Mechanistic study of attenuation of monosodium glutamate mixed high lipid diet induced systemic damage in rats by Coccinia grandis.

In the context of failure of treatment for non alcoholic fatty liver disease (NAFLD)-mediated systemic damages, recognition of novel and successful characteristic drug to combat these anomalous situations is earnestly required. The present study is aimed to evaluate protective value of ethanol extract of Coccinia grandis leaves (EECGL), naturally occurring medicinal plant, on NAFLD-mediated systemic damage induced by high lipid diet along with monosodium glutamate (HM)-fed rats. Our study uncovered that EECGL significantly ameliorates HM-induced hyperlipidemia, increased lipogenesis and metabolic disturbances (via up regulation of PPAR-α and PPAR-γ), oxidative stress (via reducing the generation of reactive oxygen species and regulating the redox-homeostasis) and inflammatory response (via regulating the pro-inflammatory and anti-inflammatory factors with concomitant down regulation of NF-kB, iNOS, TNF-α and up regulation of eNOS). Furthermore, EECGL significantly inhibited HM-induced increased population of cells in sub G0/G1 phase, decreased Bcl2 expression and thereby loss of mitochondrial membrane potential with over expression of Bax, p53, p21, activation of caspase 3 and 9 indicated the apoptosis and suppression of cell survival. It is perhaps the first comprehensive study with a mechanistic approach which provides a strong unique strategy for the management of HM-induced systemic damage with effective dose of EECGL.

Ferulic acid (FA) abrogates γ-radiation induced oxidative stress and DNA damage by up-regulating nuclear translocation of Nrf2 and activation of NHEJ pathway.

The present study was aimed to evaluate the radioprotective effect of ferulic acid (FA), a naturally occurring plant flavonoid in terms of DNA damage and damage related alterations of repair pathways by gamma radiation. FA was administered at a dose of 50 mg/kg body weight for five consecutive days prior to exposing the swiss albino mice to a single dose of 10 Gy gamma radiation. Ionising radiation induces oxidative damage manifested by decreased expression of Cu, Zn-SOD (SOD stands for super oxide dismutase), Mn-SOD and catalase. Gamma radiation promulgated reactive oxygen species (ROS) mediated DNA damage and modified repair pathways. ROS enhanced nuclear translocation of p53, activated ATM (ataxia telangiectasia-mutated protein), increased expression of GADD45a (growth arrest and DNA-damage-inducible protein) gene and inactivated Non homologous end joining (NHEJ) repair pathway. The comet formation in irradiated mice peripheral blood mononuclear cells (PBMC) reiterated the DNA damage in IR exposed groups. FA pretreatment significantly prevented the comet formation and regulated the nuclear translocation of p53, inhibited ATM activation and expression of GADD45a gene. FA promoted the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and activated NHEJ repair pathway to overcome ROS mediated oxidative stress and DNA damage. Therefore, the current study stated that FA can challenge the oxidative stress by (i) inducing nuclear translocation of Nrf2, (ii) scavenging ROS, and (iii) activating NHEJ DNA repair process.

Gossypetin ameliorates ionizing radiation-induced oxidative stress in mice liver--a molecular approach.

Radioprotective action of gossypetin (GTIN) against gamma (γ)-radiation-induced oxidative stress in liver was explored in the present article. Our main aim was to evaluate the protective efficacy of GTIN against radiation-induced alteration of liver in murine system. To evaluate the effect of GTIN, it was orally administered to mice at a dose of 30 mg/kg body weight for three consecutive days prior to γ-radiation at a dose of 5 Gy. Radioprotective efficacy of GTIN were evaluated at physiological, cellular, and molecular level using biochemical analysis, comet assay, flow cytometry, histopathology, immunofluorescence, and immunoblotting techniques. Ionizing radiation was responsible for augmentation of hepatic oxidative stress in terms of lipid peroxidation and depletion of endogenous antioxidant enzymes. Immunoblotting and immunofluorescence studies showed that irradiation enhanced the nuclear translocation of nuclear factor kappa B (NF-κB) level, which leads to hepatic inflammation. To investigate further, we found that radiation induced the activation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK)-mediated apoptotic pathway and deactivation of the NF-E2-related factor 2 (Nrf2)-mediated redox signaling pathway, whereas GTIN pretreatment ameliorated these radiation-mediated effects. This is the novel report where GTIN rationally validated the molecular mechanism in terms of the modulation of cellular signaling system' instead of ' This is the novel report where GTIN is rationally validated in molecular terms to establish it as promising radioprotective agents. This might be fruitful especially for nuclear workers and defense personnel assuming the possibility of radiation exposure.

Seabuckthron (Hippophae rhamnoides L.) leaf extract ameliorates the gamma radiation mediated DNA damage and hepatic alterations.

In vitro assessment showed that H. rhamnoides (HrLE) extract possessed free radical scavenging activities and can protect gamma (gamma) radiation induced supercoiled DNA damage. For in vivo study, Swiss albino mice were administered with HrLE (30 mg/kg body weight) for 15 consecutive days before exposing them to a single dose of 5 Gy of beta radiation. HrLE significantly prevented the radiation induced genomic DNA damage indicated as a significant reduction in the comet parameters. The lipid peroxidation, liver function enzymes, expression of phosphorylated NFkappaB (p65) and IkappaBalpha increased whereas the endogenous antioxidants diminished upon radiation exposure compared to control. Pretreatment of HrLE extract ameliorated these changes. Based on the present results it can be concluded that H. rhamnoides possess a potential preventive element in planned and accidental nuclear exposures.

Protective effect of coconut water concentrate and its active component shikimic acid against hydroperoxide mediated oxidative stress through suppression of NF-κB and activation of Nrf2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Conventionally coconut water has been used as an 'excellent hydrating' drink that maintain the electrolyte balance and help in treating diverse ailments related to oxidative stress including liver function. The present study was aimed to elucidate whether and how the coconut water concentrate (CWC) and its major active phytoconstituent shikimic acid (SA) can effectively protect murine hepatocytes from the deleterious effect of hydroperoxide-mediated oxidative stress. MATERIALS AND METHODS: Bioactivity guided fractionation of CWC resulted in the isolation of a couple of known compounds. Freshly isolated murine hepatocytes were exposed to hydrogen peroxide (H2O2) (1 and 3mM) in the presence or absence of CWC (200 and 400 µg/ml) and SA (40 µM) for the determination of antioxidative, DNA protective, cellular ROS level by modern methods, including immunoblot and flowcytometry to find out the possible mechanism of action. RESULTS: Pre-treatment of hepatocyte with CWC and SA showed significant prevention of H2O2-induced intracellular ROS generation, nuclear DNA damage along with the formation of hepatic TBARS and cellular nitrite. Further, the H2O2 induced cell death was arrested in the presence of CWC through the inhibition of CDC42 mediated SAPK/JNK pathways and activation of other molecules of apoptotic pathways, including Bax and caspase3. Moreover, CWC and SA help in maintaining the GSH level and endogenous antioxidants like Mn-SOD, to support intracellular defense mechanisms, probably through the transcriptional activation of Nrf2; and inhibition of nuclear translocation of NF-κB. CONCLUSION: CWC and its active components SA reversed the H2O2 induced oxidative damage in hepatocytes, probably through the inhibition of NF-κB, with the activation of PI3K/Akt/Nrf2 pathway and reduction of apoptosis by interfering the SAPK/JNK/Bax pathway.