五子衍宗丸通过miR-146a-5p/USP3/NF-κB轴改善帕金森病
Wuzi Yanzong Pill improves Parkinson's disease via miR-146a-5p/USP3/NF-κB axis.
摘要(中文译文)
神经炎症以小胶质细胞活化失调为特征，是帕金森病（PD）的标志性病理改变。然而，针对炎症消退机制的治疗策略仍十分有限。本研究整合了PD临床队列、MPTP诱导及miR-146a诱导的小鼠模型，以及LPS刺激和miR-146a活化的细胞模型。结合组学分析、行为学检测和分子生物学实验，我们系统评价了五子衍宗丸（WYP）的抗炎保护作用。采用UHPLC-Q-Exactive-MS/MS、AP-SMALDI Orbitrap MSI及药代动力学分析相结合的方法鉴定了WYP的活性植物代谢产物。在PD患者中，WYP显著改善了运动功能障碍，抑制了促炎细胞因子，并提高了神经递质水平。外泌体miRNA测序分析表明，miR-146a-5p可能作为PD的生物标志物，且与疾病严重程度呈正相关。动物实验进一步显示，WYP改善了MPTP诱导及miR-146a诱导的PD小鼠模型的运动症状和神经炎症。双荧光素酶报告基因实验证实泛素特异性蛋白酶3（USP3）是miR-146a-5p的直接靶基因。在LPS活化的BV2小胶质细胞模型中，WYP干预降低了细胞来源外泌体中miR-146a-5p的含量，并减轻了其对神经元细胞的促炎损伤作用。成分分析显示，WYP中有16种植物代谢产物可进入血液循环，其中11种可透过血脑屏障进入脑组织。值得注意的是，京尼平苷酸、金丝桃苷、山奈酚、原儿茶酸和五味子醇A显著抑制了BV2细胞中促炎因子的表达，提示它们可能是WYP抗炎作用的主要活性成分。WYP通过调控miR-146a-5p/USP3/NF-κB通路改善PD。同时，WYP的活性植物代谢产物已被鉴定。这些发现为WYP作为PD潜在治疗药物提供了实验依据。
Abstract
Neuroinflammation, characterized by dysregulated activation of microglia, is a hallmark of Parkinson's disease (PD). Nevertheless, therapeutic strategies aimed at the mechanism of inflammation resolution remain limited. This study integrated PD clinical cohorts, MPTP-induced and miR-146a-induced mouse models, as well as LPS-stimulated and miR-146a-activated cell models. Combined with omics analysis, behavioral detection and molecular biology experiments, we systematically evaluated the anti-inflammatory protective effects of Wuzi Yanzong Pills (WYP). The active plant metabolites of WYP were identified using a combination of UHPLC-Q-Exactive-MS/MS, AP-SMALDI Orbitrap MSI, and pharmacokinetic analysis. In PD patients, WYP significantly improved motor dysfunction, inhibited pro-inflammatory cytokines, and elevated neurotransmitter levels. Exosomal miRNA sequencing analysis indicated that miR-146a-5p may serve as a biomarker for PD and is positively correlated with disease severity. Animal experiments further showed that WYP improved motor symptoms and neuroinflammation in MPTP- and miR-146a-induced PD mice models. A dual-luciferase reporter assay confirmed ubiquitin specific peptidase 3 (USP3) as a direct target gene of miR-146a-5p. In an LPS-activated BV2 microglial cell model, WYP intervention reduced the content of miR-146a-5p in cell-derived exosomes and mitigated their pro-inflammatory damaging effects on neuronal cells. Component analysis revealed that 16 plant metabolites in WYP can enter the bloodstream, among which 11 can cross into the brain. Notably, geniposidic acid, hyperoside, kaempferol, protocatechuic acid, and schisandrol A significantly suppressed the expression of pro-inflammatory factors in BV2 cells, suggesting that they may be the main active components underlying the anti-inflammatory effects of WYP. WYP improves PD by regulating the miR-146a-5p/USP3/NF-κB pathway. Meanwhile, the active plant metabolites of WYP have been identified. These findings provide experimental evidence for WYP as a potential therapeutic agent for PD.
如何引用
AMA
Lei Xu, Ziqi Feng, Zhixin Li, Shaochen Qin, Lixia Yang, Baoguo Xiao, et al. Wuzi Yanzong Pill improves Parkinson's disease via miR-146a-5p/USP3/NF-κB axis.. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2026; doi:10.1016/j.phymed.2026.158417.
APA
Lei Xu, Ziqi Feng, Zhixin Li, Shaochen Qin, Lixia Yang, Baoguo Xiao, et al (2026). Wuzi Yanzong Pill improves Parkinson's disease via miR-146a-5p/USP3/NF-κB axis.. Phytomedicine : international journal of phytotherapy and phytopharmacology. https://doi.org/10.1016/j.phymed.2026.158417
GB/T 7714
Lei Xu, Ziqi Feng, Zhixin Li, Shaochen Qin, Lixia Yang, Baoguo Xiao, et al. Wuzi Yanzong Pill improves Parkinson's disease via miR-146a-5p/USP3/NF-κB axis.[J]. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2026 doi:10.1016/j.phymed.2026.158417.
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