High-altitude Tibetan fermented milk ameliorated cognitive dysfunction by modified gut microbiota in Alzheimer's disease transgenic mice.

Alzheimer's disease (AD) is a complex neurodegenerative disease that is regarded as a growing global challenge. Accumulating evidence linking gut microbiota with AD has become intriguing. The purpose of this study was to investigate how Tibetan fermented milk affected memory impairment in amyloid precursor protein (APP)/presenilin-1 (PS1) mice, using APP/PS1 transgenic mice as examples. We used Tibetan fermented milk (the yogurt samples with the highest microbial diversity were selected by 16S sequencing) as an intervention in such mice for 20 weeks, with aseptic maintenance feed as their basic diet. At the end of the intervention, we collected fecal samples for 16S ribosomal ribonucleic acid (rRNA) sequencing. We evaluated the effects of Tibetan fermented milk on the mice's cognitive function by behavioral examination, and deposition of amyloid beta (Aß) in the hippocampus and cortex of the mice by immunohistochemistry (IHC). Results showed that Tibetan fermented milk could improve cognitive impairment in APP/PS1 mice, including spatial learning/memory and object recognition/memory. Sequencing of 16S ribosomal RNA in mouse feces showed that Tibetan fermented milk increased intestinal microbial diversity and elevated the relative abundance of Bacteroides and Faecalibacterium spp. Mucispirillum and Ruminiclostridium were highly abundant in APP/PS1 mice. Additionally, correlation analysis revealed that cognitive function was correlated negatively with Mucispirillum abundance and positively with Muribaculum and Erysipelatoclostridium abundance. Tibetan fermented milk could also reduce deposition of Aß in the cerebral cortex and hippocampus. Our data suggested that long-term intake of Tibetan fermented milk had a beneficial effect on the composition of intestinal flora, which was correlated with cognitive improvements in APP/PS1 mice and seemed to help prevent and treat AD-induced cognitive decline.

Effects of the aqueous extract of a Tibetan herb, Rhodiola algida var. tangutica on proliferation and HIF-1α, HIF-2α expression in MCF-7 cells under hypoxic condition in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola algida var. tangutica is a traditional Tibetan herb. Its root and rhizome have been successfully used as an effective clinical remedy for the prevention and treatment of cancer and high-altitude sickness. This study aimed to investigate the effect of Rhodiola algida var. tangutica on hypoxic MCF-7 breast cancer cells and the underlying mechanisms. MATERIALS AND METHODS: The antiproliferative effects of R. algida on MCF-7 breast cancer cells were compared in vitro under hypoxic and normal conditions by using MTT analysis. The influence of R. algida on cancer cell apoptosis was determined by flow cytometry. The expression levels of hypoxia-inducible factor (HIF)-1α and HIF-2α were evaluated by western blot analysis. RESULTS: R. algida inhibited the proliferation of MCF-7 breast cancer cells in a dose- and time-dependent manner. The results of flow cytometry indicated that the antiproliferative effect of R. algida was mediated by apoptosis induction. Pretreatment with R. algida significantly suppressed the hypoxia-induced proliferation and expression of HIF-1α and HIF-2α in MCF-7 breast cancer cells. CONCLUSIONS: R. algida might exert an anti-carcinogenic effect on MCF-7 breast cancer cells by decreasing the protein levels of HIF-1α and HIF-2α, which are overexpressed under hypoxic conditions. This effect might be elicited by inhibiting the hypoxia-induced proliferation of MCF-7 breast cancer cells.