Title: Effects of Chenpi Jiaosu on serum metabolites and intestinal microflora in a dyslipidemia population: a randomized controlled pilot trial

Fei Tan ¹ Yuying Zheng ^2,3,4,5 Chengcheng Wang ¹ Jiaying Huang ^6* Xin Liu ^7* Weiwei Su ^8* Xinyan Chen ^1* Zhimin Yang ^1*

• ¹ State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China
• ² The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
• ³ Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, China
• ⁴ Guangdong Engineering Research Center of Commercialization of Medical Institution Preparations and Traditional Chinese Medicines, Guangzhou, China
• ⁵ Guangdong Engineering Technology Research Center of Commercialization of Linnan Special Medical Institution Preparations, Guangzhou, China
• ⁶ Shenzhen Longgang Orthopedics Hospital, Shenzhen, Guangdong Province, China
• ⁷ Guangzhou Baiyunshan Guanghua Pharmaceutical Co., Ltd, Guangzhou, China
• ⁸ School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong Province, China

Dyslipidemia is a key contributor to atherosclerosis and cardiovascular and cerebrovascular events. Effective management of dyslipidemia is crucial for preventing these diseases. However, current therapeutic drugs can cause liver damage and other side effects, limiting their long-term use. Tangerine Peel Enzyme Drink, also known as "Chenpi Jiaosu (CPJS), is a health food derived from tangerine peel that has been shown to reduce blood lipid. In the randomized, double-blind, parallel-controlled clinical study involving 72 participants, with 55completing the study, those in the CPJS group experienced significant decrease in body weight and triglycerides after 8 weeks of intervention (p value<0.05. Throughout the study, safety indicators including liver and kidney function, creatine kinase, blood routine test, urine routine test, remained normal. Serum metabolomics analysis o revealed 93 differential metabolites in the CPJS group before and after treatment, encompassing fatty acyl, glycerophospholipids, organic acids, and more. KEGG analysis indicated that CPJS influences lipid metabolism, energy metabolism, amino acid metabolism and other pathways. Intestinal microbial detection suggested that CPJS can increase specific intestinal microorganisms to regulate lipid metabolism. Our study confirms that CPJS can improve lipid metabolism by affecting triglyceride metabolism and demonstrates its effectiveness and safety. Additionally, we found that CPJS improves blood lipid levels through various metabolic pathways and regulates intestinal microorganism, although further research is needed to elucidate its specific mechanism.