Neem (Azadirachta indica) treatment decreases spontaneous motor activity in rats: implications for its central sedative action

The administration of a crude steroidal extract of neem (Azadirachta indica A. Juss) leaf significantly decreased the total spontaneous motor activity (SMA) scores in rats receiving either 100 mg/kg body weight (i.p.) twice per week for 6 weeks (p <0.01) or a single dose (p <0.05), indicating that neem may have a sedative effect on rats. Single dose (acute) treatment also significantly decreased (p <0.01) the amplitude of the peak twitch force of the gastrocnemius muscle in vivo, but the neem extract exerted no significant effect on amplitude or conduction velocity of the compound action potential of the toad sciatic nerve preparation in vitro. It is therefore concluded that the depression of the SMA may be due to an effect of neem on the central nervous system and/or muscle strength, but not on peripheral nerve conduction. © 1997 John Wiley & Sons, Ltd.     

Chemopreventive activity of Azadirachta indica on two‐stage skin carcinogenesis in murine model

The present study reports the chemopreventive activity of aqueous Azadirachta indica leaf extract (AAILE) in a murine two‐stage skin carcinogenesis model. Skin tumors were induced by topical application of 7,12‐dimethylbenz(a)anthracene (DMBA) (500 nmol/100 µL for 2 weeks) followed by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) (1.7 nmol/100 µL of acetone, twice weekly) as a promoter. Male LACA mice were divided into four groups: control, DMBA/TPA, AAILE and AAILE + DMBA/TPA. AAILE was administered orally at a dose level of 300 mg/kg body weight thrice a week for 20 weeks. 100% tumor incidence was observed in the DMBA/TPA treated animals, whereas the AAILE + DMBA treated animals exhibited a tumor incidence of 58.3% only. A significant reduction in the mean tumor burden (54.5%) and mean tumor volume (45.6%) was observed in the mice that received AAILE along with DMBA/TPA. Topical application of DMBA/TPA to the skin resulted in well‐developed carcinomas associated with decreased expression of pro‐apoptotic protein such as caspase 3 and enhanced expression of antiapoptotic protein such as bcl‐2 when compared with the control counterparts. However, adminstration of AAILE inhibited skin carcinogenesis with induction of pro‐apoptotic proteins such as bax, caspase 3, caspase 9 and inhibition of antiapoptotic proteins such as bcl‐2. These results suggest that the induction of apoptosis may be one of the mechanisms underlying the chemopreventive effects of A. indica. Copyright © 2010 John Wiley & Sons, Ltd.     

Antipyretic effect of Azadirachta indica in bacteria endotoxin induced fever in the rat

Fever was induced in rats with a single i.p. injection of 30 μg/kg E. coli endotoxin. The effect of the alcohol leaf extract of Azadirachta indica was investigated in this model. Pretreatment of rats with the leaf extract (125–375 mg/kg) did not significantly reduce endotoxin-induced fever. The rectal temperature remained significantly high. In contrast, administration of the same doses of the extract during the early phase of fever development (during temperature rise) produced a significant fall in the rectal temperature to near normal. The maximum rise was 1.0°C which later dropped to 0.18°C, and was sustained even beyond the experimental session. The data obtained suggest the beneficial antipyretic effect of the leaf extract of Azadirachta indica in bacteria endotoxin induced fever. © 1998 John Wiley & Sons, Ltd.     

Evaluation of antiplaque activity of Azadirachta indica leaf extract gel--a 6-week clinical study

Various chemical agents have been evaluated over the years with respect to their antimicrobial effects in the oral cavity; however, all are associated with side effects that prohibit regular long-term use. Therefore, the effectiveness of neem (Azadirachta indica A. Juss) leaf extract against plaque formation was assessed in males between the age group of 20-30 years over a period of 6 weeks. Present study includes formulation of mucoadhesive dental gel containing Azadirachta indica leaf extract (25 mg/g). A 6-week clinical study was conducted to evaluate the efficacy of neem extract dental gel with commercially available chlorhexidine gluconate (0.2% w/v) mouthwash as positive control. Microbial evaluation of Streptococcus mutans and Lactobacilli species was carried out to determine the total decrease in the salivary bacterial count over a period of treatment using a semi-quantitative four quadrant streaking method. The results of the study suggested that the dental gel containing neem extract has significantly (P<0.05) reduced the plaque index and bacterial count than that of the control group.     

Evaluation of the antimalarial properties and standardization of tablets of Azadirachta indica (Meliaceae) in mice

The antimalarial activities of the tablet suspension of the bark and leaf of Azadirachta indica were evaluated on Plasmodium yoelli nigeriensis infected mice. The tablet suspensions exhibited high prophylactic, mode-rate suppressive and a very minimal curative schizonticidal effect. No animal was cured of the infection in the curative test and there was not much increase in the survival time of the animals compared with the control. The tablet suspensions from the leaf and bark at a concentration of 800 mg/kg and chloroquine at a concentration of 62.5 mg/kg body weight produced average percentage (%) parasitaemia of 79.6%, 68.2% and 99.5% for leaf, bark and chloroquine, respectively, in chemosuppression. Also in the prophylactic treatment, the tablet suspensions at 800 mg/kg and pyrimethamine at a concentration of 0.35 mg/kg gave an average parasitaemia reduction of 75.3%, 65.6% and 98.3% for the leaf, bark and pyrimethamine, respectively. There was a clear indication that both tablet suspensions from the leaf and bark possess antimalarial activity and a suspension from the former is relatively more effective than the bark. Extrapolation of the results from the antimalarial activity of the tablet suspension of the crude plant parts showed that an adult human would need to ingest a minimum of 48 g of the powdered plant material per day, an amount that is impracticable. A survival index value of 0.33 was obtained with the 800 mg/kg dose level, indicating that the tablet suspension has some moderate beneficial effect.     

Concurrent administration of aqueous Azadirachta indica (neem) leaf extract with DOCA-salt prevents the development of hypertension and accompanying electrocardiogram changes in the rat

The effect of concurrent administration of Azadirachta indica leaf extract with DOCA-salt was investigated in the development of hypertension.Over 5-6 week old, inbred male Wistar rats with a starting weight of 190 g were given either: (1) twice weekly subcutaneous (s.c.) injections of vehicle (soyabean oil, 0.25 mL per animal) for the first 2 weeks, plus normal drinking water (controls); (2) twice weekly (s.c.) injections (weeks 1 and 2 only) of 15 mg/kg DOCA dissolved in vehicle, plus drinking water containing 1.0% NaCl and 0.03% KCl (DOCA-salt group); or (3) 20 mg/kg of aqueous neem extract daily, in addition to the DOCA-salt treatment (DOCA-salt-neem group). All groups (8-12 animals) received normal rat pellets ad libitum and their BP was measured weekly. Terminally, the animals were anaesthetized and ECGs recorded using s.c. pins in a lead II configuration.The mean arterial pressure was significantly lower (p < 0.05) in the control (97 +/- 3.7 mmHg) and DOCA-salt-neem (87 +/- 3.4 mm Hg) groups than in the DOCA-salt group (115 +/- 7.1 mm Hg). PR and RR intervals and the duration of the QRS complex were shorter (p < 0.05) in the DOCA-salt group than in the control and DOCA-salt-neem groups. Amplitude of the QRS complex was increased (p < 0.05) in the DOCA-salt group compared with both the DOCA-salt-neem and the control groups.Daily administration of 20 mg/kg neem-leaf extract concurrently with DOCA-salt for 5 weeks, prevents the development of hypertension and the accompanying alterations in the ECG patterns seen in DOCA-salt treated rats.     

Radiosensitizing effects of neem (Azadirachta indica) oil.

Radiosensitization by neem oil was studied using Balbc/3T3 cells and SCID cells. Neem oil enhanced the radiosensitivity of the cells when applied both during and after x-irradiation under aerobic conditions. Neem oil completely inhibited the repair of sublethal damage and potentially lethal damage repair in Balbc/3T3 cells. The cytofluorimeter data show that neem oil treatment before and after x-irradiation reduced the G(2) + M phase, thus inhibiting the expression of the radiation induced arrest of cells in the G(2) phase of the cell cycle. However, SCIK cells (derived from the SCID mouse), deficient in DSB repair, treated with neem oil did not show any enhancement in the radiosensitivity. There was no effect of neem oil on SLD repair or its inhibition in SCIK cells. These results suggest that neem oil enhanced the radiosensitivity of cells by interacting with residual damage after x-irradiation, thereby converting the sublethal damage or potentially lethal damage into lethal damage, inhibiting the double-strand break repair or reducing the G(2) phase of the cell cycle.     

Studies on the hypoglycaemic activity of Punica granatum seed in streptozotocin induced diabetic rats.

The hypoglycaemic activity of Punica granatum Linn. (Family Punicaceae) seed extract on rats made diabetic by streptozotocin (STZ) was investigated. The methanol extract of the seed at doses of 300 and 600 mg/kg, and chlorpropamide 200 mg/kg was administered to STZ diabetic rats. The seed extract (150, 300 and 600 mg/kg, orally) caused a significant reduction of blood glucose levels in STZ induced diabetic rats by 47% and 52%, respectively, at the end of 12 h.     

注射Azadirachta indica水提物对大鼠血红蛋白和血糖含量的影响(英文)

Presently, there is a growing interest in herbal remedies. Neem (Azadirachta indica) has been used in traditional medicine over centuries. In the present study, the effects of water extracts of Azadirachta indica seeds, stems, flowers and bark on the changes of hemoglobin content (Hb) and glucose levels in the blood of Rattus norvegicus were investigated. Different doses of A. indica water extracts of seeds, stems, flowers and bark were injected to the tested animals every 48 h for 14 days. Significant decrease in both hemoglobin content and glucose levels in the blood samples in all groups of injected rats were compared to control group. However, in all groups higher decrease was shown in the rats injected with 1 g·mL-1 of A. indica water extracts. In addition, the present study showed no significant relationship between decreased hemoglobin content and glucose levels in blood samples, and increased doses injected. In conclusion, A. indica has the potential to decrease both hemoglobin content and blood glucose levels.     

Evaluation of the antidiabetic action of Mangifera indica in mice

The leaves of Mangifera indica were assessed for antidiabetic properties using normoglycaemic, glucose-induced hyperglycaemia and streptozotocin (STZ) induced diabetic mice. The aqueous extract produced a reduction of blood glucose level in normoglycaemic and glucose-induced hyperglycaemia, but did not have any effect on streptozotocin-induced diabetic mice. The hypoglycaemic effect of the aqueous extract was compared with that of an oral dose of chlorpropamide under the same conditions. The results of this study indicate that the aqueous extract of the leaves of Mangifera indica possess hypoglycaemic activity.     

Ultrastructural changes in Leydig cells and cauda epididymal spermatozoa induced by Azadirachta indica leaves in albino rats

The effects of Azadirachta indica leaves (500 mg/kg body weight, orally/day), testosterone (0.25 mg/kg body weight/day, intramuscularly) and a combination of these two were investigated as to whether Azadirachta indica leaves affect the morphology of Leydig cells and epididymal sperm and their organelles at the ultrastructural level. Azadirachta indica treated rats showed atrophic seminiferous tubules with widening intercellular spaces. Leydig cells exhibited characteristics of degeneration such as indented nuclei; the commencement of degeneration was evident from less chromatin; the reduced amount of a marked decrease in organelle content and scarcity of other cell types of the interstitium in highly vacuolated cytoplasm, which were seem from both light and electron microscopic observations. The number of Leydig cells and their nuclear diameter were reduced significantly. Pathological changes in the spermatozoa of the cauda epididymis were observed and the spermatozoa retained cytoplasmic droplets. It is suggested that regression of Leydig cells and the absence of interstitium cell types indicates an androgen deficiency, which affects the spermatozoa in the epididymis by disturbing the internal epididymal milieu. The antiandrogenic and antispermatogenic properties of Azadirachta indica leaves appear to lead to a reduced fertilizing ability of the sperm.     

Possible mechanism of hepatoprotective activity of Azadirachta indica leaf extract: part II

Hepatoprotective activity of Azadirachta indica leaf extract against paracetamol induced hepatic damage in rats has already been reported. In the present investigation effects of Azadirachta indica leaf extract on blood and liver glutathione, Na+K(+)-ATPase activity and thiobarbutiric acid reactive substances against paracetamol induced hepatic damage in rats have been studied with a view to elucidate possible mechanism behind its hepatoprotective action. It was interesting to observe that Azadirachta indica leaf extract has reversal effects on the levels of above mentioned parameters in paracetamol hepatotoxicity. Possible mechanism behind the results are discussed.     

Evaluation of anti-inflammatory potential of Pavetta indica Linn. leaf extract (family: Rubiaceae) in rats

The anti-inflammatory potential of methanol extract of Pavetta indica Linn. leaves (Family: Rubiaceae) was evaluated against several models of inflammation such as carragenin, histamine and dextran induced pedal inflammation in rats. The extract showed 48.41%, 41.10% and 24.22% inhibition respectively; when compared to that of control animals. The effect was comparable with that of the standard drug indomethacin, a standard non-steroidal anti-inflammatory drug. Simultaneous subplantar administration of the extract and carrageenin in a mixture helps in differentiating true anti-inflammatory action from an apparent anti-inflammatory effect due to counter-irritant activity. The methanol extract also effectively and significantly reduced cotton pellet induced granuloma. The percentage of inhibition was 62.78 at the dose 500 mg/kg, thereby suggesting its activity in the proliferative phase of the inflammatory process.     

Antifertility Effects of Aqueous and Steroidal Extracts of Neem Leaf (Azadirachta indica) in Male Wistar Rats

The antifertility efficacy of both aqueous and steroidal extracts of neem ( Azadirachta indica A. Juss) leaves was studied in male Wistar rats. Intraperitoneal injections of the steroidal extract at a dose of 100 mg/kg body weight, twice a week for 10 weeks resulted in impaired spermiogenesis, increased the number of headless spermatozoa and significantly decreased ( p <0.01) motility of cauda spermatozoa, leading to a decline in the fertility index. Feeding of a 0.8% (w/v) aqueous neem leaf extract in drinking water for 7 weeks decreased serum testosterone ( p <0.01) but no effect was observed in the fertility index. © 1997 by John Wiley & Sons, Ltd.     

A comprehensive review of phytochemical profile,bioactives for pharmaceuticals,and pharmacological attributes of Azadirachta indica

Azadirachta indica L. is a multipurpose medicinal tree of family Meliaceae. It occurs in tropical and semitropical regions of the world. Different parts of this miraculous tree are used to treat pyrexia, headache, ulcer, respiratory disorders, cancer, diabetes, leprosy, malaria, dengue, chicken pox, and dermal complications. The tree is popular for its pharmacological attributes such as hypolipidemic, antifertility, microbicidal, antidiabetic, anti‐inflammatory, hepatoprotective, antipyretic, hypoglycemic, insecticidal, nematicidal, antiulcer, antioxidant, neuroprotective, cardioprotective, and antileishmaniasis properties. A. indica is also rich in various phytochemicals for pharmaceuticals such as alkaloids, steroids, flavonoids, terpenoids, fatty acids, and carbohydrates. The fungicidal potential of the tree is due to the presence of azadirachtin and nimbin. Herein, we have compiled a comprehensive review of phytochemical profile, pharmacological attributes, and therapeutic prospective of this multipurpose tree.     

Effect of Coccinia indica leaf extract on plasma antioxidants in streptozotocin- induced experimental diabetes in rats

The present study was carried out to investigate the antioxidant effect of an ethanolic extract of Coccinia indica leaves, an indigenous plant used in Ayurvedic Medicine in India, in Streptozotocin-diabetic rats. Oral administration of Coccinia indica leaf extract (CLEt) (200 mg/kg body weight) for 45 days resulted in a significant reduction in plasma thiobarbituric acid reactive substances, hydroperoxides, vitamin E and ceruloplasmin. The extract also caused a significant increase in plasma vitamin C and reduced glutathione, which clearly shows the antioxidant property of CLEt. The effect of CLEt at 200 mg/kg body weight was more effective than glibenclamide.     

Chemomodulatory effects of Azadirachta indica on the hepatic status of skin tumor bearing mice

The liver plays an important role in the modulation of the process of carcinogenesis, as it is the primary site for the biotransformation of xenobiotics including carcinogens as well as anticancer drugs. The present study was designed to evaluate the biochemical alterations occurring in the liver of 7,12-dimethylbenz(a)anthracene (DMBA) induced skin tumor bearing male Balb/c mice and their modulation by aqueous Azadirachta indica leaf extract (AAILE). It was observed that skin tumor induction caused hepatic damage characterized by a decreased hepatosomatic index and significantly increased (p < 0.001) activities of the hepatic tissue injury marker enzymes, namely alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase. However, upon treatment with AAILE, the above-mentioned alterations, including the increased activities of hepatic tissue injury marker enzymes, were significantly reversed, which signified the hepato-protective efficacy of Azadirachta indica. Increased oxidative stress was also observed in the hepatic tissue of skin tumor bearing mice as revealed by a significant increase (p < 0.001) in lipid peroxidation levels and a decrease in reduced glutathione contents and activities of various antioxidant enzymes studied, namely glutathione-S-transferase, glutathione peroxidase and glutathione reductase. The AAILE treatment reduced oxidative stress by decreasing lipid peroxidation levels and enhancing the reduced glutathione contents and activities of various antioxidant enzymes. The activities of the xenobiotic biotransformation enzymes, namely cytochrome P450, cytochrome b5 and glutathione-S-transferase, were found to be decreased in the hepatic tissue of tumor bearing mice. Treatment with AAILE further caused a decrease in the activity of cytochrome P450 and cytochrome b5, whereas it up-regulated the activity of glutathione-S-transferase. The significance of these observations with respect to the progress of the process of carcinogenesis is explained in the present research article.     

Preventive effects of Azadirachta indica on benzo(a)pyrene-DNA adduct formation in murine forestomach and hepatic tissues

In the present investigation, the effects of aqueous Azadirachta indica leaf extract (AAILE) on (3)H-benzo(a)pyrene-DNA [(3)H-B(a)P-DNA] adduct formation, the status of biotransformation enzymes and reduced glutathione (GSH) content were evaluated in the forestomach and liver of Balb/c mice. Two weeks of AAILE treatment reduced the (3)H-B(a)P-DNA adduct levels by 31.6% in forestomach tissue. Similarly, (3)H-B(a)P-DNA adduct levels were decreased by 34.7% in the liver of AAILE treated mice compared with their control counterparts. After AAILE treatment, the cytochrome P450 content decreased, whereas the GSH content increased significantly in the hepatic tissue. In the forestomach as well as in the liver, the cytochrome b5 content declined, whereas an increase in glutathione-S-transferase (GST) activity was observed in both tissues. These observations suggested that AAILE may have reduced the metabolic activation of (3)H-B(a)P with enhanced detoxification of its active metabolites, hence the observed decrease in the levels of (3)H-B(a)P-DNA adducts. These molecular and biochemical modulations observed at the initiation phase of carcinogenesis seems to be significant and could be correlated with the chemopreventive effects of A. indica against B(a)P induced forestomach tumorigenesis.     

Ameliorative effects of ethanolic leaf extract of Azadirachta indica on renal histologic alterations in streptozotocin-induced diabetic rats

We studied the effect of ethanolic leaf extract of Azadirachta indica (AIE) on the microanatomy of the kidney of streptozotocin-induced diabetic rats. Thirty male Wistar rats (161-190 g) were randomly assigned to one of five treatment groups of six animals each: control, diabetic, diabetic + AIE, diabetic + metformin, AIE only. Diabetes was induced with a single intraperitoneal dose of streptozotocin (70 mg/kg body weight). AIE and metformin were administered orally for 50 days (50 d) at 500 mg/kg bw/d and 350 mg/kg bw/d, respectively. Blood glucose was estimated by glucose oxidase method; plasma urea and creatinine were assayed; and paraffin sections of the kidney were stained by periodic acid-Schiff technique. Untreated diabetic rats exhibited marked hyperglycemia. Renal histopathology of these animals showed features of diabetic nephropathy, with nodular glomerulosclerosis and vacuolation of proximal tubule cells (Armanni-Ebstein phenomenon). These feature were absent in the diabetic rats treated with AIE. Besides, plasma urea and creatinine were not significantly different from the control in this group (p > 0.05), in contrast to the untreated diabetic rats, where significant increases in these markers (p < 0.05). These findings showed that the leaf extract of Azadirachta indica ameliorates hyperglycemia and diabetic nephropathy in rats.     

Antiplasmodial and antipyretic screening of Mangifera indica extract

The stem bark extract of Mangifera indica was evaluated for antiplasmodial activity against Plasmodium yoelii nigeriensis. The extract was also screened for antipyretic activity in mice. The extract exhibited a schizontocidal effect during early infection, and also demonstrated repository activity. A reduction in yeast-induced hyperpyrexia was also produced by the extract. © 1998 John Wiley & Sons, Ltd.