Yishen Huashi granule modulated lipid metabolism in diabetic nephropathy via PI3K/AKT/mTOR signaling pathways
Tingting Zhao,
Qian Xiang,
Beifeng Lie,
Deqi Chen,
Minyi Li,
Xi Zhang,
Junzheng Yang,
Bao He,
Wei Zhang,
Ruixue Dong,
Yadi Liu,
Junling Gu,
Quan Zhu,
Yijing Yao,
Tingting Duan,
Zhenghai Li,
Youhua Xu
Affiliations
Tingting Zhao
Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macao, PR China
Qian Xiang
Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macao, PR China
Beifeng Lie
Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Dongpeng Road 71, Guangzhou, PR China
Deqi Chen
Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Dongpeng Road 71, Guangzhou, PR China
Minyi Li
Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Dongpeng Road 71, Guangzhou, PR China
Xi Zhang
Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macao, PR China
Junzheng Yang
Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Dongpeng Road 71, Guangzhou, PR China
Bao He
Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Dongpeng Road 71, Guangzhou, PR China
Wei Zhang
Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macao, PR China
Ruixue Dong
School of Pharmacy, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macao, PR China
Yadi Liu
Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macao, PR China
Junling Gu
Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macao, PR China
Quan Zhu
Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Dongpeng Road 71, Guangzhou, PR China
Yijing Yao
Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macao, PR China
Tingting Duan
Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Dongpeng Road 71, Guangzhou, PR China; Corresponding author.
Zhenghai Li
Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Dongpeng Road 71, Guangzhou, PR China; Corresponding author.
Youhua Xu
Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macao, PR China; School of Pharmacy, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macao, PR China; Department of Endocrinology, Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine, Zhuhai, PR China; Macau University of Science and Technology Zhuhai MUST Science and Technology Research Institute, Hengqin, Zhuhai, PR China; Corresponding author. Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macao, PR China.
Aim: Diabetic nephropathy (DN) is the primary cause of end-stage renal disease worldwide. Although etiology for DN is complex and still needs to be fully understood, lipid metabolism disorder is found to play a role in it. Previously, we found Yishen Huashi (YSHS) granule could inhibit diabetic damage and reduce level of microalbuminuria (mALB) in DN animals. To explore its role and mechanism in lipid metabolism under DN settings, this study was designed. Materials and methods: DN rats were induced by streptozotocin (STZ), HepG2 and CaCO2 cells were applied for in vitro study. Hematoxylin-Eosin (HE), periodic acid–Schiff (PAS) staining, and Transmission Electron Microscopy (TEM) were applied for histological observation; 16s Sequencing was used for intestinal microbiota composition analysis; western blotting (WB) and immunofluorescence were carried out for molecular biological study, and enzyme-linked immunosorbent assay (ELISA) was used for lipid determination. Results: YSHS administration significantly reduced levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL-C), while increased level of high-density lipoprotein (HDL-C); meanwhile, histological changes and steatosis of the liver was ameliorated, integrity of the intestinal barrier was enhanced, and dysbacteriosis within intestinal lumen was ameliorated. Mechanism study found that YSHS modulated mitophagy within hepatocytes and inhibited mTOR/AMPK/PI3K/AKT signaling pathway. Conclusion: In conclusion, we found in the present study that YSHS administration could ameliorate lipid metabolism disorder in DN animals, and its modulation on intestinal-liver axis played a significant role in it.
