Work

The evaluation and molecular mechanisms of hepatotoxicity induced by trans-emodin dianthrones isolated from Polygonum multiflorum Thunb. in vitro

Year: 2025

Type: article

Abstract: ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum multiflorum Thunb. (PM) is a traditional Chinese medicine with pharmacological activities such as anti-inflammatory, anti-oxidation and anti-aging. An increasing number of reports have documented liver injury associated with PM both domestically and internationally. In our previous study, we found that dianthrones from PM showed strong hepatotoxicity in the zebrafish model and may be potential toxicity markers. However, the in vitro hepatotoxicity and molecular mechanisms of dianthrones remain to be elucidated. AIM OF THE STUDY: Trans-emodin dianthrones is a dianthrones compound isolated from PM. In this study, we focused on the hepatotoxicity and molecular mechanism of the trans-emodin dianthrones. MATERIALS AND METHODS: HepG2 cells were used to evaluate hepatotoxicity and study the molecular mechanism of trans-emodin dianthrones in vitro. After administration of trans-emodin dianthrones, CCK-8 was used to detect cell viability, biochemical method was used to detect hepatotoxicity and antioxidant levels, reactive oxygen species (ROS) content and mitochondrial membrane potential (MMP) were analyzed by flow cytometry, the expression levels of JNK/Bax signaling pathway, PI3K/AKT/mTOR signaling pathway and apoptosis-related proteins were detected by Western blotting. Redox and mitochondria-related gene expression levels were detected by qPCR. RESULTS: Trans-emodin dianthrones reduced cell viability and activated apoptosis and the process was regulated by JNK/Bax and PI3K/AKT/mTOR pathways. Trans-emodin dianthrones activates JNK and AKT, thereby initiating the ROS-driven apoptosis cascade and increasing ROS-mediated cell damage, highlighting the importance of ROS stress in PM-induced hepatotoxicity. CONCLUSION: Trans-emodin dianthrones exhibited significant hepatotoxicity at the level of HepG2 cells, and its mechanism is related to inhibiting the antioxidant system, causing mitochondrial dysfunction and inducing apoptosis induced by JNK/Bax and PI3K/AKT/mTOR pathways.

Source: Journal of Ethnopharmacology

DOI: 10.1016/j.jep.2025.119916