Medically reviewed on Feb 19, 2018
Scientific Name(s): Azadirachta indica A. Juss. Family: Meliaceae
Common Name(s): Neem , margosa , nim , nimba , nimbatiktam , Arishtha , Praneem
Limited clinical trials exist to support therapeutic claims. Neem has been used as an insecticide, insect repellent, and oral dentifrice, and in traditional medicine to treat malaria, diabetes, worms, and cardiovascular and skin diseases. It reportedly has contraceptive, antiulcer, and fungicidal properties, as well as applications relevant to cancer.
There are inadequate clinical trials to support specific therapeutic doses of neem.
Specific contraindications have not been identified. The use of oral neem oil in children cannot be supported due to reported deaths.
Information regarding safety and efficacy in pregnancy and lactation is lacking. Avoid use.
None well documented.
Research reveals few or no adverse reactions in adults with the use of neem at normal doses.
The seeds of neem are poisonous in large doses. Severe poisoning in infants from neem oil have been reported.
The neem (formerly known as Melia azadirachta L.) is a large evergreen tree that grows up to 20 m in height, with spreading branches that form a broad crown. The plant is found throughout India and neighboring regions, where it is cultivated commercially. The plant is often confused with Melia azedarach L., the chinaberry or Persian lilac. 1 , 2 Leaves grow alternately with leaflets containing 8 to 19 leaves. 2 The tree yields high-quality timber and a commercial gum.
Almost every part of the neem tree is used in traditional medicine (eg, Ayurveda, Unani, Siddha, Amchi) in many countries, with some 700 preparations described. The stem, root bark, and young fruits are used as a tonic and astringent, and the bark has been used as an analgesic and to treat malaria and cutaneous diseases. The tender leaves have been used in the treatment of worm infections, ulcers, and cardiovascular diseases, as well as in the treatment of leprosy. Indian farmers have used the leaves for hundreds of years as a pesticide and insect repellent. 3 , 4 , 5
The seed kernels of neem yield about 10% of a fixed oil, comprised primarily of glycerides. The yellow, bitter oil has a garlic-like odor and contains approximately 2% of bitter principles including azadirachtin, azadiradione, azadirone, gedunin, nimbidin, nimbin, ninmbolide, nimbinin, nimbidol, margolene, mahmoodin, salanin, meldenin, vepinin, and other related limonoid triterpenes. Azadirachtin is the most active insecticidal component of neem, with a yield of about 5 g from 2 kg of seeds. 2 , 3 , 6 , 7 , 8 , 9 , 10 , 11 All parts of the tree yield beta-sitosterol. The leaves also contain quercetin, gallic acid, catechin, carotenes, and ascorbic acid. 2 Low concentrations of aflatoxin have been reported. 12 , 13
Uses and Pharmacology
The variety of components in neem gives the plant and its extracts a number of pharmacologic activities. However, high-quality clinical trials are lacking.Antimicrobial
In in vitro studies, neem oil exerted an antibacterial effect and antifungal action against numerous clinical isolates. 2 , 14 Neem has been traditionally used as an antimalarial. 3 Neem leaf extracts (containing gedunin, nimbolide, meldenin, and nimocinol) showed in vitro action against chloroquin and pyrimethamine-resistant strains of Plasmodium falciparum . 2 , 3 , 15 , 16 Compared with eucalyptus oil and DEET, neem oil was a poor mosquito repellent. 17Clinical data
A small clinical study evaluated the effect of neem leaf extract 1,000 mg given daily for 30 days in HIV-positive patients. No other antiretroviral drugs were coadministered, and a difference in hemoglobin, CD4+ counts and erythrocyte sedimentation rate (ESR) was shown. In vitro studies in lymphocytes from the same patients revealed a protectant effect of neem extract on HIV invasion of the lymphocytes. 15
Chemical compounds with identified anticancer effects include limonin glucopyranoside, azadirone, azadirachtin, nimbolide and deoxonimbolide, quercetin, and kaemferol, as well as the antioxidants beta-carotene and ascorbic acid. 2 , 3 , 9 , 10 , 11 , 24 , 25 Suggested mechanisms of action include up-regulation of immune response, 26 , 27 , 28 antioxidant/radical scavenging activity, 2 , 3 antiandrogenic action, 29 inhibition of mitosis, 2 down-regulation of inflammation, 24 and modulation of phase 2 enzymes. 2 , 30Animal data
Studies in mice and hamsters with neem leaf extracts showed decreased tumor burden and tumor incidence, 2 , 31 reduced chromosomal aberrations in induced cancers, and induced apoptosis. 31 Neem leaf extract showed an adjuvant immune response to tumor growth in mice as well as protection from leucopenia caused by chemotherapy. 26Clinical data
Clinical trials are lacking. Reports exist of the use of neem seed oil in individual patients with epidermal cancer and parotid tumor, but clinical outcome measures were not adequately reported. 3 Human cancer cell line studies include antiandrogenic effects against prostate cancer cells, 29 induction of oral squamous cell cancer apoptosis, 3 , 30 and cytotoxic effects on breast cancer cells. 26 Nimbolide extracted from neem flowers interfered with the cell cycle of leukemic and melanoma cell lines and induced apoptosis. 25 , 31Cardiovascular
Ethanol extracts of neem leaf induced important and dose-dependent hypotensive action in rats, but bradycardia, as well as cardiac arrhythmia, was also observed. 2 Crude extracts of neem root and stem bark have shown diuretic and hypotensive action. 2 , 3 Sodium nimbidinate induced diuresis in dogs to a greater extent than urea.Clinical data
Deep intramuscular (IM) injection of sodium nimbidinate resulted in adequate diuresis in a small study of patients with congestive cardiac failure. 3Contraceptive
Spermicidal action of the leaf extract has been demonstrated in mouse, rat, rabbit, monkey, and human spermatozoa in vitro. 2 , 3 , 32 , 33 , 34 Salanin and sodium nimbidinate compounds are spermicidal to rat and human spermatozoa. 3 , 40 Antiandrogenic properties have been demonstrated in rats, 32 and oral neem extract decreased total sperm count and sperm motility in rats as well as increasing the proportion of abnormal sperm. 3 , 35 , 36Clinical data
Vaginal neem oil has been evaluated for safety in women. Endometrial biopsy was normal and no effect on menstrual or ovulatory cycles was shown in a small study. Intravaginal neem oil (1 mL) was shown to be spermicidal. 3 , 37 Transient genital itching/burning was noted among women given a neem-based vaginal tablet. 18Dermatology
Neem and tumeric paste, and ethanol extracts of neem in propylene glycol have been effective against scabies, as well as dermatophytes such as Trichophyton and other fungal infections in a limited number of clinical trials. 2 , 3 , 41Head lice
Numerous trials have investigated the effect of neem leaf extract on induced hyperglycemia in laboratory animals. Effects comparable with glibenclamide have been reported, with an extra-pancreatic action suggested by some researchers. 2 , 3 , 43 , 44Clinical data
In a small trial of patients (N = 10) with type 2 diabetes, both ethanol and aqueous extracts of neem seeds decreased blood glucose levels. 45Gastrointestinal
The aqueous extract of neem bark and seeds has been investigated in animals. Reduced free and total acidity, and reduced volume of gastric secretions was demonstrated. A protective action against aspirin-induced gastric lesions has also been demonstrated. 2 , 3 , 8 Chemical constituents salanin, rimbidin, and nimbidin may have antisecretory/gastroprotective actions, while activity against H. pylori has also been shown in vitro. 2Clinical data
There are inadequate clinical trials to support specific therapeutic doses of neem.
Based on animal studies, an estimated safe dose of neem oil 0.2 mL/kg has been suggested in adults. 12 Deep IM injections of sodium nimbidinate 250 mg daily have been used in a trial in congestive cardiac failure. 3 Intravenous (IV) ethanol extracts of neem leaf caused cardiac arrhythmia in rats and should be avoided. 2
None well documented.
The limited clinical trial data available report few or no adverse reactions in adults with the use of neem at normal doses. 8 IV ethanol extracts of neem leaf caused cardiac arrhythmia in rats. 2 Topical applications of neem over a 1-year period yielded no adverse reactions. 3 Transient genital itching/burning was noted among women using a neem-based vaginal tablet. 18
The seeds of neem, which are poisonous in large doses, resemble the more toxic drupes of M. azadarach , and the two are sometimes confused. 4
Severe poisoning in 13 infants who had received oral doses of neem oil 5 to 30 mL has been reported. Toxicity was characterized by metabolic acidosis, drowsiness, seizures, coma, hepatoencephalopathy, and death. 3 , 4 , 13 , 47 Management of poisoning is largely symptomatic, with no specific antidote available. 3 , 13
Neem oil traditionally has been considered to be a relatively safe product in adults. The oral LD 50 of neem oil is 14 mL/kg in rats and 24 mL/kg in rabbits. In rats, a dose of up to 80 mL/kg caused stupor, respiratory distress, depression of activity, diarrhea, convulsions, and death. 48 Gross examination of all organs except the lungs was normal after acute dosing.
Neem oil was nonmutagenic in an Ames mutagenicity assay. 49 Azadirachtin has been shown to be biodegradable, nonmutagenic, and nontoxic to warm-blooded animals, fish, and birds. The Environmental Protection Agency has approved the use of a neem formulation as a pesticide for limited use on nonfood crops. 50
Bibliography1. Azadirachta indica A. Juss. USDA, NRCS. 2007. The PLANTS Database ( http://plants.usda.gov , August, 2008). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.
2. Subapriya R, Nagini S. Medicinal properties of neem leaves: a review. Curr Med Chem Anticancer Agents . 2005;5(2):149-156.
3. Brahmachari G. Neem—an omnipotent plant: a retrospection. Chembiochem . 2004;5(4):408-421.
4. Sinniah D, Baskaran G. Margosa oil poisoning as a cause of Reye's syndrome. Lancet . 1981;1(8218):487-489.
5. Azadirachta indica A. Juss syn. Melia azadirachta Linn. (Meliaceae). Medicinal & Aromatic Plants Abstracts (MAPA) . 1987;9:465.
6. Windholz M, ed. The Merck Index . 10th ed. Rahway, NJ: Merck and Co.; 1983.
7. Schroeder DR, Nakanishi K. A simplified isolation procedure for azadirachtin. J Nat Prod . 1987;50(2):241-244.
8. Bandyopadhyay U, Biswas K, Chatterjee R, et al. Gastroprotective effect of Neem ( Azadirachta indica ) bark extract: possible involvement of H(+)-K(+)-ATPase inhibition and scavenging of hydroxyl radical. Life Sci . 2002;71(24):2845-2865.
9. Nanduri S, Thunuguntla SS, Nyavanandi VK, et al. Biological investigation and structure-activity relationship studies on azadirone from Azadirachta indica A. Juss. Bioorg Med Chem Lett . 2003;13(22):4111-4115.
10. Sastry BS, Suresh Babu K, Hari Babu T, et al. Synthesis and biological activity of amide derivatives of nimbolide. Bioorg Med Chem Lett . 2006;16(16):4391-4394.
11. Genupur A, Jesu JL, Srinivasan N, Kamalakaran AS, Sundar RS. Synthesis and cytotoxicity of novel isomeric C-seco limonoids. Eur J Med Chem . 2006;41(8):997-1002.
12. Boeke SJ, Boersma MG, Alink GM, et al. Safety evaluation of neem ( Azadirachta indica ) derived pesticides. J Ethnopharmacol . 2004;94(1):25-41.
13. Dhongade RK, Kavade SG, Damle RS. Neem oil poisoning. Indian Pediatr . 2008;45(1):56-57.
14. Rao DV, Singh I, Chopra P, Chhabra PC, Ramanujalu G. In vitro antibacterial activity of Neem oil. Indian J Med Res . 1986;84:314-316.
15. Udeinya IJ, Mbah AU, Chijioke CP, Shu EN. An antimalarial extract from neem leaves is antiretroviral. Trans R Soc Trop Med Hyg . 2004;98(7):435-437.
16. Khalid SA, Duddeck H, Gonzalez-Sierra M. Isolation and characterization of an antimalarial agent of the neem tree Azadirachta indica . J Nat Prod . 1989;52(5):922-926.
17. Moore SJ, Lenglet A, Hill N. Field evaluation of three plant-based insect repellents against malaria vectors in Vaca Diez Province, the Bolivian Amazon. J Am Mosq Control Assoc . 2002;18(2):107-110.
18. Joshi SN, Katti U, Godbole S, et al. Phase Ι safety study of Praneem polyherbal vaginal tablet use among HIV-uninfected women in Pune, India. Trans R Soc Trop Med Hyg . 2005;99(10):769-774.
19. Prashant GM, Chandu GN, Murulikrishna KS, Shafiulla MD. The effect of mango and neem extract on four organisms causing dental caries: Streptococcus mutans , Streptococcus salivavius , Streptococcus miti s, and Streptococcus sanguis : an in vitro study. Indian J Dent Res . 2007;18(4):148-151.
20. Pai MR, Acharya LD, Udupa N. Evaluation of antiplaque activity of Azadirachta indica leaf extract gel—a 6-week clinical study. J Ethnopharmacol . 2004;90(1):99-103.
21. Sharma S, Saimbi CS, Koirala B, Shukla R. Effect of various mouthwashes on the levels of interleukin-2 and interferon-gamma in chronic gingivitis. J Clin Pediatr Dent . 2008;32(2):111-114.
22. Patel VK, Venkatakrishna-Bhatt H. Folklore therapeutic indigenous plants in periodontal disorders in India (review, experimental and clinical approach). Int J Clin Pharmacol Ther Toxicol . 1988;26(4):176-184.
23. Vanka A, Tandon S, Rao SR, Udupa N, Ramkumar P. The effect of indigenous Neem Azadirachta indica (correction of Adirachta indica ) mouth wash on Streptococcus mutans and lactobacilli growth. Indian J Dent Res . 2001;12(3):133-144. Erratum in: Indian J Dent Res . 2001;12(4):193.
24. Kaul D, Shukla AR, Sikand K, Dhawan V. Effect of herbal polyphenols on atherogenic transcriptome. Mol Cell Biochem . 2005;278(1-2):177-184.
25. Roy MK, Kobori M, Takenaka M, et al. Antiproliferative effect on human cancer cell lines after treatment with nimbolide extracted from an edible part of the neem tree ( Azadirachta indica ). Phytother Res . 2007;21(3):245-250.
26. Mandal-Ghosh I, Chattopadhyay U, Baral R. Neem leaf preparation enhances Th1 type immune response and anti-tumor immunity against breast tumor associated antigen. Cancer Immun . Mar 30 2007;7:8.
27. Bose A, Baral R. Natural killer cell mediated cytotoxicity of tumor cells initiated by neem leaf preparation is associated with CD40-CD40L-mediated endogenous production of interleukin-12. Hum Immunol . 2007;68(10):823-831.
28. Bose A, Haque E, Baral R. Neem leaf preparation induces apoptosis of tumor cells by releasing cytotoxic cytokines from human peripheral blood mononuclear cells. Phytother Res . 2007;21(10):914-920.
29. Kumar S, Suresh PK, Vijayababu MR, Arunkumar A, Arunakaran J. Anticancer effects of ethanolic neem leaf extract on prostate cancer cell line (PC-3). J Ethnopharmacol . 2006;105(1-2):246-250.
30. Niture SK, Rao US, Srivenugopal KS. Chemopreventative strategies targeting the MGMT repair protein: augmented expression in human lymphocytes and tumor cells by ethanolic and aqueous extracts of several Indian medicinal plants. Int J Oncol . 2006;29(5):1269-1278.
31. Subapriya R, Bhuvaneswari V, Nagini S. Ethanolic neem ( Azadirachta indica ) leaf extract induces apoptosis in the hamster buccal pouch carcinogenesis model by modulation of Bcl-2, Bim, caspase 8 and caspase 3. Asian Pac J Cancer Prev . 2005;6(4):515-520.
32. Khillare B, Shrivastav TG. Spermicidal activity of Azadirachta indica (neem) leaf extract. Contraception . 2003;68(3):225-229.
33. Tewari RK, Pathak S, Prakash AO. Biochemical and histological studies of reproductive organs in cyclic and ovariectomized rats supporting a non-hormonal action for neem oil. J Ethnopharmacol . 1989;25(3):281-293.
34. Prakash AO, Tewari RK, Mathur R. Non-hormonal post-coital contraceptive action of neem oil in rats. J Ethnopharmacol . 1988;23(1):53-59.
35. Sinha KC, Riar SS, Tiwary RS, et al. Neem oil as a vaginal contraceptive. Indian J Med Res . 1984;79:131-136.
36. Riar SS, Devakumar C, Ilavazhagan G, et al. Volatile fraction of neem oil as a spermicide. Contraception . 1990;42:479-487.
37. Lal R, Sankaranarayanan A, Mathur VS, Sharma PL. Antifertility effect of neem oil in female albino rats by the intravaginal & oral routes. Indian J Med Res . 1986;83:89-92.
38. Kubo I, et al. New insect ecdysis-inhibitory limonoid deacetylazadirachtinol isolated from Azadirachta indica (meliaceae) oil. Tetrahedron . 1986;42:489.
39. Salehzadeh A, Jabbar A, Jennens L, et al. The effects of phytochemical pesticides on the growth of cultured invertebrate and vertebrate cells. Pest Manag Sci . 2002;58(3):268-276.
40. Siddiqui BS, Afshan F, Faizi S, Naeem-Ul-Hassan Naqvi S, Tariq RM. Two new triterpenoids from Azadirachta indica and their insecticidal activity. J Nat Prod . 2002;65(8):1216-1218.
41. Heukelbach J, Feldmeier H. Scabies. Lancet . 2006;367(9524):1767-1774.
42. Abdel-Ghaffar F, Semmler M. Efficacy of neem seed extract shampoo on head lice of naturally infected humans in Egypt. Parasitol Res . 2007;100(2):329-332.
43. Saxena A, Vikram NK. Role of selected Indian plants in management of type 2 diabetes: a review. J Altern Complement Med . 2004;10(2):369-378.
44. Khosla P, Bhanwra S, Singh J, Seth S, Srivastava RK. A study of hypoglycaemic effects of Azadirachta indica (Neem) in normaland alloxan diabetic rabbits. Indian J Physiol Pharmacol . 2000;44(1):69-74.
45. Waheed A, Miana GA, Ahmad SI. Clinical investigation of hypoglycemic effect of seeds of Azadirachta-indica in type-2 (NIDDM) diabetes mellitus. Pak J Pharm Sci . 2006;19(4):322-325.
46. Bandyopadhyay U, Biswas K, Sengupta A, et al. Clinical studies on the effect of Neem ( Azadirachta indica ) bark extract on gastric secretion and gastroduodenal ulcer. Life Sci . 2004;75(24):2867-2878.
47. Sinniah R, Sinniah D, Chia LS, Baskaran G. Animal model of margosa oil ingestion with Reye-like syndrome. Pathogenesis of microvesicular fatty liver. J Pathol . 1989;159(3):255-264.
48. Gandhi M, Lal R, Sankaranarayanan A, Banerjee CK, Sharma PL. Acute toxicity study of the oil from Azadirachta indica seed (neem oil). J Ethnopharmacol . 1988;23(1):39-51.
49. Polasa K, Rukmini C. Mutagenicity tests of cashewnut shell liquid, rice-bran oil and other vegetable oils using the Salmonella typhimurium /microsome system. Food Chem Toxicol . 1987;25(10):763-766.
50. Plants' natural defenses may be key to better pesticides. Chem Eng News . 1985;63:47.
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