Ginsenoside Rh2 attenuates CDAHFD-induced liver fibrosis in mice by improving intestinal microbial composition and regulating LPS-mediated autophagy.

BACKGROUND: Nowadays, liver diseases are threatening more and more people all over the world and one of the main causes is liver fibrosis. However, there is no effective way to reverse liver fibrosis. PURPOSE: To investigate whether ginsenoside Rh2 (G-Rh2) can alleviate liver fibrosis and elucidate its underlying mechanism. METHODS: In vivo and in vitro methods were adopted in this research. Choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) was used to feed mice to induce liver fibrosis, and HSC-T6 cells were used to establish an LPS-induced model of liver fibrosis. Through histopathological staining, hematoxylin-eosin (H&E) staining, western blot analysis, intestinal bacteria 16SrRNA sequencing, and other technical means, the research explored whether G-Rh2 possesses anti-fibrotic activity. RESULTS: G-Rh2 could notably alleviate CDAHFD-induced liver fibrosis in mice. In particular, it could alleviate liver injury and reduce plasma lipopolysaccharide (LPS) levels. Additionally, G-Rh2 could repair intestinal injury as well as regulate intestinal microbial diversity and composition. HSC-T6 cells could be activated and autophagy could be induced further by LPS in vitro. After being treated with G-Rh2, autophagy was restrained and activation of hepatic stellate cells (HSCs) was controlled. Deeper research showed that G-Rh2 restrained the activation of HSCs via stimulating the AKT-mTOR signaling pathway, restraining autophagy. CONCLUSION: The results of our studies clearly suggest that G-Rh2 repairs intestinal injury, improves intestinal microbial composition, reduces plasma LPS levels, and activates the AKT-mTOR signaling pathway to restrain LPS-mediated autophagy, thus playing an important role in anti-hepatic fibrosis. G-Rh2 was found to have the potential to effectively alleviate liver fibrosis.

Sinomenine suppresses TNF-alpha-induced VCAM-1 expression in human umbilical vein endothelial cells.

Sinomenine (SN), an alkaloid prepared from the root of Sinomenium acutum Rehd. Et wils, is used to alleviate the symptoms of rheumatism in Chinese medicine. In the present study, the potential inhibition of TNF-alpha-induced VCAM-1 expression on human umbilical vein endothelial cells (HUVECs) was evaluated in vitro. HUVECs were isolated from freshly collected umbilical cords. Positive controls were stimulated with TNF-alpha, omitting SN. Negative controls were cultured omitting TNF-alpha and SN. Experimental groups were co-cultured with TNF-alpha and SN at different concentrations (0.25, 0.5, and 1.0 mol/L), or TNF-alpha and Dexamethasone (Dex) at a concentration of 1.0 x 10(-6) mol/L. Cells were harvested after culturing with the above drugs for 12 h. VCAM-1 mRNA expression was detected by real-time quantitative PCR, and VCAM-1 expression was detected by flow cytometry. The experimental data indicated that VCAM-1 mRNA and VCAM-1 were induced by TNF-alpha. The relative VCAM-1 mRNA expression decreased in the experimental groups (p<0.05). Concentrations of SN at 0.5 and 1.0 mol/L inhibited expression of VCAM-1 (p<0.05). SN at concentration of 0.25 mol/L and Dex at concentration of 1.0 x 10(-6) mol/L did not show an inhibitory effect on VCAM-1 expression in TNF-alpha-induced HUVECs. Our preliminary data indicates that SN has an inhibitory effect in vitro on TNF-alpha-induced VCAM-1 expression at both mRNA level and protein level in HUVECs, and suggests that SN may be a novel method of immunotherapy for rheumatic carditis or rheumatic heart disease.

Protective effects of non-mitogenic human acidic fibroblast growth factor on hydrogen peroxide-induced damage to cardiomyocytes in vitro.

AIM: To study the protective effect of non-mitogenic human acidic fibroblast growth factor (FGF) on cardiac oxidative injury in vivo. METHODS: Ventricular cardiomyocytes were isolated from 1- to 3-d-old neonatal SD mice and cultured in Dulbecco's minimum essential medium supplemented with 15% fetal bovine serum under an atmosphere of 50 mL/L CO2-95% air at 37 degrees, as well as assessed by immunocytochemical assay. We constructed the cardiomyocyte injury model by exposure to a certain concentration of H2O2. Cellular viability, superoxide dismutase (SOD) activity, leakage of maleic dialdehyde and anti-apoptosis effect were included to evaluate the cardiac protective effect of non-mitogenic human acidic FGF. RESULTS: Over 50% of the cardiomyocytes beat spontaneously on the 2nd d of culture and synchronously beat after being cultured for 3 d. Forty-eight hours after plating was completed, the purity of such cultures was 95% myocytes, assessed by an immunocytochemical assay. Cellular viability dramatically decreased with the increasing of the concentration of H2O2. Non-mitogenic human acidic FGF showed significant resistance to the toxic effect of H2O2, significantly increased the cellular viability as well as the activity of SOD, and dramatically decreased the leakage of maleic dialdehyde as well as the cellular apoptosis rate. CONCLUSION: Hydrogen peroxide shows strong cytotoxicity to the cultured cardiac myocytes, and non-mitogenic human acidic FGF shows strong cardio-protective effect when exposed to a certain concentration of H2O2.

[Study on antiradiation effect of panaxatriol].

OBJECTIVE: To study antiradiation effect of panaxatriol (PT) and to provide an experiment basis for developing relative radiation-resistant skin care products. METHODS: Mice were treated with PT or normal saline (the control group) before X-ray irradiation and were to observe the number of chromosme aberrations killed 3 hours after irradiation. The chromosome samples of bone marrow cells were prepared and chromatid mutation as well as aberrant cells. RESULTS: PT can reduce the frequency of chromatid mutative induced by X-ray. Antiradiation effect was positively correlated with the dose of PT and the duration of drug, and negatively correlated with the dose of X-rays. CONCLUSION: PT has significant antiradiation effect.