Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Jilin 130012, PR China.
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Jilin 130012, PR China; National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun Jilin 130012, PR China; Institute of Changbai Mountain Resource and Health, Jilin University, Fusong Jilin 134504, PR China.
Phytomedicine. 2024 Dec;135:156113. doi: 10.1016/j.phymed.2024.156113. Epub 2024 Oct 1.
The liver plays a crucial role in detoxification and metabolism. When its capacity to metabolize foreign substances is exceeded, it can lead to acute liver injury (ALI). Therefore, preventing liver disease and maintaining daily liver health are of utmost importance. Xiaobugan Decoction (XBGD), a traditional Chinese medicine (TCM) formula, is recorded in 'Fuxingjue', is used in folk practice to promote liver health and regulate respiration. However, the hepatoprotective mechanisms of XBGD remained unclear.
We investigated the prophylactic and hepatoprotective effects of XBGD and explored its related molecular mechanisms using a mouse model of carbon tetrachloride (CCl)-induced ALI.
XBGD composition was determined using analytical methods, and the main compounds were identified using ultra-high-performance liquid chromatography coupled with Q-Exactive focus mass spectrum (UHPLC-QE-MS) and high-performance liquid chromatography (HPLC). A CCl-induced L02 cell injury model was employed to explore the protective effects of XBGD on liver cells, and a CCl-induced ALI mouse model was used to investigate the hepatoprotective effects of XBGD.
Cellular experiments demonstrated that XBGD had a protective function against L02 cell damage by increasing cell viability, restoring alanine aminotransferase (ALT), aspartate aminotransferase (AST), and superoxide dismutase (SOD) levels, reducing malondialdehyde (MDA) content, and improving mitochondrial membrane potential (ΔΨm). In the mouse ALI model, XBGD prevented ALI by reducing ALT, AST, and alkaline phosphatase (ALP) levels and inhibiting oxidative stress. Quantitative real-time polymerase chain reaction (qPCR), immumohistochemical staining and western blotting results revealed that XBGD exerted hepatoprotective effects by reducing inflammatory responses and inhibiting cell apoptosis. Furthermore, H-NMR metabolomics indicated that XBGD regulates hepatic and intestinal metabolism, whereas 16S rDNA sequencing demonstrated the regulatory effects of XBGD on the gut microbiota. Correlation analysis highlighted the close relationship among gut microbiota, metabolites, and ALI indicators.
XBGD is a promising TCM for the prevention of CCl-induced ALI via regulation of microbiota and metabolism. This study provides a new perspective on the development of hepatoprotective measures and the prevention of liver disease in daily life.
肝脏在解毒和新陈代谢中起着至关重要的作用。当肝脏代谢外来物质的能力超过其能力时，可能会导致急性肝损伤（ALI）。因此，预防肝病和维护日常肝脏健康至关重要。小柴胡汤（XBGD）是一种中药（TCM）配方，记录在《复兴诀》中，用于民间实践以促进肝脏健康和调节呼吸。然而，XBGD 的保肝机制尚不清楚。
我们使用四氯化碳（CCl）诱导的 ALI 小鼠模型，研究了 XBGD 的预防和保肝作用，并探讨了其相关的分子机制。
使用分析方法确定 XBGD 的组成，使用超高效液相色谱-四极杆静电场轨道阱高分辨质谱联用（UHPLC-QE-MS）和高效液相色谱（HPLC）鉴定主要化合物。使用 CCl 诱导的 L02 细胞损伤模型探讨 XBGD 对肝细胞的保护作用，使用 CCl 诱导的 ALI 小鼠模型探讨 XBGD 的保肝作用。
细胞实验表明，XBGD 通过提高细胞活力、恢复丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和超氧化物歧化酶（SOD）水平、降低丙二醛（MDA）含量和改善线粒体膜电位（ΔΨm），对 L02 细胞损伤具有保护作用。在小鼠 ALI 模型中，XBGD 通过降低 ALT、AST 和碱性磷酸酶（ALP）水平并抑制氧化应激来预防 ALI。实时定量聚合酶链反应（qPCR）、免疫组织化学染色和蛋白质印迹结果表明，XBGD 通过减轻炎症反应和抑制细胞凋亡发挥保肝作用。此外，1 H-NMR 代谢组学表明，XBGD 调节肝和肠道代谢，而 16S rDNA 测序表明 XBGD 对肠道微生物群具有调节作用。相关性分析突出了肠道微生物群、代谢物和 ALI 指标之间的密切关系。
XBGD 是一种有前途的 TCM，可通过调节微生物群和代谢物预防 CCl 诱导的 ALI。本研究为开发保肝措施和日常生活中预防肝病提供了新视角。
