7 Medicinals

Since antiquity neem has been renowned for healing. The earliest Sanskrit medical writings refer to the benefits of its fruits, seeds, oil, leaves, roots, and bark.1 Each of these has long been used in the Indian Ayurveda and Unani systems of medicine. Thus, over thousands of years, millions of Asians have used neem medicinally. In addition, in places where the tree has been introduced in recent times, such as tropical America and Africa, it has also established a reputation as a useful cure for various ailments.

Today, the best-established and most widely recognized uses are based on its merits as a general antiseptic. Neem preparations are reportedly efficacious against a variety of skin diseases, septic sores, and infected burns. The leaves, applied in the form of poultices or decoctions, are also recommended for boils, ulcers, and eczema. The oil is used for skin diseases such as scrofula, indolent ulcers, and ringworm.

Cures for many more ailments have been claimed but have not been independently confirmed by trials under controlled conditions. Nonetheless, there are intriguing indications that neem might in future be used much more widely. These promising, but unproved, applications include anti-inflammatory, hypotensive, and anti-ulcer treatments.

A summary of some recent results in medical and veterinary studies follows.

FUNGICIDES

Neem has proved effective against certain fungi that infect the human body. Such fungi are an increasing problem and have been difficult to control by synthetic fungicides. For example, in one laboratory study,2 neem preparations showed toxicity to cultures of 14 common fungi, including members of the following genera:

• Trichophyton—an "athlete's foot" fungus that infects hair, skin, and nails;
• Epidermophyton—a "ringworm" that invades both skin and nails of the feet;
• Microsporum—a ringworm that invades hair, skin, and (rarely) nails;
• Trichosporon—a fungus of the intestinal tract;
• Geotrichum—a yeast like fungus that causes infections of the bronchi, lungs, and mucous membranes; and
• Candida—a yeast like fungus that is part of the normal mucous flora but can get out of control, leading to lesions in mouth (thrush), vagina, skin, hands, and lungs.

ANTIBACTERIALS

In trials neem oil has suppressed several species of pathogenic bacteria, including:

• Staphylococcus aureus.3 A common source of food poisoning and many pus-forming disorders (for example, boils and abscesses), this bacterium also causes secondary infections in peritonitis, cystitis, and meningitis. Many strains are now resistant to penicillin and other antibiotics, one reason for the widespread occurrence of staphylococcal infections in hospitals.
• Salmonella typhosa.4 This much-feared bacterium, which lives in food and water, causes typhoid, food poisoning, and a variety of infections that include blood poisoning and intestinal inflammation. Current antibiotics are of only uncertain help in treating it.

However, neem has many limitations as an antibiotic. In the latter test, neem showed no antibacterial activity against certain strains of the above bacteria, and none against Citrobacter, Escherichia coli, Enterobacter, Klebsiella pneumoniae, Proteus mirabilis, Proteus morgasi, Pseudomonas aeruginosa, Pseudomonas EO1, and Streptococcus faecalis.

ANTIVIRAL AGENTS

In India, there is much interesting, but anecdotal, information attributing antiviral activity to neem. Its efficacy-particularly against pox viruses—is strongly believed, even among those of advanced medical training. Smallpox, chicken pox, and warts have traditionally been treated with a paste of neem leaves—usually rubbed directly onto the infected skin.

Experiments with smallpox, chicken pox, and fowl pox suggest that there may be a true biological basis for this practice. Crude neem extracts absorbed the viruses, effectively preventing them from entering uninfected cells.5 Unfortunately, no antiviral effects were seen once the infection was established within the cell. Thus neem was effective prevention, but not cure.

Recent pharmacological studies have supported the belief that neem leaves possess some antiviral activity. So far these are only preliminary and unconfirmed results, but they are intriguing, nonetheless. In the United States, aqueous neem-leaf extracts have shown low to moderate inhibition of the viral DNA polymerase of hepatitis B virus.6 In Germany, an ethanolic neem-kernel extract has proved effective against herpes virus.7 And in horticultural studies, crude extracts also seemed to effectively bind certain plant viruses, and so limit infection (see Chapter 6).

Should these early results prove to be soundly based, an array of extremely virulent and difficult diseases of people—not to mention of wildlife and livestock—might be treated.

DERMATOLOGICAL INSECTS

Given all of neem's insecticidal properties, it is perhaps not unexpected that it is a common folk remedy against maggots and head lice. In Haiti, for instance, crushed leaves are rubbed into open wounds that have become maggot infested. And in India and Bangladesh, villagers apply neem oil to the hair to kill head lice, reportedly with great success.

DENTAL TREATMENTS

As noted earlier, both in India and Africa millions of people use twigs as "toothbrushes" every day. For many the twig is neem. Dentists have endorsed this ancient practice, finding it effective in preventing periodontal disease.8 It is unclear whether the benefit is due to regular gum massage, to preventing plaque buildup, to neem's inherent antiseptic action, or to all three.

Figure

People using neem sticks as disposable toothbrushes are commonly seen in rural regions of South Asia and Africa. Research has found that neem twigs contain antiseptic ingredients and they are able to maintain healthy teeth and gums. (M. Elvin-Lewis)

As also noted earlier, a German company uses neem (actually, extracts of bark) as the active ingredient in toothpastes and other oral hygiene preparations. It claims that its tests prove neem bark to be highly effective at both preventing and healing gum inflammations and periodontal disease.

CHAGAS' DISEASE

Extracts of neem reportedly affect the kissing bugs that transmit the much-feared Chagas' disease (see sidebar, page 64). They do not kill the insect; instead they "immunize" it against parasites that live inside it for part of their life cycle.9 The discovery may point the way to controlling this major health problem in Latin America, although delivering neem materials to these tiny bloodsuckers in rural hovels is perhaps impossible in practice.

Chagas' Disease

About 20 million Latin Americans are infected with Chagas' disease; many live as helpless cripples, unable to work or enjoy life. A parasite (Trypanosoma cruzi) causes this major health problem. It lives and reproduces inside nerve and muscle cells, particularly those of the heart, and drains its victims of all their energy.

The parasite—a trypanosome related to the well-known one that causes the dreaded sleeping sickness in Africa—is spread by the so-called ''kissing bugs." Similar to large bedbugs, these insects inhabit cracks and crevices in the walls and roofs of huts and houses in rural areas. Emerging at night, they bite and suck the blood of any sleeping people, pets, or livestock they encounter.

In this way kissing bugs pick up the parasite, but they pass it on not through their bite, but through their droppings. The parasite develops and multiplies within the bug's hind-gut, and, in its infective stage, passes out with the excrement. Kissing bugs often defecate while they are feeding, and when the victim wakes up and scratches the itchy bump, the excrement, together with the parasite's infective stage, is rubbed into the wound and enters the bloodstream.

So far, there is no truly satisfactory control for this dread disease, but laboratories in Germany and Brazil have recently produced the makings of a possible breakthrough involving neem.

At the Max Planck Institute for Biochemistry in Martinsried, Germany, Heinz Rembold has been raising one species of kissing bug, Rhodnius prolixus, to study the effects of azadirachtin on its hormone system. He found that azadirachtin prevents young kissing bugs from molting and therefore from ever maturing, and it interferes with the adults' ability to reproduce.

The other prong of this research is being done at the Oswaldo Cruz Institute in Rio de Janeiro, Brazil. There, Eloi Garcia and his research team keep both parasite-free and parasite-infected kissing bugs. Recently, when they fed blood laced with azadirachtin to a group of infected bugs, they made a surprising discovery: 20 days later, the bugs were parasite free.

Rembold and Garcia believe that azadirachtin somehow disrupts the carefully synchronized arrangement that allows the parasite to develop and multiply within the insect's gut. They found that even a few micrograms of azadirachtin taken up with a blood meal proved effective and that the bugs remained free of infection even 20 days after they had eaten blood laden with parasites.*

*

Garcia et al., 1984.

The research was done both in Germany and Brazil, and has shown that feeding neem to the bugs not only frees them of parasites, but azadirachtin prevents the young insects from molting and the adults from reproducing.

The researchers conclude that azadirachtin does not simply kill the parasite because they can dose it with azadirachtin and it remains infectious. In any case, they point out that the bug excretes most of the azadirachtin within a few minutes of eating it.

Even with this short exposure, however, azadirachtin somehow disrupts the delicate host-parasite relationship. According to the research leader: "The bug has been affected in such a fundamental way that it is no longer attractive to, or a viable host for, the parasite."

Trypanosomes like these have always been extremely difficult to control. Like the AIDS virus, they constantly "change their coat," so that creating vaccines against them is difficult at best. Whether neem will provide the key to their control is uncertain, but, at the very least, it may be a valuable research tool for understanding the basis of the relationship between the host and the powerful parasite it passes on to millions of people.

MALARIA

Practitioners of the Indian Ayurveda medicine system have been preparing neem in oral doses for malarial patients for centuries.10 Neem's antimalarial activity was reported in Ayurveda books as far back as 2000 B.C. (by Charaka) and 1500 B.C. (by Sushruta). Even outside India—in Nigeria and Haiti, for example—neem-leaf teas are used to treat malaria.

People as Pests

Sticking forlornly out of the ground, only five leaves left on its skimpy branches, the seedling is dwarfed by the placard proclaiming its name and planting date: Azadirachta indica, 15 November 1986. A neem tree.

According to H.J. von Maydell's field guide Trees and Shrubs of the Sahel, the neem is "fast-growing: two-thirds of the height (to 20 meters) may be reached after three years." Photos from India show an evergreen with well leafed branches forming a thick canopy. Yet this specimen in dryland Africa is barely one meter tall, a twig holding grimly onto life in what should be the favorable environment of an agroforestry research station.

"What happened to that little thing?" asks a visitor. The reply is revealing: "It got browsed by too many people. It was planted as part of a trial, but after a few months the farm manager noticed it wasn't growing. Other trees around it were doing well, so he knew it wasn't soil deficiency or lack of rain. He thought it must be animals eating the leaves, so he fenced it in with wire mesh. There are dik-diks (small antelopes) and rabbits here, and he concluded they really liked neem leaves."

"But the tree still didn't grow. Finally he decided to watch, and found farm workers were picking the leaves—for medicine. In Kiswahili, the tree is called mwarubaini, which means '40 cures.' It's said to be able to cure 40 diseases, and everybody wanted some of that medicine. He had to order them not to touch the tree.

"And that's the only reason it's still alive."

Tom Pawlick

Agroforestry Today 1(2):2-5

In the past, researchers were unable to confirm that neem products can affect the malaria parasite Plasmodium falciparum. And it was not for want of trying. Various groups researching antimalarials repeatedly tested neem. The results—in infected mice, ducks, and chickens—were inconsistent and usually negative.

Nonetheless, there is recent evidence that improper extraction methods may explain the earlier failures. Certain extracts of neem leaf and neem seed have now proved effective against the malarial parasite, and the structure of one active component has been determined.11 This compound, gedunin, is another limonoid. It is said to be as effective as quinine on malaria-infected cell cultures.

In India, it was recently reported that components of the ethanol extract of neem leaves and seeds were effective against chloroquine-sensitive and chloroquine-resistant strains of the malaria parasite.12 Although all the different extracts tested suppressed the growth of parasites within 72 hours, the most potent were the ethanol extracts of neem leaves and the medium-polar extracts of neem seeds.

Although these are preliminary results, they indicate a potentially valuable line of research. Malaria is creeping back into areas where it had been eliminated earlier this century. It now infects approximately 110 million people annually, causing up to 2 million deaths. Moreover, there is a growing problem of resistance to the conventional treatments.

On the other hand, caution is also needed. As noted earlier, anecdotal evidence from Nigeria suggests that drinking neem-leaf teas over an extended period may lead to liver damage.

PAIN RELIEF AND FEVER REDUCTION

Neem may also be a ready source of low-cost analgesic (pain relieving), or antipyretic (fever-reducing) compounds. It is used for these purposes everywhere it is grown. In trials, positive results have been obtained for significant analgesic, antipyretic, and anti-inflammatory effects. This may explain its wide use for treating fevers in general. Some of the anti-inflammatory compounds have even been patented.13

BIRTH CONTROL

Research has shown that neem oil acts as a powerful spermicide. This finding is preliminary and may eventually prove of little consequence, but it may also prove of paramount importance. Perhaps 80 percent of the expected population explosion, which may double the number of people on earth in the next 40 years, will occur in countries where neem can be grown. An inexpensive birth-control method that can be produced in the backyards of even the remotest and poorest villages could be a vital resource.

Neem and Birth Control

Scientists at India's Defence Institute of Physiology and Allied Sciences (DIPAS) have isolated a neem-oil extract (Nim 76) that they believe can be refined into a new birth control method. Their trials have found that neem oil is strongly spermicidal. Rhesus monkey and human spermatozoa, for example, became totally immotile within 30 seconds of contacting the oil.

Studies in 20 rats, 8 rabbits, 14 rhesus monkeys, and 10 human volunteers showed that neem oil applied intravaginally before sexual intercourse prevented pregnancy. Histopathological studies on the rat tissues (vagina, cervix, and uterus) showed no ill effects. By contrast, nonyl-phenoxy polyethoxy ethanol, the spermicide in a popular vaginal contraceptive cream, produced obvious irritation. Radioisotope studies indicated that neem oil was not absorbed from the vagina.

DIPAS scientists maintain that neem oil might be an ideal contraceptive: it is a natural product, readily available, inexpensive, and nontoxic. Moreover, they anticipate that it will be widely accepted. The only disadvantage, they say, is neem oil's unpleasant odor. However, adding a small amount of scent masks most of the smell without reducing the spermicidal property.

All in all, they conclude, neem oil has particular potential for widespread use by the poor. It seems likely to be the cheapest contraceptive available, and villagers in remote areas may well accept it as a regular method of birth control because sophisticated methods are financially beyond their reach and because they are extremely apprehensive about sterilization and other sophisticated methods.

In a scientific article in the Indian Journal of Medical Research, DIPAS researchers report that tests also show that Nim 76 can prevent a fertilized egg from implanting in the wall of the uterus. Nim 76 was effective in rats and rabbits if applied on day 2 to day 7 of the expected pregnancy. The minimum effective dose was very small (only 25 µ1 for rats). And a month after the applications ceased, the animals were completely fertile again. According to the researchers, there were no deleterious effects on subsequent pregnancies or offspring (see Appendix B, page 104).

Indian scientists have demonstrated that neem oil is a potential new contraceptive for women (see sidebar). It kills spermatozoa within 30 seconds and has proved effective both in laboratory trials and in practice—where an intravaginal dose of I ml of neem oil was used. Histopathology failed to reveal any side effects.

As a follow-up to these experiments, the Indian army provided neem oil to 20 soldiers and their families as a birth-control measure. This trial was considered so successful that the colonel in charge of the program was honored by the prime minister. A neem-oil formulation called "Sensal" is now sold in India for contraceptive purposes.

Neem-leaf extracts have also shown promise as male birth-control products because they reduce fertility in a variety of male mammals. Reportedly, there was no impotence or loss of libido.14

More details of these tentative but potentially far-reaching discoveries are given both in the sidebar (opposite) and in Appendix B.

VETERINARY MEDICINE

Ancient practice and initial testing of neem derivatives against various livestock pests indicated that this is an area of particular promise for the future. Some possibilities are discussed below.

Controlling Insects

Insects of veterinary importance are obvious targets for neem products. Some examples follow:

• Maggots Indians have traditionally crushed neem leaves and rubbed them into open wounds on cattle to eliminate maggots.
• Horn flies As noted in chapter 5, azadirachtin passes through the ruminant digestive tract and remains long enough that horn flies will not develop in the manure.
• Blowflies As also noted earlier, neem oil and neem-seed extract deterred the female blowfly, Lucilia sericata, from laying its eggs on sheep. Moreover, in Sri Lanka the oil is rubbed on cattle as a fly repellent.15
• Biting flies Azadirachtin also exerts an ovicidal effect in eggs of the blood-sucking fly Stomoxys calcitrans.16

Controlling Bacteria

The Staphylococcus aureus bacterium, mentioned earlier, also causes mastitis (inflammation of the mammary glands) in cows. Neem's apparent ability to control certain strains of this bacterium may thus be of great economic importance to dairying in the nations where neem grows.

Also, the salmonella bacterium, in addition to affecting people, causes abortion in horses, cattle, and sheep, as well as a variety of infections in poultry and livestock.

Controlling Intestinal Worms

Trials in Germany showed that neem also works against intestinal nematodes in animals.17

A WORD OF CAUTION

Medicines from plants should, of course, be treated with the same caution as medicines from laboratories. Neem oil seems to be of particular concern. Consuming it, although widely practiced in parts of Asia, is not recommended. Doses as small as 5 ml have killed infants,18 and animal studies showed acute toxicity at doses as low as 14-24 ml per kg of body weight.19 It seems possible that this was caused by contaminants rather than by the oil itself. In Germany, toxicological tests using oil obtained from clean neem kernels resulted in no toxicity, even at a concentration of 5,000 mg per kg of body weight in rats. Nonetheless, caution is called for.

The leaves or leaf extracts also should not be consumed by people or fed to animals over a long period. There are anecdotal reports of renal failure in Ghanaians who were drinking leaf teas as a malaria treatment.

None of this should be confused with earlier statements. The compounds and seed-kernel extracts responsible for the insecticidal activity appear to be essentially nontoxic to mammals (see Appendix A).20

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Footnotes

1 The tree's Sanskrit name was "arishtha," meaning "reliever of sickness."

2 Khan and Wassilew. 1987.

3 Schneider, 1986.

4 Patel and Trivedi, 1962.

5 Rao et al., 1969; Rae and Sethi, 1972.

6 Information from D.W. Unander.

7 Information from H. Schmutterer.

8 M. Elvin-Lewis, 1980; Henkes, 1986.

9 Information from H. Rembold and E.S. Garcia.

10 This is normally done by decocting or extracting about 500 g of leaves in alcohol or water.

11 Khalid et al., 1986; Khalid et al., 1989.

12 Badam et al., 1987.

13 Terumo Corporation 1983, 1985. Anti-inflammatory polysaccharides from Melia azadirachta. Japan Kokai Tokyo Koho JP 82-05532 and 83-225021.

14 Sadre et al., 1984.

15 Ganesalingham, 1987.

16 Gill, 1972. In one trial, neem-kernel dust incorporated into the diet of the larvae resulted in 100 percent mortality within 2 days at a 10 percent treatment level. At 5 percent treatment, 91 percent of larvae died within 2 days, and 100 percent mortality was reached in 7 days.

17 Information from H. Schmutterer. To be effective, the preparations had to have relatively high concentrations of azadirachtin.

18 Sinniah and Baskaran. 1981.

19 Gandhi et al., 1988.

20 Koul et al., 1990.

Copyright © National Academy of Sciences.