Gui Shao Tea Extracts Inhibit Gastric Cancer Growth in Vitro and in Vivo and Prolong Survival in Nude Mice.

BACKGROUND: Gui Shao Tea (GST), a long-aged tea with a Chinese herbal aroma, can treat many stubborn and malignant diseases, according to traditional Chinese medicine. This research aimed to discover and define GST, study the anti-gastric cancer effects of GST extracts and preliminarily elucidate the mechanism of action in the PI3K/Akt signaling pathway and the gut microbiota. METHODS: GST was analyzed by GC/MS and HPLC. Cell proliferation, the cell cycle and apoptosis were evaluated by a CCK8 assay and flow cytometry. The effects of GST extracts on tumor inhibition and survival time were explored by a gastric cancer xenograft model in nude mice. The PI3K/Akt signaling pathway was assessed by western blotting and immunohistochemistry. Gut microbiota detection and fecal microbiota transplantation were performed to examine whether the tumor inhibition observed in mice was related to gut microbiota changes. RESULTS: The ingredients in GST, mostly terpenes and their derivatives, were novel and more concentrated than those in tea made from the branches and leaves of the same plant species, Camellia sinensis, picked and produced the same year, while the levels of polyphenols and alkaloids were significantly reduced. In BGC-823, MGC-803, and SGC-7901 gastric cancer cells, GST extracts significantly inhibited proliferation (p = 0.037), induced G0/G1 arrest (p < 0.001) and promoted early apoptosis (p = 0.041). In mice, gastric tumor growth was significantly inhibited in both the high-dose (HTF) and middle-dose (MTF) GST-fed groups. The inhibition rate in the HTF group was 33.77% on Day 14 (p = 0.042), and that in the MTF group was 55.21% on Day 14 (p = 0.002) and 61.6% on Day 28 (p = 0.008). The survival time of MTF group mice was significantly prolonged by 22.2% (p = 0.013). GST extracts inhibited the PI3K/AKT signaling pathway in gastric cancer cells (p = 0.016) and tissues (p = 0.029), downregulated the protein p-Rb and further downregulated E2F1, thereby affecting the cell cycle and proliferation. GST extracts altered the gut microbiota in mice, but these alterations alone were insufficient to inhibit gastric cancer growth. CONCLUSIONS: We confirmed the anti-gastric cancer effects of GST extracts, which might provide new approaches and methods for research and development of gastric cancer drugs.

Alginate oligosaccharide improves lipid metabolism and inflammation by modulating gut microbiota in high-fat diet fed mice.

Alginate oligosaccharides are associated with some beneficial health effects. Gut microbiota is one of the most recently identified factors in the development of several metabolic diseases induced by high-fat diet. Our objective was to evaluate how alginate oligosaccharides impact on high-fat diet­induced features of metabolic disorders and whether this impact is related to modulations in the modulation of the gut microbiota. C57BL/6J mice were fed with chow diet, high-fat diet, or high-fat diet supplemented with alginate oligosaccharides for 10 weeks. Alginate oligosaccharide treatment improved lipid metabolism, such as reducing levels of TG and LDL-C and inhibiting expression of lipogenesis genes. Alginate oligosaccharide administration reduced the levels of fasting blood glucose and increased the levels of serum insulin. Alginate oligosaccharide treatment was found to lower the expression of markers of inflammation, including IL1ß and CD11c. Alginate oligosaccharide treatment modulated gut microbial communities and markedly prompted the growth of Akkermansia muciniphila, Lactobacillus reuteri, and Lactobacillus gasseri. Additionally, alginate oligosaccharide intervention significantly increased concentrations of short-chain fatty acids, such as acetic acid, propionic acid, and butyric acid, as well as decreased levels of endotoxin. Alginate oligosaccharides exert beneficial effects via alleviating metabolic metrics induced by high-fat diet, which is associated with increase in A. muciniphila, L. reuteri, and L. gasseri, as well as the release of microbiota-dependent short-chain fatty acids and inhibition of endotoxin levels.