Asiatic acid abridges pre-neoplastic lesions, inflammation, cell proliferation and induces apoptosis in a rat model of colon carcinogenesis.

The utmost aim of this present study was to investigate the anti-inflammatory, antiproliferative and proapoptotic potential of Asiatic acid (AA) on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in experimental rats. Rats were divided into six groups and received modified pellet diet for 32 weeks. Group 1 served as control rats. Group 2 received AA (4 mg/kg b.w. p.o.). Group 3-6 rats received 15 DMH (20 mg/kg b.w., s.c.) injections once a week starting from the 4th week. Besides DMH, rats received AA (4 mg/kg b.w. p.o.) in group 4 starting 2 weeks before carcinogen treatment till the end of the last DMH; group 5 starting 2 days after last DMH till the end of the experiment; and group 6 throughout the experiment. Pre-neoplastic lesions, xenobiotic metabolizing enzymes, inflammation, cell proliferation and apoptotic markers were analysed in our study. Our results ascertained AA supplementation to DMH-exposed rats significantly decreased the incidence of aberrant crypt foci (ACF) and phase I xenobiotic enzymes; and increased the phase II xenobiotic enzymes and mucin content as compared to DMH-alone-exposed rats. Moreover the increased expressions of mast cells, argyrophilic nucleolar organizer regions (AgNORs), proliferating cell nuclear antigen (PCNA) and cyclin D1 observed in the DMH-alone-exposed rats were reverted and were comparable with those of the control rats, when treated with AA. Concordantly AA also induced apoptosis by downregulating the expression of Bcl-2 and upregulating Bax, cytochrome c, caspase-3 and -9 in the DMH-alone-exposed rats. Thus AA was able to inhibit DMH-induced colon carcinogenesis by detoxifying the carcinogen, decreasing the preneoplastic lesions by virtue of its anti-inflammatory, antiproliferative and proapoptotic effects. Therefore our findings suggest that AA could be used as an effective chemopreventive agent against DMH induced colon carcinogenesis.

Antihyperlipidemic and antiapoptotic potential of zingerone on alcohol induced hepatotoxicity in experimental rats.

The ultimate aim of this present study was to investigate the antihyperlipidemic and antiapoptotic potential of zingerone (ZO) on alcohol induced hepatotoxicity in experimental rats. Male albino wistar rats were divided in four groups. Groups 1 and 2 rats received isocaloric glucose and dimethyl sulphoxide (2% DMSO), liver toxicity was induced in groups 3 and 4 by supplementing 30% ethanol post orally for 60 days. In addition to, groups 2 and 4 received zingerone (20 mg/kg body weight in 2% DMSO) daily during the final 30 days of the experimental period. Ethanol alone administered rats showed increased levels/activities of plasma total cholesterol (TC), triglycerides (TG), free fatty acids (FFA), phospholipids (PL), low density lipoproteins (LDL), very low density lipoproteins (VLDL), tissue TC, TG, FFA, PL, HMG-CoA reductase, phase I xenobiotic enzymes, collagen and fat accumulation, DNA damage and increased Bax, caspase-3 and caspase-9 expressions and decrease in the levels/activities of plasma high density lipoproteins (HDL), lipoprotein lipase (LPL), lecithin cholesterol acyl transferase (LCAT), phase II xenobiotic enzymes and a decreased Bcl-2 expression. Zingerone supplementation was able to counter and reverse the ethanol induced changes in all the above parameters in experimental rats. Together results portray zingerone exhibits antihyperlipidemic and antiapoptotic potential on alcohol induced hepatotoxicity.

Asiatic acid attenuates pre-neoplastic lesions, oxidative stress, biotransforming enzymes and histopathological alterations in 1,2-dimethylhydrazine-induced experimental rat colon carcinogenesis.

Asiatic acid (AA), a pentacyclic triterpenoid, derived from the tropical medicinal plant Centella asiatica is known to exhibit numerous pharmacological properties. We hypothesized that AA will have chemopreventive potential against 1,2-dimethylhydrazine (DMH)-induced experimental colon carcinogenesis in male Wistar rats. Rats were arbitrarily divided into six groups. Group I rats were processed as control. Group II rats received AA (8 mg/kg b.w., p.o.) and groups III-VI rats received subcutaneous injections of DMH (20 mg/kg b.w.) once a week, for the first four weeks. In addition, groups IV-VI rats received AA at the doses of 2, 4 and 8 mg/kg b.w., respectively, for 16 weeks. Our results discovered that supplementation with AA to the DMH-exposed rats significantly decreased the incidence of polyps and Aberrant crypt foci (ACF) as compared to the DMH-alone-exposed rats. Moreover, in the AA-supplemented DMH-exposed rats, we ascertained increased activities of the antioxidants and decreased levels of lipid peroxidation (LPO) in the liver and circulation and enhanced levels of both LPO and antioxidants in the colon, which were altered in the DMH-alone-exposed rats. Furthermore, we also observed altered activities of vitamins C and E and biotransforming enzymes in DMH-alone-exposed rats, which were reversed on AA supplementation. All the observations were supported by our histological findings. Thus, we can conclude that, AA could be used as an effective chemopreventive agent against DMH-induced colon carcinogenesis.

The in vivo antineoplastic and therapeutic efficacy of troxerutin on rat preneoplastic liver: biochemical, histological and cellular aspects.

PURPOSE: Troxerutin (TXER), a trihydroxyethylated derivative of the natural bioflavonoid rutin, abundantly found in tea, various fruits and vegetables, is known to exhibit ample pharmacological properties. In the present investigation, we examined the antineoplastic, therapeutic efficacy and furthermore the possible mechanisms of action of TXER against NAFLD/NASH progression to hepatocarcinogenesis. METHODS: The effect of TXER (12.5, 25 or 50 mg/kg b.w/day) was evaluated on the nitrosodiethylamine (NDEA) model of hepatocarcinogenesis in rats, after 16 weeks of oral treatment, with special focus on liver specific enzymes, xenobiotic metabolizing enzymes, antioxidant status, lipid peroxidation profile, DNA damage, fibrosis, cell proliferation and inflammatory status. RESULTS: Administration of TXER to hepatocellular carcinoma-bearing rats restored the enzyme activities and the hepatic architecture. Furthermore, TXER significantly curtailed NDEA-induced DNA damage, cell proliferation, inflammation, fibrosis and hepatic hyperplasia. CONCLUSION: This study provides the evidence that troxerutin exerts a significant therapeutic effect against liver cancer by modulating liver function enzymes, xenobiotic enzymes, oxidative damage, inhibiting cell proliferation, suppressing inflammatory response and induction of apoptosis.

Antioxidant and anti-inflammatory role of zingerone in ethanol-induced hepatotoxicity.

Alcoholic liver disease is a direct result of alcohol-induced hepatotoxicity coupled with impaired hepatic regenerative activity. Our aim of the study was to investigate the beneficial effect of zingerone on hepatic oxidative stress and inflammation induced by ethanol in experimental rats. Male albino Wistar rats were divided into four groups. Rats of groups 1 and 2 received isocaloric glucose and dimethyl sulfoxide (2 % DMSO). Hepatotoxicity was induced in groups 3 and 4 by supplementing 30 % ethanol post orally for 60 days. Rats of groups 2 and 4 received zingerone (20 mg/kg body weight in 2 % DMSO p.o) daily during the final 30 days of the experimental period. Ethanol alone administered rats showed significant increase in the plasma and tissue lipid peroxidation markers such as thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes, and a significant decrease in the activities of plasma and tissue enzymic and non-enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, reduced glutathione, vitamin C, and vitamin E. Moreover, the presence of mast cells and increase in the expressions of inflammatory markers such as NF-κB, COX-2, TNF-α, and IL-6 and decrease in the expression of Nrf2 in the liver was observed in ethanol-fed rats. Supplementation with zingerone to ethanol-fed rats reversed the changes induced by ethanol in the experimental rats. Thus, zingerone, through its antioxidant and anti-inflammatory effects, may represent a therapeutic option to protect against ethanol-induced hepatotoxicity.

Biosynthesis of silver nanoparticle and its application in cell wall disruption to release carbohydrate and lipid from C. vulgaris for biofuel production.

Microalgae are the fledging feedstocks yielding raw materials for the production of third generation biofuel. Assorted and conventional cell wall disruption techniques were helpful in extracting lipids and carbohydrates, nevertheless the disadvantages have led the biotechnologists to explore new process to lyse cell wall in a faster and an economical manner. Silver nanoparticles have the ability to break the cell wall of microalgae and release biomolecules effectively. Green synthesis of silver nanoparticles was performed using a novel bacterial isolate of Bacillus subtilis. Characterisation of nanosilver and its effect on cell wall lysis of microalgae were extensively analysed. Cell wall damage was confirmed by lactate dehydrogenase assay and visually by SEM analysis. This first piece of research work on direct use of nanoparticles for cell wall lysis would potentially be advantageous over its conventional approaches and a greener, cost effective and non laborious method for the production of biodiesel.

Combined therapeutic efficacy of carvacrol and X-radiation against 1,2-dimethyl hydrazine-induced experimental rat colon carcinogenesis.

Colon cancer is one of the most commonly diagnosed cancers, and is a major cause of cancer morbidity and mortality worldwide. The objective of the present study is to evaluate the combined therapeutic efficacy of carvacrol (CVC) and X-radiation against 1,2-dimethylhydrazine-induced colon cancer. Male albino Wistar rats were randomly divided into six groups. Group 1 served as control; group 2 received 40 mg/kg b.wt of CVC orally everyday throughout the experimental period (32 weeks); groups 3-6 received subcutaneous injections of DMH (20 mg/kg b.wt), once a week for the first 15 weeks; group 4 received a single dose of X-radiation at the 31st week; group 5 received CVC (40 mg/kg b.wt) two days after the last injection of DMH and continued everyday till the end of the experimental period; group 6 received CVC as in group 5 and radiation as in group 4. DMH-treated rats showed increased incidence of aberrant crypt foci (ACF), dysplastic aberrant crypt foci (DACF), mast cell number, argyrophilic nucleolar organizer regions; elevated activities of phase I enzymes, decreased activities of phase II enzymes, decreased mucin content and altered colonic and liver histology as compared to control rats. Though the individual treatments with CVC and X-radiation to DMH-treated rats reversed the above changes, the combined treatment with both CVC and X-radiation showed a marked effect. Our findings emphasize the potential role of combined therapeutic effect of CVC and X-radiation against DMH-induced colon carcinogenesis.

Production of marine microalgal biodiesel through interesterification using novel Bacillus lipase.

In this study, enzymatic interesterification is carried out using encapsulated lipase as biocatalyst with methyl acetate as acyl acceptor in a solvent free system. Lipase, isolated from a marine bacterial isolate. Bacillus sp.S23 (KF220659.1) was immobilized in a sodium alginate beads. This investigation elaborated on the effects of various parameters namely enzyme loading, temperature, water, molar ratio, reaction time and agitation for interesterification. The study resulted in the following optimal conditions- 1.5 g immobilised lipase, 1:12 molar ratio of oil to methyl acetate, 35 °C, 8 % water, 60 h reaction time, 250 rpm of agitation. With the standardized condition, the maximum conversion efficiency was 95.68%. The immobilized beads, even after 10 cycles of repeated usage showed high stability in the presence of methyl acetate and no loss of lipase activity. The microalgal biodiesel composition was analysed by Gas Chromatography. The current study was efficient in using immobilized lipase for interesterification process, as the method turned to be cost effective and ecofriendly, no solvent was involved and enzyme being encapsulated in a natural polymer.