中药复方黄芩清热除痹胶囊通过 LncRNA H19/APN/PI3K/AKT 级联减轻痛风性关节炎的脂代谢紊乱和炎症反应。

Chinese herbal compound Huangqin Qingrechubi capsule reduces lipid metabolism disorder and inflammatory response in gouty arthritis the LncRNA H19/APN/PI3K/AKT cascade.

机构信息

Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui, University of Traditional Chinese Medicine, Hefei, China.

Institute of Rheumatology, Anhui University of Chinese Medicine, Hefei, China.

出版信息

Pharm Biol. 2023 Dec;61(1):541-555. doi: 10.1080/13880209.2023.2191641.

CONTEXT

Gouty arthritis (GA) is a characteristically inflammatory disease often associated with lipid metabolism disorder. Huangqin Qingrechubi capsule (HQC) has been used for the treatment of GA.

OBJECTIVE

To explore the mechanism of HQC in the treatment of GA.

MATERIALS AND METHODS

A total of 30 GA patients (GA group) and 30 healthy subjects [normal control (NC) group] were recruited. The GA group was treated with HQC (3.6 g/d) for 10 days. Lipid metabolism and inflammation indexes were detected. Five herbal names of HQC, or 'gouty arthritis', 'hyperlipidemia' and 'inflammation' were used as key words to search related databases for network pharmacological analysis. Subsequently, GA-fibroblast-like synoviocytes (FLSs) were stimulated with GA-peripheral blood mononuclear cells (PBMCs) (3:1) and treated with HQC drug-containing serum (20%). RT-qPCR, Western blot, and ELISA were conducted to further explore the mechanism of HQC in improving GA.

RESULTS

In clinical observation, HQC decreased the expression of lncRNA H19 and IL-1β, and increased the expression of adiponectin (APN) and IL-4 in the GA group (about half). Through network pharmacology, the PI3K/AKT signaling pathway was identified. Cell experiments showed that HQC treatment reduced the viability of GA-FLSs (49.61%), up-regulated the expression of IL-4 (155.18%), IL-10 (165.13%), and APN (31.24%), and down-regulated the expression of lncRNA H19 (33.70%), IL-1β (64.70%), TNF-α (78.32%), p-PI3K (48.80%), and p-AKT (53.48%).

DISCUSSION AND CONCLUSIONS

HQC improved lipid metabolism disorder and inflammatory response of GA by regulating the lncRNA H19/APN/PI3K/AKT. Maintaining the stability of lipid metabolism may be an effective way to alleviate GA.

背景

痛风性关节炎（GA）是一种特征性炎症性疾病，常伴有脂质代谢紊乱。黄芩清热除痹胶囊（HQC）已用于治疗 GA。

目的

探讨 HQC 治疗 GA 的作用机制。

材料和方法

共招募 30 例 GA 患者（GA 组）和 30 例健康受试者[正常对照组（NC）组]。GA 组给予 HQC（3.6 g/d）治疗 10 d。检测脂质代谢和炎症指标。以“痛风性关节炎”、“高脂血症”和“炎症”等 HQC 中的 5 种草药名称作为关键词，搜索相关数据库进行网络药理学分析。随后，用 GA-外周血单个核细胞（PBMC）（3:1）刺激 GA-成纤维样滑膜细胞（FLS），并用含 HQC 药物的血清（20%）处理。采用 RT-qPCR、Western blot 和 ELISA 进一步探讨 HQC 改善 GA 的作用机制。

结果

临床观察发现，HQC 降低了 GA 组 lncRNA H19 和 IL-1β的表达，增加了脂联素（APN）和 IL-4 的表达（约为一半）。通过网络药理学分析，鉴定出 PI3K/AKT 信号通路。细胞实验表明，HQC 处理降低了 GA-FLSs 的活力（49.61%），上调了 IL-4（155.18%）、IL-10（165.13%）和 APN（31.24%）的表达，下调了 lncRNA H19（33.70%）、IL-1β（64.70%）、TNF-α（78.32%）、p-PI3K（48.80%）和 p-AKT（53.48%）的表达。