Research on the anti-hepatic fibrosis effects and active components of the medicinal plant Tithonia diversifolia

IF 2.5 3区医学 Q3 CHEMISTRY, MEDICINAL Fitoterapia Pub Date : 2025-01-01 DOI:10.1016/j.fitote.2024.106317

Jialin Wang , Haini Li , Ting Wang , Haifeng Xie , Yang Ruan , Chaofeng Zhang

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Abstract

Background

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.

Objective

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.

Methods

Firstly, carbon tetrachloride (CCl₄) 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.

Results

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.

Conclusion

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.

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药用植物穿山甲抗肝纤维化作用及活性成分的研究。

背景：民间药用植物Tithonia difolia A. Gray传统上被用于治疗肝炎和肝癌。然而，该植物提取物的抗纤维化作用及其主要活性物质尚不清楚。目的：本研究旨在阐明百里叶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。方法：首先，采用腹腔注射四氯化碳（CCl4）诱导小鼠肝纤维化，观察百里叶乙醇提取物对肝纤维化的保护作用。然后，通过液相色谱-质谱（LC-MS/MS）分析、柱层析和光谱分析等方法对该提取物中的30个化合物进行鉴定。此外，研究倍半萜内酯类化合物对TGF-β诱导的肝星状细胞活化的抗纤维化作用。结果：三叶草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及病理组织胶原沉积。共鉴定出31种化合物，包括9种倍半萜、6种酚酸、6种脂肪酸、5种苯丙素和3种黄酮类化合物。值得注意的是，获得了一种以前未报道的倍半萜内酯，即1β-乙氧基多元福林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通路，对TGF-β1诱导的HSC-T6活化具有显著的抗纤维化作用。结论：综上所述，三叶草提取物可有效缓解肝纤维化，其倍半萜内酯为主要成分。在未来，大果内酯型倍半萜内酯Tagitinin C可被开发作为抗纤维化治疗的前体化合物。

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来源期刊

Fitoterapia 医学-药学

CiteScore

5.80

自引率

2.90%

发文量

198

审稿时长

1.5 months

期刊介绍： Fitoterapia is a Journal dedicated to medicinal plants and to bioactive natural products of plant origin. It publishes original contributions in seven major areas: 1. Characterization of active ingredients of medicinal plants 2. Development of standardization method for bioactive plant extracts and natural products 3. Identification of bioactivity in plant extracts 4. Identification of targets and mechanism of activity of plant extracts 5. Production and genomic characterization of medicinal plants biomass 6. Chemistry and biochemistry of bioactive natural products of plant origin 7. Critical reviews of the historical, clinical and legal status of medicinal plants, and accounts on topical issues.