A plant-based medicinal food inhibits the growth of human gastric carcinoma by reversing epithelial-mesenchymal transition via the canonical Wnt/ß-catenin signaling pathway.

BACKGROUND: Natural products, especially those with high contents of phytochemicals, are promising alternative medicines owing to their antitumor properties and few side effects. In this study, the effects of a plant-based medicinal food (PBMF) composed of six medicinal and edible plants, namely, Coix seed, Lentinula edodes, Asparagus officinalis L., Houttuynia cordata, Dandelion, and Grifola frondosa, on gastric cancer and the underlying molecular mechanisms were investigated in vivo. METHODS: A subcutaneous xenograft model of gastric cancer was successfully established in nude mice inoculated with SGC-7901 cells. The tumor-bearing mice were separately underwent with particular diets supplemented with three doses of PBMF (43.22, 86.44, and 172.88 g/kg diet) for 30 days. Tumor volumes were recorded. Histopathological changes in and apoptosis of the xenografts were evaluated by hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, respectively. Serum levels of TNF-α, MMP-2, and MMP-9 were detected by enzyme-linked immunosorbent assay. The mRNA expression levels of ß-catenin, GSK-3ß, E-cadherin, N-cadherin, MMP-2/9, Snail, Bax, Bcl-2, Caspase-3/9, and Cyclin D1 were evaluated via real-time quantitative polymerase chain reaction. The protein expression levels of GSK-3ß, E-cadherin, N-cadherin, and Ki-67 were determined by immunohistochemistry staining. RESULTS: PBMF treatment efficiently suppressed neoplastic growth, induced apoptosis, and aggravated necrosis in the xenografts of SGC-7901 cells. PBMF treatment significantly decreased the serum levels of MMP-2 and MMP-9 and significantly increased that of TNF-α. Furthermore, PBMF treatment notably upregulated the mRNA expression levels of GSK-3ß, E-cadherin, Bax, Caspase-3, and Caspase-9 but substantially downregulated those of ß-catenin, N-cadherin, MMP-2, MMP-9, Snail, and Cyclin D1 in tumor tissues. The Bax/Bcl-2 ratio was upregulated at the mRNA level. Moreover, PBMF treatment remarkably increased the protein expression levels of GSK-3ß and E-cadherin but notably reduced those of Ki-67 and N-cadherin in tumor tissues. CONCLUSIONS: The PBMF concocted herein exerts anti-gastric cancer activities via epithelial-mesenchymal transition reversal, apoptosis induction, and proliferation inhibition. The underlying molecular mechanisms likely rely on suppressing the Wnt/ß-catenin signaling pathway.

A Compound of Chinese Herbs Protects against Alcoholic Liver Fibrosis in Rats via the TGF-ß1/Smad Signaling Pathway.

Alcoholic liver fibrosis (ALF) has become a major public health concern owing to its health impacts and the lack of effective treatment strategies for the disease. In this study, we investigated the effect of a compound composed of Chinese herbs Pueraria lobata (Willd.), Salvia miltiorrhiza, Schisandra chinensis, and Silybum marianum on ALF. An ALF model was established. Rats were fed with modified Lieber-Decarli alcohol liquid diet and injected with trace CCl4 at late stage. The rats were then treated with several doses of the compound. Biochemical and fibrosis-relevant parameters were measured from the sera obtained from the rats. Liver tissues were obtained for hematoxylin and eosin and Masson's trichrome staining. Matrix metalloproteinase-13 and tissue inhibitor of metalloproteinase-1 were determined by immunohistochemistry assays. The mRNA and protein expression levels of transforming growth factor-ß1 (TGF-ß1), Smad2, Smad3, and Smad7 on the livers were also measured by quantitative polymerase chain reaction and Western blot. Results showed that the compound treatment alleviated pathological lesions in the liver, decreased the serum levels of hyaluronan, laminin, and hydroxyproline, and diminished the expression of hepatic tissue inhibitor of metalloproteinase-1. Compound treatment also increased hepatic matrix metalloproteinase-13 expression and inhibited the TGF-ß1/Smad signaling pathway. In conclusion, the compound has a protective effect against ALF in rats, and an underlying mechanism is involved in the TGF-ß1/Smad signaling pathway.