Protective role of cinnabar and realgar in Hua-Feng-Dan against LPS plus rotenone-induced neurotoxicity and disturbance of gut microbiota in rats
Protective role of cinnabar and realgar in Hua-Feng-Dan against LPS plus rotenone-induced neurotoxicity and disturbance of gut microbiota in rats
复制标题
化风丹中朱砂和雄黄对脂多糖加鱼藤酮引起的大鼠神经毒性和肠道菌群紊乱的保护作用
DOI：
10.1016/j.jep.2019.112299
复制
发表时间：
2020-01-30
影响因子：
5.4
通讯作者：
Zhang, Feng
中科院分区：
文献类型：
--
作者：
Chen, Ce;Zhang, Bin-Bin;Zhang, Feng
民族药理学相关性：化风丹（HFD）是一种用于神经系统疾病的传统中药。HFD含有朱砂（HgS）和雄黄（As 4S 4）。朱砂和雄黄在HFD的ethnopharmacological基础是未知的。目的的研究：为了解决朱砂和雄黄在HFD产生的神经保护作用，对神经退行性疾病和肠道microbiots.Materials和方法：脂多糖（LPS）加鱼藤酮（ROT）引起的大鼠多巴胺能（DA）神经元损伤损失作为帕金森病动物模型。给大鼠单次注射LPS。四个月后，大鼠用阈值剂量的ROT进行攻击。HFD的临床剂量通过饲料给药，从ROT给药开始，持续46天。通过旋转棒和Y-迷宫测试检测行为功能障碍。通过免疫组化染色和western bolt分析评估DA神经元损失和小胶质细胞活化。收集结肠内容物提取细菌DNA，然后用16 S rRNA引物进行实时PCR分析。结果：LPS加ROT诱导的神经毒性，表现为黑质DA神经元丢失，行为功能受损和小胶质细胞活化增加。HFD原（含10%朱砂和10%雄黄）挽救了DA神经元的损失，改善了行为功能障碍，并减弱了小胶质细胞的激活。与HFD原方相比，还原HFD（3%朱砂和3%雄黄）方也有疗效，但程度较轻，而去HFD（不含朱砂和雄黄）方无效。在肠道微生物组分析中，HFD-原始改善了LPS加ROT增加的Verrucomicrobiaceae和Lactobacteriaceae以及减少的Enterobacteriaceae，并且HFD-减少的程度较小。结论：朱砂和雄黄是HFD中的活性成分，在神经退行性模型和肠道微生物群中发挥有益作用。
Ethnopharmacological relevance: Hua-Feng-Dan (HFD) is a traditional Chinese medicine used for neurological disorders. HFD contains cinnabar (HgS) and realgar (As4S4). The ethnopharmacological basis of cinnabar and realgar in HFD is not known.Aim of the study: To address the role of cinnabar and realgar in HFD-produced neuroprotection against neurodegenerative diseases and disturbance of gut microbiota.Materials and methods: Lipopolysaccharide (LPS) plus rotenone (ROT)-elicited rat dopaminergic (DA) neuronal damage loss was performed as a Parkinson's disease animal model. Rats were given a single injection of LPS. Four months later, rats were challenged with the threshold dose of ROT. The clinical dose of HFD was administered via feed, starting from ROT administration for 46 days. Behavioral dysfunction was detected by rotarod and Y-maze tests. DA neuron loss and microglial activation were assessed via immunohistochemical staining and western bolt analysis. The colon content was collected to extract bacterial DNA followed by real-time PCR analysis with 16S rRNA primers.Results: LPS plus ROT induced neurotoxicity, as evidenced by DA neuron loss in substantia nigra, impaired behavioral functions and increased microglial activation. HFD-original (containing 10% cinnabar and 10% realgar) rescued loss of DA neurons, improved behavioral dysfunction and attenuated microglial activation. Compared with HFD-original, HFD-reduced (3% cinnabar and 3% realgar) was also effective, but to be a less extent, while HFD-removed (without cinnabar and realgar) was ineffective. In analysis of gut microbiome, the increased Verrucomicrobiaceae and Lactobacteriaceae, and the decreased Enterobacteeriaceae by LPS plus ROT were ameliorated by HFD-original, and to be the less extent by HFD-reduced.Conclusion: Cinnabar and realgar are active ingredients in HFD to exert beneficial effects in a neurodegenerative model and gut microbiota.