Wogonin mitigates acetaminophen-induced liver injury in mice through inhibition of the PI3K/AKT signaling pathway

• Published in: Journal of ethnopharmacology 2024-10, Vol.332, p.118364, Article 118364
• Main Authors: Zhao, Wenyingzi, Luo, Huishan, Lin, Zelong, Huang, Linwen, Pan, Zhaoyu, Chen, Liji, Fan, Longxiu, Yang, Shilong, Tan, Huishi, Zhong, Cailing, Liu, Hongbin, Huang, Chongyang, Wang, Jun, Zhang, Beiping
• Format: Article
• Language: English
• Subjects: Acetaminophen - toxicity; Animals; Anti-Inflammatory Agents - pharmacology; Chemical and Drug Induced Liver Injury - drug therapy; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - pathology; Chemical and Drug Induced Liver Injury - prevention & control; Drug-induced liver injury; Flavanones - pharmacology; Flavanones - therapeutic use; Inflammatory response; Liver - drug effects; Liver - metabolism; Liver - pathology; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; Oxidative Stress - drug effects; Phosphatidylinositol 3-Kinases - metabolism; PI3K/AKT; Proto-Oncogene Proteins c-akt - metabolism; RAW 264.7 Cells; Scutellaria baicalensis - chemistry; Signal Transduction - drug effects; Wogonin
• ISSN: 0378-8741; 1872-7573; 1872-7573
• DOI: 10.1016/j.jep.2024.118364

Scutellaria baicalensis Georgi (SBG), a widely used traditional Chinese medicine, exhibits anti-inflammatory and antioxidant properties. Wogonin is one of the primary bioactive components of SBG. Acetaminophen (APAP)-induced liver injury (AILI) represents a prevalent form of drug-induced liver damage and is primarily driven by inflammatory responses and oxidative stress. To investigate the therapeutic effects of Wogonin on AILI and the underlying mechanisms. C57BL/6 J mice were pre-treated with Wogonin (1, 2.5, and 5 mg/kg bodyweight) for 3 days, followed by treatment with APAP (300 mg/kg bodyweight). The serum and liver tissue samples were collected at 24 h post-APAP treatment. Bone marrow-derived macrophages and RAW264.7 cells were cultured and pre-treated with Wogonin (5, 10, and 20 μM) for 30 min, followed by stimulation with lipopolysaccharide (LPS; 100 ng/mL) for 3 h. To examine the role of the PI3K/AKT signaling pathway in the therapeutic effect of Wogonin on AILI, mice and cells were treated with LY294002 (a PI3K inhibitor) and MK2206 (an AKT inhibitor). Wogonin pre-treatment dose-dependently alleviated AILI in mice. Additionally, Wogonin suppressed oxidative stress and inflammatory responses. Liver transcriptome analysis indicated that Wogonin primarily regulates immune function and cytokines in AILI. Wogonin suppressed inflammatory responses of macrophages by inhibiting the PI3K/AKT signaling pathway. Consistently, Wogonin exerted therapeutic effects on AILI in mice through the PI3K/AKT signaling pathway. Wogonin alleviated AILI and APAP-induced hepatotoxicity in mice through the PI3K/AKT signaling pathway. Wogonin, a principal component of the traditional Chinese medicine Scutellaria baicalensis Georgi (SBG), effectively mitigates acetaminophen (APAP)-induced liver injury (AILI). It achieves this by modulating the PI3K/AKT pathway in both mice and cellular models. [Display omitted] •Wogonin is a key anti-inflammatory and antioxidant constituent of Scutellaria baicalensis Georgi.•Wogonin mitigates acetaminophen (APAP)-induced liver injury in mice with antioxidant and anti-inflammatory effects.•The hepatoprotective effects of Wogonin are mediated by the PI3K/AKT signaling pathway.