地黄紫草颗粒通过网络药理学和实验验证调控 AGE/RAGE/NF-κB 信号通路以抑制银屑病小鼠的炎症反应

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Chong Lyu, Xianhua Qiao, Zhe Shi, Juanjuan Gao, Xiao Li, Shibin Jiang, Chengcheng Wang
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引用次数: 0

摘要

目的:银屑病是一种免疫介导的皮肤病,世界各地均有发生,具有高发病率和慢性化的特点。银屑病发病机制复杂,难以治愈。因此,不断探索银屑病的发病机制,寻找新的药物治疗方法,对于提高银屑病的治疗效率,减少银屑病患者的心理伤害至关重要。地黄紫草颗粒(DHZCG)中的有效成分能有效治疗银屑病。因此,本研究旨在分析地黄紫草颗粒的有效成分及其治疗银屑病的潜在机制:方法:通过中药系统药理学数据库和分析平台(TCMSP)筛选出DHZCG的有效成分。从 GeneCards、OMIM 和 DisGENET 数据库中检索银屑病的遗传信息。进行了蛋白质-蛋白质相互作用(PPI)分析,并构建了成分-目标-疾病网络。通过 GO 和 KEGG 分析筛选了重要的分子生物学过程和信号通路。通过 AutoDock Vina(1.1.2)对活性成分和关键靶点进行了分子对接。建立银屑病小鼠模型,分为对照组、模型组、低剂量 DHZCG 组(L-DHZCG)、中剂量 DHZCG 组(M-DHZCG)和高剂量 DHZCG 组(H-DHZCG)。对各组小鼠的皮肤进行血栓素和伊红(HE)染色以确定病理变化,并使用银屑病面积严重性指数(PASI)评分来评估皮肤损伤。用 ELISA 和 RT- PCR 分别测定小鼠血清和皮肤组织中炎症因子 TNF-a、IL-17A 和 IL-23 的水平。用 Western 印迹法分析 AGE/RAGE 信号通路相关蛋白的表达。免疫荧光用于检测炎症因子 NF-kB 的表达。免疫组化法测定皮肤组织中 IL-1β 和 TNF-a 的表达:结果:发现了60个与DHZCG治疗银屑病相关的基因,包括编码IL-6、TNF-a、AKT1、IL-1β、TP53、NFKB1、BCL2和MAPK3的核心基因。通过构建银屑病小鼠模型,DHZCG治疗有效地减轻了皮肤损伤,并显著降低了血清和受损皮肤中TNF-a、IL-17A、IL- 23、IL-1b和NF-kB等有效因子的水平。此外,DHZCG 对这些炎症因子水平的降低与 AGE/RAGE 信号通路的下调有关:结论:DHZCG可通过下调AGE/RAGE/NF-kB信号通路来减少炎症并缓解银屑病。这项研究有利于为银屑病药物的研发提供理论依据,并为银屑病的临床治疗提供个性化治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dihuangzicao Granules Regulate the AGE/RAGE/NF-κB Signaling Pathway to Inhibit Inflammation in Psoriatic Mice via Network Pharmacology and Experimental Validation.

Aim: Psoriasis is an immune-mediated skin disease that occurs worldwide and is characterized by high prevalence and chronicity. Psoriasis has a complex pathogenesis and is difficult to cure. Therefore, continuous exploration of the pathogenesis of psoriasis and the search for new drug treatment methods are crucial for improving treatment efficiency and reducing psychological damage to psoriasis patients. The active ingredients in Dihuang Zicao granules (DHZCG) can effectively treat psoriasis. Therefore, this study aimed to analyze the active ingredients of DHZCG and their potential mechanisms for treating psoriasis.

Methods: The effective components of DHZCG were screened via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Genetic information for psoriasis was retrieved from the GeneCards, OMIM and DisGENET databases. Protein-Protein Interaction (PPI) analysis was performed, and component‒target‒disease networks were constructed. Important molecular biological processes and signaling pathways were screened via GO and KEGG analyses. Molecular docking of the active ingredients and key targets was performed via AutoDock Vina (1.1.2). A mouse model of psoriasis was established and divided into a control group, model group, low-dose DHZCG group (L-DHZCG), medium-dose DHZCG group (M-DHZCG), and high-dose DHZCG group (H-DHZCG). Hematoxylin and Eosin (HE) staining was performed to determine the pathological changes in the skin of each group of mice, and the Psoriasis Area Severity Index (PASI) score was used to assess skin damage. ELISA and RT‒ PCR were used to measure the levels of the inflammatory factors TNF-a, IL-17A, and IL-23 in the serum and skin tissue of the mice, respectively. Western blotting was used to analyze the expression of proteins related to the AGE/RAGE signaling pathway. Immunofluorescence was used to examine the expression of the inflammatory factor NF-kB. Immunohistochemistry was used to measure IL-1β and TNF-a expression in skin tissues.

Results: Sixty genes associated with psoriasis treatment by DHZCG, including core genes encoding IL-6, TNF-a, AKT1, IL-1β, TP53, NFKB1, BCL2, and MAPK3, were identified. Through the construction of a psoriasis mouse model, DHZCG treatment effectively reduced skin damage and significantly decreased the levels of the validated factors TNF-a, IL-17A, IL- 23, IL-1b, and NF-kB in the serum and damaged skin. Furthermore, the reduction in the levels of these inflammatory factors by DHZCG is associated with the downregulation of the AGE/RAGE signaling pathway.

Conclusion: DHZCG reduces inflammation and alleviates psoriasis by downregulating the AGE/RAGE/NF-kB signaling pathway. This study is beneficial for providing a theoretical basis for the development of drugs for psoriasis and for offering personalized treatment strategies for the clinical management of psoriasis.

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来源期刊
CiteScore
3.10
自引率
5.60%
发文量
327
审稿时长
7.5 months
期刊介绍: Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.
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