The Indian neem tree, Azadirachta indica, has long been known as a source of folk medical treatments, and it is cultivated throughout the tropical regions of the world. Research on its medical applications is ongoing, and evidence-based treatments in dermatology may be something to look for in the future.
The tree is native to the Indian subcontinent and Southeast Asia. Neem has been considered a highly and diversely curative tree for thousands of years in India. In addition to various medical applications, neem has been deemed an effective natural source of insecticide, pesticide and agrochemicals (Chembiochem. 2004;5:408-21). Modern interest in neem in the West emerged in the 1970s largely in relation to its applications as an insecticide, particularly given its low toxicity in mammals (Chembiochem. 2004;5:408-21). In this discussion, which will touch on the folk uses of the tree, the focus will be on recent research and dermatologic applications.
Diverse Medical Uses of Neem
Neem has garnered global attention in recent years because of its broad medical applications, already firmly and extensively established in homeopathic medicine, Ayurveda, Unani, Siddha, Amchi, and other traditional health approaches (Chembiochem. 2004;5:408-21; Curr. Med. Chem. Anticancer Agents 2005;5:149-6). Inflammation, infections, fever, skin diseases, and dental disorders have been treated traditionally using all parts of the neem tree (i.e., leaves, flowers, seeds, fruit, roots, and bark), with more than 140 constituents isolated from the plant, of which at least 35 are believed to be biologically active (J. Ethnopharmacol. 2004;92:23-36). It has also been used traditionally for wound healing and to treat dandruff (Phytother. Res. 2004;18:343-57).
The neem leaf and its constituent components, in particular, have been reported to impart wide-ranging salubrious activity, including antibacterial, anticarcinogenic, antifungal, antihyperglycemic, anti-inflammatory, antimalarial, antimutagenic, antioxidant, antiulcer, antiviral, and immunomodulatory qualities (Curr. Med. Chem. Anticancer Agents 2005;5:149-6). The key bioactive constituents of neem appear to be azadirachtin, nimbin, nimbinin, nimbidin, 6-desacetylnimbin, salannin, and beta-sitosterol. (Phytother. Res. 2004;18:343-57; Arch. Insect Biochem. Physiol. 1997;35:199-20; J. Ethnopharmacol. 2004;92:23-36). Medical research of neem and its constituents has focused, of late, on applications as a spermicide and a treatment for scabies, although anticarcinogenic properties of the ancient tree (one of the Sanskrit names for which is “Arishtha,” translated as “reliever of sickness” [Chembiochem. 2004;5:408-21]) have also received attention.
In 2005, Joshi et al. assessed the safety of Praneem polyherbal tablets (which contain purified extracts of Azadirachta indica) as a microbicide, given in vitro evidence of activity against HIV. Twenty HIV-uninfected women participated in the phase I open-label study during which they administered the intravaginal tablets on 14 consecutive days. Praneem has also been shown to exhibit contraceptive activity. No serious adverse events were reported. Seventeen episodes of genital irritation were reported by nine subjects, transient itching was reported by eight; two participants complained of burning during urination, and one reported lower abdominal pain, genital burning, and intermenstrual spotting. The investigators concluded that Praneem polyherbal tablets are safe for once daily intravaginal use for 14 consecutive days in sexually active HIV-uninfected women (Trans. R. Soc. Trop. Med. Hyg. 2005:99:769-74). They followed up on these results with a phase II trial on which they reported in 2008. In this double-blind, placebo-controlled, randomized phase II trial, 100 HIV-uninfected eligible women provided consent and enrolled (142 were originally screened), with 50 randomly assigned to the study product arm and 50 to the placebo arm. Study subjects were asked to use the study product at least 30 minutes prior to each sexual act during the ensuing 6-month time frame. There were no HIV seroconversions or other serious adverse events associated with Praneem, and none of the participants discontinued use of the product; transient genital discomfort emerged as the main reported mild adverse result. The investigators found Praneem polyherbal intravaginal tablets to be safe for low-risk women to use for up to 6 months. Further, they suggested that, given the failure of other products to prevent HIV infection among women, preclinical evaluations of Praneem are urgently needed prior to launching studies of effectiveness (Sex. Transm. Infect. 2008;84:343-7).
Neem Antimicrobial Properties
Neem was also used among other herbal ingredients in a pessary (Praneem polyherbal pessary) studied in 2001 as an alternative to nonoxynol-9–containing products, which have been shown to provoke inflammation and genital ulceration after frequent use. A Praneem polyherbal cream (composed of purified extracts of dried Azadirachta indica seeds, Sapindus mukerossi fruit pericarps, and quinine hydrochloride) was previously shown in the early 1990s to be a safe and effective spermicidal formulation. The water-soluble cream caused no irritation or sensitization in animal or human tests, and demonstrated high contraceptive efficacy after intravaginal application in rabbits and monkeys (Contraception 1993;48:591-6). In the 2001 study, the polyherbal formulation combined purified ingredients from Azadirachta indica leaves, Sapindus mukerossi (pericarp of fruit), and Mentha citrata oil, and was investigated for spermicidal and contraceptive activity. Researchers used the Sander-Cramer slide test to detect spermicidal action on human sperm in vitro and postcoital tests in vivo; rabbits were used to examine the contraceptive action of the formulation. In the rabbit test, pregnancy was prevented in all 15 animals administered the polyherbal pessary; in the control group, 13 of 15 rabbits became pregnant. Potent spermicidal action against human sperm was the primary finding of the in vitro and in vivo human tests, with a potentiation of the spermicidal action by eightfold noted as well as the prevention of sperm migration into the cervical mucous (Indian J. Med. Res. 2001;113:135-41).