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Neem Leaf, Studies

Antibacterial

The antibacterial activity was assessed against six bacterial strains--Pseudomonas testosteroni, Staphylococcus epidermidis, Klebsiella pneumoniae, Bacillus subtilis, Proteus morganii, Micrococcus flavus. Agar disc diffusion method and Agar ditch diffusion method were used to study the antibacterial activity of all these plants. Ps. testosteroni and K. pneumoniae were the most resistant bacterial strains. A. indica showed strong activity against tested bacterial strains. Therefore, we conclude that A. indica may prove to be a promising agent, and further exploration into this compound should be performed to determine its full therapeutic potential. In addition, its leaf extract can also be used as a lead molecule in combating the diseases caused by the studied bacterial strains."

Antiviral

Cancer

Diabetes

Metabolic Syndrome

The protective effect of Azadirachta indica (neem) against metabolic syndrome.

Other Effects

Clinical pharmacology

Ringworm

A 70% ethanol extract of the leaves was used for the treatment of ringworm in seven patients. External applications of a 40% solution of the extract twice per day to the affected areas for 5–10 days were reported to be effective (no further details available)

Experimental pharmacology

Anxiolytic and analgesic activities

Intragastric administration of 10.0–200.0 mg/kg body weight (bw) of an aqueous extract of Neem leaf produced anxiolytic effects similar to those of 1.0 mg/kg bw of diazepam in rats in the elevated-plus-maze and open-field behavior tests. The analgesic effect of an extract of the leaves was assessed in mice using the acetic acid writhing test and the tail flick test. Intragastric administration of 10.0–100.0 mg/kg bw of the extract reduced the incidence

of writhing and enhanced tail-withdrawal latencies

Antiandrogenic activity

Intragastric administration of 20.0 mg, 40.0 mg or 60.0 mg of powdered leaves per day to rats for 24 days resulted in a decrease in the weight of the seminal vesicles and ventral prostate, and a reduction in epithelial height, nuclear diameter and secretory material in the lumen of these organs. Decreases in total protein and acid phosphatase activities were also observed. These regressive histological and biochemical changes suggest that the leaves have an antiandrogenic property. Histological and biochemical changes were also observed in the caput and cauda epididymis of rats treated orally with similar doses of the powdered leaves given daily for 24 days. The height of the epithelium and the diameter of the nucleus in both regions were reduced. Serum testosterone concentrations were also

reduced in animals receiving the highest dose. Intragastric administration of an aqueous extract of the leaves (dose not specified) to male mice daily for 10 weeks resulted in a significant (P < 0.01) reduction in total serum testosterone and bilirubin.

Antihepatotoxic activity

The effect of an aqueous extract of the leaves was evaluated in paracetamol induced hepatotoxicity in rats. Intragastric administration of 500.0 mg/kg bw of the extract significantly (P < 0.01) reduced elevated levels of serum aspartate aminotransferase, alanine aminotransferase and γ-glutamyl transpeptidase.

Anti-inflammatory activity

Intragastric administration of 200.0 mg/kg bw of an aqueous extract of the leaves to rats decreased inflammation and swelling in the cotton pellet granuloma assay. Intraperitoneal injection of 200.0–400.0 mg/kg bw of an aqueous extract of the leaves to rats reduced carrageenan-induced footpad edema.

Antihyperglycemic activity

A hypoglycemic effect was observed in normal and alloxan-induced diabetic rabbits after administration of 50.0 mg/kg bw of an ethanol extract of the leaves. The effect was more pronounced in diabetic animals, and reduced blood glucose levels. The hypoglycemic effect was comparable to that of glibenclamide. Pretreatment with the extract 2 weeks prior to alloxan treatment partially prevented the rise in blood glucose levels as compared with control diabetic animals. Intragastric administration of 50.0–400.0 mg/kg bw of a 70% ethanol extract of the leaves significantly (P < 0.001) reduced elevated blood glucose levels in normal and streptozocin-induced diabetic rats. A 70% ethanol extract of the leaves significantly (P < 0.05) blocked the inhibitory effect of serotonin on insulin secretion mediated by glucose in isolated rat pancreas.

Antimalarial activity

An aqueous or ethanol extract of the leaves inhibited the growth of Plasmodium falciparum in vitro, with median inhibitory concentrations of 115.0 μg/ml and 5.0 μg/ml, respectively. Nimbolide, a constituent of the extract, inhibited the growth of P. falciparum in vitro with a median effective concentration of 2.0 μg/ml. However, intragastric administration of 746.0 mg/kg bw of the aqueous extract, 62.5 mg/kg bw of the ethanol extract or 12.5 mg/kg bw of nimbolide had no such effect in Plasmodium infected mice. P. berghei-infected mice showed parasite suppression

after intragastric administration of 125.0–500.0 mg/kg bw of a dried methanol extract of the leaves per day for 4 days, but all the animals died after 5 days. A 95% ethanol extract of the leaves at concentrations of up to 500.0 mg/ml did not inhibit the growth of P. falciparum in vitro.

Antimicrobial and antiviral activity

A methanol extract of the leaves, 1.0 mg/ml, inhibited plaque formation in six antigenic types of coxsackievirus B at 96 hours in vitro. The minimal inhibitory concentrations were not toxic to Vero African green monkey kidney cells. The subtoxic concentration was 8.0 mg/ml and the cytotoxic concentration was 10.0 mg/ml.

An aqueous extract of the leaves, at various concentrations depending on the organism, inhibited the growth of Bacteroides gingivalis, B. intermedius, Streptococcus salivarius and S. viridans in vitro  A petroleum ether extract of the leaves, at various concentrations depending on the organism, inhibited the growth of Epidermophyton floccosum, Microsporum canis, M. gypseum, Trichophyton concentricum, T. violaceum and T. rubrum.

Antioxidant activity

The effect of the leaves on hepatic lipid peroxidation and antioxidant status during gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine was assessed in rats. Intragastric administration of 100.0 mg/kg bw of an aqueous extract of the leaves decreased lipid peroxidation in the liver of tumour-bearing animals, which was accompanied by a decrease in the activities of glutathione peroxidase, glutathione-Stransferase and γ-glutamyl transpeptidase, and a reduction in glutathione level. Administration of 100.0 mg/kg bw of an extract of the leaves suppressed lipid peroxidation and increased hepatic levels of glutathione and glutathione-dependent enzymes. Intragastric administration of 100.0 mg/kg bw of an aqueous extract of the leaves three times per week to hamsters with buccal pouch carcinogenesis induced by 7,12-dimethylbenz[α]anthracene reduced lipid peroxidation and increased the glutathione concentration in the oral mucosa of tumor-bearing animals.

Antiulcer activity

The antiulcer effects of an aqueous extract of the leaves were investigated in rats exposed to 2-hour cold-restraint stress or given ethanol for 1 hour. The extract, administered orally in doses of 10.0 mg/kg bw, 40.0 mg/kg bw or 160.0 mg/kg bw as single- or five-dose pretreatments produced a dose-dependent reduction in the severity of gastric ulcers induced by stress and a decrease in gastric mucosal damage provoked by ethanol. The extract prevented mast cell degranulation and increased the amount of adherent gastric mucus in stressed animals. Intragastric administration

of 40.0 mg/kg bw of an aqueous extract of the leaves per day for 5 days to rats inhibited stress-induced depletion of gastric wall adherent cells and mucus production.

Cardiovascular effects

Intragastric administration of 200.0 mg/kg bw of an alcohol extract of the leaves to anesthetized rabbits decreased the heart rate from 280 to 150 beats per minute, and had a weak antiarrhythmic effect against ouabain-

induced dysrhythmia. Intravenous administration of 100.0 mg/ kg bw, 300.0 mg/kg bw or 1000.0 mg/kg bw of an ethanol extract of the leaves to rats resulted in initial bradycardia followed by cardiac arrhythmias. The treatment produced a dose-related fall in blood pressure that was immediate, sharp and persistent. Pretreatment with atropine or mepyramine failed to prevent the hypotensive effect of the extract.

Immune effects

The effect of an aqueous extract of the leaves on humoral and cell-mediated immune responses was assessed in mice treated with ovalbumin. At doses of 10.0 mg/kg bw, 30.0 mg/kg bw or 100.0 mg/kg bw, the extract produced no appreciable effects on organ/body weight indices for liver, spleen and thymus compared with controls. In tests for humoral immune responses, IgM and IgG levels, and antiovalbumin antibody titres were higher in mice receiving the highest dose of extract than in animals in the control group. In tests for cell-mediated immune responses, mice receiving the highest dose of extract showed enhancement of macrophage migration inhibition and footpad thickness. Intragastric administration of 100.0 mg/kg bw of an aqueous extract of the leaves to normal and

stressed rats lowered blood glucose and triglyceride levels, attenuated stress-induced elevations of cholesterol and urea, and suppressed humoral responses.

The effect of powdered leaves on humoral and cell-mediated immune responses was assessed in chickens infected with infectious bursal disease. A dose of 2.0 g/kg bw per day given in the diet increased antibody titres against Newcastle disease virus antigen and enhanced inflammatory reactions to chloro-2,4-dinitrobenzene in the skin contact test.

(WHO-VOL3 pg 100-104)