地菍总黄酮改善大鼠非酒精性脂肪肝的作用机制

doi:10.16431/j.cnki.1671-7236.2025.08.042

Abstract

Abstract: 【Objective】 The purpose of this study was to investigate the effect and mechanism of total flavonoids of Melastoma dodecandrum Lour.(TFMD) on nonalcoholic fatty liver disease (NAFLD) in rats. 【Method】 In vitro,HepG2 cells were divided into 6 groups:Control group,NAFLD model group,TFMD high,medium and low dose groups (25,50 and 100 μg/mL TFMD),iron death inhibitor group (Fer-1,2 μmol/L Fer-1),6 duplicate wells per group.HepG2 cells were treated with 0.25 mmol/L palmitic acid for 24 h to establish cell model in all groups except for control group,and HepG2 cells in TFMD low,medium and high dose groups and the iron death inhibitor group were treated with corresponding concentrations of TFMD and Fer-1 for 24 h,respectively.The cell viability was determined by cytotoxicity assay.The contents of total cholesterol (TC) and triglyceride (TG) in HepG2 cells were detected by related kits,and the effects of TFMD on the lipid peroxidation level of NAFLD in vitro model were evaluated by detecting the activities of superoxide dismutase (SOD),contents of glutathione (GSH) and malondialdehyde (MAD).The level of reactive oxygen species (ROS) in HepG2 cells was detected by DCFH-DA fluorescence probe method.In vivo,SD rats were fed with high fat diet to establish NAFLD model,and were randomly divided into 6 groups:Control group,NAFLD model group,TMFD high,middle and low dose groups,and polyene phosphatidylcholine (PPC) group,with 10 rats in each group.After the success of modeling was judged,the corresponding drug intervention was given immediately.Rats in PPC group were given intragastric administration of PPC (0.07 g/kg BW),and the rats in TMFD low,medium and high dose groups were given intragastric administration of TMFD (0.33,0.50 and 0.75 g/kg BW) for 6 weeks.Rats in control group and NAFLD model group were given the same volume of saline.At the end of the treatment period,the contents of TG,TC,high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol (LDL-C),the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum of NAFLD rats, the contents of MDA and Fe²⁺,and the total antioxidant capacity (T-AOC) and the activity of catalase (CAT) in liver of NAFLD rats were detected by related kits.The hepatic pathological changes of NAFLD rats were observed by hematoxylin-eosin staining and oil red O staining.The expression of NF-E2-related factor 2 (Nrf2),peroxisome proliferator-activated receptor γ (PPARγ),peroxisome proliferative receptor gamma coactivator 1α (PGC-1α),NAD(P)H quinone dehydrogenase 1 (NQO1),RelA (NF-κB P65),glutathione peroxidase 4 (GPX4) and Kelch-like ECH-associated protein 1 (Keap1) were detected by Western blotting. 【Result】 In vitro test results showed that compared with control group,the activity of HepG2 cells in NAFLD model group was extremely significantly decreased (P＜0.01),the contents of TG,TC and MDA were extremely significantly increased (P＜0.01),and the content of GSH and activity of SOD were extremely significantly decreased (P＜0.01).The level of ROS in HepG2 cells was extremely significantly increased (P＜0.01),and the fluorescence intensity was significantly enhanced.Compared with NAFLD model group,the activity of HepG2 cells in TFMD groups and Fer-1 group was extremely significantly increased (P＜0.01),the contents of TG,TC and MDA were extremely significantly decreased (P＜0.01),and the content of GSH and activity of SOD were extremely significantly increased (P＜0.01).The level of ROS in HepG2 cells was extremely significantly decreased (P＜0.01),and the fluorescence intensity was significantly decreased.The results of in vivo study showed that compared with control group,the content of HDL-C in serum of rats in NAFLD model group was extremely significantly decreased (P＜0.01),while the contents of TC,TG and LDL-C were extremely significantly increased (P＜0.01).Compared with NAFLD model group,the content of HDL-C in serum of rats in TFMD groups and PPC group was extremely significantly or significantly increased (P＜0.01 or P＜0.05),the content of LDL-C was extremely significantly or significantly decreased (P＜0.01 or P＜0.05),and the contents of TG and TC were extremely significantly decreased (P＜0.01).Pathological observation showed that compared with control group,the hepatocytes of the NAFLD model group had a large number of fat vacuoles,disorderly and uneven arrangement,severe fatty degeneration in the hepatocytes,a large number of red lipid droplets in the hepatocyte,and the volume of lipid droplets became larger and had a certain tendency to aggregate.The morphology of hepatocytes was neat,the degree of fatty degeneration was significantly decreased,the number of red lipid droplets in the liver was reduced,and the volume became smaller in TMFD groups and PPC group.Compared with control group,the activities of AST and ALT in serum of rats in NAFLD model group were extremely significantly increased (P＜0.01),the activity of CAT and T-AOC in the liver of rats in NAFLD model group were extremely significantly decreased (P＜0.01),and the contents of MDA and Fe²⁺ were extremely significantly increased (P＜0.01).Compared with NAFLD model group,the activities of AST and ALT in serum of rats in TFMD groups and PPC group were extremely significantly or significantly decreased (P＜0.01 or P＜0.05),the content of MDA in liver of rats in TFMD groups and PPC group was extremely significantly or significantly decreased (P＜0.01 or P＜0.05), T-AOC was extremely significantly or significantly increased (P＜0.01 or P＜0.05),the activity of CAT was extremely significantly increased (P＜0.01),and the content of Fe²⁺ was extremely significantly decreased (P＜0.01).Western blotting results showed that the expressions of PPARγ,PGC-1α,Nrf2,NQO1 and GPX4 proteins in liver of rats in NAFLD model group were extremely significantly lower than those in control group (P＜0.01),the expressions of Keap1 and NF-κB P65 proteins were extremely significantly increased (P＜0.01).Compared with NAFLD model group,the expressions of PPARγ,PGC-1α,Nrf2,NQO1 and GPX4 proteins were extremely significantly increased (P＜0.01) in TFMD groups and PPC group,the expressions of Keap1 and NF-κB P65 proteins were extremely significantly decreased (P＜0.01). 【Conclusion】 The mechanism of TFMD intervention on NAFLD was related to the regulation of iron metabolism and lipid peroxidation imbalance in the body,and TFMD inhibit the iron death of related cells in the liver by regulating PPARγ/PGC-1α/Nrf2 signaling pathway.

Key words: total flavonoids of Melastoma dodecandrum Lour.; NAFLD; ferroptosis; PPARγ/PGC-1α/Nrf2 pathway; mechanism of action

CLC Number:

S853.74

LI Xiaoxiao, YANG Qiuli, KE Jincheng, LIN Huilyu, LIU Chengxiang, YANG Yuanyuan, NONG Pihao, JIANG Hanting, LI Li. Mechanism of Action of Total Flavonoids of Melastoma dodecandrum Lour.Improving Nonalcoholic Fatty Liver Disease in Rats[J]. China Animal Husbandry & Veterinary Medicine, 2025, 52(8): 3939-3953.

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Mechanism of Action of Total Flavonoids of Melastoma dodecandrum Lour.Improving Nonalcoholic Fatty Liver Disease in Rats

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