Wang Jialin, Li Haini, Wang Ting, Xie Haifeng, Ruan Yang, Zhang Chaofeng
Sino-Jan Joint Lab of Natural Health Products Research, School of Traditional Chinese Medicines, China Pharmaceutical University, Nanjing 210009, China.
Chengdu Biopurity Phytochemicals Ltd., Chengdu 611131, China.
Fitoterapia. 2025 Jan;180:106317. doi: 10.1016/j.fitote.2024.106317. Epub 2024 Nov 26.
The medicinal folk plant Tithonia diversifolia A. Gray has traditionally been used to treat hepatitis and liver cancer. However, the anti-fibrotic effect of this plant extract and its main active substances remain unclear.
This study aims to elucidate the anti-fibrotic effect of T. diversifolia ethanol extract, identify the main active substances, and explore their possible molecular mechanisms.
Firstly, carbon tetrachloride (CCl) was injected intraperitoneally to induce liver fibrosis in mice to investigate the protective effect of T. diversifolia ethanol extract. Then, thirty compounds in this extract were identified through liquid chromatography-mass spectrometry (LC-MS/MS) analysis, column chromatography, and spectroscopic analysis. In addition, the anti-fibrotic effect of sesquiterpene lactone compounds were investigated on TGF-β-induced hepatic stellate cell activation.
The T. diversifolia ethanol extract significantly inhibits symptoms of carbon tetrachloride-induced liver fibrosis and the collagen deposition in pathological tissues by suppressing the protein expression of various pro-fibrotic factors. A comprehensive profile of thirty-one compounds was established, including nine sesquiterpenes, six phenolic acids, six fatty acids, five phenylpropanoids, and three flavonoids. Notably, one previously unreported sesquiterpene lactone, namely 1β-ethoxydiversifolin 3-O-methyl ether (1), together with twenty-nine known compounds were obatined. Sesquiterpene Tagitinin C shows significant anti-fibrotic effects on TGFβ1-induced HSC-T6 activation by inducing cell apoptosis and regulating the TGF-β1/Smad pathway.
The above results indicate that the T. diversifolia extract can effectively alleviate liver fibrosis, with sesquiterpene lactones being a major component. In the future, the germacranolides-type of sesquiterpene lactone Tagitinin C can be developed as a precursor compound for anti-fibrotic therapy.
药用民间植物肿柄菊传统上用于治疗肝炎和肝癌。然而，这种植物提取物及其主要活性物质的抗纤维化作用仍不清楚。
本研究旨在阐明肿柄菊乙醇提取物的抗纤维化作用，鉴定其主要活性物质，并探讨其可能的分子机制。
首先，腹腔注射四氯化碳（CCl）诱导小鼠肝纤维化，以研究肿柄菊乙醇提取物的保护作用。然后，通过液相色谱-质谱联用（LC-MS/MS）分析、柱色谱和光谱分析鉴定该提取物中的30种化合物。此外，研究了倍半萜内酯化合物对转化生长因子-β（TGF-β）诱导的肝星状细胞活化的抗纤维化作用。
肿柄菊乙醇提取物通过抑制多种促纤维化因子的蛋白表达，显著抑制四氯化碳诱导的肝纤维化症状和病理组织中的胶原沉积。建立了31种化合物的综合图谱，包括9种倍半萜、6种酚酸、6种脂肪酸、5种苯丙素和3种黄酮。值得注意的是，获得了一种以前未报道的倍半萜内酯，即1β-乙氧基肿柄菊内酯3-O-甲基醚（1），以及29种已知化合物。倍半萜Tagitinin C通过诱导细胞凋亡和调节TGF-β1/Smad途径，对TGFβ1诱导的HSC-T6活化具有显著的抗纤维化作用。
上述结果表明，肿柄菊提取物可有效减轻肝纤维化，倍半萜内酯是主要成分。未来，吉马烷型倍半萜内酯Tagitinin C可开发为抗纤维化治疗的前体化合物。
