Abstract

The leguminosae of Sophora moorcroftiana (Benth.) Benth.ex Baker is a drought-resistant endemic Sophora shrub species from the Qinghai-Tibet Plateau, and its seeds have hepatoprotective effects. To study the effect of S. moorcroftiana seeds on liver injury and the molecular mechanism underlying the beneficial effects, liquid chromatography-mass spectrometry was used to detect the main active components in the ethanol extract of S. moorcroftiana seeds (SM). Male mice were divided into six groups (n = 8): normal control (NC), CCl₄, SM (50, 100, 200 mg/kg), and dimethyl diphenyl bicarboxylate (150 mg/kg) groups. Mice were treated as indicated (once/day, orally) for 14 days, and CCl₄ (2 mL/kg) was administered intraperitoneally. The serum and liver of mice were used for biochemical assays. To explore the underlying mechanism, HepG2 cells were treated with SM, stimulated with tert-butyl hydroperoxide (t-BHP, 50 μM), and analyzed by Western blotting. The major active compounds of SM were alkaloids including 22 compounds. Serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) decreased in the SM (200 mg/kg) group. SM can activate the expression of pregnane X receptor (PXR) and downstream molecules cytochrome P4503A11 enzyme (CYP3A11), UDP glucuronosyltransferase 1 family polypeptide A 1 (UGT1A1), and inhibit the multidrug resistance protein 2 (MRP2). In addition, SM improved cell viability in t-BHP-induced HepG2 cells (64% to 83%) and decreased the activation of the mitogen-activated protein kinase (MAPK) pathway. The main compounds in SM were alkaloids. SM showed hepatoprotective effects possibly mediated by the suppression of oxidative stress through the MAPK pathway.

摘要

Sophora moorcroftiana (Benth.) Benth.ex Baker的豆科是青藏高原抗旱特有的槐属灌木品种，其种子具有保肝作用。为研究山茱萸种子对肝损伤的影响及其有益作用的分子机制，采用液相色谱-质谱法检测山茱萸种子乙醇提取物中的主要活性成分。雄性小鼠分为六组（n  = 8）：正常对照组（NC）、CCl ₄、SM（50、100、200 mg/kg）和二甲基二苯甲酸二甲酯（150 mg/kg）组。小鼠按指示（每天一次，口服）处理 14 天，CCl ₄(2 mL/kg) 腹膜内给药。小鼠的血清和肝脏用于生化测定。为了探索潜在的机制，HepG2 细胞用 SM 处理，用叔丁基过氧化氢（t-BHP，50 μM）刺激，并通过蛋白质印迹分析。SM的主要活性成分为生物碱，共22种。SM (200 mg/kg) 组的血清丙氨酸转氨酶 (ALT)、天冬氨酸转氨酶 (AST) 和碱性磷酸酶 (ALP) 下降。SM可激活孕烷X受体（PXR）及下游分子细胞色素P4503A11酶（CYP3A11）、UDP葡萄糖醛酸转移酶1家族多肽A 1（UGT1A1）的表达，并抑制多药耐药蛋白2（MRP2）。此外，SM 提高了 t-BHP 诱导的 HepG2 细胞的细胞活力（64% 至 83%），并降低了丝裂原活化蛋白激酶 (MAPK) 通路的激活。SM中的主要化合物是生物碱。SM 显示可能通过 MAPK 途径抑制氧化应激介导的保肝作用。