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Mechanisms of Xiaozhi Qinggan Decoction in Treatment of Metabolic Dysfunction-associated Steatotic Liver Disease by Regulating Ferroptosis
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 32, Issue 6, Pages: 109-119(2026)
- 作者机构：
1.中国中医科学院 西苑医院，北京 100091
2.首都医科大学 附属北京中医医院，北京 100010
- 作者简介：
- 基金信息：
DOI：10.13422/j.cnki.syfjx.20260140
CLC： R277;R285;R289Received：13 November 2025，
Revised：2025-12-22，
Accepted：23 December 2025，
Online First：25 December 2025，
Published：20 March 2026
- 稿件说明：
移动端阅览
董海航,涂钰莹,李兴榕等.消脂清肝汤调控铁死亡治疗代谢障碍相关性脂肪性肝病的作用机制[J].中国实验方剂学杂志,2026,32(06):109-119.
DONG Haihang,TU Yuying,LI Xingrong,et al.Mechanisms of Xiaozhi Qinggan Decoction in Treatment of Metabolic Dysfunction-associated Steatotic Liver Disease by Regulating Ferroptosis[J].Chinese Journal of Experimental Traditional Medical Formulae,2026,32(06):109-119.
董海航,涂钰莹,李兴榕等.消脂清肝汤调控铁死亡治疗代谢障碍相关性脂肪性肝病的作用机制[J].中国实验方剂学杂志,2026,32(06):109-119. DOI： 10.13422/j.cnki.syfjx.20260140.
DONG Haihang,TU Yuying,LI Xingrong,et al.Mechanisms of Xiaozhi Qinggan Decoction in Treatment of Metabolic Dysfunction-associated Steatotic Liver Disease by Regulating Ferroptosis[J].Chinese Journal of Experimental Traditional Medical Formulae,2026,32(06):109-119. DOI： 10.13422/j.cnki.syfjx.20260140.
摘要
目的
2
通过网络药理学和体内外实验探讨消脂清肝汤（XQD）通过调控铁死亡防治代谢障碍相关性脂肪性肝病（MASLD）的作用机制。
方法
2
体内实验：高脂饮食法（HFD）建立MASLD小鼠模型，随机分为阳性药（水飞蓟宾，50 mg·kg
-1
）组，XQD低、中、高（4.725、9.45、18.9 g·kg
-1
）剂量组，并设正常组。除正常组外其余小鼠造模4周后灌胃给药8周，检测肝功能和血脂水平，评估肝脏组织病理变化，酶联免疫吸附测定法检测丙二醛（MDA）、超氧化物歧化酶（SOD）、还原型谷胱甘肽（GSH）和氧化型谷胱甘肽（GSSG）及亚铁离子（Fe
2+
）表达。实时荧光定量聚合酶链式反应（Real-time PCR）和蛋白免疫印迹法（Western blot）检测肿瘤抑制蛋白53（p53）、溶质载体家族7成员11（SLC7A11）与谷胱甘肽过氧化物酶4（GPX4）的表达。网络药理研究：获得XQD有效成分及治疗MASLD的潜在靶点进行功能富集和通路富集分析，分子对接验证靶点结合活性。体外实验：细胞毒性实验筛选XQD含药血清最佳浓度，人肝癌细胞（HepG2）经空白质粒（ov-NC）及p53过表达（ov-p53）质粒转染，游离脂肪酸（FFA）诱导构建肝细胞脂质沉积模型，分为正常组、FFA（1.0 mmol·L
-1
）模型组、ov-NC+XQD（15%）组及ov-p53+XQD（15%）组，荧光探针检测细胞内Fe
2+
相对水平，油红O染色检测脂质蓄积情况，Western blot检测p53、SLC7A11与GPX4蛋白表达。
结果
2
与正常组比较，模型组第12周体、肝质量、肝指数、空腹血糖、糖耐量AUC值、血清肝功能及血脂水平显著升高（
P
<
0.01），病理染色提示肝脏出现脂肪变性和炎症浸润；肝组织MDA、SOD及Fe
2+
水平显著升高（
P
<
0.01），GSH、GSSG水平及GSH/GSSG值显著降低（
P
<
0.01）；肝组织p53 mRNA及蛋白表达显著升高（
P
<
0.01），SLC7A11、GPX4表达显著降低（
P
<
0.01）。与模型组比较，XQD低、中剂量组第12周体质量明显降低（
P
<
0.05）；水飞蓟宾组及XQD中、高剂量组肝质量、肝指数明显降低（
P
<
0.05）；四组空腹血糖及糖耐量AUC值明显降低（
P
<
0.05，
P
<
0.01）。病理染色提示炎症和肝脏脂肪变性缓解，血清肝功能及血脂水平明显降低（
P
<
0.05，
P
<
0.01）；MDA、SOD水平显著降低，GSH、GSSG水平及GSH/GSSG值明显升高（
P
<
0.05，
P
<
0.01），肝组织Fe²
+
水平显著降低（
P
<
0.01），肝脏p53 mRNA及蛋白表达明显下调（
P
<
0.05，
P
<
0.01），SLC7A11、GPX4的表达明显上调（
P
<
0.05，
P
<
0.01）。网络药理学表明，XQD核心活性成分为槲皮素、山柰酚、木犀草素、丹参酮Ⅱ
A
和异鼠李素等，关键核心基因为p53，且活性成分与p53蛋白结合稳定。体外实验中XQD含药血清优势剂量的浓度为15%。与正常组比较，模型组与Fe²
+
和脂质蓄积水平升高，p53蛋白表达显著上调（
P
<
0.01），SLC7A11和GPX4蛋白表达显著下调（
P
<
0.01）。与模型组比较，空载体组Fe²
+
水平、脂质蓄积水平显著降低，p53蛋白表达显著下调，SLC7A11和GPX4显著上调，p53过表达组的p53达显著上调（
P
<
0.01），SLC7A11和G
PX4均显著下调（
P
<
0.01）。
结论
2
XQD可通过下调p53、上调SLC7A11和GPX4的途径抑制铁死亡，改善肝细胞氧化损伤及脂质过氧化，从而治疗MASLD。
Abstract
Objective
2
To investigate the mechanism of Xiaozhi Qinggan decoction （XQD） in preventing and treating metabolic dysfunction-associated steatotic liver disease （MASLD） by regulating ferroptosis， network pharmacology， in vitro and
in vivo
experiments.
Methods
2
In the
in vivo
experiment， mouse MASLD models were established by high-fat diet （HFD） induction. The model mice were randomly assigned to a positive control group （silybin， 50 mg·kg
-1
）， low-， medium- and high-dose XQD groups （4.725， 9.45， 18.9 g·kg
-1
）， with a normal control group. After 4 weeks of modeling， mice except the normal group were administered intragastrically for 8 consecutive weeks. Liver function， serum lipid levels， hepatic histopathology， as well as the levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， reduced glutathione （GSH） and oxidized glutathione （GSSG） and Fe
2+
were detected. The mRNA and protein expression of p53， SLC7A11 and GPX4 were determined by quantitative Real-time quantitative polymerase chain reaction（Real-time PCR） and Western blot. In the network pharmacology analysis， active components and potential targets of XQD for MASLD were screened， followed by functional and pathway enrichment analyses， and molecular docking was performed to verify the target binding activity. In the
in vitro
experiment， the optimal concentration of XQD-containing serum was screened by cytotoxicity assay. HepG2 cells were transfected with ov-NC or ov-p53 plasmid， and a lipid accumulation model was induced by free fatty acid （FFA， 1.0 mmol·L
-1
）. Cells were divided into a normal group， FFA model group， ov-NC+XQD （15%） group and ov-p53+XQD （15%） group. Intracellular Fe
2+
level and l
ipid accumulation were evaluated， and the protein expression of p53， SLC7A11 and GPX4 was measured by Western blot.
Results
2
Compared with the normal group， the model group exhibited markedly elevated body weight， liver weight， liver index， fasting blood glucose， AUC of glucose tolerance test， serum liver function and blood lipid levels at week 12 （
P
<
0.01）. Hepatic steatosis and inflammatory infiltration were observed by pathological staining. Additionally， hepatic levels of MDA， SOD and Fe
2+
were increased （
P
<
0.01）， while GSH， GSSG and the GSH/GSSG ratio were decreased （
P
<
0.01）. The mRNA and protein expression of hepatic p53 was upregulated （
P
<
0.01）， whereas the expression of SLC7A11 and GPX4 was downregulated （
P
<
0.01）. Compared with the model group， the low- and medium-dose XQD groups showed significantly decreased body weight at week 12 （
P
<
0.05）. The silybin group， together with the medium- and high-dose XQD groups， presented reduced liver weight and liver index （
P
<
0.05）. Fasting blood glucose and the AUC of glucose tolerance test were lowered in all four treatment groups （
P
<
0.05，
P
<
0.01）. Pathological staining revealed alleviated hepatic steatosis and inflammation， accompanied by decreased serum liver function and blood lipid levels （
P
<
0.05，
P
<
0.01）. Moreover， hepatic MDA and SOD levels were markedly reduced， while GSH， GSSG and the GSH/GSSG ratio were significantly elevated （
P
<
0.05，
P
<
0.01）. Hepatic Fe
2+
level was decreased （
P
<
0.01）. The mRNA and protein expression of hepatic p53 was downregulated， and the expression of SLC7A11 and GPX4 was upregulated （
P
<
0.05，
P
<
0.01）. Network pharmacology analysis identified quercetin， kaempferol， luteolin，
tanshinone IIA and isorhamnetin as the core active components of XQD， with p53 serving as the key target. Stable binding was verified between these active components and the p53 protein. The optimal concentration of XQD-containing serum
in vitro
was determined to be 15%. Compared with the normal group， the model group showed increased intracellular Fe
2+
and lipid accumulation， significantly upregulated p53 protein expression （
P
<
0.01）， and markedly downregulated SLC7A11 and GPX4 protein expression （
P
<
0.01）. Compared with the model group， the ov-NC group exhibited reduced Fe
2+
and lipid accumulation， downregulated p53 expression， and upregulated SLC7A11 and GPX4 expression. In the ov-p53 group， p53 expression was upregulated （
P
<
0.01）， while SLC7A11 and GPX4 expression was downregulated （
P
<
0.01）.
Conclusion
2
XQD inhibits ferroptosis by downregulating p53 and upregulating SLC7A11 and GPX4， thereby alleviating oxidative stress and lipid peroxidation in hepatocytes and improving MASLD.
关键词
Keywords
references
YOUNUSSI Z M ， KALLIGEROS M ， HENRY L . Epidemiology of metabolic dysfunction-associated steatotic liver disease ［J］. Clin Mol Hepatol ， 2025 ， 31 ： 32 - 50 .
HUANG D Q ， WONG V W S ， RINELLA M E ， et al . Metabolic dysfunction-associated steatotic liver disease in adults ［J］. Nat Rev Dis Primers ， 2025 ， 11 （ 1 ）： 14 .
TARGHER G ， BYRNE C D ， TILG H . MASLD：A systemic metabolic disorder with cardiovascular and malignant complications ［J］. Gut ， 2024 ， 73 （ 4 ）： 691 - 702 .
MAK L Y ， LIU K ， CHIRAPONGSATHORN S ， et al . Liver diseases and hepatocellular carcinoma in the Asia-pacific region：Burden，trends，challenges and future directions ［J］. Nat Rev Gastroenterol Hepatol ， 2024 ， 21 （ 12 ）： 834 - 851 .
OCHOA-ALLEMANT P ， HUBBARD R A ， KAPLAN D E ， et al . Cause-specific mortality in patients with steatotic liver disease in the United States ［J］. J Hepatol ， 2025 ， 83 （ 4 ）： 860 - 869 .
中华医学会肝病学分会 . 代谢相关（非酒精性）脂肪性肝病防治指南（2024年版） ［J］. 中华肝脏病杂志 ， 2024 ， 32 （ 5 ）： 418 - 434 .
Liver Disease Branch of Chinese Medical Association . Guidelines for the prevention and treatment of metabolic dysfunction-associated （non-alcoholic） fatty liver disease （Version 2024） ［J］. Chin J Hepatol ， 2024 ， 32 （ 5 ）： 418 - 434 .
中国中西医结合学会消化系统疾病专业委员会 . 非酒精性脂肪性肝病中西医结合诊疗专家共识（2025年） ［J］. 中国中西医结合消化杂志 ， 2025 ， 33 （ 4 ）： 339 - 350 .
Digestive System Diseases Professional Committee of Chinese Association of Integrative Medicine . Expert consensus on integrated traditional Chinese and western medicine diagnosis and treatment of non alcoholic fatty liver disease（2025） ［J］. Chin J Integr Trad West Med Dig ， 2025 ， 33 （ 4 ）： 339 - 350 .
赛俊婷 ， 李秀惠 . 脂肪肝中医证候学研究进展 ［J］. 临床肝胆病杂志 ， 2024 ， 40 （ 10 ）： 1929 - 1932 .
SAI J T ， LI X H . Research progress on TCM syndrome types of fatty liver disease ［J］. J Clin Hepatol ， 2024 ， 40 （ 10 ）： 1929 - 1932 .
刘燕玲 ， 洪慧闻 ， 马素云 ， 等 . 消脂清肝胶囊治疗非酒精性脂肪肝的临床疗效评价 ［J］. 北京中医药大学学报 ， 2007 ， 30 （ 11 ）： 790 - 792 .
LIU Y L ， HONG H W ， MA S Y ， et al . Clinical evaluation of Xiaozhi Qinggan capsule in the treatment of non-alcoholic fatty liver disease ［J］. J Beijing Univ Trad Chin Med ， 2007 ， 30 （ 11 ）： 790 - 792 .
叶景林 . 消脂清肝汤对NAFLD（痰阻血瘀型）的临床疗效及相关机制的探索性研究 ［D］. 北京 ： 中国中医科学院 ， 2017 .
YE J L . Exploratory study on the clinical efficacy and related mechanisms of Xiaozhi Qinggan decoction in NAFLD of phlegm-stasis obstruction pattern ［D］. Beijing ： China Academy of Chinese Medical Sciences ， 2017 .
DU K ， WANG L ， JUN J H ， et al . Aging promotes metabolic dysfunction-associated steatotic liver disease by inducing ferroptotic stress ［J］. Nat Aging ， 2024 ， 4 （ 7 ）： 949 - 968 .
YIN X ， LIU Z ， LI C ， et al . Hinokitiol ameliorates MASH in mice by therapeutic targeting of hepatic Nrf2 and inhibiting hepatocyte ferroptosis ［J］. Phytomedicine ， 2025 ， 139 ： 156472 .
ZHAI Y ， LIU L ， ZHANG F ， et al . Network pharmacology：A crucial approach in traditional chinese medicine research ［J］. Chin Med ， 2025 ， 20 （ 1 ）： 8 .
ZHOU Y ， WANG M ， WANG Z ， et al . Polysaccharides from hawthorn fruit alleviate high-fat diet-induced NAFLD in mice by improving gut microbiota dysbiosis and hepatic metabolic disorder ［J］. Phytomedicine ， 2025 ， doi： 10.1016/j.phymed.2025.156458 http://dx.doi.org/10.1016/j.phymed.2025.156458 .
MIAO L ， TARGHER G ， BYRNE C D ， et al . Current status and future trends of the global burden of MASLD ［J］. Trends Endocrinol Metab ， 2024 ， 35 （ 8 ）： 697 - 707 .
ZHANG X ， LAU H C H ， YU J . Pharmacological treatment for metabolic dysfunction-associated steatotic liver disease and related disorders：Current and emerging therapeutic options ［J］. Pharmacol Rev ， 2025 ， 77 （ 2 ）： 100018 .
XU Y ， LI Y ， LI J ， et al . Ethyl carbamate triggers ferroptosis in liver through inhibiting GSH synthesis and suppressing Nrf2 activation ［J］. Redox Biol ， 2022 ， 53 ： 102349 .
HE F ， ZHANG P ， LIU J ， et al . ATF4 suppresses hepatocarcinogenesis by inducing SLC7A11 （xCT） to block stress-related ferroptosis ［J］. J Hepatol ， 2023 ， 79 （ 2 ）： 362 - 377 .
OOI G J ， MEIKLE P J ， HUYNH K ， et al . Hepatic lipidomic remodeling in severe obesity manifests with steatosis and does not evolve with non-alcoholic steatohepatitis ［J］. J Hepatol ， 2021 ， 75 （ 3 ）： 524 - 535 .
FUJII J ， IMAI H . Oxidative metabolism as a cause of lipid peroxidation in the execution of ferroptosis ［J］. Int J Mol Sci ， 2024 ， 25 （ 14 ）： 7544 .
WANG S ， DU R ， LIU J ， et al . Multi-approach analysis reveals the mechanism by which Shugan Xiaozhi decoction protects against metabolic dysfunction-associated steatohepatitis ［J］. Phytomedicine ， 2025 ， 141 ： 156712 .
KANG R ， KROEMER G ， TANG D . The tumor suppressor protein p53 and the ferroptosis network ［J］. Free Radic Biol Med ， 2019 ， 133 ： 162 - 168 .
URSINI F ， MAIORINO M . Lipid peroxidation and ferroptosis：The role of GSH and GPx4 ［J］. Free Radic Biol Med ， 2020 ， 152 ： 175 - 185 .
ALTOMARE A ， BARON G ， GIANAZZA E ， et al . Lipid peroxidation derived reactive carbonyl species in free and conjugated forms as an index of lipid peroxidation：Limits and perspectives ［J］. Redox Bio ， 2021 ， 42 ： 101899 .
LUO J ， XU L ， FENG J ， ET al . Tumor microenvironment-activated and ROS-augmented nanoplatform amplified PDT against colorectal cancer through impairing GPX4 to induce ferroptosis ［J］. ACS Appl Mater Interfaces ， 2025 ， 17 （ 29 ）： 41586 - 41596 .
JIANG J J ， ZHANG G F ， ZHENG J Y ， et al . Targeting mitochondrial ROS-mediated ferroptosis by quercetin alleviates high-fat diet-induced hepatic lipotoxicity ［J］. Front Pharmacol ， 2022 ， 13 ： 876550 .
CHEN Y ， REN F ， YANG N ， et al . The mechanism study of quercetin isolated from Zanthoxylum bungeanum Maxim.inhibiting ferroptosis and alleviating MAFLD through p38 MAPK/ERK signaling pathway based on lipidomics and transcriptomics ［J］. Front Pharmacol ， 2025 ， 16 ： 1517291 .
CAI X ， ZHANG Y ， ZHU W ， et al . Kaempferol inhibits atherosclerotic plaque development via dual-targeting of p53-p21-p16 senescence pathway and Nrf2/HO-1/NQO1 antioxidant mechanism：Insights from combined in vivo and in vitro research ［J］. Int Immunopharmacol ， 2025 ， 166 ： 115587 .
YUAN Y ， ZHAI Y ， CHEN J ， et al . Kaempferol ameliorates oxygen-glucose deprivation/reoxygenation-induced neuronal ferroptosis by activating Nrf2/SLC7A11/GPX4 axis ［J］. Biomolecules ， 2021 ， 11 （ 7 ）： 923 .
CHEN S ， LI P ， SHI K ， et al . Tanshinone Ⅱ A promotes ferroptosis in cutaneous melanoma via STAT1-mediated upregulation of PTGS2 expression ［J］. Phytomedicine ， 2025 ， doi： 10.1016/j.phymed.2025.156702 http://dx.doi.org/10.1016/j.phymed.2025.156702 .
WANG T X ， DUAN K L ， HUANG Z X ， et al . Tanshinone functions as a coenzyme that confers gain of function of NQO1 to suppress ferroptosis ［J］. Life Sci Alliance ， 2023 ， 6 （ 1 ）： e202201667 .
GANBOLD M ， OWADA Y ， OZAWA Y ， et al . Isorhamnetin alleviates steatosis and fibrosis in mice with nonalcoholic steatohepatitis ［J］. Sci Rep ， 2019 ， 9 （ 1 ）： 16210 .
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