Preliminary exploration of the regulatory mechanism of total saponins from Anemarrhena chinensis on adipose tissue in obese mice based on the NLRP3 neurotransmitter pathway
With changes in people’s lifestyles and dietary structures, the incidence of obesity continues to rise. Currently, this issue has begun to involve developing countries and third world countries, becoming a global public health problem. Obesity is a state of excessive accumulation of adipose tissue in the body, which is divided into fat type obesity and abdominal type obesity according to the location of adipose tissue accumulation in the body. Research has found that macrophages (ATMs) in the visceral adipose tissue of obese patients exhibit significant infiltration and the expression of a large number of pro-inflammatory cytokines. These cell phenotypes show a special state of transition from M2 to M1 (inflammatory), which accelerates the occurrence of chronic inflammation in adipose tissue and increases the expression of NLRP3 in ATMs. The increased expression of NLRP3 activates the expression of downstream GDF3, thereby upregulating the levels of catecholamine hydrolases such as MAOA, ultimately leading to a decrease in the content of catecholamine neurotransmitters in adipose tissue, a decrease in lipid breakdown ability, and fat accumulation, resulting in abdominal obesity. Saponins from Anemarrhena as polyphenols Bge. (SAa B) are the most abundant active ingredients extracted and isolated from Anemarrhena, with pharmacological activities such as lowering blood sugar, anti-inflammatory, antioxidant, antithrombotic, and improving depression. The preliminary research of our research group found that SAaB has hypoglycemic and lipid-lowering effects on diabetes rats, and diabetes is closely related to obesity and lipid metabolism. However, whether SAaB has an intervention effect on obesity is still unclear, and there is no pharmacological mechanism research. Therefore, this study induced obesity model in C57BL/6J male mice through high-fat diet, investigated the intervention effect of SAaB on obese mice and the regulatory effect of related gene expression in adipose tissue, in order to elucidate its mechanism of regulating obesity.

Adipose tissue is an important organ in the body, whose main function is to store and secrete fatty acids (FFAs), balance blood sugar and lipids, and secrete various hormones and cytokines that affect energy metabolism and participate in inflammatory reactions. Research shows that with the increase of age, the incidence rate of inflammation and insulin resistance increases, which leads to the decline of adipose tissue function, fat accumulation around the abdomen and viscera, and then leads to abdominal obesity. In this study, a long-term high-fat diet led to an increase in body mass, elevated blood glucose, TC, TG, LDL-C, decreased HDL-C, and accumulation of fat around the abdomen in mice, resulting in abdominal obesity.

Our research group’s preliminary experiments and Fu et al. found that SAa B can reduce the levels of cholesterol and low-density lipoprotein in plasma, and has the effect of lowering blood sugar, but its specific mechanism of action is still unclear. This study found through the intervention of SAa B in an obese mouse model that the SAa B-H group of obese mice had reduced body mass, decreased abdominal fat, decreased fasting blood glucose levels and serum TC, TG, LDL-C levels, increased HDL-C levels, and improved pathological status of adipose tissue, which is consistent with the above research results.

The accumulation of a large amount of fat can cause the degradation of fat itself and the production of free fatty acids (FFAs), which stimulate macrophages in adipose tissue to produce ceramides, induce local tissue inflammation, and accelerate the development of obesity. NLRP3 can regulate the chronic inflammatory response of the body, and it can be activated by metabolites such as FFAs. The expression levels of NL-RP3, GDF3, and Caspase-1 are upregulated in adipose tissue of high-fat diet induced obese mice, thereby upregulating the expression of catecholamine hydrolase and IL-1 β levels. The catecholamine neurotransmitter is the most important fat breakdown stimulating hormone in the body. This study found that the expression of GDF3, Caspase-1, IL-1 β, NLRP3, and MAOA was upregulated in adipose tissue of obese mice. After 7 weeks of SAa B treatment, the expression level of GDF3 mRNA in adipose tissue of SAa B-M and SAa B-H mice decreased, and the expression levels of Caspase-1 and IL-1 β mRNA in adipose tissue of SAa B-H group mice decreased; The expression levels of NLRP3 protein in adipose tissue of SAa B-M and SAa B-H mice were reduced, and the expression levels of MAOA protein in adipose tissue of SAa B-L, SAa B-M, and SAa B-H mice were reduced. The above results indicate that SAa B can intervene in the occurrence of adipose tissue inflammation in obese mice, reduce the expression of catecholamine hydrolases, and thereby increase the levels of catecholamine neurotransmitters in adipose tissue, improving lipid breakdown ability.

In summary, SAa B can reduce the body mass and fat weight of obese mice, improve the blood glucose and lipid metabolism disorders caused by obesity, and improve the pathological state of adipose tissue. It can enhance the lipid breakdown ability of obese mice and alleviate obesity symptoms. Its mechanism of action may be to inhibit the secretion of catecholamine hydrolases and the expression of inflammatory factors through the NL-RP3 neurotransmitter pathway, improve lipid breakdown ability and reduce inflammatory response. In subsequent studies, gene silencing, gene knockout and other technologies can be further verified to provide new theoretical basis for the prevention and treatment of obesity by traditional Chinese medicine.