Inhibitory effects of total ginsenoside on bleomycin-induced pulmonary fibrosis in mice.

Pulmonary fibrosis is the final outcome of a variety of diffuse pulmonary interstitial diseases, and it has an unclear pathogenesis. There is no effective drug treatment, so the clinical prognosis is poor. As an effective component of ginseng, total ginsenoside (TG) inhibits acute lung injury. This study determined whether TG has protective effects on pulmonary fibrosis and investigated its protective mechanisms. A pulmonary fibrosis model in BALB/c mice was established by injecting the bleomycin chemotherapeutic agent into the trachea. TG (40, 80, and 160 mg/kg/d) was given continuously for 28 days from the second day after development of the model. Pulmonary fibrosis was determined by measuring the lung coefficient, haematoxylin and eosin, and Masson's trichrome staining of lung samples, and detection of alpha smooth muscle actin expression in lung tissues. To investigate the mechanisms of anti-pulmonary fibrosis by TG, we detected the genes and proteins of the transforming growth factor-ß1 (TGF-ß1)/Smad signalling pathway and matrix metalloproteinase (MMP) system. Treatment with TG (40, 80, and 160 mg/kg/d) ameliorated pulmonary fibrosis induced by bleomycin in mice, downregulated the expression of TGF-ß1, Smad2, Smad3, MMP-2, MMP-9, and tissue inhibitor of metalloproteinase-1, and upregulated the protein expression of Smad7. These results suggest that the protective effects of TG on pulmonary fibrosis induced by bleomycin are related to regulation of the TGF-ß1/Smad signalling pathway and MMP system.

Anticancer activity of tetrandrine by inducing pro-death apoptosis and autophagy in human gastric cancer cells.

OBJECTIVES: To investigate the antitumour property of tetrandrine by inducing autophagy and apoptosis in human gastric cancer cells, and to explore the potential molecular mechanisms. METHODS: The antitumour activity of tetrandrine was assessed through MTT assay. Apoptosis was measured by flow cytometry and microscopic examination of cellular morphology. The mitochondrial membrane potential was detected by staining with Rh-123. Induction of autophagy was monitored by transmission electron microscopy observation, using GFP-LC3 transfection. KEY FINDINGS: The results revealed that tetrandrine exhibits significant antitumour activity against gastric human cancer cell and the antigastric tumour activity was depended on inducing autophagy and apoptosis through upregulating the apoptosis-related protein (cleaved PARP, cleaved caspase-3 and cleaved caspase-9) and autophagy-related protein (Beclin-1, LC3-II and p62), and decreasing the phosphorylation of AKT/mTOR, PS6K and P-4EBP1. Adding the inhibitor of autophagy, 3-MA or Baf-A1, increased the viability of tetrandrine-exposed gastric cancer cells, which confirmed the role of autophagy played in the gastric cancer cell death induced by tetrandrine. CONCLUSIONS: These results demonstrated that the antitumour effects of tetrandrine by inducing autophagy and apoptosis involving Akt/mTOR pathway. Thus, tetrandrine may be a promising lead compound to be further developed in future for cancer therapy.