Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt.
Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia.
Chin J Integr Med. 2024 Dec;30(12):1090-1100. doi: 10.1007/s11655-024-3808-3. Epub 2024 Sep 19.
To explore the prophylactic and therapeutic effects of Alhagi maurorum ethanolic extract (AME) in concanavalin A (Con A)-induced hepatitis (CIH) as well as possible underlying mechanisms.
Polyphenols in AME were characterized using high performance liquid chromatography (HPLC). Swiss albino mice were divided into 4 groups. Normal group received intravenous phosphate-buffered saline (PBS); Con A group received 40 mg/kg intravenous Con A. Prophylaxis group administered 300 mg/(kg·d) AME orally for 5 days before Con A intervention. Treatment group received intravenous Con A then administered 300 mg/kg AME at 30 min and 3 h after Con A intervention. After 24 h of Con A injection, hepatic injury, oxidative stress, and inflammatory mediators were assessed. Histopathological examination and markers of apoptosis, inflammation, and CD4 cell infiltration were also investigated.
HPLC analysis revealed that AME contains abundant polyphenols with pharmacological constituents, such as ellagic acid, gallic acid, ferulic acid, methylgallate, and naringenin. AME alleviated Con A-induced hepatic injury, as manifested by a significant reduction in alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase (P<0.01). Additionally, the antioxidant effect of AME was revealed by a significant reduction in oxidative stress markers (nitric oxide and malondialdehyde) and restored glutathione (P<0.01). The levels of proinflammatory cytokines (tumor necrosis factor-α, interferon-γ, and interleukin-6) and c-Jun N-terminal kinase (JNK) activity were reduced (P<0.01). Histopathological examination of liver tissue showed that AME significantly ameliorated necrotic and inflammatory lesions induced by Con A (P<0.01). Moreover, AME reduced the expression of nuclear factor kappa B, pro-apoptotic protein (Bax), caspase-3, and CD4 T cell hepatic infiltration (P<0.01). The expression of anti-apoptotic protein Bcl-2 was increased (P<0.01).
AME has hepatoprotective and ameliorative effects in CIH mice. These beneficial effects are likely due to the anti-inflammatory, antioxidant, and anti-apoptotic effects of the clinically important polyphenolic content. AME could be a novel and promising hepatoprotective agent for managing immune-mediated hepatitis.
探索沙冬青醇提物（AME）在伴刀豆球蛋白 A（Con A）诱导的肝炎（CIH）中的预防和治疗作用及其可能的机制。
采用高效液相色谱法（HPLC）对 AME 中的多酚进行表征。将瑞士白化病小鼠分为 4 组。正常组静脉注射磷酸盐缓冲盐水（PBS）；Con A 组静脉注射 40 mg/kg Con A。预防组在 Con A 干预前 5 天每天口服 300 mg/（kg·d）AME。治疗组在静脉注射 Con A 后 30 min 和 3 h 时给予 300 mg/kg AME。在 Con A 注射后 24 h，评估肝损伤、氧化应激和炎症介质。还进行了组织病理学检查和凋亡、炎症和 CD4 细胞浸润的标志物研究。
HPLC 分析表明，AME 含有丰富的具有药理学成分的多酚，如鞣花酸、没食子酸、阿魏酸、甲基没食子酸和柚皮素。AME 缓解了 Con A 诱导的肝损伤，表现为丙氨酸氨基转移酶、天冬氨酸氨基转移酶和碱性磷酸酶显著降低（P<0.01）。此外，AME 通过降低氧化应激标志物（一氧化氮和丙二醛）和恢复谷胱甘肽（P<0.01）显示出抗氧化作用。促炎细胞因子（肿瘤坏死因子-α、干扰素-γ和白细胞介素-6）和 c-Jun N 末端激酶（JNK）活性的水平降低（P<0.01）。肝组织的组织病理学检查表明，AME 显著改善了 Con A 诱导的坏死和炎症病变（P<0.01）。此外，AME 降低了核因子 kappa B、促凋亡蛋白（Bax）、半胱天冬酶-3 和 CD4 T 细胞肝浸润的表达（P<0.01）。抗凋亡蛋白 Bcl-2 的表达增加（P<0.01）。
AME 对 CIH 小鼠具有保肝和改善作用。这些有益作用可能归因于其具有抗炎、抗氧化和抗凋亡作用的临床重要多酚含量。AME 可能是一种新型有前途的免疫介导性肝炎的保肝剂。
