Antitumor Study of the Miao Medicine Indigofera stachyodes by Integrating Multiple Chemometrics Network Pharmacology and Experimental Validation

TL;DR

This study identifies antitumor compounds in the Miao medicine Indigofera stachyodes and validates their effects on cancer cell growth.

Contribution

A novel integration of chemometrics, network pharmacology, and experimental validation to identify antitumor compounds in I. stachyodes.

Findings

Four compounds (fisetin, wogonin, luteolin, and liquiritigenin) showed antitumor activity against HepG2 cells.

The PI3K-AKT signaling pathway was predicted to mediate the antitumor effects of these compounds.

In vitro experiments confirmed the compounds' antiproliferative effects with measured IC50 values.

Abstract

Indigofera stachyodes Lindl. (I. stachyodes), a fundamental herb in Miao ethnomedicine, possesses a broad pharmacological profile including antitumor potential. However, its antitumor bioactive compounds and their underlying mechanisms remain poorly characterized. Here, we developed a spectrum-effect relationship analysis integrated with UPLC-Q-TOF-MS/MS, which enabled the identification of 7 compounds with potential antitumor activity from I. stachyodes. A secondary screening of candidate compounds was performed using network pharmacology, which led to the identification of fisetin, luteolin, wogonin, and liquiritigenin as potential antitumor compounds. Enrichment analysis and molecular docking studies predicted the key involvement of the PI3K-AKT signaling pathway in mediating the antitumor activities of these compounds. Subsequently, in vitro cell experiments confirmed that the fisetin, wogonin, luteolin and liquiritigenin inhibited the proliferation of HepG2 cells, with IC50 values of 82.13 ± 6.74, 123.38 ± 5.71, 141.76 ± 6.37, and 151.04 ± 3.08 µM, respectively, while exhibiting moderate antitumor activity compared to chemotherapeutic agents. This antiproliferative effect was further corroborated by confocal laser scanning microscopy (CLSM). These results not only validate the potential of I. stachyodes as a source for antitumor agents but also provide a foundation for its further development.

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