Tanshinone IIA exerts therapeutic effects by acting on endogenous stem cells in rats with liver cirrhosis.

BACKGROUND AND OBJECTIVE: Liver cirrhosis (LC), the major pathway for the progression and development of chronic liver disease, is an advanced stage of liver disease. It is the third most common chronic noncommunicable disease after cardiovascular diseases and malignant tumors. Tanshinone IIA (Tan), an extract of Salvia miltiorrhiza (S. miltiorrhiza), has been proven to promote the proliferation and differentiation of stem cells. Moreover, its protective effect in liver injury has received widespread attention. The present study investigated whether Tan plays a therapeutic role in LC by promoting endogenous stem cell proliferation and differentiation. MATERIALS AND METHODS: LC models were established by intraperitoneal injection of an olive oil solution containing 50 % carbon tetrachloride (CCL4) combined with 10 % alcohol in the drinking water. After successful model establishment, the animals were randomly divided into four groups and injected with physiological saline or low-, medium-, or high-dose (10, 20, or 40 mg/kg) Tan for seven consecutive days. The protective effect of Tan on LC was observed by western blotting, serological examination and histopathological staining. Furthermore, immunofluorescence double-labeling of 5-bromo-2-deoxyuridine (BrdU) and the liver cell markers albumin and CK-18 or the liver stem cell markers EPCAM and OV-6 was used to evaluate the proliferation and differentiation of endogenous liver stem cells. RESULTS: We confirmed successful establishment of the LC model by observing transaminase levels and hematoxylin-eosin (HE) and Masson staining of liver sections in CCL4-treated and healthy rats. After Tan treatment, HE and Masson staining of paraffin sections of liver tissue showed that Tan treatment significantly improved histological injury to the liver. Serological tests showed that albumin-bilirubin (ALBI) scores and models for end-stage liver disease (MELD) were lower. Immunofluorescence and immunohistochemical staining showed that the newly proliferated cells were colocalized with ALB, OV-6, EPCAM, and CK-18, indicating that new expression of these markers occurred after Tan injection. All results were most significant in the medium-dose treatment group. CONCLUSION: Tan can alleviate liver injury induced by CCL4 combined with alcohol in rats and plays a therapeutic role in LC by promoting the proliferation and differentiation of endogenous liver stem cells.

Ginsenoside Rd therapy improves histological and functional recovery in a rat model of inflammatory bowel disease.

Ginsenoside Rd (GRd) is a biologically active component of ginseng that stimulates the proliferation of endogenous stem cells. The objective of our research was to evaluate the utility of GRd in gastrointestinal mucosal regeneration in a rat model of inflammatory bowel disease (IBD) and to clarify whether GRd exerts its pharmacological effects by modulating endogenous intestinal stem cells. The IBD rat model was established via subcutaneous injection of indomethacin, and 10, 20, or 40 mg/kg GRd or an equal volume of physiological saline was then administered orally to rats in different groups every day for seven consecutive days. We observed that GRd treatment, especially 20 mg/kg GRd, significantly reduced indomethacin-induced damage compared with that in the control group. By measuring the mRNA and protein levels of the intestinal stem cell markers Bmi and Msi-1 and the intestinal epithelial cell marker CDX-2 as well as by double-labelling these markers with 5-bromo-2-deoxyuridine (BrdU), we inferred that GRd could stimulate the proliferation and differentiation of endogenous intestinal stem cells in IBD model rats, leading to improved recovery of intestinal function.

Granulocyte colony-stimulating factor enhances the therapeutic efficacy of bone marrow mesenchymal stem cell transplantation in rats with experimental acute pancreatitis.

INTRODUCTION: Acute pancreatitis (AP) is one of the most common diseases involving necrotic inflammation. Bone marrow mesenchymal stem cells (BMMSCs) have the potential of multi-directional differentiation and self-renewal for tissue repair. It remains less clear if granulocyte colony-stimulating factor (G-CSF) can improve the therapeutic effect of BMMSC transplant in AP. Therefore, we explored this issue in a rat model of experimental AP. RESULTS: Transplanted PKH26-positive BMMSCs were present in the injured pancreatic tissue, with some cells co-expressed pancreatic cellular markers, including Pax-4, Ngn3 and Nkx-6. Pathological, biochemical and serological data suggested an improvement in histological and functional recovery in these animals relative to control. Overall, the AP model rats received BMMSCs and G-CSF co-treatment showed better recovery in terms of tissue regeneration and blood biochemical levels relative to other groups. MATERIALS AND METHODS: BMMSCs from donor rats were labeled with the fluorescent dye PKH26 and transfused into recipient rats with AP induced by L-arginine. The animals were divided into a control group, and groups treated with BMMSCs, G-CSF, and BMMSCs together with G-CSF. Therapeutic effects were evaluated histologically with immunohistochemistry and immunofluorescence, together with biochemical measurement of pancreatic markers. CONCLUSION: G-CSF therapy with BMMSC transplantation improves histological and functional outcomes in rats with experimental AP.