TY - JOUR
T1 - Exocarpium Citri Grandis alleviates the aggravation of NAFLD by mitigating lipid accumulation and iron metabolism disorders
AU - Deng, Guanghui
AU - Liu, Chang
AU - Zhao, Jiamin
AU - Wang, Ming
AU - Li, Yunjia
AU - Yang, Menghan
AU - Ye, Haixin
AU - Li, Junjie
AU - Qin, Mengchen
AU - Wu, Chaofeng
AU - Shi, Hao
AU - Liao, Yuxin
AU - Zhou, Zhaoxi
AU - Zhang, Shiqing
AU - Lam Yung, Ken Kin
AU - Gao, Lei
N1 - The project was financially supported by the National Natural Science Foundation of China ( 82074131 , 81774170 ), Guangdong Basic and Applied Basic Research Foundation ( 2018B030306012 , 2022A1515220179 , 2021A1515011667 ), the Outstanding Youth Development Scheme project of Southern Medical University ( G621299870 ), Young Elite Scientists Sponsorship Program by CACM ( 2021-QNRC2-B28 ), China Postdoctoral Science Foundation ( 2022M721532 ).
Publisher Copyright:
© 2023 Elsevier B.V.
PY - 2023/9/15
Y1 - 2023/9/15
N2 - Ethnopharmacological relevance: Exocarpium Citri grandis (ECG, Huajuhong in Chinese), the epicarp of C. grandis ‘Tomentosa’, has been used for hundreds of years as an anti-inflammatory, expectorant, hypoglycemic, and lipid-lowering medication in China. Nevertheless, there have been few papers that have explored the mechanism behind ECG's hypolipidemic characteristics from the perspective of treating nonalcoholic fatty liver disease (NAFLD). Aim of study: The purpose of our study was to confirm the therapeutic and preventative effects of ECG in NAFLD by regulating lipid accumulation and iron metabolism, and to explore the specific mechanism of ECG in enhancing hepatic iron transport and excretion capabilities. Study design: We constructed a NAFLD model by feeding male C57BL/6 J mice with a high-fat diet for 12 weeks. Mice were gavaged with ECG beginning in the seventh week of modeling, and three dosage gradients were established: low dose group (2.5 g/kg/d), medium dose group (5 g/kg/d) y, and high dose group (10 g/kg/d) until the end of model construction in week 12. Materials and methods: We used network pharmacology to analyze the relationship between ECG and NAFLD. In addition, we constructed a nonalcoholic fatty liver disease model by feeding male C57BL/6 J mice a high-fat diet for 12 weeks. Finally, lipid accumulation, iron accumulation, inflammation and oxidative stress were evaluated by serological index detection, histological detection, immunofluorescent and immunohistochemical staining, and western blotting. Results: Network pharmacology confirmed the treatment effect of ECG in NAFLD. Three active components of ECG, including Naringenin, Naringin and Neohesperidin, were detected by UHPLC-HRMS analysis. The results of serum TC, TG, LDL concentration, HE staining, Oil red staining and Nile red staining demonstrated that ECG could improve lipid metabolism disorders. The results of serum iron concentration, liver tissue iron concentration, iron metabolism-related proteins Ferritin light chain, Ferroportin1, Transferrin receptor, and Transferrin demonstrated that ECG improved the iron transport and storage capacities of hepatic cells. Conclusions: Our results demonstrated that ECG relieved liver injury by inhibiting lipid accumulation and iron accumulation in NAFLD.
AB - Ethnopharmacological relevance: Exocarpium Citri grandis (ECG, Huajuhong in Chinese), the epicarp of C. grandis ‘Tomentosa’, has been used for hundreds of years as an anti-inflammatory, expectorant, hypoglycemic, and lipid-lowering medication in China. Nevertheless, there have been few papers that have explored the mechanism behind ECG's hypolipidemic characteristics from the perspective of treating nonalcoholic fatty liver disease (NAFLD). Aim of study: The purpose of our study was to confirm the therapeutic and preventative effects of ECG in NAFLD by regulating lipid accumulation and iron metabolism, and to explore the specific mechanism of ECG in enhancing hepatic iron transport and excretion capabilities. Study design: We constructed a NAFLD model by feeding male C57BL/6 J mice with a high-fat diet for 12 weeks. Mice were gavaged with ECG beginning in the seventh week of modeling, and three dosage gradients were established: low dose group (2.5 g/kg/d), medium dose group (5 g/kg/d) y, and high dose group (10 g/kg/d) until the end of model construction in week 12. Materials and methods: We used network pharmacology to analyze the relationship between ECG and NAFLD. In addition, we constructed a nonalcoholic fatty liver disease model by feeding male C57BL/6 J mice a high-fat diet for 12 weeks. Finally, lipid accumulation, iron accumulation, inflammation and oxidative stress were evaluated by serological index detection, histological detection, immunofluorescent and immunohistochemical staining, and western blotting. Results: Network pharmacology confirmed the treatment effect of ECG in NAFLD. Three active components of ECG, including Naringenin, Naringin and Neohesperidin, were detected by UHPLC-HRMS analysis. The results of serum TC, TG, LDL concentration, HE staining, Oil red staining and Nile red staining demonstrated that ECG could improve lipid metabolism disorders. The results of serum iron concentration, liver tissue iron concentration, iron metabolism-related proteins Ferritin light chain, Ferroportin1, Transferrin receptor, and Transferrin demonstrated that ECG improved the iron transport and storage capacities of hepatic cells. Conclusions: Our results demonstrated that ECG relieved liver injury by inhibiting lipid accumulation and iron accumulation in NAFLD.
KW - Exocarpium Citri Grandis
KW - Iron metabolism
KW - Lipid metabolism
KW - Nonalcoholic fatty liver disease
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=85154598119&partnerID=8YFLogxK
U2 - 10.1016/j.jep.2023.116559
DO - 10.1016/j.jep.2023.116559
M3 - Journal article
C2 - 37116730
AN - SCOPUS:85154598119
SN - 0378-8741
VL - 313
JO - Journal of Ethnopharmacology
JF - Journal of Ethnopharmacology
M1 - 116559
ER -
