What is neem

Neem (Azadirachta indica) is commonly known as Indian lilac, is a tree in the mahogany family Meliaceae, genus Azzadirachta ¹. Neem is also named “Nimba”, “holy tree”, “Vembu”, “Arishtha”, “Indian neem tree”, “wonder tree”, “village pharmacy”, “divine tree”, or “panacea of all diseases”. Neem has a good growth rate and may reach approximately 15–20 meters in height, sometimes up to 35–40 meters ². Neem is one of two species in the genus Azadirachta and is native to the Indian subcontinent, i.e. India, Burma, Nepal, Pakistan, Bangladesh, Sri Lanka, and Maldives ². 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.

Neem has been extensively used in Ayurveda, Unani and Homoeopathic medicine. All parts of the neem tree- leaves, flowers, seeds, fruits, roots and bark have been used traditionally for the treatment of inflammation, infections, fever, skin diseases and dental disorders ³, but neem seeds seem to be the most important part of the plant due to their oil content and various bioactive compounds. Also, neem seeds have an increased content of azadirachtin, a natural insecticide ⁴. The lipid content of neem seeds varies from 20% to 32% ⁵ and the content of sterols, fatty acids, and proteins has also been reported. Neem seed oil contains more than 100 active compounds, called triperpenoids and linonoids: saladucin, valassin, meliacin, nimbin, nimbicin, geducin, and azadirachtin, one of the most important biopesticides ⁶. Neem seeds seem to be the most important part of neem, but neem leaves, fruits, kernel bark, flowers, roots, twigs, and wood may also be used for their beneficial activities ⁷, ⁸, ⁹, ¹⁰. 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 antifeedant, ovipositional deterrence repellency, growth disruption, sterility and larvicidal action against insects ¹¹. 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 ¹², whereas an application of neem cake powder resulted in drastic reduction in the late instar larvae and pupae of culicine mosquitoes in paddy field ¹³.

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” ¹⁴. In rural India, peoples often used water decoction of neem leaves for the prevention and treatment of various ailments.

Neem contains a wide range of biological active compounds, including nimbin, nimbidin, nimbolinin, nimbolide, nimbidol, sodium nimbinate, gedunin, mahmoodin, salannin, flavonoids, limonoids, tannins, and alkaloids. These phytochemicals act on bacterial cell wall by binding to adhesins forming complex causing inactivation of proteins and cell function ¹⁵. Nimbidin has anti-inflammatory, anti-arthritic, antipyretic, hypoglycemic, and anti-bacterial property ¹⁶. It is active against Klebsiella, Staphylococcus, and Serratia species. It is also active against Streptococcus mutans and Streptococcus faecalis ¹⁷. The first polyphenolic flavonoids from fresh neem leaves were quercetin and beta-sitosterol ¹⁸. All of those compounds occupy essential places in cancer development and management, through antitumor activity ¹⁹, antioxidant activity, and the inhibitory effect exerted on the development of malignant cells by modulation of cellular proliferation, tumor suppressor genes, and apoptosis ²⁰.

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 ²¹ stated that neem oil was effective by reducing the growth of the plaque-causing microorganisms. Bohora et al ²² found that neem extract showed significant antimicrobial effect against Enterococcus faecalis and Candida albicans. But a study by Kumar and Sidhu ²³ stated that neem extract was ineffective and did not inhibit the growth of Enterococcus faecalis; similar negative result was obtained in another study ²⁴.

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 ²⁵.

Figure 1. Neem

Neem bioactive compounds

Neem protects itself from the multitude of pests with a multitude of pesticidal ingredients. Over 1000 research articles published on neem has uncovered over 300 structurally diverse constituents, one third of which are limonoids (also called “triterpenes”) including nimbolide, azadarachtin, and gedunin ²⁶.

Of the numerous pesticidal agents isolated so far from neem kernels, azadirachtin is the most active against insects. In addition to inhibiting their growth, it interferes with their powers of taste. Many leaf eating insects are repelled by plants to which even small amounts of azadirachtin have been applied.

Azadirachtin, salannin, and nimbin all have the same basic limonoid structure. This differs from, but is not unlike, that of the sterols to which the insect molting hormones (“ecdysones”) belong. An insect ingesting traces of these compounds is deeply affected because these “hormone mimics” block the parts of the brain that produce the hormones necessary to growth and development. In many cases, for instance, the insect’s body may be ready to change while the hormones to complete the molt are not available. These deep-seated hormonal effects are the reason for neem’s subtle, powerful, and yet insect-specific influences.

Figure 2. Chemical structures of neem’s main ingredients

[Source ²⁷ ]

Limonoids

So far, at least nine neem limonoids have demonstrated an ability to block insect growth, affecting a range of species that includes some of the most deadly pests of agriculture and human health. New limonoids are still being discovered in neem, but azadirachtin, salannin, meliantriol, and nimbin are the best known and, for now at least, seem to be the most significant.

Azadirachtin

One of the first active ingredients isolated from neem, azadirachtin has proved to be the tree’s main agent for battling insects. It appears to cause some 90 percent of the effect on most pests. It does not kill insects—at least not immediately. Instead it both repels and disrupts their growth and reproduction. Research over the past 20 years has shown that it is one of the most potent growth regulators and feeding deterrents ever assayed. It will repel or reduce the feeding of many species of pest insects as well as some nematodes. In fact, it is so potent that a mere trace of its presence prevents some insects from even touching plants.

Azadirachtin is structurally similar to insect hormones called “ecdysones,” which control the process of metamorphosis as the insects pass from larva to pupa to adult. It affects the corpus cardiacum, an organ similar to the human pituitary, which controls the secretion of hormones. Metamorphosis requires the careful synchrony of many hormones and other physiological changes to be successful, and azadirachtin seems to be an “ecdysone blocker.” It blocks the insect’s production and release of these vital hormones. Insects then will not molt. This of course breaks their life cycle.

On average, neem kernels contain between 2 and 4 mg of azadirachtin per gram of kernel. The highest figure so far reported—9 mg per g—was measured in samples from Senegal.

Meliantriol

Another feeding inhibitor, meliantriol, is able, in extremely low concentrations, to cause insects to cease eating. The demonstration of its ability to prevent locusts chewing on crops was the first scientific proof for neem’s traditional use for insect control on India’s crops.

Salannin

Yet a third triterpenoid isolated from neem is salannin. Studies indicate that this compound also powerfully inhibits feeding, but does not influence insect molts. The migratory locust, California red scale, striped cucumber beetle, houseflies, and the Japanese beetle have been strongly deterred in both laboratory and field tests.

Nimbin and Nimbidin

Two more neem components, nimbin and nimbidin, have been found to have antiviral activity. They affect potato virus X, vaccinia virus, and fowl pox virus. They could perhaps open a way to control these and other viral diseases of crops and livestock.

Nimbidin is the primary component of the bitter principles obtained when neem seeds are extracted with alcohol. It occurs in sizable quantities—about 2 percent of the kernel.

Others

Certain minor ingredients also work as antihormones. Research has shown that some of these minor neem chemicals even paralyze the “swallowing mechanism” and so prevent insects from eating. Examples of these newly found limonoids from neem include deacetylazadirachtinol. This ingredient, isolated from fresh fruits, appears to be as effective as azadirachtin in assays against the tobacco budworm, but it has not yet been widely tested in field practice ²⁷.

Two compounds related to salannin, 3-deacetylsalannin and salannol, recently isolated from neem, also act as antifeedants.

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.

Neem effects on insects

The growing accumulation of experience demonstrates that neem products work by intervening at several stages of an insect’s life. The ingredients from this tree approximate the shape and structure of hormones vital to the lives of insects (not to mention some other invertebrates and even some microbes). The bodies of these insects absorb the neem compounds as if they were the real hormones, but this only blocks their endocrine systems. The resulting deep-seated behavioral and physiological aberrations leave the insects so confused in brain and body that they cannot reproduce and their populations plummet.

Increasingly, approaches of this kind are seen as desirable methods of pest control: pests don’t have to be killed instantly if their populations can be incapacitated in ways that are harmless to people and the planet as a whole. In the 1990s this is particularly important: many synthetic pesticides are being withdrawn, few replacements are being registered, and rising numbers of insects are developing resistance to the shrinking number of remaining chemical controls.

The precise effects of the various neem-tree extracts on a given insect species are often difficult to pinpoint. Neem’s complexity of ingredients and its mixed modes of action vastly complicate clarification. Moreover, the studies to date are hard to compare because they have used differing test insects, dosages, and formulations. Further, the materials used in various tests have often been handled and stored differently, taken from differing parts of the tree, or produced under different environmental conditions.

But, for all the uncertainty over details, various neem extracts are known to act on various insects in the following ways:

• Disrupting or inhibiting the development of eggs, larvae, or pupae;
• Blocking the molting of larvae or nymphs;
• Disrupting mating and sexual communication;
• Repelling larvae and adults;
• Deterring females from laying eggs;
• Sterilizing adults;
• Poisoning larvae and adults;
• Deterring feeding;
• Blocking the ability to “swallow” (that is, reducing the motility of the gut);
• Sending metamorphosis awry at various stages; and
• Inhibiting the formation of chitin. Chitin is the material comprising the insect’s exoskeleton. Stopping the formation of a new “skin” for the next stage in its development is one way that azadirachtin acts to regulate the growth of an insect.

As noted earlier, neem extracts have proved as potent as many commercially available synthetic pesticides. They are effective against dozens of species of insects at concentrations in the parts-per-million range. At present, it can be said that repellency is probably the weakest effect, except in some locust and grasshopper species. Antifeedant activity (although interesting and potentially extremely valuable) is probably of limited significance; its effects are short-lived, and highly variable. Blocking the larvae from molting is likely to be neem’s most important quality. Eventually, this larvicidal activity will be used to kill off many pest species.

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 ²⁸. 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.

Neem potential health uses

The active principles from neem bark, neem leafs, neem seeds, and other parts of neem are exploited for their immunomodulatory, antiseptic, diuretic, antipyretic, antiparasitic, antimicrobial, analgesic, antifeedant, contraceptive, pediculicide, antiulcer, antimutagenic, and anticancer effects ²⁹, ³⁰, ³¹.

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.

Figure 3. Neem health effects

[Source ² ]

Neem toxicity

Neem has been used in a more concentrated form, as extracts, in order to treat or prevent various diseases, including cancer. Neem toxicity profile is outlined according to the solvent used to process the plant in order to obtain concentrated fractions ³².

Lethal Dose 50 (LD50) is the amount of a material, given all at once, which causes the death of 50% (one half) of a group of test animals. The LD50 is one way to measure the short-term poisoning potential (acute toxicity) of a material. In animal models (mice), studies have shown an LD50 for methanolic neem leaf extracts was 13 g/kg ³³ and for methanolic extracts of neem flowers, the LD50 was 12 g/kg ³⁴. In contrast to the methanolic extract, aqueous neem fractions are considered nontoxic and the LD50 is higher than 2.5 g/kg ³⁵.

A study by Tarbousch et al. ³⁶ showed that oral doses of azadirachtin are able to produce adverse effects. Their results indicated that oral administration of this phytochemical did not produce morphological consequences on mouse fetuses. Also, daily administration of 5–50 mg/kg of azadiractin did not produce adverse effects on the reproductive system or on fetus development ³⁷.

In the United States, azadirachtin is considered a nontoxic pesticide. Furthermore, the oil extracted from neem seeds is able to cause death in rats if it is administered intravenously or intraperitoneally and has an LD50 of 14 mL/kg ³⁸.

For humans, a daily dose of 15 mg/kg can be toxic, and nonaqueous extracts have demonstrated the presence of allergens in the skin prick test for allergenic activity ³².

Table 1. Acute toxicity of neem in different mammalians

Part of Neem (Azadirachta indica)	Nature of the Extract	Test Animal	Dose/Mode of Administration	Duration	LD50	Effect Observed	References
Leaves	Aqueous extract	Mice	200, 500, 1000, and 2500 mg/kg b.w./oral	1 d	>2500 mg/kg	No significant changes	35
		Mice	1250, 2500, and 5000 mg/kg b.w./oral	14 d	>5000 mg/kg	No significant changes	39
		Rats	0.05, 0.071, 0.084, 0.092, and 0.1 g/mL/intramuscular injection	2 d	6.2 mL/kg	Acute toxicity	40
		Rabbit	2.5 and 5 mg/kg b.w./oral	14 d	–	No significant changes	41
	Ethanolic extract	Mice	5 g/kg b.w./oral	7 d	>5 g/kg	No significant changes	42
		Mice	1000 mg/kg b.w./oral	1 d	>1000 mg/kg	No significant changes	43
		Rats	20, 200, or 2000 mg/kg b.w./oral	14 d	>2000 mg/kg	No significant changes	44
		Mice	50, 200, 400, 800, 1000, 1500, 2000, 3000, 4000, and 5000 mg/kg b.w./oral	1 d	>5000 mg/kg	No significant changes	45
		Rats	2000 and 5000 mg/kg b.w./oral	14 d	>5000 mg/kg	No significant changes	46
	Methanolic extract	Mice	10, 100, and 1000 mg/kg bw/intraperitoneal route	1 d	31.62 mg/kg	Highly toxic	47
Stem Bark	Methanolic extract	Mice	10, 100, and 1000 mg/kg b.w./intraperitoneal route	1 d	489.90 mg/kg	Moderately toxic	47
	Ethanolic extract	Rats	100, 200, 400, 800, 1600, 3200, and 6400 mg/kg b.w./intraperitoneal route	1 d	870 mg/kg	Acute toxicity	48
Seed	Aqueous extract	Rats	0.1, 0.15, 0.17, and 0.2 g/mL/intramuscular injection	2 d	9.4 mL/kg	Acute toxicity	40
Flowers	Methanolic extract	Rats	6, 9, and 12 g/kg b.w./oral	14 d	>12 g/kg	No significant changes	49
Neem oil	–	Mice	18.40, 23.00, 28.80, 36.00, and 45.00 g/kg b.w./oral	14 d	31.95 g/kg	No significant changes	50

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 ¹¹. The pesticide action of neem oil is attributed to azadirachtin, which is used as an insecticide for arthropod pests ⁵¹. 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 ⁵².

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 ⁵³. The neem oil formulation tested by Dua and co-workers ⁵³ 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 ⁵⁴. 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 ⁵⁴.

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 ¹², whereas an application of neem cake powder resulted in drastic reduction in the late instar larvae and pupae of culicine mosquitoes in paddy field ¹³.

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

Species	Larvicidal activity (ppm)
	LC50 (Mean ± sd)	LC90 (Mean ± sd)
Anopheles stephensi	1.6 ± 0.4 (1.1 – 2.5)*	3.4 ± 0.5 (2.7 – 4.0)
Culex quinquefasciatus	1.8 ± 0.5 (1.2 – 2.6)	3.5 ± 0.6 (2.8 – 4.2)
Aedes aegypti	1.7 ± 0.3 (1.3 – 2.1)	3.7 ± 0.5 (3.1 – 4.3)

Footnotes: Water depth: 2.5 cm; * 95% confidence limits; Number of replicates: 5

[Source ⁵³]

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 ⁵³]

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

Breeding sites	Pre treatment larval density	pH	Percent reduction of larval density (Mean ± sd)
			Day-1	Day-2	Day-3	Day-7
Tyres	10.3 ± 4.1	8.0–9.0	94.3 ± 4.5	98.6 ± 1.4	100	100
Machinery scraps	14.5 ± 8.6	8.0–9.0	96.0 ± 3.0	100	100	100
Iron container	19.2 ± 5.7	8.5	98.1 ± 1.5	100	100	100
Iron box	11.0 ± 6.0	8.0–8.5	96.9 ± 2.0	100	100	100
Iron tanks	9.0 ± 2.6	8.0–8.5	85.2 ± 6.5	100	100	100
Plastic scrap	6.0	8.5	100	100	100	100
			95.1 ± 5.2	99.7 ± 0.3	100	100

Footnote: Total replicates: 21.

[Source ⁵³]

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 ⁵⁵. Azadirachtin (C₃₅H₄₄O₁₆), a complex tetranortriterpenoid, is implicated in causing the effects seen in neem oil poisoning ⁵⁶. 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 ⁵⁷. Lai et al. ⁵⁸, 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 ⁵⁸. Sundaravalli et al. ⁵⁷, 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. ⁵⁵, 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 ⁵⁹. The patient recovered completely with symptomatic treatment. Iyyaduria et al. ⁵⁶, 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. ⁶⁰, 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 ⁶¹.

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 ⁶². 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 ⁶³. 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.

References

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