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连翘果实水提物通过 TLR4/MyD88/NF-κB 和 TGF-β/smads 信号通路减轻肝纤维化。

Forsythiae Fructuse water extract attenuates liver fibrosis via TLR4/MyD88/NF-κB and TGF-β/smads signaling pathways.

机构信息

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu, 611137, China.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu, 611137, China.

出版信息

J Ethnopharmacol. 2020 Nov 15;262:113275. doi: 10.1016/j.jep.2020.113275. Epub 2020 Aug 15.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Forsythiae Fructuse water extract (FSE) is a water-soluble component extracted from the traditional Chinese medicine Forsythiae Fructuse (The fruit of Forsythia suspensa (Thunb.) Vahl) usually used to treat inflammatory diseases. However, little is known about the therapeutic effect of FSE on liver fibrosis.

AIM OF THE STUDY

The purpose of our study was to investigate the therapeutic effect of FSE on liver fibrosis and reveal the underlying mechanism.

MATERIALS AND METHODS

Liver fibrosis model was established by subcutaneous injection of olive oil containing 40% CCl. Rat liver tissue morphologic pathology was investigated by using HE staining, Masson staining and Sirius red staining. Several biochemical markers including liver (ALT, AST, AKP, γ-GT), fibrosis (HA, LN, PC III, Col IV) and inflammation (IL-6, IL-1β, TNF-α) were determined by using Elisa kits. Immunohistochemistry was used to observe the distribution of α-SMA and COL1 in liver tissue. Effects of FSE on inflammatory pathway (TLR4/MyD88/NF-κB) and fibrotic pathway (TGF-β/smads) were detected by western blot and qPCR.

RESULTS

The results showed that hepatic histopathological injury, abnormal liver function, fibrosis and inflammation induced by CCl were improved by FSE (2.5, 5 g/kg). Immunohistochemistry and western blot results indicated that the expression of α-SMA and COL1 in liver tissue was inhibited by FSE (2.5, 5 g/kg). Western blot and qPCR results further proved that FSE (2.5, 5 g/kg) inhibited the transduction of TLR4/MyD88/NF-κB and TGF-β/smads signaling pathways.

CONCLUSION

FSE can inhibit the expression of inflammatory factors and fibrotic cytokines, reduce liver injury, and inhibit the development of liver fibrosis through TLR4/MyD88/NF-κB and TGF-β/smads signaling pathways.

摘要

草药学相关性

连翘果实水提取物(FSE)是从传统中药连翘(连翘)中提取的一种水溶性成分,通常用于治疗炎症性疾病。然而,对于 FSE 治疗肝纤维化的疗效知之甚少。

研究目的

本研究旨在探讨 FSE 对肝纤维化的治疗作用,并揭示其潜在机制。

材料与方法

采用皮下注射含有 40%橄榄油的 CCl 建立肝纤维化模型。采用 HE 染色、Masson 染色和天狼猩红染色观察肝组织形态病理学变化。采用 Elisa 试剂盒测定肝(ALT、AST、AKP、γ-GT)、纤维化(HA、LN、PC III、Col IV)和炎症(IL-6、IL-1β、TNF-α)等生化标志物。采用免疫组织化学观察α-SMA 和 COL1 在肝组织中的分布。采用 Western blot 和 qPCR 检测 FSE 对炎症通路(TLR4/MyD88/NF-κB)和纤维化通路(TGF-β/smads)的影响。

结果

结果表明,FSE(2.5、5g/kg)可改善 CCl 诱导的肝组织病理损伤、肝功能异常、纤维化和炎症。免疫组织化学和 Western blot 结果表明,FSE(2.5、5g/kg)可抑制肝组织中α-SMA 和 COL1 的表达。Western blot 和 qPCR 结果进一步证实,FSE(2.5、5g/kg)抑制了 TLR4/MyD88/NF-κB 和 TGF-β/smads 信号通路的转导。

结论

FSE 可通过 TLR4/MyD88/NF-κB 和 TGF-β/smads 信号通路抑制炎症因子和纤维化细胞因子的表达,减轻肝损伤,抑制肝纤维化的发展。

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