Cardioprotective Effects of 20(S)-Ginsenoside Rh2 against Doxorubicin-Induced Cardiotoxicity In Vitro and In Vivo.

Doxorubicin (DOX) is considered as one of the best antineoplastic agents. However, its clinical use is restricted by its associated cardiotoxicity, which is mediated by the production of reactive oxygen species. In this study, 20(S)-ginsenoside Rh2 (Rh2) was explored whether it had protective effects against DOX-induced cardiotoxicity. In vitro study on H9C2 cell line, as well as in vivo investigation in one mouse and one rat model of DOX-induced cardiomyopathy, was carried out. The results showed that pretreatment with Rh2 significantly increased the viability of DOX-injured H9C2 cells. In the mouse model, Rh2 could suppress the DOX-induced release of the cardiac enzymes into serum and improved the occurred pathological changes through ameliorating the decreased antioxidant biomolecules and the cumulated lipid peroxidation malondialdehyde in heart tissues. In the rat model, Rh2 could attenuate the change of ECG resulting from DOX administration. Furthermore, Rh2 enhanced the antitumor activity of DOX in A549 cells. Our findings thus demonstrated that Rh2 pretreatment could effectively alleviate heart injury induced by DOX, and Rh2 might act as a novel protective agent in the clinical usefulness of DOX.

In vitro and in vivo antifibrotic effects of rosmarinic acid on experimental liver fibrosis.

This study was carried out to investigate whether rosmarinic acid (RA) has antifibrotic effect on experimental liver fibrosis in vitro and in vivo and its possible mechanism. Culture of hepatic stellate cells (HSCs) determine proliferation and expression of transforming growth factor-beta1 (TGF-beta1), connective transforming growth factor (CTGF) and alpha-smooth muscle actin (alpha-SMA). In carbon tetrachloride (CCL(4))-induced rat liver fibrosis model, determined biochemical indicator, liver fibrosis grade and histopathological changes, immunohistochemical detected liver TGF-beta1 and CTGF expression. The results indicated that RA could inhibit HSCs proliferation, inhibit TGF-beta1, CTGF and alpha-SMA expression in cultured HSCs. It has marked evident in reducing fibrosis grade, ameliorating biochemical indicator and histopathological morphology, reducing liver TGF-beta1 and CTGF expression in CCL(4)-induced liver fibrosis. These findings suggest that RA has potentially conferring antifibrogenic effects.

Cornin ameliorates cerebral infarction in rats by antioxidant action and stabilization of mitochondrial function.

This study was conducted to investigate the efficacy of cornin, an iridoid glycoside, in an experimental cerebral ischemia induced by middle cerebral artery occlusion (MCAO) and reperfusion (I/R), and to elucidate the potential mechanism. Adult male Sprague-Dawley rats were subjected to MCAO for 1 h, then reperfusion for 23 h. Behavioral tests were used to evaluate the damage to central nervous system. The cerebral infarct volume and histopathological damage were assessed to evaluate the brain pathophysiological changes. Spectrophotometric assay methods were used to determine the activities of superoxide dismutase (SOD) and glutathione-peroxidase (GPx). Contents of malondialdehyde (MDA), the generation of reactive oxygen species (ROS) as well as respiratory control ratio and respiratory enzymes of the brain mitochondria were also determined. The results showed that cornin significantly decreased neurological deficit scores, and reduced cerebral infarct volume and degenerative neurons. Meanwhile, cornin significantly increased the brain ATP content, improved mitochondrial energy metabolism, inhibited the elevation of MDA content and ROS generation, and attenuated the decrease of SOD and GPx activities in brain mitochondria. These findings indicate that cornin has protective potential against cerebral ischemia injury and its protective effects may be due to amelioration of cerebral mitochondrial function and its antioxidant property.

Effect of astilbin on experimental diabetic nephropathy in vivo and in vitro.

Astilbin, a flavonoid compound, was isolated from the rhizome of Smilax glabra Roxb. This study was conducted to investigate the efficacy of astilbin on experimental diabetic nephropathy (DN) in vivo and in vitro and its possible mechanisms. Astilbin was added in high glucose stimulated HK-2 cells, streptozotocin-induced experimental DN, randomized to receive intragastric ( I. G.) astilbin to observe its anti-renal lesion effect. Results showed that astilbin inhibited high glucose stimulated HK-2 cell production of transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF) in vitro, especially CTGF; analogic results was also found in vivo. I. G. of astilbin 2.5 mg/kg or 5 mg/kg significantly ameliorated renal function, reduced kidney index, while it increased body weight and survival time in animals. In addition there was no significant difference in blood glucose level between the STZ-treated group and the astilbin groups. Furthermore, astilbin ameliorated the pathological progress of renal morphology. Astilbin can exert an early renal protective role to DN, inhibit production of TGF-beta1 and especially of CTGF. We suggest that astilbin inhibition of CTGF may be a potential target in DN therapy. This work provides the first evidence for astilbin as a new candidate of DN therapeutic medicine.

Effect of cornuside on experimental sepsis.

This study was conducted to investigate the efficacy of cornuside, a secoiridoid glucoside compound, in cultured macrophages as well as in an experimental model of sepsis induced by cecal ligation and puncture (CLP) in rats. Cornuside was added to cultured macrophages at different concentrations, and all CLP rats were randomized to receive an intravenous injection of the corresponding drug followed by observation of its antisepsis effect. Our results showed that cornuside downregulated the levels of TNF- alpha, IL-6, and NO production in a dose-dependent manner in activated macrophages, while it upregulated the level of IL-10. Intravenous injection of cornuside or imipenem alone or in combination reduced CLP-induced lethality in rats after CLP. In addition, serum levels of TNF- alpha, IL-6, triggering receptor expressed on myeloid cells, and endotoxin were downregulated. On the other hand, the serum levels of IL-10 were upregulated. Decreased bacterial counts in blood, peritoneum, spleen, liver, and mesenteric lymph nodes and decreased myeloperoxidase in lung, liver, and small intestine also were found after cornuside injection. These data indicate that the antisepsis therapeutic effect of cornuside is mediated by decreased local and systemic levels of a wide spectrum of inflammatory mediators. This work provides first evidence for the clinic use of cornuside as a new immunomodulatory drug that has the capacity to inhibit the inflammatory response in sepsis.

Protective effect of salvianic acid a on acute liver injury induced by carbon tetrachloride in rats.

Previous research has shown that salvianic acid A [2-(3,4-dihydroxyphenyl)-2-hydroxy-propanoic acid, SA] extracted from Salvia miltiorrhiza BGE (Danshen) markedly inhibits lipid peroxidation of mitochondrial membrane of hepatic cells in vitro. The present study was conducted to examine protective effect of SA on liver injury induced by carbon tetrachloride (CCl4) and its possible mechanism in vivo. Male Sprague-Dawley rats weighing 180-200 g were used in the experiments. Five mmol/kg CCl4 in olive oil was given to rats i.p. Spectrophotometrical method was used to measure activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum, activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as well as malondialdehyde (MDA) level in hepatic tissue and the rate of superoxide anion (O2*-) generation in hepatic submitochondrial particles. Hepatic histological structure was observed under light microscopy. CCl4 caused significant changes of activities of the enzymes, MDA level, and the rate of O2*- generation and histopathological changes of acute hepatic injury were noted. SA reversed the significant changes induced by CCl4. These results demonstrate that SA produces protective action on acute hepatic injury induced by CCl4 via an antioxidative mechanism.

[Protective effect of ligusticum chuanxiong phthalides on focai cerebral ischemia in rats and its related mechanism of action].

OBJECTIVE: To study the protective effect of ligusticum chuanxiong phthalides on cerebral ischemia in rats and its related mechanism of action. METHOD: Middle cerebral artery occlusion (MCAO) model, thrombosis formation, platelet aggregation and hemorrheological parameters were measured to evaluate the protective effect of ligusticum chuanxiong phthalides. RESULT: Ligusticum chuanxiong phthalides could markedly decrease the infarct size and behavior deficits score, inhibit the thrombus formation and platelet aggregation, ameliorate hemorrheological parameters with a dose-dependent manner in rats. CONCLUSION: Ligusticum chuanxiong phthalides has protective effects on focal cerebral ischemia in rats, and its mechanism may be relevant to its inhibition of platelet-dependent thrombosis and amelioration of hemorrheological parameters.

[Protective effect of hydroxysafflor yellow A on experimental cerebral ischemia in rats].

AIM: To investigate the protective effect of hydroxysafflor yellow A (HSYA), a soluble element extracted from Carthamus tinctorius L., on focal cerebral ischemia in rats. METHODS: Focal cerebral ischemia in male Wistar-Kyoto (WKY) rats were induced by permanent middle cerebral artery occlusion (MCAO). Three doses of 1.5, 3.0 and 6.0 mg x kg(-1) of HSYA were administrated to three groups of rats, separately, via sublingular vein injection 30 min after the onset of ischemia. 24 h after ischemia in rats, neurological deficit scores were evaluated and the infarction area of brain was assessed by quantitative image analysis. The in vitro neuroprotective effect of HSYA was tested in cultured fetal cortical neurons exposed to glutamate and sodium cyanide (NaCN). RESULTS: HSYA at doses of 3.0 and 6.0 mg x kg(-1) exerted significant neuroprotective effects on rats with focal cerebral ischemic injury as expressed by neurological deficit scores and reduced the infarct area as compared with saline group, and the potency of HSYA at dose of 6.0 mg x kg(-1) was similar to that of 0.2 mg x kg(-1) of nimodipine. In vitro studies, HSYA significantly inhibited neurons damage induced by exposure to glutamate and NaCN in cultured fetal cortical cells. CONCLUSION: HSYA has potential neuroprotective action against focal cerebral ischemia in rats and cultured rat fetal cortical neurons as well.