Xu Bo, Yao Guang-Tao, Xie Jun, Ran Lei, A Xin-Yu, Xiao Lian-Bo
Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai 201203,China Shanghai University of Traditional Chinese Medicine Shanghai 201203,China.
Shanghai University of Traditional Chinese Medicine Shanghai 201203,China.
Zhongguo Zhong Yao Za Zhi. 2023 Aug;48(16):4459-4466. doi: 10.19540/j.cnki.cjcmm.20230410.401.
This study aims to investigate the hepatotoxicity of Psoraleae Fructus water extract and the underlying mechanism in rats. Forty-eight rats were randomly assigned into four groups: a blank group and low-(BZGL, 6.25 g·kg(-1)), medium-(BGZM, 12.5 g·kg(-1)), and high-dose(BGZH, 25 g·kg~(-1)) Psoraleae Fructus water extract groups. The rats were treated for 28 days, and toxicity and mortality were observed daily. After 28 days, the rats were sacrificed, and the body weight, liver index, and liver-to-brain ratio were calculated. The morphological changes in the liver tissue were observed, and the serum levels of related biochemical indicators were measured. The results showed that compared with the blank group, Psoraleae Fructus water extracts of different doses decreased the body weight, increased the liver index and liver-to-brain ratio, and caused liver hypertrophy and pathological changes. Pathological examination revealed that the rats in Psoraleae Fructus water extract groups had bile duct hyperplasia, inflammatory cell infiltration, and liver cell fibrosis. Compared with the blank group, BGZL elevated the levels of alanine transaminase(ALT), α-glutathione S-transferase(α-GST), and total bile acid(TBA)(P<0.05), and BGZM and BGZH elevated the levels of ALT, TBA, α-GST, γ-glutamyl transferase(γ-GT), purine nucleoside phosphorylase(PNP), ornithine carbamoyltransferase(OCT), and arginase(ArgI)(P<0.05). Compared with the blank group, Psoraleae Fructus water extracts of different doses down-regulated the mRNA and protein levels of bile salt export pump(BSEP) and farnesoid X receptor(FXR) and up-regulated the mRNA and protein levels of tumor necrosis factor-α(TNF-α), nuclear factor kappaB(NF-κB), and cholesterol 7 alpha-hydroxylase(CYP7A1)(P<0.05). The results suggested that Psoraleae Fructus water extract caused toxicity in rats, showing a dose-toxicity relationship. Psoraleae Fructus water extract may cause liver damage, which may be due to its effect on liver bile acid secretion and induction of inflammation.
本研究旨在探讨补骨脂水提取物对大鼠的肝毒性及其潜在机制。48只大鼠随机分为四组：空白组以及低剂量（6.25 g·kg⁻¹，补骨脂低剂量组）、中剂量（12.5 g·kg⁻¹，补骨脂中剂量组）和高剂量（25 g·kg⁻¹，补骨脂高剂量组）补骨脂水提取物组。大鼠接受治疗28天，每天观察毒性和死亡率。28天后，处死大鼠，计算体重、肝脏指数和肝脑比。观察肝组织的形态学变化，并检测血清相关生化指标水平。结果显示，与空白组相比，不同剂量的补骨脂水提取物均降低了体重，增加了肝脏指数和肝脑比，并导致肝脏肥大和病理改变。病理检查显示，补骨脂水提取物组大鼠出现胆管增生、炎性细胞浸润和肝细胞纤维化。与空白组相比，补骨脂低剂量组升高了丙氨酸转氨酶（ALT）、α-谷胱甘肽S-转移酶（α-GST）和总胆汁酸（TBA）水平（P<0.05），补骨脂中剂量组和高剂量组升高了ALT、TBA、α-GST、γ-谷氨酰转移酶（γ-GT）、嘌呤核苷磷酸化酶（PNP）、鸟氨酸氨甲酰转移酶（OCT）和精氨酸酶（ArgI）水平（P<0.05）。与空白组相比，不同剂量的补骨脂水提取物下调了胆盐输出泵（BSEP）和法尼酯X受体（FXR）的mRNA和蛋白水平，上调了肿瘤坏死因子-α（TNF-α）、核因子κB（NF-κB）和胆固醇7α-羟化酶（CYP7A1）的mRNA和蛋白水平（P<0.05）。结果表明，补骨脂水提取物对大鼠具有毒性，呈现剂量-毒性关系。补骨脂水提取物可能导致肝损伤，这可能与其对肝脏胆汁酸分泌的影响及炎症诱导作用有关。
