Neem

Scientific Name(s): Azadirachta indica A. Juss. Family: Meliaceae

Common Name(s): Neem , margosa , nim , nimba , nimbatiktam , Arishtha , Praneem

Uses

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.

Dosing

There are inadequate clinical trials to support specific therapeutic doses of neem.

Contraindications

Specific contraindications have not been identified. The use of oral neem oil in children cannot be supported due to reported deaths.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Avoid use.

Interactions

None well documented.

Adverse Reactions

Research reveals few or no adverse reactions in adults with the use of neem at normal doses.

Toxicology

The seeds of neem are poisonous in large doses. Severe poisoning in infants from neem oil have been reported.

Botany

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.

History

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

Chemistry

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. 17

Clinical 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

Vaginal neem extract tablets have been studied in sexually active women based on in vitro studies showing efficacy against Neisserria gonorrhoeae , Chlamydia trachomatis , and Herpes simplex . 2 , 18

The use of Neem oil and chewing on neem twigs have demonstrated varying efficacy versus oral flora and microorganisms responsible for dental caries. 19 , 20 , 21 , 22 , 23

Cancer

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 , 30

Animal 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. 26

Clinical 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 , 31

Cardiovascular
Animal data

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. 3

Contraceptive
Animal data

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 , 36

Clinical 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. 18

Dermatology

Neem oil contains azadirachtin, deactyl-azadirachtinol, salannin, nimbin, and other chemical compounds that have demonstrated pesticidal action. 16 , 38 , 39 , 40

Scabies

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 , 41

Head lice

Neem seed extract was 80% to 97% effective against both adult and egg lice in small studies. 2 , 3 , 42

Diabetes
Animal data

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 , 44

Clinical 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. 45

Gastrointestinal
Animal data

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. 2

Clinical data

Clinical studies conducted in small numbers of patients have shown healing of duodenal ulcers with administration of neem bark extract over 30 days. 2 , 46

Dosage

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

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Avoid use. Antiandrogenic properties have been demonstrated in rats. 3 , 29 , 32

Interactions

None well documented.

Adverse Reactions

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

Toxicology

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

Bibliography

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