What is neem

Neem (Azadirachta indica) is commonly known as Indian lilac, is a tree in the mahogany family Meliaceae. Neem is one of two species in the genus Azadirachta and is native to the Indian subcontinent, i.e. India, Nepal, Pakistan, Bangladesh, Sri Lanka, and Maldives. Neem typically is grown in tropical and semi-tropical regions, their large size and preference for wet areas. Neem trees now also grow in islands located in the southern part of Iran. Its fruits and seeds are the source of neem oil.

These features describe the habit of neem plant:

• fast growing tree can grow 12 to 24m high
• compound leaves 20 to 40cm long, made up of 20 to 30 leaflets and leaflets between 3 to 8cm long. Neem leaflets are vibrant yellowy green with distinctive toothed margins.
• Neem fruit are green, ripening to yellow. Neem fruits are similar to olives in size and shape.

All the parts of neem tree is commonly used in traditional Indian medicine for household remedy against various human diseases as well as pest control ¹, ², ³. Neem-based pesticides are now extensively used in agriculture practices all over the world. It contains azadirachtin, which is a predominant insecticidal active ingredient, having antefeedent, ovipositional deterrence repellency, growth disruption, sterility and larvicidal action against insects ⁴. There are various reports of control of mosquito breeding under field conditions. An emulsion of neem oil in water was found to be effective in controlling breeding of Culex quinquefasciatus (mosquito vector of Japanese encephalitis virus), Anopheles stephensi (mosquito vector of malaria in urban India) and Aedes aegypti larvae (larvae of the mosquito vector of Yellow fever virus & Dengue fever) in pools, tanks and coolers up to 2 to 3 weeks ⁵, whereas an application of neem cake powder resulted in drastic reduction in the late instar larvae and pupae of culicine mosquitoes in paddy field ⁶.

For centuries, millions of Indian have cleaned their teeth with neem twigs, smeared skin disorders with neem leaf juice, taken neem tea as a tonic, and placed neem leaves in their beds, books, grain bins, cupboards, and closets to keep away troublesome bugs. The tree has relieved so many different pains, fevers, infections, and other complaints so that it has been called “the village pharmacy” ⁷. In rural India, peoples often used water decoction of neem leaves for the prevention and treatment of various ailments.

Bioactive compounds in neem include: nimbidin, nimbolide, gedunin, mahmoodin, flavonoids, tannins, and alkaloids. These phytochemicals act on bacterial cell wall by binding to adhesins forming complex causing inactivation of proteins and cell function ⁸. Nimbidin has anti-inflammatory, anti-arthritic, antipyretic, hypoglycemic, and anti-bacterial property ⁹. It is active against Klebsiella, Staphylococcus, and Serratia species. It is also active against Streptococcus mutans and Streptococcus faecalis ¹⁰.

Neem is commonly seen as a medicinal tree and versatile plant having a wide spectrum of biological activities. Various studies have been put forward on its antimicrobial properties. A study by Elavarasu et al ¹¹ stated that neem oil was effective by reducing the growth of the plaque-causing microorganisms. Bohora et al ¹² found that neem extract showed significant antimicrobial effect against Enterococcus faecalis and Candida albicans. But a study by Kumar and Sidhu ¹³ stated that neem extract was ineffective and did not inhibit the growth of Enterococcus faecalis; similar negative result was obtained in another study ¹⁴.

Neem Weed status

Neem is considered a weed in many areas, including some parts of the Middle East, most of Sub-Saharan Africa including West Africa and Indian Ocean states, and some parts of Australia ¹⁵.

Figure 1. Neem

Neem Uses

Neem leaves are dried in India and placed in cupboards to prevent insects eating the clothes, and also in tins where rice is stored. Neem leaves are dried and burnt in the tropical regions to keep away mosquitoes. These flowers are also used in many Indian festivals like Ugadi. As an ayurvedic herb, neem is also used in baths.

As a vegetable

The tender shoots and flowers of the neem tree are eaten as a vegetable in India. A souplike dish called Veppampoo charu (Tamil) (translated as “neem flower rasam”) made of the flower of neem is prepared in Tamil Nadu. In Bengal, young neem leaves are fried in oil with tiny pieces of eggplant (brinjal). The dish is called nim begun and is the first item during a Bengali meal that acts as an appetizer. It is eaten with rice.

Neem is used in parts of mainland Southeast Asia, particularly in Cambodia, Laos (where it is called kadao), Thailand (where it is known as sadao or sdao), Myanmar (where it is known as tamar) and Vietnam. Even lightly cooked, the flavour is quite bitter and the food is not enjoyed by all inhabitants of these nations, though it is believed to be good for one’s health. In Myanmar, young neem leaves and flower buds are boiled with tamarind fruit to soften its bitterness and eaten as a vegetable. Pickled neem leaves are also eaten with tomato and fish paste sauce in Myanmar.

Head lice

An anti-louse shampoo (Licener®) based on a neem seed extract was tested in vivo and in vitro on its efficacy to eliminate head louse infestation by a single treatment. The hair of 12 children being selected from a larger group due to their intense infestation with head lice were incubated for 10 min with the neem seed extract-containing shampoo ¹⁶. It was found that after this short exposition period, none of the lice had survived, when being observed for 22 h. In all cases, more than 50-70 dead lice had been combed down from each head after the shampoo had been washed out with normal tap water. A second group of eight children had been treated for 20 min with identical results. Intense combing of the volunteers 7 days after the treatment did not result in the finding of any motile louse neither in the 10-min treated group nor in the group the hair of which had been treated for 20 min. Other living head lice were in vitro incubated within the undiluted product (being placed inside little baskets the floor of which consisted of a fine net of gauze). It was seen that a total submersion for only 3 min prior to washing 3× for 2 min with tap water was sufficient to kill all motile stages (larvae and adults). The incubation of nits at 30°C into the undiluted product for 3, 10, and 20 min did not show differences. In all cases, there was no eyespot development or hatching larvae within 7-10 days of observation. This and the fact that the hair of treated children (even in the short-time treated group of only 10 min) did not reveal freshly hatched larval stages of lice indicate that there is an ovicidal activity of the product, too.

Other uses

Insufficient evidence to rate effectiveness for:

• Skin diseases such as psoriasis, eczema, alopecia, diabetic ulcer, warts, vitiligo, pemphigus, pompholyx, leprosy, and many other more very common and rare diseases.
• Antisnake venom activity
• Digestive disorders
• Anticarcinogenic activity
• Antioxidant effect
• Anti-inflammatory activity
• Sexually transmitted disease
• Immune system
• Antiviral
• Antibacterial activity

Studies in human are to rate the effectiveness of neem or neem oil for these uses.

What is neem oil

Neem oil (margosa oil) is a vegetable oil obtained from the seed kernels of Neem tree (Azadirachta indica). Neem oil is deep yellow in color and has garlic–like odor. It contains active ingredients like azadirachtin, nimbin, picrin, and sialin.

Neem oil, as a traditional medical remedy, is used as anti-bacterial, anti-fungal, insect repellent, and treatment of skin diseases. Traditional routes of administration of Neem extracts included oral, vaginal, and topical use. Neem oil comprises mainly triglycerides, steroids (campesterol, beta-sitosterol, stigmasterol) and many triterpenoids, of which azadirachtin is the most well-known and studied. The azadirachtin content of neem oil varies from 300 ppm to over 2500 ppm, depending on the extraction technology and quality of the neem seeds crushed.

What is neem oil used for

One of the most extensively used “natural” plant derived insecticides is neem ⁴. The pesticide action of neem oil is attributed to azadirachtin, which is used as an insecticide for arthropod pests ¹⁷. Commercially available neem based insecticides are used to control many crop pests and this is considered as a “green” approach to pest control, permitted in organic production systems ¹⁸.

Neem oil was shown to be toxic to Anopheles stephensi (mosquito vector of malaria in urban India), Culex quinquefasciatus (mosquito vector of Japanese encephalitis virus) and Aedes aegypti larvae (larvae of the mosquito vector of Yellow fever virus & Dengue fever) with median lethal concentrations (LC50) of 1.6, 1.8 and 1.7 ppm respectively ¹⁹. The neem oil formulation tested by Dua and co-workers ¹⁹ was also found to be effective in controlling mosquito larvae under natural field conditions, which could be used as an alternative for malaria control.

Recently, entomopathogenic fungi have been formulated in neem oil and tested against larval and adult An. gambiae and adult C. quinquefasciatus ²⁰. The results showed that the formulation of fungus + neem was more effective than neem alone for adults and larvae. The “formulation” of fungus in water was not as effective as fungus formulated in neem oil against adults, although larvae were not exposed to formulations of fungus without neem ²⁰.

An emulsion of neem oil in water was found to be effective in controlling breeding of Culex quinquefasciatus, Anopheles stephensi and Aedes aegypti in pools, tanks and coolers up to 2 to 3 weeks ⁵, whereas an application of neem cake powder resulted in drastic reduction in the late instar larvae and pupae of culicine mosquitoes in paddy field ⁶.

Table 1. Larvicidal activity of neem oil formulation against mosquito in laboratory

[Source ¹⁹]

Table 2. Larvicidal activity of neem oil formulation against mosquitoes larvae in field

Mosquito species	Breeding sites	Pre treatment density	Percent reduction of larval density (mean ± sd)
			Day-1	Day-2	Day-3	Week-1	Week-2	Week-3
Culex	Pits	28.9 ± 10.6	95.9 ± 3.5	90.2 ± 6.9	87.2 ± 11.0	87.5 ± 8.2	85.9 ± 8.0	80.5 ± 7.3
	Tanks	26.8 ± 11.5	91.9 ± 5.8	93.2 ± 3.2	97.7 ± 1.9	92.4 ± 8.0	86.2 ± 8.2	80.7 ± 9.2
	Drains	115.7 ± 64.6	99.4 ± 0.6	98.8 ± 1.2	98.6 ± 1.4	84.9 ± 4.6	85.0 ± 11.8	77.8 ± 11.0
			95.5 ± 4.1	94.1 ± 4.3	94.5 ± 5.5	89.9 ± 2.5	85.7 ± 0.8	79.7 ± 1.6
Anopheles	Pits	13.5 ± 7.5	96.2 ± 4.5	100	100	100	85.4 ± 14.1	76.6 ± 9.6
	Tanks	10.4 ± 5.7	98.2 ± 1.8	100	100	100	87.0 ± 9.7	77.7 ± 10.0
	Drains	13.0 ± 6.7	100	100	100	100	98.7 ± 1.3	97.0 ± 3.0
			98.1 ± 1.9	100	100	100	90.4 ± 7.2	83.8 ± 11.5

[Source ¹⁹]

Table 3. Larvicidal activity of neem oil formulation against Aedes mosquitoes in field

[Source ¹⁹]

Neem oil poisoning

Neem oil has widespread use in Indian subcontinent due to its many bioactive properties. Neem oil poisoning is rare in adults. In children, neem oil is reported to cause toxic encephalopathy and Reye’s–like syndrome ²¹. Azadirachtin (C₃₅H₄₄O₁₆), a complex tetranortriterpenoid, is implicated in causing the effects seen in neem oil poisoning ²². Azadirachtin manifests its toxicity possibly by interfering with mitochondrial bioenergetics, resulting in inhibition of the generation of the electrochemical proton gradient (primary form of energy generated in mitochondria). Acute poisoning with inhibitors of electron transporting complexes causes symptoms such as muscle weakness, easy fatigability, hypotension, headache, facial flushing, nausea, confusion, and aggravation of latent myocardial angina. The inability to utilize oxygen is manifested as a cytotoxic hypoxia wherein the chemicals cause a metabolic acidosis and hyperpnea, despite normal pO2.

In children, there are several case reports of Neem oil poisoning causing vomiting, hepatic toxicity, metabolic acidosis, and encephalopathy ²³. Lai et al. ²⁴, reported 22 cases of neem oil poisoning in infants, who were given single doses of Neem oil (few drops to 5 ml), presented with features of toxic encephalopathy, metabolic acidosis, and hepatic toxicity. The infants recovered completely with supportive treatment ²⁴. Sundaravalli et al. ²³, in a case series of 12 children with neem oil poisoning, who were given single dose of Neem oil (25-60 ml), reported fatality in 10 cases with features of toxic encephalopathy and metabolic acidosis. Sinnaih et al. ²¹, reported Reyes–like syndrome in fatal cases of Neem oil poisoning in a case series of 13 children.

In adults, there are few case reports of Neem poisoning. A case report of neem oil poisoning involving a 73-year-old male who presented with vomiting, seizures, metabolic acidosis, and toxic encephalopathy – 1 hour after accidental ingestion of 20 ml of Neem oil ²⁵. The patient recovered completely with symptomatic treatment. Iyyaduria et al. ²², reported a case of a 35-year-old female with suicidal poisoning, who presented after ingestion of 250 ml of Neem pesticide with encephalopathy and metabolic acidosis with no evidence of hepatic and renal complications. She recovered completely with supportive management. Bhasker et al. ²⁶, reported a 35-year-female with Neem oil poisoning who presented with bilateral visual loss. Cranial MR imaging, showed symmetrical altered signal intensity bilaterally in the putamen region with extension to the posterior limb of the internal capsule. Laboratory findings were within normal limits, and she recovered completely with supportive management.

There is no specific antidote available, and gastric lavage is not recommended for Neem oil poisoning. The management is primarily symptomatic and recovery is usually complete ²⁷.

What is Reye Syndrome

Reye syndrome is a rare illness that can affect the blood, liver, and brain of someone who has recently had a viral infection ²⁸. It always follows another illness. Although it mostly affects children and teens, anyone can get it. It can develop quickly and without warning. It is most common during flu season.

Symptoms include

• Nausea and vomiting
• Listlessness
• Personality change – such as irritability, combativeness or confusion
• Delirium
• Convulsions
• Loss of consciousness

If these symptoms occur soon after a viral illness, seek medical attention immediately. Reye syndrome can lead to a coma and brain death, so quick diagnosis and treatment are critical. Treatment focuses on preventing brain damage. There is no cure.

Neem oil allergic contact dermatitis

Allergic contact dermatitis from neem oil has been described previously in 3 patients ²⁹. The allergen(s) is/are unknown.

Summary

Neem has been used as an herbal medication since ancient times, is still popular today and probably will continue to be used in the future because it contains various bioactive phytochemicals that could provide therapeutic effects.

Establishing whether or not therapeutic effects of neem are beneficial to patients will require good clinical research and generation of scientific evidence. There is a need for continued efforts that focuses on various diseases, which are then validated in clinical trials that will help in developing neem as a promising therapeutic agent. Without such evidence, it will remain unclear whether these untested and unproven medical treatments are truly beneficial. It is advisable that the discriminate and proper use of neem preparations could be safe and provide therapeutic benefits however the indiscriminate or improper use can be unsafe and harmful- e.g. neem current use as pesticide and to kill mosquitos larvae.

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