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银屑灵优化方治疗寻常型银屑病的疗效及其基于 microRNA 表达谱和网络药理学分析的自噬调控作用。

The Benefit of the Optimized Formula of Yinxieling in Psoriasis Vulgaris via Regulation on Autophagy Based on microRNA Expression Profile and Network Pharmacology Analysis.

机构信息

State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, People's Republic of China.

Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, People's Republic of China.

出版信息

Drug Des Devel Ther. 2024 Jun 14;18:2257-2272. doi: 10.2147/DDDT.S459622. eCollection 2024.

DOI:10.2147/DDDT.S459622
PMID:38895176
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11185257/
Abstract

BACKGROUND

Psoriasis is a widespread chronic, immune-mediated skin disease with frequent recurrences, and is extremely harmful to the physical and mental health of patients, causing enormous suffering and exerting considerable economic burdens on the health care system as a whole. In more than a decade of clinical use, the optimized formula of Yinxieling (PSORI-CM01) has consistently demonstrated its effectiveness for treating psoriasis. However, its underlying mechanism remains largely unexplored.

METHODS

The network pharmacology analysis was conducted to predict the mechanism and protective effect of PSORI-CM01 in treating psoriasis. Subsequently, we collected blood samples from 21 patients with psoriasis as part of a randomized, double-blind, and double-dummy clinical trial for microRNA expression profiling. Finally, it was experimentally confirmed that PSORI-CM01 improved psoriasis by regulating miR-20a-3p and miR-3184-3p expression.

RESULTS

As a result of the network pharmacology analysis, PSORI-CM01 improved psoriasis through the regulation of autophagy, cellular apoptosis, cellular proliferation, and anti-inflammatory processes. In the target-miRNA regulatory network, these key targets were mainly associated with the regulation of hsa-miR-20a-3p, hsa-miR-155-5p, has-miR-3184-3p, hsa-miR-328-3p and hsa-miR-124-3p. Based on the microRNA expression profiling results, the PSORI-CM01 treatment group exhibited five up-regulated genes and 16 down-regulated genes compared with the healthy control group. In particular, miR-20a-3p and miR-3184-3p were the primary differentially expressed microRNAs, and they were significantly enriched in the signaling pathways involving autophagy, apoptosis, proliferation, and anti-inflammation. Further experiments confirmed that PSORI-CM01 effectively regulates miR-20a-3p and miR-3184-3p, resulting in increased autophagy.

CONCLUSION

We demonstrated by combining network pharmacology and clinical studies of miRNA expression profiles in PBMCs that PSORI-CM01 effectively modulated miR-20a-3p and miR-3184-3p, leading to an increase in autophagy and a decrease in keratinocyte proliferation.

摘要

背景

银屑病是一种广泛存在的慢性、免疫介导的皮肤病,常反复发作,对患者身心健康危害极大,给患者带来极大的痛苦,给整个医疗保健系统带来了巨大的经济负担。在十多年的临床应用中,优化配方的银屑灵(PSORI-CM01)始终表现出对银屑病的治疗效果。然而,其潜在机制在很大程度上仍未得到探索。

方法

通过网络药理学分析预测 PSORI-CM01 治疗银屑病的机制和保护作用。随后,我们收集了 21 名银屑病患者的血样,作为一项随机、双盲、双模拟临床试验的一部分,进行 microRNA 表达谱分析。最后,实验证实 PSORI-CM01 通过调节 miR-20a-3p 和 miR-3184-3p 的表达来改善银屑病。

结果

通过网络药理学分析,PSORI-CM01 通过调节自噬、细胞凋亡、细胞增殖和抗炎过程来改善银屑病。在靶标-miRNA 调控网络中,这些关键靶点主要与 hsa-miR-20a-3p、hsa-miR-155-5p、has-miR-3184-3p、hsa-miR-328-3p 和 hsa-miR-124-3p 的调节有关。基于 microRNA 表达谱分析结果,与健康对照组相比,PSORI-CM01 治疗组有 5 个上调基因和 16 个下调基因。特别是 miR-20a-3p 和 miR-3184-3p 是主要差异表达的 microRNAs,它们显著富集在自噬、凋亡、增殖和抗炎相关的信号通路中。进一步的实验证实 PSORI-CM01 能有效调节 miR-20a-3p 和 miR-3184-3p,从而增加自噬。

结论

我们通过结合网络药理学和 PBMCs 中 microRNA 表达谱的临床研究,证明 PSORI-CM01 能有效调节 miR-20a-3p 和 miR-3184-3p,从而增加自噬,减少角质形成细胞增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77e1/11185257/232a4d635d04/DDDT-18-2257-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77e1/11185257/8f8318bb6b0e/DDDT-18-2257-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77e1/11185257/0b6e3d684758/DDDT-18-2257-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77e1/11185257/23818ec05b6d/DDDT-18-2257-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77e1/11185257/df3699313503/DDDT-18-2257-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77e1/11185257/ad829c5b99a7/DDDT-18-2257-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77e1/11185257/232a4d635d04/DDDT-18-2257-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77e1/11185257/8f8318bb6b0e/DDDT-18-2257-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77e1/11185257/0b6e3d684758/DDDT-18-2257-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77e1/11185257/23818ec05b6d/DDDT-18-2257-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77e1/11185257/df3699313503/DDDT-18-2257-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77e1/11185257/ad829c5b99a7/DDDT-18-2257-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77e1/11185257/232a4d635d04/DDDT-18-2257-g0006.jpg

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