeudamiento creciente y pobreza aguda. Esta situación ejerce una enorme presión por explorar recursos locales, útiles para combatir estos déficits y mejorar la calidad de vida de la gente. Uno de los recursos con gran potencial disponibles en el siglo XXI es el árbol del nim (Azadirachta indica A. Juss). El nim pertenece a la familia Meliaceae. Es el árbol más versátil de los trópicos, con potenciales inmensos y variados. Posee la más alta cantidad de productos útiles no provenientes de la madera que cualquier otra especie de árbol. Se emplean hojas, corteza, flores, frutos, semillas, resina, aceite y torta de nim. Biológicamente, el nim tiene numerosos ingredientes bioactivos con diversas aplicaciones. Estos ingredientes son conocidos por tener actividad antialergénica, antidermática, antialimentaria, antiviral, antimicótica, antiinflamatoria, antipiorréica, antiácaros, insecticida, larvicida, antiimplantación, nematicida, espermicida y otras actividades biológicas. Este ensayo es un intento por reunir todos los resultados de investigaciones importantes sobre el nim que tengan relevancia directa con el ambiente, la industria, la medicina y la agricultura.
INTRODUCCIÓN
El nim es un árbol tropical perenne, nativo del subcontinente indio (Roxburgh, 1874). Debido a sus propiedades medicinales se ha empleado en la medicina Ayurveda por más de 4,000 años. La mayoría de las partes de la planta como frutos, semillas, hojas, corteza y raíces contienen compuestos con usos antisépticos, antivirales, antipiréticos, antiinflamatorios, antiulcerosos y antimicóticos probados. El nim es considerado como parte de la diversidad genética de la India. Tiene un gran potencial en el área de manejo de plagas, protección ambiental y medicina. El nim es una fuente natural de insecticidas, pesticidas y agroquímicos orgánicos (Brahmachari, 2004). Es el árbol más investigado en el mundo y se dice que es el árbol más prometedor del siglo XXI. Se adapta a un amplio rango de factores climáticos, topográficos y edáficos. Crece bien en suelos secos, pedregosos y superficiales, y hasta en suelos arcillosos y poco profundos. El árbol del nim requiere poca agua y mucha luz solar (Sateesh, 1998). Crece naturalmente en áreas donde las precipitaciones oscilan entre 450 y 1 200 mm. Sin embargo, se ha introducido exitosamente en áreas donde las precipitaciones alcanzan apenas de 150 a 200 mm. El nim crece en altitudes de hasta 1 500 m (Jattan et al., 1995; Chari, 1996). Puede desarrollarse en el amplio rango de temperatura que va de 0° a 49°C (Hegde, 1995). No soporta áreas cubiertas de agua o suelos poco drenados. El rango de pH adecuado para su crecimiento es de 4 a 10. Los árboles del nim tienen la capacidad de neutralizar suelos ácidos gracias a una propiedad única de extracción de calcio (Hegde, 1995).
Principios biológicamente activos aislados de diferentes partes de la planta incluyen: azadiractina, meliacina gedunina, salanina, nimbina, valassin y muchos otros derivados de estos principios. La meliacina forma los principios amargos del aceite de semilla de nim; la semilla contiene también ácido tícnico (5-metil 2 butánico), resposable del olor distintivo del aceite (Schmutterer, 1990; Uko and Kamalu, 2001; Lale, 2002). Estos compuestos pertenecen a productos naturales llamados triterpenoides (limonoides). Los principios activos son ligeramente hidrofílicos, pero libremente lipofílicos y altamente solubles en solventes orgánicos como hidrocarbono, alcoholes, cetonas y ésteres (Schmutterer and Singh, 1995). Por lo tanto, este ensayo se enfocará en la relevancia del nim y sus productos en la agricultura, la industria, la biomedicina y el medio ambiente.
ORIGEN Y DISTRIBUCIÓN DEL NIM
Dos especies de Azadirachta han sido reportadas: Azadirachta indica A. Juss, nativa del subcontinente indio y Azadirachta excelsa Kack, limitada a Filipinas e Indonesia (Jattan et al., 1995; Hegde, 1995). La primera crece como un árbol salvaje en India, Bangladesh, Birmania, Pakistán, Sri, Lanka, Malasia, Tailandia e Indonesia. Actualmente se puede ver el crecimiento exitoso de árboles de nim en aproximadamente 72 países alrededor del mundo, en Asia, África, Australia y en América del Norte, América Central y Sudamérica (Ahmed et al., 1989; Sidhu, 1995; Sateesh, 1998; Fathima, 2004).
Hay un estimado de 25 millones de árboles creciendo por toda India, del cual 5.5 % se encuentran en Karnataka, que está en tercer lugar, seguido de Uttar Pradesh (55.7 %) y Tamil Nadu (17.8 %), ocupando los primeros dos lugares respectivamente. Los otros estados de la India donde el árbol de nim se encuentra creciendo incluyen Andhra Pradesh, Assam, Bihar, Delhi, Guyarat, Hariana, Himachal Pradesh, Kerala, Madhya Pradesh, Maharashtra, Megalaya, Orissa, Punyab, Rajastán, Bengala Occidental junto con las Islas Andamán y Nicobar, los territorios de la Unión (Sindhuveerendra, 1995; Chakraborthy y Konger, 1995; Bahuguna, 1997; Fathima, 2004). India se establece como el primer productor de semilla de nim, con alrededor de 442 300 toneladas de semillas producidas anualmente, cosechando 88 400 toneladas de aceite de nim y 353 800 toneladas de torta de nim.
CLASIFICACIÓN TAXONÓMICA DEL NIM
El nim es un miembro de la familia de la caoba. Tiene propiedades similares a su familiar más cercano, Melia azederach. La palabra Azadirachta se deriva del persa “azaddhirakt” (que significa “árbol noble”). La clasificación taxonómica del nim es la siguiente:
Es un árbol perenne, resistente y de rápido crecimiento, con un tronco recto y largo con ramas, moderadamente grueso, áspero, con una corteza agrietada longitudinalmente. Los árboles maduros alcanzan de 7 a 15 m de altura (23-50 pies) (Ogbuewu, 2008). El árbol comienza produciendo drupas amarillentas ovaladas (fruto) en un lapso de aproximadamente 4 años, se vuelve totalmente productivo en 10 años y puede vivir por más de 200 años. Las hojas son compuestas, imparipinnadas, compuestas de hasta 15 folíolos acomodados en pares alternos con folíolos terminales (Ogbuewu, 2008). Los folíolos son estrechos, lanceolados, de hasta 6 cm de largo. Las flores son abundantes, de olor dulce, con panículas en las axilas de la hoja. La propagación de la semilla en viveros, seguida de la plantación directa en el campo es el método aceptado para producir sembradíos (Ogbuewu, 2008). Las flores de nim maduran de mayo a agosto (Koul et al., 2006) en la India.
QUÍMICA DEL NIM
Entre los mayores constituyentes del nim se encuentran los terpenos y los limonoides. Los principales compuestos activos en los limonoides son azadirachtin, 3-diacetil-3-cinnamoylazadirachtin, I-tigloyl-3-acetil-II-methoxyazadirachtin, 22, 23-dihidro-23β-methoxyazadirachtin, nimbanal, 3-tigloylazadirachtol, 3-acetil-salannoV nimbidioV margocin, margocinin, margocilin y otros (Ogbuewu, 2008). Los terpenoides son isoazadirolide, 6 nimbocinolide, nimbonone, nibonolone, methylgrevillate y Margosinone. El nim aumenta la producción de Glutatione-s-transferasa, mejorando así la capacidad del hígado de desintoxicarse a sí mismo de contaminación química.
EL NIM Y LA PROTECCIÓN DEL MEDIO AMBIENTE
Forestación: La plantación a gran escala de árboles de nim ayuda a combatir la desertización, deforestación, erosión del suelo y a reducir el excesivo calentamiento global (Sateesh, 1998). El nim tiene un alto índice de fotosíntesis y libera más oxígeno que muchas otras especies de árboles, purificando así la atmósfera (Nigam et al., 1994). Los productos de nim tienen actividad purificadora de agua. El polvo de hoja de nim podría ser empleado como biosorbente para la extracción de tintes como el Rojo Congo del agua (Bhattacharyya and Sharma, 2004). Se ha encontrado que la temperatura bajo el nim es de ~10°C, menos que la temperatura circundante en los meses calientes de verano en el norte de la India. En la agroforestería, los beneficios del producto del nim incluían desde proporcionar sombra, leña, madera, protección contra el viento, abrigo, hasta control contra la desertización en la zona semiárida del norte de Nigeria.
El nim tiene la capacidad de volver a retoñar después de haber sido cortado y de volver a desarrollar su follaje después de una poda radical. Así que es altamente apropiado para su producción en línea vertical. En Arabia Saudita se espera que la plantación del nim totalmente desarrollada provea sombra a alrededor de dos millones de peregrinos (Ahmed et al., 1989). En Nigeria, el nim conforma cerca del 90% de los árboles en las plantaciones forestales establecidas en los 12 estados dentro de la zona de la Savannah que están bajo el programa de forestación, incluyendo Nigeria (Nwokeabia, 1994). En Chad, el nim constituye aproximadamente 17% de la cobertura de árboles (Ohabuike, 1995). Las plantaciones de nim han sido utilizadas para frenar la expansión del desierto de Sahara en los países desde Somalia hasta Mauritania.
PERSPECTIVAS PARA EL CONTROL DE PLAGAS
La dependencia de químicos sintéticos durante principios y mediados del siglo veinte ha propiciado la síntesis a gran escala de químicos más novedosos (pesticidas). Muchas veces, los efectos secundarios de los pesticidas sintéticos son más serios que los problemas mismos. También se sabe que causan problemas de salud a granjeros de países tanto en vías de desarrollo como desarrollados. De acuerdo a las estimaciones de la Organización Mundial de la Salud, anualmente ocurren 220,000 muertes debido a envenenamiento agudo por pesticidas sintéticos (Sateesh, 1998).
Se sabe que los pesticidas a base de nim son mucho más seguros en este aspecto. Hoy en día el nim ha ganado importancia internacional, ya que todas las comunidades se han inclinado hacia la tecnología verde. Los productos de nim no tienen efectos adversos en humanos o animales, ni efectos residuales en los productos agrícolas. Esto lo convierte en el mejor y más confiable substituto de los nocivos pesticidas. La demanda de pesticidas químicos se verá reducida por el uso a gran escala de pesticidas a base de nim, que a su vez reducirán la carga de químicos sintéticos en el medio ambiente.
Actualmente, las sociedades modernas, encontrándose atrapadas en la red de su propia creación, están dispuestas a volver a la naturaleza por remedios y el nim provee una solución prometedora al respecto. La madera de nim es duradera y resistente a las termitas, por lo que se usa como rastrojo. La actividad pesticida del nim abarca un gran espectro, teniendo propiedades repelentes, fagodeterrentes (antialimentarias), de regulación de crecimiento de insectos, y contra la ovoposición, fecundidad y salud de éstos. Schmutterer and Singh (1995) hicieron un listado de 143 especies de plagas de insectos sensibles a los productos de nim. Estos principios actúan como análogos del ecdysteroid, que afectan el corpus cardiacum y merman el proceso de reproducción y crecimiento en la mayoría de los insectos, causando esterilidad en las hembras y cambios degenerativos en los testículos del macho, debido a un disturbio en el metabolismo del insecto.
Fórmulas como: Margosan O(R), Neemix (™), Azatin(R), NIM-20 y NIM-76 demostraron no tener efectos tóxicos en mamíferos (Schmutterer, 1990; Govindachari et al., 2000), por lo que en Estados Unidos Neemix (™) fue registrado para su uso en verduras por su inocuidad inherente. En la mayoría de las pruebas, los productos de nim resultaron igual o en algunas ocasiones mejores que los productos sintéticos como Pirimiphos-methyl (Actellic 25 EC), Permetrina y Lindano (γBHC) (Ogunwolu and Oddunlami, 1996; Lale and Mustapha, 2000). Además, los insectos conocidos como “oriental yellow scale” , Aonidiela orientalis, amenazan la supervivencia de esta joya en la Savannah con necrosis, clorosis y quemadura de todo el follaje al inyectarle metabolitos tóxicos.
Los pesticidas a base de nim son baratos, fáciles de preparar, y altamente efectivos; por lo tanto, constituyen una fuente importante de pesticidas para los granjeros pobres de países tercermundistas (Brahmachari, 2004). Los pesticidas orgánicos de nim son sistemáticos en la naturaleza y proporcionan a las plantas protección contra plagas. Los insectos polinizadores, abejas y otros organismos útiles no se ven afectados por los insecticidas a base de nim (Tanzubil, 1996).
Posibles fertilizantes orgánicos: La torta de nim es un fertilizante útil y barato. Los restos de la planta son una fuente potencial de abono orgánico (Brahmachari, 2004). Se ha producido torta de nim bañada en urea que cuando se usa incrementa la asimilación de nitrógeno en comparación con la urea no tratada. La hojas de nim podrían ser empleadas como fuente para la preparación de vermicomposta con potencial pesticida y fertilizante (Gajalakshmi and Abbasi, 2004).
La fijación Biológica del nitrógeno (BNF ) mantiene la fertilidad del nitrógeno (N) del suelo. Microorganismos no simbióticos como bacterias fotosintéticas y algas verde-azules mejoran este proceso. También se sabe que aumentan la fertilidad del suelo y la capacidad de retención de agua. En experimentos del área se descubrió que la torta de nim estimula el crecimiento del alga al reprimir a los pasteadores, especialmente a los ostrácodos (clase: crustacea). La biomasa de las algas verde-azules se triplicó y la fijación del nitrógeno aumentó 10 veces (Grant et al., 1983). El mecanismo subyacente es un efecto tóxico agudo en vez de un efecto anti alimentario en los ostrácodos. La torta de nim mezclada con fertilizante de urea mejora la eficiencia del fertilizante utilizado en la producción de cosecha al liberar gradualmente nitrógeno a los cultivos (Ketkar, 1983). En las plantaciones de tomate, la torta de nim redujo significativamente el índice de los nematodos nodulares de las raíces a cero, con crecimiento mejorado de los tomates. La torta inhibió la aparición de larvas y la eclosión de huevos. Estos efectos del nim permiten la explotación por parte de nigerianos, hindús y otros asiáticos.
EL NIM Y LA AGRICULTURA
Alimento para animales: La industria ganadera en países en vía de desarrollo ha sido atacada por numerosos problemas, que incluyen escasos ingredientes de alimentación que compiten estrictamente con la necesidad alimenticia del hombre.
Los altos costos de los alimentos convencionales han llevado a muchos granjeros ganaderos fuera del negocio, lo que causa la reducción de la producción total de proteína animal y de la disponibilidad para la necesidad alimenticia del hombre. Se ha informado que la provisión de alimento por sí sola representa 60-80% del costo total de la producción de ganado tan sólo en los países en vías de desarrollo (Igboeli, 2000; Esonu, 2006). En vista de esto, los ganaderos muestran un interés creciente por encontrar ingredientes alimentarios no convencionales de calidad comparable, que se cree son más baratos, como harina de hojas y semillas de plantas etnomedicinales (Okoli et al., 2001, 2002).
En un esfuerzo por desarrollar nuevos alimentos para la cría de animales, cierto número de investigadores ha estudiado recientemente la composición aproximada de la torta de semilla de nim (Bawa et al., 2006; Uko and Kamalu, 2001), la harina de la hoja (Oforjindu, 2006; Esonu et al., 2005, 2006; Ogbuewu et al., 2010a, b), y su uso como alimento para aves domésticas y conejos (Sokunbi and Egbunike, 2000a; Ogbuewu, 2008). Los resultados del análisis aproximado mostró que la harina de hoja de nim contenía 92.42% de materia seca, 7.58% de humedad, 20.68% de proteína cruda, 16.60% de fibra cruda, 4.13% de extracto de éter, 7.10% de ceniza y 43.91% de extracto libre de nitrógeno (Esonu et al., 2005; Oforjindu, 2006; Ogbuewu, 2008).
La torta de nim también ha sido ampliamente utilizada como alimento animal (Bawa et al., 2006; Uko and 2007). A pesar del sabor amargo de sus componentes, el ganado consume dietas que contienen un porcentaje variado de torta de nim.
Al tratar alcalinamente la torta de nim en sosa cáustica se obtiene un producto de buen sabor, pues se remueven los triterpenoides tóxicos (Devakumar and Dev, 1993). Nagalakshmi et al. (1996) y Verma et al. (1998) reportaron sobre los efectos benéficos del grano de nim tratado alcalinamente (10-20 g NaOH), incorporado al alimento para aves: esto dio como resultado un mayor valor nutrimental y utilización de proteína con crecimiento espectacular. Sin embargo, no se observó una diferencia significativa entre los diferentes grupos alimenticios en cuanto a ingestión de alimentos, producción de huevos, calidad de los huevos, fertilidad, eclosionabilidad y peso de las gallinas (Nagalakshmi et al., 1996; Verma et al. 1998).
El aceite de nim y la torta de semilla de nim desaceitados son empleados como alimento animal. El aceite de nim, rico en cadenas largas de ácidos grasos es empleado como alimento de aves. La torta de semilla de nim desgrasada es rica en aminoácidos esenciales, proteínas crudas, fibra, sulfuro y nitrógeno (Uko and Kamalu, 2007).
Agroquímicos ecológicos: Aproximadamente un tercio de los alimentos del mundo son destruidos por más de 20,000 especies de plagas de campo y de almacén, y enfermedades (McEwen, 1978). Para prevenir esta pérdida se aplica una gran cantidad de pesticidas sintéticos, de los cuales solo 0.1% combaten las plagas meta y más del 99% contaminan el ecosistema (Sateesh, 1998). Además, el uso de agroquímicos sintéticos ha tenido como resultado el desarrollo de plagas resistentes y patógenas. Químicos inocuos, biodegradables, ecológicos y productos botánicos suaves son, en la agricultura actual, una alternativa necesaria a los químicos sintéticos, peligrosos y recalcitrantes (Sateesh, 1998).
El nim encabeza la lista de las 2,400 especies de plantas que han sido registradas por presentar propiedades antimicrobiales, y se le considera como la fuente más confiable de propiedad agroquímica ecológica. El nim también se emplea como un agente de bio-control para controlar muchas de las enfermedades de las plantas (Kak, 2000). Los insecticidas de nim no son fitotóxicos, duran mucho y son efectivos contra una amplia variedad de insectos y plagas.
Los productos del nim son efectivos contra más de 350 especies de artrópodos, 12 especies de nematodos, 15 especies de hongos, 4 cepas de virus, 2 especies de caracoles y 1 especie de crustáceo (Saxena et al., 1989; Nigam et al., 1994; Singh and Raheja, 1996; Mehta, 1997).
Dos titrerpenoides tetracíclicos- meliantetyraolenone y odoratone-aislados del nim mostraron actividad contra Anopheles stephensi (Siddiqui et al., 2003). Más de 195 especies de insectos se ven afectadas por los extractos de nim, y los insectos que se han vuelto resistentes a los pesticidas sintéticos también son controlados con estos extractos. La idea de que el uso a gran escala de insecticidas a base de nim pudiera llevar a la resistencia de las plagas, como se ha observado con los pesticidas sintéticos, no ha sido probada como correcta. Esto es porque los insecticidas a base de nim tienen un efecto de contacto relativamente débil en los insectos y también tienen un modo único de acción en el ciclo de vida del insecto y su fisiología. Hoy en día, muchos pesticidas orgnánicos de nim se encuentran en el mercado mundial (Khanna, 1992; Brahmachari, 2004). Formulaciones de nim disponibles en el mercado como Achook (0.15% E.C.), Bioneem (0.03% E.C.), Nimbicidine (0.03% E.C.) y Neemark (0.03% E.C.) mostraron actividad antifúngica contra los hongos patógenos viz., Fusarium oxysporum, Alternaria solani, Curvularia lunata, Helminthosporium sp. y Sclerotium rolfsii (Bhonde et al., 1999).
EL NIM Y LA BIOMEDICINA
Uso etnoveterinario: En países tercermundistas, el nim se ha empleado por siglos para cuidar la salud de humanos y ganado de diversas formas. En las aves, la corteza se usa para tratar heridas, diarrea, garrapatas y piojos (Ogbuewu, 2008). En la industria avícola, la aflatoxicosis causada por Aspergillus flavus, que se origina a parir de alimento de aves contaminado, se prevé usando hojas de nim. El extracto de hojas de nim evita que Aspergillus parasiticus produzca aflatoxinas (Allameh et al., 2002) y que Penicillium expansum produzca patulinas (Mossini et al., 2004). La torta procesada de nim tiene actividad contra gusanos y se puede utilizar como un excelente alimento para aves. Las hojas son utilizadas para tratar abscesos y también son aplicadas después de la castración (Ogbuewu, 2008). También son efectivas contra sangrados, infecciones de ubre, fiebre, pezuñas infectadas y piojos en rumiantes. La hojas de nim tiene efectos anti hipoglucémicos e hipocolesterolémico en conejos (Sokunbi and Egbunike, 2000b; Ogbuewu et al., 2010a, b) y aves de corral (Oforjindu, 2006; Esonu et al., 2006). Las semillas se usan para el tratamiento de garrapatas en rumiantes, y la corteza, semillas, hojas y raíces se emplean como insecticida repelente.
Todas las partes de la planta, así como la resina y el aceite son efectivos contra gusanos, heridas en la boca, glositis, inflamación del hígado, ictericia, disentería y heridas intestinales (Ketkar and Ketkar, 1995). También se usan para la constipación, indigestión, desórdenes respiratorios y de garganta, asma e inflamación de las membranas mucosas en el tracto respiratorio y pulmones. También se emplean en problemas de la piel, incluyendo tiña, alopecia, eccema, urticaria, ácaros, garrapatas y piojos. Otros usos menores incluyen metritis, orquitis y tétanos, fiebre bocina, reumatismo, interrupción de la orina, inflamación del hígado, mastitis, otitis y abscesos en el oído (Ogbuewu, 2008). Extractos acuosos y de alcohol de flores de nim muestran un efecto letal contra el parásito de la filaria Setaria cervi en el ganado. Los insectos que se encuentran en el ganado como larvas, moscas de los cuernos, moscas azul y moscas picadoras se controlan tradicionalmente con nim.
El nim y sus usos etnomedicinales: En África Occidental, India, Birmania, etc., los extractos acuosos y de alcohol de la corteza y hojas del nim son agentes efectivos contra la malaria, particularmente en cepas resistentes a la cloroquina. Uno de los componentes activos, genudin fue tan efectivo como la quinina al controlar singificativamente la malaria (Khalid et al., 1989; Subapriya and Nagini, 2005). El mecanismo es posiblemente la óxido-reducción de las células rojas (RBC ) en los parásitos. El parásito plasmodium genera oxidante, mientras que el extracto de nim reduce las células oxidadas para destruir el parásito de la malaria.
Además, la corteza y hojas de nim poseen una fuerte propiedad antiséptica, garantizando su uso como ingrediente activo en las pastas de dientes en India y Alemania. Mientras que el extracto de hojas muestra potenciales laxativos al incrementar las defecaciones (Uko et al., 1995), la sobredosis pudiera producir severos dolores intestinales o prolapso rectal. Kloos and McCullough (1987) reportaron el potencial del aceite de semilla de nim contra la esquitosomiasis, gracias a su efecto ovicida, mulluscicidal y cercariacidal que actúa como principio activo. Diversos herbolarios opinaron que los productos de nim tienen amplios efectos quimioterapéuticos espectrales en el platelminto, la solitaria y los nematodos. El gel dental que contiene extracto de hoja de nim reduce el índice de placa oral y gérmenes (Pai et al., 2004).
El nim se usa para tratar la fiebre de la malaria en el sistema de medicina ayurvédica. El aceite de nim trató las picaduras de mosquitos, y las placas repelentes de mosquitos están ahora disponibles en el noreste de India. El gedunin (un limonoide) obtenido del nim tiene actividad contra el organismo patógeno de la malaria, similar a la de la quinina. Los limonoides del nim (Azadirachtin, salannin, deacetylgedunin) mostraron alta bioactividad larvicida, pupicidal, y anti ovoposicional contra el vector de la malaria- Anopheles stephensi. Las suspensiones en tableta de la corteza y hoja de nim mostraron efecto moderado contra el patógeno de la malaria, Plasmodium sp. (Isah et al., 2003). La fracción de extracto metanólico de las hojas de nim, cuando se aplicaron contra los virus del grupo Coxsackie B, produjo in vitro un efecto antiviral y virucida (Badam et al., 1999). Se observó actividad anticancerígena en el extracto de hoja de nim en el sistema murino (Dasgupta et al., 2004). La inyección de preparado de hoja de nim en el tumor de ratones redujo el crecimiento del tumor, exhibiendo actividad anticancerígena (Baral and Chattopadhyay, 2004). Se observó inducción de la apoptosis en los ovocitos de rata cuando se trató con extracto de hoja de nim (Chaube et al., 2006). La carcinogénesis en la cavidad bucal de los hámster fue inhibida por el extracto etanólico de hoja de nim (Subapriya et al., 2005). Se observó buena actividad antioxidante en el extracto acuoso de hoja de nim y en los extractos etanólicos de flor y corteza del tallo (Subapriya et al., 2005). El extracto de corteza de nim tiene el potencial de controlar la hipersecreción gástrica y úlceras gastroesofágicas y gastroduodenales (Bandyopadhyayk et al., 2004). El extracto acetona-agua de hoja de nim mostró actividad antiretroviral por medio de la inhibición de la citoadherencia. El extracto aumentó la concentración de la hemoglobina, el recuento medio de células CD4+ y la tasa de sedimentación de eritrocitos en pacientes con HVI/SIDA (Udeinya et al., 2004). La mejora en la producción de anticuerpos y en la respuesta celular mediada gracias a los componentes del nim ayuda en el tratamiento del SIDA.
EL NIM Y LA REPRODUCCIÓN
El aceite de semilla de nim, los extractos de hojas y el NIM-76 actúan como un espermicida poderoso e inhibieron significativamente la espermatogénesis, redujeron la movilidad del esperma, y su número, y produjeron el cese de la fertilidad. Estas condiciones se revirtieron al retirar los productos de nim después de 4 a 6 semanas (Sadre et al., 1983). Ogbuewu et al. (2009) no reportaron una reducción significativa del líbido de conejos machos alimentados con dietas a base de hojas de nim en diferentes grados. Además, el aceite de semilla de nim posee propiedades contra la implantación y abortivas. Sinha et al. (1984) descubrió que el espermatozoide del hombre y del macaco Rhesus permanecieron inmóviles y murieron 30 minutos después del contacto con NSO en una dosis intravaginal de 1.0mL. Una biopsia vaginal reveló que no había efectos secundarios, mientras que estudios radioisotópicos indicaron que no había absorción en la vagina ni efectos anti-ovulatorios (Sinha et al., 1984). Estos descubrimientos permitieron la formulación de aceite de nim “sensal”, utilizado en India como un potente contraceptivo.
Ogbuewu et al. (2009) y Mohan et al. (1997) reportaron una reducción significativa en el volumen del semen y en la cuenta espermática, una alta incidencia de anormalidades morfológicas en el espermatozoide, así como una disminución en la habilidad fertilizadora de conejos machos alimentados con dietas a base de hoja de nim, y en la incubabilidad de los huevos de pájaros alimentados con torta de grano de nim. Se ha reportado la propiedad contraceptiva del aceite de nim (Upadhyay et al., 1994). El extracto de hoja de nim tiene un efecto tóxico en los espermatozoides (Ogbuewu et al., 2009). Los extractos de hoja de nim en dosis de 3 mg causaron la inmovilización completa y la muerte del espermatozoide humano en 20 segundos (Khan and Awasthy, 2003; Khillare and Shrivastav, 2003). Un nuevo anticonceptivo vaginal, el NIM-76 fue desarrollado a partir de aceite de nim, presentando actividad antimicrobial contra Escherichia col, Klebsiella pneumoniae y Candida albicans (Ram et al., 2002). El tratamiento de extracto de hoja de nim (acuoso) causó efectos adversos en la movilidad espermática del ratón, en la morfología del acrosoma y en el número de espermatozoides (Mishra and Singh, 2005). Extractos de semilla de nim inhibieron la foliculogénesis en ratas albinas. Así, los extractos de nim pudieran ser empleados como rodenticidas orgnánicos, en lugar de los rodenticidas tóxicos y sintéticos que contaminan (Roop et al., 2005).
El NIM Y LOS METABOLITOS SANGUÍNEOS
El administrar 5 g de extracto acuoso de la hoja o un cantidad equivalente de hoja seca redujo significativamente la dosis de insulina en un 30-50%, sin efectos importantes en los niveles de azúcar en la sangre (Khosla et al., 2000; Gupta et al., 2008). El extracto acuoso de raíz y hoja de nim redujo el nivel de azúcar en la sangre de ratas, demostrando actividad antidiabética (Halim, 2003). En un estudio con conejos y conejillos de indias se reportó que al administrar extracto de hoja de Azadirachta indica se indujo una potente hipotensión dependiente de la dosis en los conejos (5-200 mg kg-1, IP) y conejillos de indias (5-40 mg kg-1). El extracto también demostró actividad anti-carrítmica (40 mg kg-1 IV) contra la disritmia inducida con ouabaína en conejos. El mecanismo de acción puede ser un efecto en el músculo liso vascular, dando lugar a la vasodilatación.
El extracto de hoja de nim produjo un efecto hepatoprotector contra el daño celular hepático en ratas, inducido con paracetamol, descubrimientos respaldados por estudios histopatológicos (Gupta et al., 2008). Tanto el extracto de hoja de nim, como el aceite de semilla produjeron un efecto hipoglucémico en conejos diabéticos y normales, comparable al de la glibenclamida. El efecto fue más marcado en los animales diabéticos. El pretratamiento con extracto de hoja o aceite de semilla de Indica, administrado dos semanas antes que la aloxana, previno parcialmente el aumento del nivel azúcar en la sangre, con respecto a los animales bajo control diabético (Gupta et al., 2008).
El administrar extracto acuoso de nim, junto con sal DOCA previno el desarrollo de hipertensión en ratas (Obiefuna and Young, 2005). El administrar extracto de hoja madura redujo el colesterol sérico significativamente, sin cambiar la proteína sérica, la urea sanguínea y los niveles de ácido úrico en ratas (Chattopadhyay et al., 2000; Ogbuewu et al., 2010a, b).
El nim y su actividad antimicrobiana: Diversos principios activos del nim han demostrado alta eficacia contra la mayoría de los patógenos. Como funguicidas, más de 14 especies de hongos son sensibles a las preparaciones de nim (Khan and Wassilew, 1987); éstas incluyen el género Trichophyton (pie de atleta), Epidermophyton (tiña de piel y uñas), Microsporum (tiña de piel y cabello) y Candida (candidiasis). SaiRam et al. (1997) reportaron que NIM-76 brindaba protección contra la candidiasis sistemática (Candida albican). El mecanismo es simplemente antifúngico e inmunomodulatorio. En Aspergillus flavus, el extracto de hoja de nim no logró reducir el crecimiento de aflatoxinas, pero redujo su formación al impedir la producción de policétidos, que es comúnmente transformado en toxinas. Diversas enfermedades, incluyendo cercospora, antracnosis, mildiú y Sigatoka están bajo investigación para establecer la eficacia del nim como fungicida para plantas. Como antibióticos, bacterias patógenas como Staphylococcus aureus, Salmonella typhi son reprimidas en forma significativa con NSO. Pruebas con NIM-76 reprimieron significativamente E. coli y K. pneumoniea, que hasta entonces eran insensibles hacia NSO (Ram et al., 2002). Como agentes antivirales, experimentos con viruela, varicela y viruela aviar mostraron la eficacia biológica de los extractos de nim. Extractos crudos de nim adsorbieron los virus al bloquear la entrada a células no infectadas. El NIM-76 reprimió réplicas del virus de la polio e inhibió la ADN-polimerasa del herpes, sin demostrar potencia una vez que la infección se establece in vivo (Rao et al., 1989). De esta forma el nim puede ser empleado contra hongos fitopatógenos como medio de control biológico (Jatav and Mathur, 2005).
Extractos de hoja y semilla de nim mostraron actividad antidermatopática contra dermatophytes viz., Trichophyton ruberum, Mentagrophytes, Trichophyton violaceum, Microsporum nanum y Epidermophyton flocosum en condiciones in vitro (Natarajan et al., 2002). El aceite de semilla de nim mostró actividad bactericida contra 14 cepas de bacterias patógenas (Baswa et al., 2001). Los extractos crudo acuoso y con disolventes de nim fueron probados contra 20 cepas de bacteria patógena, en las que el extracto crudo produjo mejores resultados (Srinivasan et al., 2001). Los extractos de hoja de nim son antimutagénicos. El extracto etanólico de hojas de nim mostró actividad antimutagénica en Channa punctatus, un modelo de pez de agua dulce (Farah et al., 2006).
USOS INDUSTRIALES
En la conferencia mundial del nim del 2002, se propuso promover el nim como una “Planta Industrial” (Kumar, 2003). Diversas industrias, incluyendo la farmacéutica, cosmética y textil emplean el aceite de nim (Jattan et al., 1995). Muchas de estas preparaciones comerciales a base de nim están hoy en día disponibles (Khanna, 1992). En India, muchas industrias farmacéuticas Ayurvédicas explotan el nim sobremanera. El aceite de nim y hojas de nim en polvo se emplean en diversas preparaciones cosméticas como cremas para la cara, esmalte de uñas, champús, acondicionadores (Jattan et al., 1995). Un nuevo champú a base de extracto de semilla de nim resultó altamente efectivo contra piojos- más que los productos a base de permetrina- en condiciones in vitro (Heukelbach et al., 2006). La torta de nim, un subproducto de la industria de aceite de nim se emplea como alimento de ganado, fertilizante y pesticida natural. El aceite de nim se emplea comúnmente en la producción de jabón. Los Jabones de nim medicinales están ganando popularidad.
La pasta de dientes a base de nim se usa ampliamente en India y en países europeos. El nim es una fuente de numerosas preparaciones para la higiene oral y productos de cuidado bucal. La corteza produce resina y taninos que son empleados en curtidos, tinturas, etc. La pulpa de semilla de nim
se usa como una rica fuente de carbohidratos en las industrias de fermentación y para la producción de gas metano. El cultivo de nim y la elaboración de productos de nim dan empleo y oportunidades para la generación de ingresos. La recolección de semillas de nim para abastecer las industrias genera oportunidades importantes de empleo suplementario e ingresos para familias pobres, especialmente para mujeres de medios rurales. India se sitúa como el primer productor de nim, con cerca de 540 toneladas de semillas anualmente, lo que genera 107 000 toneladas de aceite de nim y 425 000 toneladas de torta de nim. Se estima que la cantidad de Azadirachtin disponible es de aproximadamente 1 600 toneladas al año, generando una cantidad enorme de materia prima para la industria pesticida. En el sector de productos, las ventas estimadas anualmente son de aproximadamente Rs. 1 000-1 200 crores. Las industrias de pequeña escala tienen un papel sumamente importante que jugar en aprovechar este potencial. Así, en India es tiempo de tomar los pasos correctos para promover el nim, tanto para el beneficio de los granjeros, como para el de las industrias (Kumar, 2003).
EL NIM Y LAS PATENTES
Durante las últimas cinco décadas se han realizado investigaciones intensivas sobre las diversas propiedades del nim. Como resultado, se han publicado un gran número de obras de investigación y libros. Se han llevado a cabo muchas conferencias nacionales e internacionales. Cientos de compuestos activos que son aislados de diversas partes del nim tienen aplicaciones en la industria médica, del cuidado de la salud, cosmética y pesticida por todo el mundo. El árbol del nim ha sido reconocido como una oportunidad comercial en el mundo entero.
Muchos procesos y productos relacionados con el nim se han patentado en Japón, Estados Unidos y en países de Europa desde 1980. En 1983, la corporación Temuro obtuvo la primera patente en Estados Unidos por su preparación terapéutica de la corteza de nim. Estados Unidos, con 54 patentes en productos de y a base de nim se coloca en primer lugar, seguido de Japón (McEwen, 1978), Australia (Chakraborthy y Konger, 1995) e India (Fathima, 2004). Desde 1995, más de 53 solicitudes de patentes están pendientes en India para su aceptación o rechazo. Con suerte, si se conceden todas estas patentes, India tendrá la mayor cantidad de patentes de nim. La mayoría de las patentes que se han concedido han sido para su aplicación en la protección de cultivos (63%), seguido del cuidado de la salud (13%), uso industrial (5%), cuidado veterinario (5%), cosméticos (6%) y otros (8%). A nivel organización, las cantidades más grandes de patentes pertenecen a Certis-W.R. Grace, seguido de Rohm and Hass (Kak, 2000), CSIR-India (Fathima, 2004), Trifolio (Jattan et al., 1995), Bayer (Chari, 1996) y EID Parry (Brahmachari, 2004).
CONCLUSION
Debido a sus características versátiles, el nim es justamente llamado “la farmacia del pueblo”.
El Consejo Nacional de la Investigación, Washington, USA considera al nim como una de las plantas más prometedoras de todas, y el hecho es que, a la larga, ésta pudiera beneficiar a cada una de las personas en este planeta. Probablemente ninguna otra planta produce productos tan extraños y variados o tienen tantos subproductos explotables. Sin embargo, la mayoría de los descubrimientos acerca del nim y sus productos no están patentados, a pesar de ser potencialmente valiosos, rentables, de reducir la incidencia de resistencia en plagas y parásitos, con un aumento en la producción agrícola, protección ambiental y servicio de atención a la salud para humanos y ganado. Se infiere, de lo anterior, que la planta del nim es, en efecto, una joya a nivel mundial. Acorde con estos beneficios, las investigaciones sobre el nim deben ser dirigidas hacia la identificación y cuantificación de los principios activos y hacia el patentado de estos descubrimientos, posibilitando, así, su inmediata accesibilidad a la humanidad.
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