Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, 510120, China; Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, 510120, China.
Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
J Ethnopharmacol. 2024 Oct 5;332:118364. doi: 10.1016/j.jep.2024.118364. Epub 2024 May 18.
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.
黄芩（SBG）是一种广泛应用的传统中药，具有抗炎和抗氧化作用。汉黄芩素是 SBG 的主要生物活性成分之一。对乙酰氨基酚（APAP）诱导的肝损伤（AILI）是一种常见的药物性肝损伤形式，主要由炎症反应和氧化应激驱动。
研究汉黄芩素对 AILI 的治疗作用及其机制。
C57BL/6J 小鼠用汉黄芩素（1、2.5 和 5mg/kg 体重）预处理 3 天，然后用 APAP（300mg/kg 体重）处理。APAP 处理后 24 小时采集血清和肝组织样本。骨髓来源的巨噬细胞和 RAW264.7 细胞用汉黄芩素（5、10 和 20μM）预处理 30 分钟，然后用脂多糖（LPS；100ng/mL）刺激 3 小时。为了研究 PI3K/AKT 信号通路在汉黄芩素治疗 AILI 中的作用，用 LY294002（PI3K 抑制剂）和 MK2206（AKT 抑制剂）处理小鼠和细胞。
汉黄芩素预处理剂量依赖性地减轻了小鼠的 AILI。此外，汉黄芩素抑制氧化应激和炎症反应。肝转录组分析表明，汉黄芩素主要调节 AILI 中的免疫功能和细胞因子。汉黄芩素通过抑制 PI3K/AKT 信号通路抑制巨噬细胞的炎症反应。同样，汉黄芩素通过 PI3K/AKT 信号通路对小鼠的 AILI 发挥治疗作用。
汉黄芩素通过 PI3K/AKT 信号通路减轻了小鼠的 AILI 和 APAP 诱导的肝毒性。
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