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

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.