Integrating Lipidomics and Gut Microbiota to Study the Anti-Hyperlipidemia Effect of Sargentodoxae Caulis Extract

Background: Sargentodoxae Caulis (SC) is the vine stem of Sargentodoxa Cuneata (Oliv.) Rehd. & E. H. Wilson in C. S. Sargent, and it in traditional Chinese medicine has been known for promoting blood circulation and removing blood stasis as recorded in the ancient book "Illustrated Classics of Materia Medica". It has been used effectively to treat blood stasis too in modern clinical practice. However, the anti-hyperlipidemia effect of SC is not fully understood. This paper aims at exploring the use of SC stems to improve the balance of blood lipids in the body, and its new role in treating hyperlipidemia. Methods: The effects of SC extract on hyperlipidemia were explored by combining lipidomics and gut microbiota. Secondly, we explored the potential mechanism of SC in treating hyperlipidemia by pathway analysis. Results: The results showed that the stem extract of SC could restore the physiological and biochemical indices of hyperlipidemia in mice, as well as repair the morphological and structural damage to tissues. Compared to the Model group, the SC extract significantly reduced the liver index, epididymal fat index, and Lee's index. It also significantly decreased serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, peroxisome proliferator-activated receptor gamma (PPAR-gamma), D-lactate, and free fatty acids, while significantly increasing the relative content of peroxisome proliferator-activated receptor alpha (PPAR-alpha). These changes were statistically significant. Non-targeted lipidomics, based on LC-MS, were utilized to investigate the lipid metabolism characteristics in serum, liver, and epididymal fat of the subjects. It was observed that, compared to the blank group, the Model group exhibited significant changes primarily in glycerol lipids and glycerophospholipids. The treatment group also displayed alterations in these lipids. A total of 38, 81, and 27 differential lipids were identified in serum, liver, and epididymal fat samples, respectively. Among these, 14 common differential lipids were found in both serum and liver samples, and their KEGG enrichment pathways were largely consistent. Among them, the sphingolipid signaling pathway and the glycerophospholipid metabolic pathway were identified as key metabolic pathways that were regulated. Our gut microbiota analysis revealed that SC diminishes the abundance of Actinobacteria by altering the cecal flora in mice. Conclusion: This alteration leads to the downregulation of genes involved in triglyceride metabolism, which in turn changes lipid processing and reduces triglyceride levels. Consequently, SC effectively combats hyperlipidemia. Notably, SC impacts key metabolic pathways, including the sphingolipid signaling and glycerophospholipid metabolism. These findings underscore SC's therapeutic potential, positioning it as a promising alternative for reducing the health risks associated with hyperlipidemia.