ABSTRACT
In our previous study, we found that Si Miao Formula (SMF) had the effect of improving the disorder of glucose metabolism caused by high fat and high sucrose diet, and significantly altered the composition of gut microbiota, especially increasing the level of Akkermansia muciniphila (A. muciniphila). However, it is unclear that the role of intestinal flora and A. muciniphila play in SMF improving blood glucose homeostasis, and the mechanism of how SMF increases the level of A. muciniphila. Therefore, this study will explore the correlation between SMF improving the insulin resistance and increasing the level of A. muciniphila, as well as the mechanism of SMF-induced growth of A. muciniphila using the in vitro and in vivo experiments. We explored the effect of intestinal flora and A. muciniphila on SMF-improved insulin resistance through fecal microbiota transplantation (FMT) and antibiotic intervention. In order to study the mechanisms underlying SMF on elevating A. muciniphila, we disassembled SMF to find the key component which can particularly elevate the number of A. muciniphila. Using the in vitro anaerobic culture system combined with cell and animal experiments, we explored the mechanism of the key component in elevating A. muciniphila. The research was approved by the Animal Ethical and Welfare Committee of Shanghai University of Traditional Chinese Medicine. Our results showed that the gut microbiota altered by SMF can improve high fat and sucrose diet induced insulin resistance in recipient mice, and the improvement was closely related to the abundance of A. muciniphila. Cortex Phellodendri played the most important role in regulating the composition of intestinal flora and increasing the number of A. muciniphila, of which, berberine was the key component of Cortex Phellodendri which up regulated A. muciniphila. We have found that berberine cannot directly promote the growth of A. muciniphila in vitro, but it can stimulate the expression of mucin, which, in turn, promote the growth of A. muciniphila. The above results show that the improved insulin sensitiviy by SMF depends on the increased level of A. muciniphila. The effect of SMF on elevating the amount of A. muciniphila might be correlated with the increased expression of mucin stimulated by berberine.
ABSTRACT
This study selected three typical Chinese herbs with cold property(Rhei Radix et Rhizoma, Scutellariae Radix, and Coptidis Rhizoma) and another three with heat property(Cinnamomi Cortex, Zingiberris Rhizoma, and Aconiti Lateralis Radix Praeparata) to observe their regulatory effects on metabolism in animal organism, especially on lipid and energy metabolism in mice after a short-(7 d) and long-term(35 d) intervention. The mRNA expression levels of lipid metabolism genes in epididymal adipose tissue and liver were determined by real-time PCR. The oxygen consumption, carbon dioxide production, and energy consumption were detected by metabolic system. After the short-term intervention, the Chinese herbs with heat property significantly reduced epididymal adipose tissue index and elevated the expression levels of acetyl-CoA carboxylase(ACC), lipoprotein lipase(LPL), and carnitine-palmityl transferase 1(CPT-1) in liver and epididymal adipose tissues. However, those with cold property promoted the expression of above-mentioned genes in epididymal adipose tissue. After the long-term intervention, cold and heat Chinese herbs had no significant effect on epididymal adipose tissue index of animals, while cold Chinese herbs could increase carbon dioxide production and energy consumption and reduce activity. These findings demonstrated that the short-term intervention effects of cold and heat Chinese herbs on animal metabolism were significantly stronger than the long-term intervention effects. Specifically, the short-term intervention with cold Chinese herbs enhanced the lipid metabolism in epididymal adipose tissue, while the heat Chinese herbs promoted lipid metabolism in epididymal adipose tissue and liver. The long-term intervention with cold and heat Chinese herbs resulted in no obvious change in lipid level, but long-term intervention with cold Chinese herbs accelerated energy consumption of the body. This study preliminarily observed the effects of cold and heat Chinese herbs on normal animal physiology from lipid and energy metabolism, which would provide reference for explaining the biological basis of Chinese herbs with cold or heat property based on biological response.