Effect of Gualou Xiebai Decoction on type II cardiorenal syndrome based on endothelial/epithelial-to-mesenchymal transition and its mechanism / 中国药理学通报

Aim To investigate the protective effects of different doses Gualou Xiebai Decoction (GXD) on type II cardiorenal syndrome (type II CRS) and explore its preliminary mechanisms. Methods The type II cardiorenal syndrome rat model was replicated by li-gating the left anterior descending coronary artery. After 10 weeks of intragastric administration, the cardiac function of the rats in each group was evaluated by echocardiography; serum were collected for biochemical testing; heart and kidney tissue samples were stained with HE and Masson to observe pathological changes. The hydroxyproline content in the heart and kidney was detected. The expression levels of endothelial/epitheli-al-to-mesenchymal transition (EndMT/EMT) related proteins in heart and kidney tissues were detecterd by immunofluorescence double staining

Progress in understanding hepatic fibrosis and renal fibrosis based on the gut-liver-kidney axis / 药学学报

Fibrosis is a pathological process of abnormal hyperplasia and excessive deposition of extracellular matrix during the process of repair after tissue and organ damage. Injury/inflammation caused by variously chronic diseases is a major trigger for fibrogenesis. Fibrosis of the liver and kidney is a common organ fibrosis. Recently, the intestinal microbiota has been shown to be extensively involved in the development of liver and kidney diseases, which may follow from changes in the intestinal microbial composition and intestinal integrity. This promotes the development of liver and/or kidney fibrosis through endocrine, cell signaling and other pathways. This paper reviews the research progress in understanding liver fibrosis and kidney fibrosis based on the gut-liver-kidney axis, which may be helpful for providing new strategies and theoretical basis for the diagnosis and treatment of hepatic and renal fibrosis.

Mechanism of total C-21 steroidal glucosides from root of Cynanchum auriculatum in activation of human hepatic stellate cells via TGF-β / 中国药理学通报

Aim To investigate the inhibitory effect of total C-21 steroidal glucosides (TCSG) from the root of Cynanchum auriculatum on activation of human hepatic stellate cells and the underlying mechanism. Methods The fibrosis model in vitro was established by treating LX-2 cells with TGF-β

Effects of total C-21 steroidal glucosides from Cynanchum auriculatum on oxidative stress pathway in mice with liver injury / 中国中药杂志

The study aimed to investigate the mechanism of hepatoprotective effect of C-21 steroidal glucosides from Cynanchum auriculatum( Baishouwu) on oxidative stress in mice with liver injury. Mice were randomly divided into normal group,model group,positive control group,Baishouwu high group and Baishouwu low group. The liver injury model was induced by intraperitoneal injection of CCl4 peanut oil solution. All mice were sacrificed to collect blood and liver specimens. The activities of serum levels of ALT and AST were detected. The content of MDA and the activity of SOD in liver homogenate were examined by colorimetry method. Tissues were stained with hematoxylin-eosin for histological examination. The hepatic protein expressions of NF-κB p65,p-IκBα,i NOS and COX-2 were detected by Western blot. The mRNA expressions of TNF-α and IL-6 were determined by RT-PCR. It was found that treatment with C-21 steroidal glucosides from Baishouwu successfully attenuated liver injury induced by CCl4,as shown by decreased levels of serum biochemical indicators( AST,ALT)( P<0. 01). Administration of total C-21 steroidal glucosides enhanced the activity of SOD( P<0. 01) and decreased the content of MDA( P<0. 01) in liver homogenate. Microscopic features suggested that treatment with C-21 steroidal glucosides from Baishouwu was effective in inhibiting CCl4-induced hepatocyte edema and degeneration. Further studies showed that NF-κB p65 overexpression induced by CCl4 was decreased by C-21 steroidal glucosides,leading to the markedly down-regulated protein expression levels of p-IκBα,i NOS and COX-2,as well as the depression of TNF-α and IL-6 mRNA expressions. In conclusion,total C-21 steroidal glucosides from Baishouwu exhibited potent effect on oxidative stress pathway in mice with liver injury induced by CCl4,with enhanced activity of SOD,decreased content of MDA,and down-regulated levels of NF-κB p65,p-IκBα,i NOS and COX-2.

Effects of total C-21 steroidal glycosides from Baishouwu on proliferation invasion and apoptosis of human hepatic cancer HepG2 cells / 中国中药杂志

This study aimed to investigate the inhibitory effect of total C-21 steroidal glycoside (TCSG) from Baishouwu on the proliferation, invasion and apoptosis of human hepatoma HepG2 cells in vitro and the relevant molecular mechanism. The experiment was divded into control group, TCSG groups (25, 60, 150 mg·L⁻¹) and positive control cisplatin group (1.33 mg·L⁻¹). Human hepatocyte L-02 cells and hepatoma HepG2 cells were treated with different concentrations of TCSG. Then, the inhibitory effect of TCSG on the proliferation of HepG2 cells was detected by CCK-8 method. Cell cycle, cell apoptosis and mitochondrial membrane potential were detected by flow cytometry. The apoptotic morphology was observed by Hoechst 33258 staining. Cell migration and invasion abilities were analyzed by Transwell chamber model. The protein expressions of Bcl-2, Bax, caspase 3, cleaved caspase 3 and Cyt C (cytosolchondrial) were detected by Western blot. Compared with the control group, the proliferation of HepG2 cells was significantly inhibited after treatment with different concentrations of TCSG for 48 h in a dose-dependent manner(<0.01), but no obvious effect was observed on the proliferation of L-02 cells. After treatment with TCSG for 48 h, apoptotic morphology such as nuclear shrinkage, fragmentation and semilunar or circular was observed; migration and invasion abilities of cells were significantly decreased, cell cycle was blocked in the G₀/G₁ phase(<0.01), mitochondrial membrane potential was remarkably decreased(<0.01), and so did the ratio of apoptosis(<0.01).Western blot results showed that the protein expressions of Bax, caspase 3, cleaved caspase 3, and Cyt C were significantly up-regulated(<0.05, <0.01), while the Bcl-2 protein was significantly down-regulated(<0.05, <0.01). Furthermore, the ratio of Bax/Bcl-2 was increased (<0.01). The results suggested that TCSG could inhibit the proliferation and invasion of HepG2 cells, and induce the apoptosis of HepG2 cells. The potential mechanism may be related to the blocking of cell cycle and the regulation of the expressions of apoptosis-related proteins by activating mitochondrial pathway.