Journal of ethnopharmacology · 2026
Network toxicology and biolayer interferometry validation reveal the mechanism of Stelleropsis tianschanica Pobed.-induced hepatotoxicity.
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Meng Xiang, Jiang Wen-Li, Shi Lei-Ling, Ma Zhi-Liang, Huang Xian-Ju
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Stelleropsis tianschanica Pobed. is a perennial herb belonging to the genus Stelleropsis in the family Thymelaeaceae of the order Myrtales, and possesses certain toxicity. In the Zhaosu region of Xinjiang, it is used medicinally as an expectorant and analgesic, and for the treatment of chronic bronchitis, cough, asthma, and skin diseases. However, beyond its therapeutic efficacy, the potential hepatotoxicity of Stelleropsis tianschanica Pobed. poses a threat to human health. Currently, research regarding its hepatotoxicity remains limited.
AIM OF THE STUDY: This study aims to integrate network toxicology, Bio-Layer Interferometry (BLI), and in vitro experiments to systematically explore the toxicological material basis and potential molecular mechanisms underlying liver injury induced by Stelleropsis tianschanica Pobed.
MATERIALS AND METHODS: In vivo acute toxicity studies and in vitro cell experiments were employed to determine the hepatotoxic parts of Stelleropsis tianschanica Pobed. Combined with LC-MS/MS analysis, network toxicology prediction, and molecular docking technology, the material basis and potential targets of hepatotoxicity were preliminarily screened. LC-MS/MS combined with Bio-Layer Interferometry (BLI) was applied, using core targets as "bait," to affinity-fish and identify active ingredients from the drug system. Finally, relevant signaling pathways were verified via in vitro cell experiments to reveal the molecular mechanism of hepatotoxicity.
RESULTS: In vivo and in vitro evaluations demonstrated that the root parts of Stelleropsis tianschanica Pobed possessed significantly higher toxicity than the aerial parts, characterized by severe liver lesions and elevated transaminases. It may induce hepatotoxic effects by targeting the EGFR-PI3K/AKT-mitochondrial pathway. Daphnoretin, Umbelliferone, and Formononetin were identified as the potential toxic material basis responsible for its hepatotoxicity.
AIM OF THE STUDY: This study aims to integrate network toxicology, Bio-Layer Interferometry (BLI), and in vitro experiments to systematically explore the toxicological material basis and potential molecular mechanisms underlying liver injury induced by Stelleropsis tianschanica Pobed.
MATERIALS AND METHODS: In vivo acute toxicity studies and in vitro cell experiments were employed to determine the hepatotoxic parts of Stelleropsis tianschanica Pobed. Combined with LC-MS/MS analysis, network toxicology prediction, and molecular docking technology, the material basis and potential targets of hepatotoxicity were preliminarily screened. LC-MS/MS combined with Bio-Layer Interferometry (BLI) was applied, using core targets as "bait," to affinity-fish and identify active ingredients from the drug system. Finally, relevant signaling pathways were verified via in vitro cell experiments to reveal the molecular mechanism of hepatotoxicity.
RESULTS: In vivo and in vitro evaluations demonstrated that the root parts of Stelleropsis tianschanica Pobed possessed significantly higher toxicity than the aerial parts, characterized by severe liver lesions and elevated transaminases. It may induce hepatotoxic effects by targeting the EGFR-PI3K/AKT-mitochondrial pathway. Daphnoretin, Umbelliferone, and Formononetin were identified as the potential toxic material basis responsible for its hepatotoxicity.