In-vitro promoted differentiation of mesenchymal stem cells towards hepatocytes induced by salidroside.

OBJECTIVES: The present study aimed to investigate whether salidroside can induce differentiation of rat mesenchymal stem cells (rMSCs) towards hepatocytes in vitro and the mechanism of hepatic differentiation of rMSCs. METHODS: rMSCs were subject to hepatic differentiation. One, two and three weeks later, the expression of alpha fetoprotein (AFP) and albumin (ALB), cytochrome P450 (CYP450)-dependent activity and inducibility, cellular uptake of low density lipoprotein (LDL) and urea synthesis were assessed and the hepatic differentiation of rMSCs was evaluated. In order to unravel the mechanism of hepatic differentiation of rMSCs in vitro, inhibitors of extracellular regulated kinase1/2 (ERK1/2), phosphatidylinositol 3-kinase (PI3K) and p38 were applied. When the process of hepatic differentiation was completed, special proteins of hepatic differentiation were detected and blocking of inhibitors was evaluated. KEY FINDINGS: Salidroside significantly induce differentiation of rMSCs towards hepatocytes. Differentiated rMSCs have typical functional hepatic characteristics. The results also showed that the ERK1/2 and PI3K signalling pathways play important roles in the regulatory effects of salidroside on hepatic differentiation of rMSCs and are involved in cell fate determinations, while the p38 signalling pathway does not. CONCLUSIONS: Salidroside can induce differentiation of rMSCs towards hepatocytes in vivo, and the ERK1/2 or PI3K signalling pathway underlie the process of hepatic differentiation.

Protective effects of steroids from Allium chinense against H2O2-induced oxidative stress in rat cardiac H9C2 cells.

Allium chinense, a traditional herbal medicine, has been used for the treatment of cardiovascular diseases for hundreds of years. In this study, A. chinense steroids (ACSs) including three steroidal glycosides and their parent aglycones were isolated from the bulbs of A. chinense. For the first time, their cardioprotective effects were evaluated in cultured rat cardiac H9C2 cells by pretreatment with ACSs for 24 h before exposure to 0.2 mm H(2)O(2). The results showed the cell viability decreased markedly when H9C2 cells were incubated with 0.2 mm H(2)O(2) alone for 2 h, while the cell lipid peroxidation (estimated by the excessive production of nitric oxide and malondialdehyde) and intracellular free calcium concentration ([Ca(2+)](i)) increased significantly. The addition of 20 microm (below the toxic concentration) of ACSs notably attenuated the cellular injury induced by H(2)O(2). The effects of ACSs in our experiments were similar to those of nimodipine, a clinically applied calcium channel blocker. Preliminary analysis of the structure-activity relationship indicated that ACSs with a spirostane-type skeleton exhibited stronger protection than that with a furostane-type skeleton, and glycosylation of the steroids could substantially lower the protective activities. The above results suggested the protective effects of steroids originated from A. chinense on the oxidative injury of H9C2 cells and ACSs may have potential for preventing cardiac injuries induced by oxidative stress.

[Hepatic and renal injury induced by Radix Aristolochiae or Guanxin Suhe Wan for a long-term in rats].

OBJECTIVE: To evaluate the toxicity of Radix Aristolochiae supplied experimental evidence of rational use of drug in clinic. METHOD: After treatment with small dose Radix Aristolochiae, Guanxin Suhe Wan (with Radix Aristolochiae) and Guanxin Suhe Wan (without Radix Aristolochiae) in different group for a long- term, respectively, the biochemical indicator of PT, ALT, AST, ALB, ALP, Crea and BUN were detected, and the kidney, liver, stomach and urinary bladder were examined by pathologic assaying. RESULT: In Radix Aristolochiae group and Guanxin Suhe Wan (with Radix Aristolochiae) group, all of biochemical indicator were changed significantly, and hepatonecrosis, renal tubular necrosis, gastric carcinoma and bladder carcinoma were discovered. CONCLUSION: Radix Aristolochiae and Guanxin Suhe Wan (with Radix Aristolochiae) can damage kidney and liver, and cause gastric carcinoma and bladder carcinoma by intensive toxicity.

[Nephrotoxicity of Radix Aristolochice and it's substitution material Radix Inulae in rats].

OBJECTIVE: To evaluate the toxicity of Radix Aristolochiae and Radix Inulae, and to supply the toxicity experimental data that Radix Inulae supersedes Radix Aristolochiae in clinic. METHOD: A long dose of Radix Aristolochice and Radix Inulae was given intragastrically to rats for six months, then drug withdrawal for a month. The hematology and biochemical indicators were measured, and the pathologic changes of kidney, liver, stomach and urinary bladder were examined. RESULT: The rats of Radix Aristolochice showed serious toxic responses of renal tubule atrophy and necrosis, meanwhile, the levels of BUN, Cr and NAG were increased obviously. Hepatonecrosis, renal tubular necrosis, gastric carcinoma and bladder carcinoma were discovered with pathologic assaying. But the rats of Radix Inulae did not. CONCLUSION: Radix Aristolochiae could damage kidney and liver, and cause gastric carcinoma and bladder carcinoma by intensive toxicity. Radix Inulae could take the place of Radix Aristolochiae to use in clinic.