Medicinal properties of Neem: New Findings
by D.P. Agrawal

For thousands of years the beneficial properties of Neem (Azadirachta indica A. Juss) have been recognized in the Indian tradition.  Each part of the neem tree has some medicinal property.  Biswas et al (2002) have recently reviewed the biological activities of some of the neem compounds, pharmacological actions of the neem extracts, and clinical studies and plausible medicinal applications of neem.  This included a safety evaluation of the Neem.

Neem has two closely related species: A. indica A. Juss and M. azedarac.  The former is popularly known as the Indian Neem (Margosa tree) or Indian Lilac, and the other as the Persian Lilac.  Neem has been extensively used in ayurveda, unani, and homoeopathic medicine.  The Sanskrit name of the Neem tree is Arishtha meaning 'reliever of sickness' and hence is considered as Sarbaroganibarini.  The tree is still regarded as 'village dispensary' in India.  The importance of the neem tree has been recognized by the US National Academy of Sciences, which published a report in 1992 entitled 'Neem – a tree for solving global problems.'

More than 135 compounds have been isolated from different parts of the neem and several reviews have also been published on the chemistry and structural diversity of these compounds.  The compounds have been divided into two major classes: isoprenoids (like diterpenoids and triterpenoids containing protomeliacins, limonoids, azadirone and its derivatives, gedunin and its derivatives, vilasinin type of compounds and C- secomeliacins such as nimbin, salanin and azadirachtin ) and non-isoprenoids, which are proteins (amino acids) and carbohydrates (polysaccharides), sulphurous compounds, polyphenolics such as flavonoids and their glycosides, dihydrochalcone, coumarin and tannins, and aliphatic compounds.

Biological activity of some Neem compounds

Nimbidin, a major crude bitter principle extracted from the oil of seed kernels of A. indica demonstrated several biological activities.  From this crude principle some tetranortriterpenes, including nimbin, nimbinin, nimbidinin, nimbolide and nimbidic acid have been isolated.

Biological activity of Neem compounds

Anti-inflammatory; Antiarthritic; Antipyretic; Hypoglycaemic; Antigastric ulcer; Spermicidal; Antifungal; Antibacterial; Diuretic; Antimalarial; Antitumour; Immunomodulatory.

Medicinal Uses

Various parts of the Neem tree have been used as traditional Ayurvedic medicine in India.  Neem oil and the bark and leaf extracts have been therapeutically used as folk medicine to control leprosy, intestinal helminthiasis, respiratory disorders, and constipation.  They have also been used as general health promoters.  Its use for the treatment of rheumatism, chronic syphilitic sores and indolent ulcer has also been evident.  Neem oil is also used to control various skin infections.  Bark, leaf, root, flower and fruit together cure blood morbidity, biliary afflictions, itching, skin ulcers, burning sensations and pthysis (see Table 1).

Immunostimulant activity

The aqueous extract of neem bark and leaf also possesses anticomplement and immunostimulant activity.  Neem oil has been shown to possess activity by selectively activating the cell-mediated immune mechanisms to elicit an enhanced response to subsequent mitogenic or antigenic challenge.

Hypoglycaemic activity

Aqueous extract of neem leaves significantly decreases blood sugar levels and prevents adrenaline as well as glucose-induced hyperglycaemia.  Recently, a hypoglycaemic effect was observed with leaf extract and seed oil, in normal as well as alloxan-induced diabetic rabbits.

Antiulcer effect

Neem leaf and bark aqueous extracts produce highly potent antiacid secretory and antiulcer activity.

Antifertility effect

Intra-vaginal application of neem oil, prior to coitus, can prevent pregnancy.  It could be a novel method of contraception.

Antimalarial activity

Neem seed and leaf extracts are effective against both choroquin-resistant and sensitive strain malarial parasites.

Antifungal activity

Extracts of neem leaf and neem oil seed kernels are effective against certain fungi including Trichophyton, Epidermophyton, Microspor Trichosporon, Geotricum and Candida.

Antibacterial activity

Oil from the leaves, seed, and bark possesses a wide spectrum of antibacterial action against Gram-negative and Gram-positive microorganisms, including M. tuberculosis and streptomycin resistant strains.  In vitro, it inhibits Vibrio cholerae Klebsiella pneumoniae, M. tuberculosis and M. pyogenes.  Antimicrobial effects of neem extract have been demonstrated against Streptococcus mutans and S. faecalis.

Antiviral activity

Aqueous leaf extract offers antiviral activity against Vaccinia virus, Chikungemya, and measles virus.

Anticancer activity

Neem leaf aqueous extract effectively suppresses oral squamous cell carcinoma induced by 7, 12-dimethylbenz[a] anthracene (DMBA), as revealed by reduced incidence of neoplasm.  Neem may exert its chemopreventive effect in the oral mucosa by modulation of glutathione and its metabolizing enzymes.

Antioxidant activity

The antioxidant activity of neem seed extract has been demonstrated in vivo during horse- grain germination.

Effect on central nervous system

Varying degrees of central nervous system (CNS) depressant activity in mice was observed with the leaf extract.  Fractions of acetone extract of leaf showed significant CNS depressant activity.

Possible medicinal applications of neem

Neem extract
Its effective in curing ringworm, eczema and scabies.  Lotion derived from neem leaf, when locally applied, can cure these dermatological diseases within three to four days in acute stage or in a fortnight in a chronic case.  A paste prepared with neem and turmeric was found to be effective in the treatment of scabies in nearly 814 people.

Neem leaf extract has been prescribed for oral use for the treatment of malaria by Indian ayurvedic practitioners from time immemorial.  Recently, a clinical trial has been carried out to see the efficacy of neem extract to control hyperlipidemia in a group of malarial patients severely infected with P. falciparum.  The lipid level, especially cholesterol, was found to be lower during therapy when compared to non-malaria patients. Reports are available regarding the use of neem to treat patients suffering from various forms of cancer.  One patient with parotid tumor and another with epidermoid carcinoma have responded successfully when treated with neem seed oi1.

NIM- 76, a refined product from neem oil, was studied in ten human volunteers, to determine whether intra-vaginal application before sexual intercourse would prevent pregnancy without an adverse effect on vagina, cervix and uterus.  The data suggested that intrauterine treatment is safe.

Safety evaluation with various parts of neem and neem products

Various studies have been reported on the safety evaluation of different parts of neem as well as its various biologically active products.

Nimbidin produces sub-acute toxicity in adult rats after daily administration of 25, 50 or 100 mg/kg for six weeks.  A significant hypoglycemic effect was observed by feeding nimbidin to fasting rabbits.  Nimbidin also has spermicidal activity.  Nimbolide, a major chemical component of neem seed oil, and nimbic acid were found to be toxic to mice when given intravenously or intraperitoneally.  They are, however, less toxic to rats and hamster.  Nimbolide and nimbic acid at a lethal dose cause death in most animals by dysfunction of kidney, small intestine and liver as well as by marked and sudden drop of arterial blood pressure.

Conclusion

It is heartening to see that a traditional Indian plant medicine has now led to several therapeutically and industrially useful preparations and compounds. It has generated enough encouragement among the scientists in exploring more information about this medicinal plant. As the global scenario is now changing towards the use of nontoxic plant products having traditional medicinal use, development of modern drugs from neem should be emphasized for the control of various diseases.  In fact, time has come to make good use of centuries-old knowledge of neem through modern approaches of drug development.  For the last few years, there has been an increasing trend and awareness in neem research.  Quite a significant amount of research has already been carried out during the past few decades in exploring the chemistry of different parts of neem. An extensive research and development work should be undertaken on neem and its products for better economic and therapeutic utilization.

Bibliography

Main Source:
Biswas, Kausik, Ishita Chattopadhyay, Ranajit K.Banerjee and Uday Bandyopadhyay. 2002. Biological activities and medicinal properties of Neem (Azadirachta indica). Current Science 82(11): 1336-1345.

Other Relevant References:
1. Chopra, R. N., Nayer, S. L. and Chopra, I. C., Glossary of Indian Medicinal Plants, CSIR, New Delhi, 1956.

2. Chopra, R. N., Chopra, I. C, Handa, K. L. and Kapur, L. D. (eds), Indigenous Drugs of India, U.N. Dhur and Sons, Kolkata, 1958, pp.51-595.

3. Kirtikar, K. R. and Basu, B. D., in Medicinal Plants (eds Blatter, E., Cains, J. F., Mhaskar, K. S.), Vivek Vihar, New Delhi, 1975, p.536.

4. Chatterjee, A. and Pakrashi, S. (eds), The Treatise on Indian Medicinal Plants, 1994, vol. 3, p. 76.

5. Schmutterer, H. (ed.), The Neem Tree: Source of Unique Natural Products for Integrated Pest Management, Medicine, Industry and Other Purposes, VCH, Weinheim, Germany, 1995, pp. 1-696.

6. Singh, R. P., Chari, M. S., Raheja, A. K. and Kraus, W., Neem and Environment, Oxford & IBH Publishing, New Delhi, 1996, Vols. I and II, pp. 1-1198.

7. Kraus, W., in The Neem Tree: Source of Unique Natural Products for Integrated Pest Management, Medicine, Industry and Purposes (ed. Schmutterer, H.), 1995, pp 35-88.

8.Vanna, G. S., Miracles of Neem Tree, Rasayan Pharmacy, New Delhi, 1976.

9. Ketkar, A. Y. and Ketkar, C. M., in The Neem Tree: Source of Unique Natural Products for Integrated Pest Management, Medicine, Industry and Other Purposes (ed. Schmutterer, H.), 1995, pp.518-525.

10. Khan, M. and Wassilew, S. W., in Natural Pesticides from the Neem Tree and Other Tropical Plants (eds Schmutterer, H. and Asher, K. R. S.), GTZ, Eschborn, Germany, 1987, pp. 645-650.

11. Jacobson, M., in The Neem Tree: Source of Unique Natural Products for Integrated Pest Management, Medicine, Industry and other Purposes (ed. Schmutterer, H.), 1995, pp. 484-495.