Department of Public Health, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
The Third School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
J Ethnopharmacol. 2022 Nov 15;298:115610. doi: 10.1016/j.jep.2022.115610. Epub 2022 Aug 13.
Niu Huang Jie Du prescription (NHJD) is a traditional Chinese medicine (TCM) widely used in patients suffering from excessive inner fire toxin (Huo Du Nei Sheng) syndrome, such as sore throat, gingival swelling, and pain, mouth and tongue sores, etc. This formula contains realgar (AsS) which is one of the 28 toxic medicinal materials promulgated by the Chinese Ministry of Health. Many studies reported its toxicity on the liver and kidney, and the detoxification effect of NHJD. However, its detoxification mechanism is still unclear.
To clarify the detoxification mechanism of NHJD to realgar, this study evaluated the detoxification effect of NHJD on realgar exposure in mice, and analyzed differences in mRNA expression profiles in liver tissues and associated functional predictions.
ICR mice were administered with NHJD, realgar, and CMC-Na as blank control for 12 weeks, respectively. Liver injury was evaluated by histopathologic examination and liver mRNA gene were sequenced by Illumina. Differentially expressed gene, functionally enrichment and protein association network analysis were conducted.
43 genes were screened out, among which 15 genes in the realgar group were decreased, but the extent of the decline has been restored in the NHJD group. The remaining 28 genes have exactly the opposite trends. Functional module analysis revealed that those detoxification function-related genes were primarily for positive regulation of glutathione metabolism, P450 on the metabolism of exogenous compounds, oxidative stress and immune-related, etc. CONCLUSIONS: The results indicated that realgar mainly causes liver damage by changing the common enzymes of drug metabolism, especially the expression of genes related to CYPs, GSTs family, oxidative stress, and complement immunity, while the TCM prescription NHJD has a regulatory effect on the abnormal expression of corresponding genes. Our results will provide some clues for the detoxification mechanism of arsenic-containing TCM prescriptions.
牛黄解毒方剂（NHJD）是一种中药，广泛用于治疗体内火毒（热毒内生）综合征患者，如咽喉痛、牙龈肿胀和疼痛、口舌生疮等。该配方含有雄黄（AsS），雄黄是中国卫生部公布的 28 种毒性中药材之一。许多研究报道了其对肝肾功能的毒性，以及 NHJD 的解毒作用。然而，其解毒机制尚不清楚。
为了阐明 NHJD 对雄黄的解毒机制，本研究评估了 NHJD 对雄黄暴露小鼠的解毒作用，并分析了肝组织中 mRNA 表达谱的差异及其相关功能预测。
ICR 小鼠分别给予 NHJD、雄黄和 CMC-Na 作为空白对照，连续给药 12 周。通过组织病理学检查评估肝损伤，并通过 Illumina 进行肝 mRNA 基因测序。进行差异表达基因、功能富集和蛋白质关联网络分析。
筛选出 43 个基因，其中雄黄组 15 个基因下调，但在 NHJD 组中已恢复到下调程度。其余 28 个基因则呈现相反的趋势。功能模块分析表明，这些解毒功能相关基因主要用于谷胱甘肽代谢的正调控、外源性化合物代谢的 P450、氧化应激和免疫相关等。
结果表明，雄黄主要通过改变药物代谢的常见酶来引起肝损伤，特别是与 CYP 家族、GSTs 家族、氧化应激和补体免疫相关的基因表达。而中药方剂 NHJD 对相应基因的异常表达具有调节作用。我们的研究结果将为含砷中药方剂的解毒机制提供一些线索。
