何首乌水提物及其活性成分大黄素通过调控胆固醇代谢抑制软骨细胞炎症缓解骨关节炎的研究

Water extracts of Polygonum Multiflorum Thunb.and its active component emodin relieves osteoarthritis by regulating cholesterol metabolism and suppressing chondrocyte inflammation

[目的]何首乌是一种被广泛应用的传统中草药,具有多种药理作用。经过炮制加工后具有不同的药理作用。然而,何首乌炮制前后的化学成分变化,以及其炮制品具补肝肾、强筋骨,进而是否具有治疗骨关节炎的功效作用尚不清楚。因此,本研究探索制首乌是否具有改善骨关节炎的药效作用,并研究制首乌中主要活性成分在防治骨关节炎作用中的分子机制。[方法]采用高效液相色谱法对炮制前后何首乌水提物进行对比分析。利用GEO数据库及R语言对骨关节炎疾病靶点进行KEGG和GO富集分析。通过GC-MS代谢组学技术测定经药物处理前后软骨细胞的代谢表征。[结果]结果显示何首乌炮制后具有改善骨关节炎的药效作用,且炮制后活性成分大黄素含量显著增加。GEO数据库分析进一步证明骨关节炎的发病进程与生物代谢途径存在较大关联。大黄素能够在一定程度上促进软骨细胞增殖,并显著抑制炎症因子的表达。代谢组学结果显示,大黄素通过调节5种代谢途径包括:氨基酸代谢、脂肪酸合成、胆固醇代谢等参与延缓软骨细胞退变,进而抑制骨关节炎的发生发展。[结论]本研究揭示了经过中药炮制后的制何首乌具有抑制骨关节炎的功效作用,并证实经过炮制后主要增量物质大黄素是产生抗炎药理活性,进而治疗骨关节炎的活性成分,本研究为制何首乌治疗骨关节炎提供了科学依据。

Objective:Polygonum multiflorum Thunb.(PMT)is a widely used traditional Chinese herbal medicine with a variety of pharmacological effects.This study investigates the chemical composition of a water extract of PMT and its potential as a therapy for osteoarthritis(OA).Methods:The components of the aqueous extract of PMT were determined using high-performance liquid chromatography(HPLC).Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of a gene expression dataset downloaded from the Gene Expression Omnibus(GEO)were performed using Limma in R language.Differential chondrocyte metabolites were determined using gas chromatography-mass spectrometry(GC-MS)before and after treatment.Results:The water extract of PMT showed good ability in improving OA,and the content of the active ingredient emodin increased significantly after processing.Analysis of the GEO database further demonstrated a strong association between OA and metabolic pathways.Emodin promotes chondrocyte proliferation and significantly reduces the number of inflammatory factors.The metabolomic results showed that emodin affected five metabolic pathways related mainly to primary bile acid biosynthesis,steroid biosynthesis,and biosynthesis of unsaturated fatty acids.Conclusions:This study revealed the pharmacological effects of PMT and emodin as the main active components,thereby providing a scientific basis for the treatment of OA.