TANG Jie, WANG Lixiang, CHEN Zexuan, HAN Han, ZHANG Tong
China Journal of Traditional Chinese Medicine and Pharmacy. 2025, 40(5): 2440-2446.
Objective: To determine the contents of main pharmacodynamic substances in Shuganzhi Prescription and to explore and reveal its action mechanism against non-alcoholic fatty liver disease (NAFLD). Methods: The content of five indexes in Shuganzhi Prescription was determined by HPLC. The cell model of NAFLD was established in vitro, and different concentrations of pharmacodynamic monomer and Shuganzhi Prescription extract were treated. Western Blot and RT-PCR were used to detect the level of PPAR pathway-related proteins or mRNA in each group. NAFLD mouse model was established, and were randomly divided into control group, model group, Simvastatin group, naringin group and polydatin group, and were administrated intragastric for 15 weeks, serum TG, TC and LDL-C levels were detected, and liver pathological sections were analyzed by HE staining and oil red O staining. Western Blot and RT-PCR were used to detect the the level of PPAR signaling pathway-related proteins or mRNA of liver. Results: The contents of naringin and polydatin in Shuganzhi Prescription were relatively high. Compared with normal control group, the protein and mRNA expression level of PPARγ, FADS1 and PCK1 in the FFA group were significantly down-regulated (P<0.01, P<0.05), and the protein expressions of PLIN2 and ACSL4 were significantly up-regulated (P<0.01, P<0.05). Compared with the FFA group, the protein expression of FADS1, PCK1, PLIN2 and ACSL4 in the Shuganzhi Prescription group were significantly reversed (P<0.01), and the protein expressions of PPARγ, FADS1, PCK1, PLIN2 and ACSL4 in the polydatin group and naringin group were significantly reversed (P<0.01, P<0.05), the protein levels of PLIN2 and ACSL4 in the hesperidin group, emodin group, saikosaponin A group, resveratrol group and specnuezhenide group were significantly down-regulated (P<0.01, P<0.05), and the protein expression of PPARγ in the resveratrol group was significantly increased (P<0.05), the expression of FADS1 protein was significantly up-regulated in group saikosaponin A group (P<0.01), and the protein levels of FADS1 and PCK1 in the specnuezhenide group were significantly up-regulated (P<0.01), and simvastatin and seven effective monomer components of Shuganzhi Prescription significantly up-regulate the mRNA levels of PPARγ and FADS1 (P<0.01, P<0.05), and simvastatin, resveratrol, hesperidin, polydatin, specnuezhenide and naringin could also significantly increase the level of PCK1 mRNA. In addition, compared with the normal control group, the levels of TG, TC and LDL-C in the serum of mice in the model group were significantly increased (P<0.01), while all the indicators of mice in the naringin group and the polydatin group decreased significantly compared with the model group (P<0.01), and steatosis occurred in the liver tissue of mice in the model group, while naringin and polydatin can alleviate the steatosis of the liver in model mice. Meanwhile, compared with the normal control group, the protein and mRNA expression level of PPARγ, FADS1 and PCK1 in liver samples of mice in the model group were significantly down-regulated (P<0.01, P<0.05), the protein and mRNA expression level of PLIN2 and ACSL4 were significantly up-regulated (P<0.01), while compared with the model group, naringin and polydatin could significantly reverse the protein expression levels of PPARγ, FADS1, PCK1, PLIN2 and ACSL4 (P<0.01, P<0.05) and the mRNA levels of PPARγ, PCK1, PLIN2 and ACSL4 (P<0.01), the FADS1 mRNA level in the polydatin group was also significantly increased (P<0.01). Conclusion: Shuganzhi Prescription exerts its efficacy against NAFLD by regulating the relevant targets of PPAR signaling pathway depends on the pharmacodynamic substances including naringin and polydatin.
