Ameliorative impact of Juniperus Macrocarpa extract on methotrexate-induced hepatic damage in rats

AbstractMethotrexate (MTX) is an antifolate medication indicated to treat an array of tumors and autoinflammatory maladies. MTX may exhibit harmful impacts on multiple organs, especially liver injury and cirrhosis. Juniperus macrocarpa is a medicinal herb enriched with polyphenols and flavonoids featuring robust anti-inflammatory and antioxidant benefits. This study aimed to evaluate the hepatoprotective effects of Juniperus macrocarpa aqueous extract on MTX-aggravated liver toxicity. The study involved 20 male middle-aged albino rats, arbitrarily allocated into 4 groups of 5 animals each. Group 1 (control) was given distilled water (DW) once daily for two weeks. Group 2 (MTX) got an intraperitoneal single dose of MTX (20 mg/kg) for two weeks. Rats in groups 3 and 4 were given daily dosages of 100 mg and 200 mg of Juniperus macrocarpa aqueous extract, respectively, for two weeks before receiving a single intraperitoneal MTX injection. Juniperus macrocarpa extracts at both low and high doses substantially alleviated the MTX-provoked biochemical alterations, as evidenced by decreased levels of inflammatory parameters including TNF-α and IL-6 and hepatic enzymes including ALT, AST, and ALP. Juniperus macrocarpa also significantly boosted levels of the antioxidant enzymes, including SOD and GPX. Moreover, Juniperus macrocarpa extract attenuated congestive and degenerative hepatic changes, as indicated by improved histopathological findings. In conclusion, the antioxidant and anti-inflammatory activities of Juniperus macrocarpa extract are a promising approach for ameliorating MTX-aggravated hepatotoxicity.<br>

摘要：甲氨蝶呤（Methotrexate, MTX）是一类抗叶酸药物，临床适应证涵盖多种肿瘤与自身炎症性疾病。MTX可对多脏器产生损害，尤以肝损伤与肝硬化为甚。大果杜松（Juniperus macrocarpa）是一种富含多酚与黄酮类化合物的药用草本，具备强效抗炎与抗氧化活性。本研究旨在评估大果杜松水提取物对甲氨蝶呤加重的肝毒性的保肝作用。
本研究选取20只中年雄性白化大鼠，随机分为4组，每组5只。第1组（对照组）每日单次灌胃蒸馏水（DW），连续给药2周。第2组（MTX组）单次腹腔注射20 mg/kg的MTX，给药周期为2周。第3、4组大鼠在接受单次腹腔注射MTX前的2周，分别每日灌胃100 mg/kg与200 mg/kg的大果杜松水提取物。
实验结果显示，高低剂量的大果杜松提取物均可显著缓解MTX诱导的生化指标异常：肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）等炎症因子，以及丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、碱性磷酸酶（ALP）等肝酶的水平均显著降低；同时，超氧化物歧化酶（SOD）与谷胱甘肽过氧化物酶（GPX）等抗氧化酶的活性显著提升。此外，大果杜松提取物可减轻肝脏充血与退行性病变，组织病理学检查结果亦得到明显改善。
综上，大果杜松提取物的抗氧化与抗炎活性有望成为改善甲氨蝶呤诱导的肝毒性的有效手段。