The total polyphenolic glycoside extract of Lamiophlomis rotata ameliorates hepatic fibrosis through apoptosis by TGF-β/Smad signaling pathway.
The total polyphenolic glycoside extract of Lamiophlomis rotata ameliorates hepatic fibrosis through apoptosis by TGF-β/Smad signaling pathway.
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DOI：
10.1186/s13020-023-00723-x
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发表时间：
2023-02-24
期刊：
影响因子：
4.9
通讯作者：
Pan, Zheng
中科院分区：
文献类型：
--
作者：
Wan, Guoguo;Chen, Zhiwei;Lei, Lei;Geng, Xiaoyu;Zhang, Yi;Yang, Congwen;Cao, Wenfu;Pan, Zheng
肝纤维化是以肝星状细胞（hepatic stellate cells，HSC）分泌的细胞外基质（extracellular matrix，ECM）过度沉积为特征的。独一味Lamiophlomis rotata（L.在传统藏医体系中，记载了治疗黄疸病的中药复方（Rotata），具有保肝作用。然而，L. Rotata对肝纤维化的作用在很大程度上仍然未知。目的：研究甘草生物活性成分的抗肝纤维化作用。rotata和可能的作用机制。本文以L.采用超高效液相色谱-飞行时间质谱联用技术（UPLC-Q/TOF/MSn）对旋花多糖（TPLR）进行分析。采用四氯化碳（CCl 4）诱导的大鼠肝纤维化模型，观察TPLR的抗肝纤维化作用，并以活化的肝星状细胞凋亡为指标，观察TPLR的抗肝纤维化作用。在UPLC-TOF-MSn图谱中共鉴定出16种化合物，包括9种苯丙素类和6种黄酮类。TPLR能显著改善CCl 4诱导的小鼠肝纤维化，抑制HSC增殖，并能沿着激活的HSC凋亡，上调caspase-3、-8、-9和-10的表达。此外，TPLR在体内和体外通过下调Smad 2/3、Smad 4的表达，上调Smad 7的表达，抑制TGF-β/Smad途径，改善肝纤维化。同时，TPLR给药后，组织和细胞中纤维连接蛋白（FN）、α-平滑肌肌动蛋白（α-SMA）和胶原I（Col 1 α1）的表达降低。这些结果初步表明TPLR具有通过TGF-β/Smad信号通路的凋亡机制来改善肝纤维化的潜力。在线版本包含补充材料，可通过10.1186/s13020-023-00723-x获取。采用UPLC-Q/TOF/MSn方法对TPRL的总离子流进行了分析。TPRL在体内外均具有抗肝纤维化作用。TPRL通过TGF-β/Smad信号通路介导细胞凋亡减轻肝纤维化。在线版本包含补充材料，可通过10.1186/s13020-023-00723-x获得。
Hepatic fibrosis is characterized by the excessive deposition of extracellular matrix (ECM) which is mainly secreted by activated hepatic stellate cells (HSCs). Lamiophlomis rotata (L. rotata) was recorded to treat jaundice in the traditional Tibetan medical system with the potential of hepatoprotection. However, the bioactivities and the possible mechanism of L. rotata on hepatic fibrosis is still largely unknown. To investigate the anti-hepatic fibrosis effects of bioactivities in L. rotata and the probable mechanism of action. Herein, total polyphenolic glycosides of L. rotata (TPLR) was purified with the selectivity adsorption resin and was analyzed by ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-Q/TOF/MSn). The anti-hepatic fibrosis effect of TPLR was evaluated by carbon tetrachloride (CCl4)-induced liver fibrosis, and was evaluated with the apoptosis of activated HSCs. In total, sixteen compounds, including nine phenylpropanoids and six flavonoids, were identified in the UPLC-TOF-MSn profile of the extracts. TPLR significantly ameliorated hepatic fibrosis in CCl4-induced mice and inhibited HSCs proliferation, Moreover, TPLR notably increased the apoptosis of activated HSCs along with up-regulated caspase-3, -8, -9, and -10. Furthermore, TPLR inhibited TGF-β/Smad pathway ameliorating hepatic fibrosis though downregulation the expression of Smad2/3, Smad4, and upregulation the expression of Smad7 in vivo and in vitro. Simultaneously, the expression of fibronectin (FN), α-smooth muscle actin (α-SMA), and Collagen I (Col1α1) were decreased in tissues and in cells with TPLR administration. These results initially demonstrated that TPLR has the potential to ameliorate hepatic fibrosis through an apoptosis mechanism via TGF-β/Smad signaling pathway. The online version contains supplementary material available at 10.1186/s13020-023-00723-x. Chemical composition of TPRL was identified by UPLC-Q/TOF/MSn in the profile of total ion current. TPRL was initially demostrated the effects of anti-hepatic fibrosis in vitro and in vivo. TPRL ameliorates hepatic fibrosis through apoptosis by TGF-β/Smad signaling pathway. The online version contains supplementary material available at 10.1186/s13020-023-00723-x.
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影响因子：
29.4
作者：
Dooley, Steven;Hamzavi, Jafar;Mertens, Peter R.
通讯作者：
Mertens, Peter R.
DOI：
10.1073/pnas.1201840109
发表时间：
2012-06-12
影响因子：
11.1
作者：
Kisseleva, Tatiana;Cong, Min;Brenner, David A.
通讯作者：
Brenner, David A.
Lamiophlomis rotata (Benth.) Kudo 的传统用途、植物化学、药理学和毒理学：综述
影响因子：
3.9
作者：
通讯作者：
--
影响因子：
6.1
作者：
Cheng, Chih-Fu;Pan, Tzu-Ming
通讯作者：
Pan, Tzu-Ming
影响因子：
13.5
作者：
Kendall, Timothy J.;Hennedige, Selina;Iredale, John P.
通讯作者：
Iredale, John P.