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东方草莓通过调节大鼠体内的FXR/CYP7A1、ERK/p38 MAPK和TLR4/MyD88/NF-κB信号通路减轻肝纤维化。

Fragaria orientalis attenuates hepatic fibrosis through modulation of FXR/CYP7A1, ERK/p38 MAPK, and TLR4/MyD88/NF-κB signaling in rats.

作者信息

Zhang Chu-Ling, Yang Hai-Yan, Yi Jia-Le, Song Meng-Ke, Yu Zhao-Da, Huang Jia-Yu, Yi Li-Tao, Li Min, Zhu Ji-Xiao

机构信息

Research Center of Traditional Chinese Medicine Resources and Ethnic Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, China.

Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen, 361021, Fujian province, PR China.

出版信息

J Pharm Pharmacol. 2025 Jul 1;77(7):922-932. doi: 10.1093/jpp/rgaf022.

DOI:10.1093/jpp/rgaf022
PMID:40443133
Abstract

OBJECTIVES

Fragaria orientalis Losinsk is widely used in Tibetan medicine to remove and eliminate yellow water, a symptom of visceral abscesses including hepatitis, suggesting that Fragaria orientalis may exert potential therapeutic benefits for liver conditions. This study aimed to elucidate the hepatoprotective mechanisms of Fragaria orientalis extract against hepatic fibrosis in rats, focusing on the FXR/CYP7A1, ERK/p38 MAPK, and TLR4/MyD88/NF-κB signaling pathways.

METHODS

Chemical profiling was measured by UPLC-Q-TOF/MS, followed by HPLC fingerprint. Hepatic fibrosis was induced in rats treated with 40% CCl4. Subsequently, the anti-fibrotic effects of Fragaria orientalis involved in different signaling pathways were examined.

RESULTS

Administration of Fragaria orientalis extract reduced serum levels of ALT, AST, ALP, TNF-α, IL-1β, and IL-6, as well as hepatic MDA, while increasing GSH-Px and SOD in liver homogenates. UPLC analysis identified key constituents, including quercetin-3-O-glucuronide and ellagic acid, contributing to its hepatoprotective profile. The extract modulated the FXR/CYP7A1, ERK/p38 MAPK, and TLR4/MyD88/NF-κB pathways, supporting its role in attenuating liver fibrosis.

CONCLUSION

In conclusion, these findings suggest that Fragaria orientalis possesses hepatoprotective effects against hepatic fibrosis, likely through modulating oxidative stress, inflammation, and bile acid regulation pathways.

摘要

目的

东方草莓在藏药中广泛用于清除和消除黄水,这是包括肝炎在内的内脏脓肿的一种症状,提示东方草莓可能对肝脏疾病具有潜在治疗益处。本研究旨在阐明东方草莓提取物对大鼠肝纤维化的肝保护机制,重点关注法尼酯X受体/细胞色素P450 7A1(FXR/CYP7A1)、细胞外调节蛋白激酶/ p38丝裂原活化蛋白激酶(ERK/p38 MAPK)和Toll样受体4/髓样分化因子88/核因子κB(TLR4/MyD88/NF-κB)信号通路。

方法

通过超高效液相色谱-四极杆飞行时间质谱联用仪(UPLC-Q-TOF/MS)进行化学图谱分析,随后进行高效液相色谱指纹图谱分析。用40%四氯化碳(CCl4)处理大鼠诱导肝纤维化。随后,研究东方草莓参与不同信号通路的抗纤维化作用。

结果

给予东方草莓提取物可降低血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)水平,以及肝脏丙二醛(MDA)水平,同时增加肝匀浆中谷胱甘肽过氧化物酶(GSH-Px)和超氧化物歧化酶(SOD)水平。超高效液相色谱分析确定了关键成分,包括槲皮素-3-O-葡萄糖醛酸苷和鞣花酸,这些成分有助于其肝保护作用。该提取物调节FXR/CYP7A1、ERK/p38 MAPK和TLR4/MyD88/NF-κB信号通路,支持其在减轻肝纤维化中的作用。

结论

总之,这些发现表明东方草莓对肝纤维化具有肝保护作用,可能是通过调节氧化应激、炎症和胆汁酸调节通路实现的。

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