Ahmed Rania F, Elgamal Abdelbaset M, El-Nashar Heba A S, Mowaad Noha A, Elgohary Rania, El-Saied Mohamed A, Farag Mohamed A, Imagawa Hiroshi, Elshamy Abdelsamed I, Abd-ElGawad Ahmed M
Department of Natural Compounds Chemistry, National Research Centre, Dokki, Giza, Egypt.
Department of Chemistry of Microbial and Natural Products, National Research Centre, Dokki, Giza, Egypt.
PLoS One. 2025 Sep 2;20(9):e0330595. doi: 10.1371/journal.pone.0330595. eCollection 2025.
Hepatic fibrosis unfolds as a pathological buildup of extracellular matrix triggered by liver injury. Thioacetamide (TAA) plays a versatile role across various fields-from industrial processes and laboratory research to chemical stabilization. Teucrium plants, widely traditional plants, owing to its myriads of pharmacological activities.
T. oliverianum ethanolic (TO-EtOH) and ethyl acetate (TO-EtOAc) extracts were explored for their bioactive metabolites via UHPLC-ESI-qTOF-MS/MS that yielded 48 compounds, mainly flavonoids and phenylethanoid glycosides, alongside phenolic acids, iridoid glycosides, and limonoids. Both extracts showed notable hepatoprotective effects in a thioacetamide (TAA)-induced liver injury model, supporting their therapeutic potential. The TAA group showed a significant increase in AST, ALT, ALP, MDA and TNF-α levels concurrent with a significant decrease of GSH level versus normal control group. In contrast, TO-EtOAC and TO-EtOH administered rats showed a decrease in liver enzymes, including ALT, AST, ALP, total bilirubin, and MDA, and an increase in GSH as compared to the TAA model group. Furthermore, both extracts considerably decreased the overall liver TNF-α content inferring anti-inflammatory action. The histo- and immunohistochemical assays of liver tissue of rats in TAA revealed prominent pathological alterations with bridging fibroplasia in multiple hepatic lobules. A restorative effect that improved hepatic morphology with apparent normal hepatic cells and nominal fibroplasia was evident in the administration of both extracts. Among both extracts, TO-EtOH appeared more effective than TO-EtOAC as manifested by a significant improvement in liver's biochemical parameters and structural organization.
This study provides robust evidence supporting the antifibrotic effects of T. oliverianum in a TAA-induced liver injury model. The anti-proliferative activity and hepatoprotective effects are likely to be mediated by its richness in phenolic acids, flavonoids and phenylethanoids.
肝纤维化是由肝损伤引发的细胞外基质病理性积聚过程。硫代乙酰胺（TAA）在从工业生产、实验室研究到化学稳定等各个领域都有广泛应用。香科科属植物是广泛应用的传统植物，具有多种药理活性。
通过超高效液相色谱-电喷雾电离-四极杆飞行时间串联质谱（UHPLC-ESI-qTOF-MS/MS）对毛叶香科科乙醇提取物（TO-EtOH）和乙酸乙酯提取物（TO-EtOAc）的生物活性代谢产物进行了研究，共鉴定出48种化合物，主要为黄酮类和苯乙醇苷类，还有酚酸类、环烯醚萜苷类和柠檬苦素类。两种提取物在硫代乙酰胺（TAA）诱导的肝损伤模型中均表现出显著的肝保护作用，证明了它们的治疗潜力。与正常对照组相比，TAA组的天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、碱性磷酸酶（ALP）、丙二醛（MDA）和肿瘤坏死因子-α（TNF-α）水平显著升高，而谷胱甘肽（GSH）水平显著降低。相比之下，与TAA模型组相比，给予TO-EtOAC和TO-EtOH的大鼠肝酶（包括ALT、AST、ALP、总胆红素和MDA）水平降低，GSH水平升高。此外，两种提取物均显著降低了肝脏中TNF-α的总体含量，表明具有抗炎作用。TAA处理大鼠肝脏组织的组织学和免疫组织化学分析显示，多个肝小叶出现明显的病理改变，伴有桥接纤维化。在给予两种提取物后，可见恢复性效果，肝脏形态改善，肝细胞明显正常，纤维化程度轻微。在两种提取物中，TO-EtOH似乎比TO-EtOAc更有效，表现为肝脏生化参数和结构组织有显著改善。
本研究提供了有力证据，支持毛叶香科科在TAA诱导的肝损伤模型中的抗纤维化作用。其抗增殖活性和肝保护作用可能是由其丰富的酚酸类、黄酮类和苯乙醇类化合物介导的。
