School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, PR China.
Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, PR China.
Phytomedicine. 2019 May;58:152874. doi: 10.1016/j.phymed.2019.152874. Epub 2019 Feb 25.
The fruits of Psoralea corylifolia L. (Fructus Psoraleae, FP) has a long history and a wide range of applications in the treatment of osteoporosis and leukoderma. Although it is well known that FP could cause hepatotoxicity and reproductive toxicity, less is known about its potential toxicity on multiple organs.
This study aims to determine the multiorgan toxicity of EtOH extract of FP (EEFP) and to investigate the underlying mechanisms through a systematic evaluation in Wistar rats.
Wistar rats were orally administered with the EEFP at doses of 1.5, 1.0 and 0.5 g/kg for 28 days. Histopathologic and clinicopathologic analyses were performed, and the hormone levels in serum and the mRNA levels of enzymes related to the production of steroid hormones in adrenal glands were detected. The area of each band of adrenal glands and the steroid levels in the adrenal glands were also measured.
After the treatment, both the histopathologic and clinicopathologic examination showed that EEFP caused liver, prostate, seminal vesicle and adrenal gland damage. Among the enzymes involved in the regulation of adrenal steroid hormone production, NET, VMAT2, and CYP11B1 were upregulated, while CYP17A1 was downregulated. Among the adrenal steroid hormones, COR and NE were upregulated, while levels of DHT and serum ACRH and CRH decreased.
Our results indicated that adrenal gland, prostate, and seminal vesicles could also be the target organs of FP-induced toxicity. Abnormal enzyme and hormone production related to the hypothalamic pituitary adrenal (HPA) axis caused by the EEFP may be the potential toxic mechanism for changes in the adrenal gland and secondary sex organs of male rats.
补骨脂(Psoralea corylifolia L.,Fructus Psoraleae,FP)的果实具有悠久的历史,广泛应用于治疗骨质疏松症和白癜风。虽然众所周知 FP 可引起肝毒性和生殖毒性,但对其潜在的多器官毒性知之甚少。
本研究旨在确定补骨脂乙醇提取物(EEFP)的多器官毒性,并通过 Wistar 大鼠的系统评价来探讨其潜在的毒性机制。
Wistar 大鼠连续 28 天经口给予 EEFP,剂量分别为 1.5、1.0 和 0.5 g/kg。进行组织病理学和临床病理学分析,检测血清中激素水平以及肾上腺中与类固醇激素生成相关的酶的 mRNA 水平。还测量了肾上腺的每个带的面积以及肾上腺中的类固醇水平。
治疗后,组织病理学和临床病理学检查均显示 EEFP 引起了肝脏、前列腺、精囊和肾上腺损伤。在参与调节肾上腺类固醇激素生成的酶中,NET、VMAT2 和 CYP11B1 上调,而 CYP17A1 下调。在肾上腺类固醇激素中,COR 和 NE 上调,而 DHT、血清 ACRH 和 CRH 水平降低。
我们的结果表明,肾上腺、前列腺和精囊也可能是 FP 诱导毒性的靶器官。EEFP 引起的与下丘脑-垂体-肾上腺(HPA)轴相关的异常酶和激素生成可能是雄性大鼠肾上腺和次级性器官变化的潜在毒性机制。