Liver diseases are one of the major causes of morbidity and mortality all over world. Environmental chemicals and pesticides are one of the most common causative factors for liver injury. Since there are no reliable hepatoprotective drugs available, many plant extracts are frequently utilized to treat liver disease. Therefore, searching for effective and safe plant based drugs for liver disorders is a matter of interest. In this study, hepatoprotective and antioxidant activity of the polyphenol rich chloroform extract of Solanum trilobatum (CST) was evaluated on CCl4 induced acute hepatotoxicity in Sprague Dawley rats. METHODS: Cytotoxic effect of CST on cancer cells as well as primary rat hepatocytes and proliferative effect on human peripheral blood lymphocyte (PBL) were evaluated in vitro. Animals were divided into 4 groups control group (received only normal saline), CCl4 group (received only CCl4 (2.0g/kg body weight), CST group (received 50 mg/kg and CCl4 (2.0g/kg body weight), CST group (received 100mg/kg and CCl4 (2.0g/kg body weight). After 14 consecutive days of treatment, the levels of hepatic biochemical markers, malondialdehyde (MDA) content, peroxidase and catalase activities were measured. The histopathological study of control and treated animals were also performed. RESULTS: Administration of CST prior to CCl4 was found to significantly inhibit the hepatotoxicity produced by CCl4 since CST restored the elevated activities of serum and liver marker enzymes and also enhanced the antioxidant enzyme levels. Histological changes caused by CCl4 were found to be significantly reversed by CST, which further confirms the dual effect of CST on CCl4-induced acute liver injury as a hepatoprotectant and antioxidant. CONCLUSIONS: The present study clearly demonstrates that CST contains therapeutic components which in combination/alone possess hepatoprotective and in vivo antioxidant effect.

The aim of this study was to assess the potential of chloroform extract of S. trilobatum (CST) on 7,12-dimethyl benz (a)anthracene (DMBA) induced skin carcinogenesis and Ehrlich ascites carcinoma cells (EAC) induced solid tumor in mice. CST was obtained by exhaustive extraction with chloroform. Skin carcinogenesis was induced in Swiss albino mice by applying DMBA, while solid tumor was induced by intramuscular injection of EAC cells. For preventing skin carcinogenesis, animals were treated with CST (5 mg/kg body weight/100 μl acetone) before and after DMBA application for 15 days. Solid tumor was treated with CST (400 mg/kg body weight) prophylatically and post inoculation. After the experimental period, several anti tumor parameters and antioxidant status of skin of treated and control animals were determined. Solid tumor progression was determined by measuring the tumor diameter for 36 days. CST was sub-fractionated with different solvents and each fraction was subjected to HPLC-MS. HPLC-MS analysis showed the presence of two components with possible anti-cancer activity viz. 3,5,7 trimethoxy flavone and vitexin per-O-acetyl. The biochemical results showed that CST treatment reduced the number of skin papillomas, tumor incidence as well as modulated the antioxidant status of the skin in a beneficial way. CST reduced the solid tumor volume induced by EAC significantly. In conclusion, CST with its biologically active components may be used as a part of cancer treatment.

The aim of the study was to evaluate the effect of chloroform extract of Solanum trilobatum (CST) on drug metabolizing and antioxidant defense enzymes for assessing its chemo preventive potential and protection of tissues from oxidative damage. The CST was obtained by soxhlet extraction with chloroform. Animals (Male Sprague Dawley rats) were divided into three groups: Group I-normal control, group II-CST (200 mg kgG1 b.wt.), group III-CST (800 mg kgG1 b.wt.). The CST was given by oral gavage once daily for 15 days. At the end of the experimental period all the rats were sacrificed and the livers, lungs and kidneys were taken for estimating the phase I and II drug metabolizing and antioxidant enzyme activities. The gain in body weight and the levels of GSH and lipid peroxides in these tissues were also determined. The results showed that the administration of CST could modulate the phase I and phase II enzymes that are critical for cancer protection. Administration of CST at 200 and 800 mg kgG1 b.wt. to animals did not cause any apparent clinical signs as survivability or visible changes caused by toxicity in the liver, lungs and kidney. Administration of CST at a dose of (800 mg kgG1 b.wt.) was found to be ineffective in elevating the phase I enzymes suggesting that CST could possibly prevent the biotransformation of carcinogens. These results clearly indicate that CST with its biologically active components could be used as a chemo preventive agent in treating various cancers.

This study was initiated to evaluate the modulating effect of chloroform extract of Solanum trilobatum (CST) on Ehrlich Ascites Carcinoma (EAC) in mice.In vitro cytotoxicity of CST on Ehrlich Ascites Cells (EAC) and Human Leukemic cells (HL-60 cells) were evaluated using trypan blue staining.To study the in vivo effect of CST, tumors were introduced into experimental animals by intraperitoneal injection.Animals were treated with CST (400 mg kgG 1 b.wt., after 24 h and 7 days of tumor inoculation for five alternate days.Cisplatin, an antitumor drug (2 mg kgG 1 b.wt.,) was used as a positive control starting from first and the seventh day of tumor inoculation, respectively.After the experimental period, antitumor parameters (ascitic tumor volume, mean survival time and viability of tumor cells), hematological studies and biochemical parameters (activities of SGOT, SGPT, ALP and LDH) were measured.Results showed that CST strongly inhibited the growth of HL-60 and EAC cell line in in vitro condition.In in vivo conditions, administration of CST reduced the tumor volume and the viability of tumor cells as well as increased the mean survival time of EAC inoculated mice.Activities of liver enzymes were found to be restored by the administration of CST.Histopathological examination showed that CST was capable of reducing the damage caused to the liver by the excessive tumor growth.The cytotoxic and antitumor effect demonstrated by this study supported the fact that the antioxidant components present in CST may be a promising source of antitumor compounds for managing different types of cancer.

The fatty acid rich fraction obtained from the petroleum ether extractable portion of Hydnocarpus laurifolia (PHL) seeds exhibited significant insecticidal action on rice bug, Leptocorisa acuta (LC50 8 mg/mL). Analysis of the fatty acid content of PHL by GC/MS showed that it contained chaulmoogric acid, hydnocarpic acid, gorlic acid, lignoceric acid, palmitic acid, oleic acid and stearic acid. Among these fatty acids chaulmoogric acid and hydnocarpic acid were present in highest amount. The PHL showed no genotoxic effect in bone marrow erythrocytes of Swiss mice as compared with methyl methane sulfonate. Metabolism of PHL was evaluated by monitoring the activities of xenobiotic metabolizing enzymes and on comparison with malathion (a synthetic pesticide) revealed that PHL was found to be metabolized and excreted from the body of Sprague-Dawley rats within 72 h of exposure.

A chloroform extract from the anticancer herb Solanum trilobatum (CST) (Nadkarni, 1979) was analyzed and compared with reference antioxidants for its in vitro antioxidative properties such as scavenging of alpha,alpha-diphenyl-beta-picryl hydrazyl (DPPH) and superoxide radicals, protection to deoxyribose degradation, reducing power, as well as inhibition of lipid peroxidation. Preliminary phytochemical analysis of CST by silica gel thin-layer chromatography showed the presence of simple phenols, phenolic acids, isoflavones, xanthones, and lignans. The antioxidative effect of CST was found to be concentration dependent to a certain extent and then leveled off with further increase in concentration. The IC50 for each antioxidative reaction studied was calculated. When compared to the reference antioxidant butylated hydroxytoluene (BHT), CST exhibited less scavenging effect on DPPH radicals and reducing power but a better superoxide radical scavenging effect. From a comparison of the hydroxyl radical scavenging effect of CST with catechin, it seemed that CST was four-times more effective than catechin. CST was also able to prevent the formation of .OH-induced malondialdehyde (MDA) in rat liver homogenate.

One month treatment of alloxan diabetic dogs with a glycoside, viz. leucopelargonin derivative (100 mg/kg/day) isolated from the bark of F. bengalensis decreased fasting blood sugar and glycosylated haemoglobin by 34% and 28% respectively. Body weight was maintained in both the treated groups while the same was decreased significantly by 10% in the control group. In cholesterol diet fed rats, as the atherogenic index and the hepatic bile acid level and the faecal excretion of bile acids and neutral sterols increased, the HMGCoA reductase and lipogenic enzyme activities in liver and lipoprotien lipase activity in heart and adipose tissue and plasma LCAT activity and the incorporation of labelled acetate into free and ester cholesterol in liver decreased significantly. On treatment with the two ficus flavonoids, viz. leucopelargonin and leucocyanin derivatives and another flavonoid quercetin (100 mg/kg/day) the above said effects except on bile acids and sterols and lipogenic enzymes were significantly reversed in the cholesterol fed rats. However in the treated rats the hepatic level of bile acids and the faecal excretion of bile acids and neutral sterols still further increased and the action of lipogenic enzyme glucose 6 phosphate dehydrogenase was still further decreased. These effects of leucopelargonidin and quercetin were better than that of the second. Toxicity studies are required to be carried out to find out if the ficus flavonoids could be used as health promoters as they are hypocholesterolemic and antioxidant in action.

Extracts from the stem bark of Streblus asper possess insecticidal activity against the fifth instar of Dysdercus cingulatus. Methanolic extract showed an LC(50) value of 5.56 microg/insect. Partition with chloroform increased the insecticidal activity (LC(50) 2.01 microg/insect). Three polyphenolic rich fractions were obtained from silica-gel column chromatography of the chloroform fraction and found to have noteworthy insecticidal activity (LC(50): 1.82 microg, 2.70 microg, 2.26 microg/insect) by topical application. This may provide a useful beginning for the development of biopesticides.

The partially purified component of Solanum trilobatum named as Sobatum was found to be cytotoxic in Dalton's lymphoma ascites (DLA), Ehrlich ascites (EA) and tissue cultured cells. It significantly inhibited the peritoneal and solid tumours induced by DLA and EA tomour cells along with the chemically induced skin carcinogenesis. Sobatum did not produce any chromosomal anomalies in the bone marrow cells of Swiss mice. In the present study, we have evaluated the chemoprotective effect of Sobatum on cyclophosphamide induced toxicity in mice. The results showed that the co-administration of Sobatum increase the total leucocyte count, haemoglobin level, average life span of animals; we concluded that Sobatum has chemoprotective action on cyclophosphamide induced toxicity.

Sobatum, the active fraction of the plant Solanum trilobatum was obtained from the petroleum ether/ethyl acetate (75:25) extractable portion. Sobatum was proven to be an anticancer agent by in vitro and in vivo methods. The aim of this study is to evaluate the effect of Sobatum on radiation-induced toxicity in mice. In this assay there are three groups. Group I, the control group, received radiation alone, while groups II and III received Sobatum (100 and 200 mg/kg body weight, respectively) with radiation. Sobatum was administered 24 h before radiation and was continued for 4 alternate days. Body weight, food intake and blood parameters were determined before radiation and every 3 days after radiation for 17 days. The results indicated that there was significantly less body weight gain and food intake in the radiation alone-treated group compared to the Sobatum-treated group. The average leukocyte count and haemoglobin level of the Sobatum-treated group was considerably improved at the end of the experimental period. Hence, it can be concluded that Sobatum reduced the side-effects of radiation-induced toxicity and suggested that it could be used along with radiation therapy.

Two flavonoid compounds, viz. 5,7-dimethyl ether of leucopelargonidin 3-0-alpha-L rhamnoside and 5,3'-dimethyl ether of leucocyanidin 3-0-alpha-D galactosyl cellobioside obtained from the bark of F. bengalensis were evaluated for their antioxidant action in hyperlipidemic rats. The results were compared with the activity of a structurally similar flavonoid, quercetin, a known antioxidant. The Ficus compounds showed significant antioxidant effects which may be attributed to their polyphenolic nature. The methylation of two hydrozyl groups in the Ficus flavonoids might have slowed down their antioxidant action as compared to quercetin.

Sobatum, the partially purified component of the plant Solanum trilobatum was obtained from the petroleum ether/ethyl acetate (75:25) extractable portion. It was identified as β-sitosterol by comparison with an authentic sample and proved to be an anticancer agent by in vitro and in vivo experiments. The aim of the present study is to evaluate the acute/subacute toxicity of sobatum and its effect on antioxidant enzymes. In the acute toxicity test, there was a single exposure of sobatum in mice in order to evaluate toxicity symptoms. In the subacute toxicity study, the exposure was usually daily so as to evaluate the target organs affected by the compound and the major toxic effects and enzymatic and histopathological changes. The results of the study suggested that sobatum did not induce any toxic symptoms or death immediately after injection or at the end of the experimental period. It was also shown that there was no change in blood parameters or antioxidant enzymes in sobatum-treated animals. Regarding histopathological evaluation, there was no development of gross abnormalities or pathological lesions observed in any of the tissues in sobatum-treated and control groups. Hence, the present study concluded that the anticancer agent, sobatum, did not produce any acute/subacute toxicities or anomalies in the synthesis of antioxidant enzymes.

Petroleum ether, chloroform, ethyl acetate and ethanol were used for the extraction of Solanum trilobatum. The partially purified component of the plant named as sobatum was obtained from the petroleum ether:ethyl acetate (75:25) extractable portion. Apart from plant extraction, an effort was also made to evaluate the effect of sobatum on chromosomes. Groups of mice were administered sobatum (100, 200 and 400 mg/kg) or cyclophosphamide (100 mg/kg) followed by coichicine, which was administered 90 minutes before sacrificing the animals for arresting mitosis. It was shown that there was no variation in the chromosome number or significant abnormalities in the sobatum and DMSO treated groups, where as cyclophosphamide induced remarkable chromosomal abnormalities. This investigation revealed that the sobatum did not have the potential to induce any chromosomal aberrations in the bone marrow erthrocytes of swiss mice.

The partially purified component of Solanum trilobatum named Sobatum was obtained from the petroleum ether/ethyl acetate (75:25) extractable portion. It was found to be cytotoxic in Dalton's Lymphoma ascites (DLA), Ehrlich ascites (EA) cell lines and tissue culture cells (L929 and Vero). Sobatum significantly inhibited peritoneal tumours induced by DLA and EA tumour cells. Sobatum was also found to reduce solid tumour growth in mice, when given either simultaneously or prophylactically, and is more active in simultaneous administration (EA). It was found that Sobatum was more active against EA cells-induced solid tumour than DLA-induced solid tumours. On exposure to 7,12-dimethylbenz(a)anthracene (DMBA), about 85.67% animals had induced skin carcinogenesis, which was significantly inhibited to 44.4% by the application of Sobatum. It can be concluded that the Sobatum has the ability to retard the development of solid tumours and DMBA-induced carcinogenesis.

The plant Solanum trilobatum is mainly used for asthma, chronic febrile affections and difficult parturition. The active principle (Sobatum) obtained from the petroleum ether extract of the plant was proved as an anticancer agent by in vitro and in vivo experiments. Here, an effort was made to evaluate the induction of micronucleus by the Sobatum in the bone marrow of swiss mice. The micronucleus assay was conducted after 24 and 72 h of second administration of the Sobatum. The first set of experiments (24 h after second administration) consisted of 4 groups with 3 male Swiss albino mice each. The first group (as control) received only dimethyl sulfoxide, the second, third and fourth groups received different doses of the Sobatum (100, 200, 400 mg/kg body weight), and the fifth group (as positive control) received cyclophosphamide (100 mg/kg body weight) by i.p. injection. In the second set of experiment (72 h after the second administration) consisting of 5 groups, the first, as control, received dimethyl sulfoxide, the second, third and fourth groups received different concentrations of the Sobatum (100, 200, 400 mg/kg body weight), and the fifth group as positive control received cyclophosphamide (100 mg/kg body weight). All the animals of the first and second sets of experiment were killed 24 and 72 h after the second medication (2 consecutive days), and bone marrow smears were prepared, stained with May-Grunwald and Giemsa stain, and evaluated for the evidence of micronucleus. The study concluded that the Sobatum fails to influence the induction of micronuclei in bone marrow erythrocytes of mice 24 and 72 h after the second administration, thereby proving that Sobatum to has no cytogenetic toxic potential.

Plant Solanum trilobatum was washed, powdered and used for extraction. The lyophilized aqueous extracted portion was tested for in vitro cytotoxicity by tissue culture technique using L929 and Vero cells. Petroleum ether, chloroform, ethyl acetate and ethanol were used for extraction and the extracted portions were subjected to in vitro tissue culture studies. It was shown that petroleum ether extract induced remarkable cytotoxicity, when compared to all other extracts with an LD50 of 7.0 μg in L929 and 5.8 μg in Vero cells. Further fractionated portions of petroleum ether extract (by adsorption chromatography) underwent tissue culture assay, and results suggest that petroleum ether/ethyl acetate (75:25) extractable portion is the most active fraction, named as sobatum, which induced an LD50 of 7.0 μg in L929 and 7.5 μg in Vero cells. Sobatum significantly inhibit the peritoneal tumours induced by Dalton's lymphoma ascites (DLA) and Ehrlich ascites (EA) tumour cell. The effect was more prominent when sobatum was administered orally as evidenced from the increased percentage of life span. Sobatum, the partially purified portion of Solanum trilobatum, was again fractionated by column chromatography and all the residues were concentrated and crystallized from methanol, giving only one pure crystalline compound, that was identified as Betasitosterol by comparing with authentic sample.

Pregnant rats received daily P.O. doses of organophosphate methyl parathion (MP) from day 6 through day 15 of gestation at doses 0.5, 1 and 1.5 mg/kg body weight. Darns were sacrificed on day 20 of gestation and fetuses were examined for external and visceral anomalies. Significant decrease in dam weight gain during pregnancy and increase in resorption rate were observed in 1.5 mg MP administered rats. No increase were seen in skeletal or visceral anomalies in treatment groups, however an increase in incidence of haemorrhagic spots in brain and upper body were seen in pups from darns treated with MP.

Pregnancy as well as exogenous administration of steroid hormones alters drug metabolizing enzymes, which could result in a change in the toxicity of malathion. The present study investigated the effect of exogenous estrogen and/or progesterone on malathion toxicity in pregnant rats and their 21-day-old pups. The activity of acetylcholinesterase in brain was taken as an index of malathion toxicity. Coadministration of estrogen plus malathion potentiated the malathion-induced toxicity while progesterone plus malathion at low dose decreased the toxicity, as evidenced by the changes in acetylcholinesterase activity in brain. The higher level of cytochrome P450 observed in estrogen plus malathion-administered rats might have stimulated the increased conversion of malathion to more potent malaoxon and also by blocking the glutathione S-transferase- and carboxylesterase-related detoxication process, resulting in increased malathion toxicity. However, coadministration of progesterone and malathion offered some degree of protection by stimulating the hepatic glutathione S-transferase- and carboxylesterase-mediated detoxication of malathion.

1 Two different concentrations (0.08 and 0.16 μg ml-1) of methyl parathion (MP), a broad-spectrum insecticide, were tested on peripheral lymphocytes of healthy non-smoking non-alcoholics (CN), chronic smokers (SM) and alcoholics with smoking habit (ALSM). 2 SM and ALSM revealed a significant increase in chromosome aberration frequencies in peripheral lymphocytes compared to the CN group. 3 MP did not induce chromosomal aberrations in vitro in the CN group at either of the concentrations tested. 4 In SM and ALSM , MP induced a significant increase in chromosomal aberrations in vitro in peripheral lymphocytes at a concentration of 0.16 μg ml-1. 5 The results indicate that the damage induced by MP in peripheral lymphocytes is potentiated by smoking and alcohol intake.

The effects of prenatal exposure to 13.78 mg, 27.56 mg or 82.6 mg malathion/100 g body weight po from 6-13 d of gestation, to 1 microgram estradiol-17-beta/d/100g body weight or 4 mg progesterone/d/100 g body weight sc from 3-20 d of gestation, or to their various combinations on brain acetylcholinesterase activity and ascorbic acid metabolism were investigated in rat dams and pups. Brain acetylcholinesterase activity was taken as an index of toxicity. Significant inhibition of acetylcholinesterase from malathion exposure was further exaggerated by estradiol-17-beta, but was reversed by progesterone. Significant increases of ascorbic acid levels and L-gulonolactone oxidase was observed with malathion toxicity. Estradiol-17-beta decreased ascorbic acid levels and stimulated dehydroascorbatase, while progesterone had no significant effect on ascorbic acid levels or on enzyme activities.