Mechanism of Ephedra-Guizhi in Treatment of Rheumatoid Arthritis Based on Network Pharmacology and Molecular Docking

SHI Liying; WEN Zeyu; SONG Yu; YU Dayong

doi:10.6054/j.jscnun.2023021

Journal of South China Normal University (Natural Science Edition) > 2023 > 55(2): 62-72. > DOI: 10.6054/j.jscnun.2023021

SHI Liying, WEN Zeyu, SONG Yu, YU Dayong. Mechanism of Ephedra-Guizhi in Treatment of Rheumatoid Arthritis Based on Network Pharmacology and Molecular Docking[J]. Journal of South China Normal University (Natural Science Edition), 2023, 55(2): 62-72. DOI: 10.6054/j.jscnun.2023021

Citation:

PDF (4514 KB)

Mechanism of Ephedra-Guizhi in Treatment of Rheumatoid Arthritis Based on Network Pharmacology and Molecular Docking

School of Life Science and Biotechnology, Dalian University, Dalian 116622, China

More Information

Received Date: June 10, 2021
Available Online: June 13, 2023

Graphical Abstract

Abstract

Abstract

The active components and corresponding target proteins in Ephedra and Guizhi were retrieved through TCMSP database, and Rheumatoid Arthritis(RA) related targets were retrieved with "rheumatoid arthritis" as the keyword in GeneCards database. After the collected two types of targets were mapped and intersected with each other, PPI network was constructed through STRING platform, and visual analysis was carried out by Cytoscape software. At the same time, the intersection targets were enriched and analyzed by GO and KEGG with the help of David 6.8 database. Finally, the core target and key active components were docking verified by Schrodinger software. Two kinds of targets are mapped, there are 134 intersection targets. PPI analysis shows that the core targets are AKT1, IL6, TP53, RELA and CCND1. Go and KEGG enrichment analysis showed that the key signal pathways were TNF signal pathway, Toll like receptor signal pathway and PI3K-Akt signal pathway. Molecular docking results showed that quercetin, luteolin and dihydroquercetin had good binding effects with AKT1, IL6 and TP53. It is concluded that the active components of Ephedra-Guizhi may play a role in the treatment of rheumatoid arthritis by inhibiting the expression of inflammatory mediators and suppressing the excessive proliferation of dendritic cells and macrophages in joint synovium to prevent pathological progression of RA.
- network pharmacology,
- rheumatoid arthritis,
- mechanism of action,
- Ephedra-Guizhi drug pair,
- molecu-lar docking

FullText(HTML)

References (25)

References

[1]	ITOH Y. Metalloproteinases in rheumatoid arthritis: potential therapeutic targets to improve current therapies[J]. Progress in Molecular Biology and Translational Science, 2017, 148(2): 327-338.
[2]	SWALES C, ATHANASOU N A, KNOWLES H J. Angiopoietin-like 4 is over-expressed in rheumatoid arthritis patients: association with pathological bone resorption[J]. PloS One, 2014, 9(10): e109524/1-8.
[3]	BRENNAN F M, MAINI R N, FELDMANN M. Role of pro-inflammatory cytokines in rheumatoid arthritis[J]. Springer Semin Immunopathol, 1998, 20(1): 133-147.
[4]	蔡雄, 周华, 徐宏喜, 等. 类风湿性关节炎的中医临床治疗研究概况[J]. 中华中医药杂志, 2005, 20(5): 309-311. https://www.cnki.com.cn/Article/CJFDTOTAL-BXYY200505020.htm CAI X, ZHOU H, XU H X, et al. Overview of TCM clinical treatment of rheumatoid arthritis[J]. Chinese Journal of Traditional Chinese Medicine, 2005, 20(5): 309-311. https://www.cnki.com.cn/Article/CJFDTOTAL-BXYY200505020.htm
[5]	WANG X M, XU W J, XU L K, et al. Antipyretic effect of Herba Ephedrae-Ramulus Cinnamomi herb pair on yeast-induced pyrexia rats: a metabolomics study[J]. Chinese Journal of Integrative Medicine, 2018, 24(9): 676-682. doi: 10.1007/s11655-017-2778-0
[6]	李肖, 秦晴, 王小帆, 等. 麻黄附子细辛汤合桃红四物汤加味治疗类风湿性关节炎30例临床观察[J]. 中国民族民间医药, 2019, 28(13): 110-112. doi: 10.3969/j.issn.1007-8517.2019.13.zgmzmjyyzz201913030 LI X, QIN Q, WANG X F, et al. Clinical observation on 30 cases of rheumatoid arthritis treated with Mahuang Fuzi Asarum Decoction and Taohong Siwu Decoction[J]. Chinese National and Folk Medicine, 2019, 28(13): 110-112. doi: 10.3969/j.issn.1007-8517.2019.13.zgmzmjyyzz201913030
[7]	YASEEN H S, ASIF M, SAADULLAH M, et al. Methano-lic extract of Ephedra ciliata promotes wound healing and arrests inflammatory cascade in vivo through downregulation of TNF-α[J]. Inflammopharmacology, 2020, 28(6): 1691-1704. doi: 10.1007/s10787-020-00713-7
[8]	JI W, HU J, YU X, et al. Study on the inhibitory effects of Ephedra Aconite Asarum Decoction on LPS-induced dendritic cells[J]. Evidence-Based Complementary and Alternative Medicine, 2017, 2017(3): 3272649/1-10.
[9]	李树东, 王艳. 桂枝芍药知母汤治疗类风湿关节炎临床研究[J]. 中外医疗, 2014, 13(25): 147-148. doi: 10.3969/j.issn.1674-0742.2014.25.074 LI S D, WANG Y. Clinical study on Guizhi Shaoyao Zhimu Decoction in the treatment of rheumatoid arthritis[J]. Chinese and Foreign Medical, 2014, 13(25): 147-148. doi: 10.3969/j.issn.1674-0742.2014.25.074
[10]	赵慧. 桂枝芍药知母汤对Ⅱ型胶原诱导的关节炎大鼠作用机制的实验研究[D]. 北京: 北京中医药大学, 2006. ZHAO H. Experimental research on the mechanisms of Guizhishaoyaozhimu decotion's effect on the type Ⅱ co-llagen-induced Rat arthritis[D]. Beijing: Beijing University of Chinese Medicine, 2006.
[11]	宋瑗瑗, 曹洪玉, 未志俞, 等. 基于分子对接探究熊果酸衍生物H21对引起炎症的关键蛋白的作用[J]. 华南师范大学学报(自然科学版), 2021, 53(2): 59-64. doi: 10.6054/j.jscnun.2021027 SONG Y Y, CAO H Y, WEI Z Y, et al. Exploring the effect of ursolic acid derivative H21 on key proteins causing inflammation based on molecular docking[J]. Journal of South China Normal University(Natural Science Edition), 2021, 53(2): 59-64. doi: 10.6054/j.jscnun.2021027
[12]	LIN K, LIN J, WU W I, et al. An ATP-site on-off switch that restricts phosphatase accessibility of Akt[J]. Science Signaling, 2012, 5(223): ra37/1-11.
[13]	BAUER M R, JONES R N, TAREQUE R K, et al. A structure-guided molecular chaperone approach for restoring the transcriptional activity of the p53 cancer mutant Y220C[J]. Future Medicinal Chemistry, 2019, 11(19): 2491-2504. doi: 10.4155/fmc-2019-0181
[14]	SHAW S, BOURNE T, MEIER C, et al. Discovery and characterization of olokizumab: a humanized antibody targeting interleukin-6 and neutralizing gp130-signaling[J]. MAbs, 2014, 6(3): 774-782.
[15]	SCOTT D L, WOLFE F, HUIZINGA T W. Rheumatoid arthritis[J]. Lancet, 2010, 376: 1094-1108. doi: 10.1016/S0140-6736(10)60826-4
[16]	SALEEM A, SALEEM M, AKHTAR M F, et al. Polystichum braunii extracts inhibit Complete Freund's adjuvant-induced arthritis via upregulation of I-κB, IL-4, and IL-10, downregulation of COX-2, PGE2, IL-1β, IL-6, NF-κB, and TNF-α, and subsiding oxidative stress[J]. Inflammopharmacology, 2020, 28(6): 1633-1648.
[17]	沈瑞明, 李国铨, 钟良宝. 木犀草素对急性痛风性关节炎模型大鼠的抗炎作用研究[J]. 海南医学院学报, 2019, 25(17): 1300-1303. https://www.cnki.com.cn/Article/CJFDTOTAL-HNYY201917006.htm SHEN R M, LI G Q, ZHONG L B. Anti inflammatory effect of luteolin on acute gouty arthritis model rats[J]. Journal of Hainan Medical College, 2019, 25(17): 1300-1303. https://www.cnki.com.cn/Article/CJFDTOTAL-HNYY201917006.htm
[18]	HOU Y, WU J, HUANG Q, et al. Luteolin inhibits prolife-ration and affects the function of stimulated rat synovial fibroblasts[J]. Cell Biology International, 2009, 33(2): 135-147.
[19]	LOU L, LIU Y, ZHOU J, et al. Chlorogenic acid and luteolin synergistically inhibit the proliferation of interleukin-1β-induced fibroblast-like synoviocytes through regulating the activation of NF-κB and JAK/STAT-signaling pathways[J]. Immunopharmacol Immunotoxicol, 2015, 37(6): 499-507.
[20]	ZHANG H Q, WANG Y J, YANG G T, et al. Taxifolin inhibits receptor activator of NF-κB ligand-induced osteoclastogenesis of human bone marrow-derived macrophages in vitro and prevents lipopolysaccharide-induced bone loss in vivo[J]. Pharmacology, 2019, 103(1/2): 101-109.
[21]	王佳奇, 陈凯, 王月亮, 等. 二氢槲皮素与二氢杨梅素抗炎活性对比研究[J]. 中国兽药杂志, 2016, 50(7): 46-52. https://www.cnki.com.cn/Article/CJFDTOTAL-ZSYY201607009.htm WANG J Q, CHEN K, WANG Y L, et al. Comparison of anti-inflammatory activity of dihydroquercetin and dihydromyricetin[J]. Chinese Journal of Veterinary Drug, 2016, 50(7): 46-52. https://www.cnki.com.cn/Article/CJFDTOTAL-ZSYY201607009.htm
[22]	YANG J, CHENG M, GU B, et al. CircRNA_09505 aggravates inflammation and joint damage in collagen-induced arthritis mice via miR-6089/AKT1/NF-κB axis[J]. Cell Death & Disease, 2020, 11(10): 833-846.
[23]	IGARASHI H, HASHIMOTO J, TOMITA T, et al. TP53 mutations coincide with the ectopic expression of activation-induced cytidine deaminase in the fibroblast-like synoviocytes derived from a fraction of patients with rheumatoid arthritis[J]. Clinical & Experimental Immunology, 2010, 161(1): 71-80.
[24]	MALEMUD C J. The PI3K/Akt/PTEN/mTOR pathway: a fruitful target for inducing cell death in rheumatoid arthritis[J]. Future Medicinal Chemistry, 2015, 7(9): 1137-1147.
[25]	HWANG S Y, KIM J Y, KIM K W, et al. IL-17 induces production of IL-6 and IL-8 in rheumatoid arthritis synovial fibroblasts via NF-κB-and PI3-kinase/Akt-dependent pathways[J]. Arthritis Research & Therapy, 2004, 6(2): 120-128.

Cited By

Get Citation

PDF

XML

Article views (269) PDF downloads (75)

Turn off MathJax

Article Contents

Abstract

References

Mechanism of Ephedra-Guizhi in Treatment of Rheumatoid Arthritis Based on Network Pharmacology and Molecular Docking

Abstract

References

Catalog

Export File

Citation

Format

Content