Ruan Lingyu, Zhao Wenli, Luo Buzha-Xi, Zheng Qi, Liu Zhichao, Liu Wenya, Ba Daji-Deng, Zhong Jiage, Luo Hui, Wang Junsong, Feng Xin
Center of Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing, 210094, China.
Institute for Tibetan Medicine, China Tibetology Research Center, Beijing, 100101, China.
J Ethnopharmacol. 2022 Jan 10;282:114629. doi: 10.1016/j.jep.2021.114629. Epub 2021 Sep 10.
'Ershiwuwei Shanhu' Pill (ESP) is a classic Tibetan medicine to treat neurological disorders in nervous system, especially for neurological pains and epilepsy. It contains many Tibet-specific mineral medicines, among which Halloysite (Halloysitum rubrum, HR) was regarded as the main active one. As mineral medicines contain heavy metals with poor solubility, the doubts about its safety restricted its clinical application and further development.
A 7-day acute toxicity of ESP and its main active mineral medicine HR was systematically studied for investigating the safety of ESP and exploring the role of HR in ESP's potential toxicity.
In this study, the acute oral toxicity assessment of formula-ESP and HR were performed on rats for 7 days at doses equivalent to 10 (1 g/kg) and 40 times (4 g/kg) the typical clinical dose (0.1 g/kg). H NMR based metabolomics profiling, aided with biochemical analysis and histopathology, was conducted to explore the global metabolic changes in the livers and kidneys of the administrated rats.
High-dose HR caused oxidative stress, energy metabolism disorders, purine metabolism impairments and amino acid metabolism imbalance in rats, resulting in hepatotoxicity and nephrotoxicity, which in accordance with the increased biochemical index in blood (ALT, AST, BUN and CRE). ESP (low-dose) induced metabolites changes were far more less than HR in livers, showcasing the distinct advantage of formula in reducing toxicity. Furthermore, low-dose ESP disturbed renal metabolism in a way similar to high-dose HR, which implies that HR might be the major source of the potential nephrotoxicity of ESP.
HR exhibited potential hepatoxicity and nephrotoxicity, but the formula- 'Ershiwuwei Shanhu' Pill which contains HR is considered relatively safe.
二十五味珊瑚丸（ESP）是一种治疗神经系统神经疾病的经典藏药，尤其适用于神经疼痛和癫痫。它含有多种西藏特有的矿物药，其中，硅灰石（赤石脂，HR）被认为是主要活性成分。由于矿物药含有难溶性重金属，对其安全性的质疑限制了其临床应用和进一步发展。
系统研究ESP及其主要活性矿物药HR的7天急性毒性，以调查ESP的安全性，并探索HR在ESP潜在毒性中的作用。
在本研究中，对大鼠进行了配方ESP和HR的急性经口毒性评估，给药7天，剂量分别相当于典型临床剂量（0.1 g/kg）的10倍（1 g/kg）和40倍（4 g/kg）。采用基于1H NMR的代谢组学分析，并辅以生化分析和组织病理学，以探索给药大鼠肝脏和肾脏的整体代谢变化。
高剂量HR导致大鼠氧化应激、能量代谢紊乱、嘌呤代谢受损和氨基酸代谢失衡，导致肝毒性和肾毒性，这与血液中生化指标（ALT、AST、BUN和CRE）升高一致。ESP（低剂量）在肝脏中诱导的代谢物变化远少于HR，显示出配方在降低毒性方面的明显优势。此外，低剂量ESP以类似于高剂量HR的方式干扰肾脏代谢，这意味着HR可能是ESP潜在肾毒性的主要来源。
HR表现出潜在的肝毒性和肾毒性，但含有HR的二十五味珊瑚丸配方被认为相对安全。
