The mechanism of Sijiqing aqueous extract in improving bronchial asthma based on network pharmacology and in vitro experiment

Published on Sep. 28, 2025Total Views: 1614 times Total Downloads: 286 times Download Mobile

Author: YUAN Fengjuan ¹ LING Bing ¹ ZHAO Yumin ¹ MA Dongjun ²  ZHANG Lijuan ³ CHEN Jingjing ¹

Affiliation: 1. Department of Pharmacy, Urumqi First People's Hospital (Urumqi Children's Hospital), Urumqi 830000, China 2. Center for Respiratory Cough and Asthma, Urumqi First People's Hospital (Urumqi Children's Hospital), Urumqi 830000, China 3. Department of Pharmacy, School of Pharmacy, Xinjiang Medical University, Urumqi 830011, China

Keywords: Sijiqing Bronchial asthma Network pharmacology Molecular docking In vitro experiment Inflammatory factors

DOI: 10.12173/j.issn.1004-4337.202504060

Reference: Yuan FJ, Ling B, Zhao YM, Ma DJ, Zhang LJ, Chen JJ. The mechanism of Sijiqing aqueous extract in improving bronchial asthma based on network pharmacology and in vitro experiment[J]. Journal of Mathematical Medicine, 2025, 38(9): 655-664. DOI: 10.12173/j.issn.1004-4337.202504060[Article in Chinese]  Copied

Abstract
Full-text
References

Abstract

Objective To explore the mechanism of Sijiqing in the treatment of bronchial asthma through network pharmacology, molecular docking simulation and in vitro cell experiments.

Methods The active ingredients and related targets of Sijiqing were retrieved and screened in the TCMSP database, the targets related to anti-inflammatory were obtained by searching in OMIM and GeneCards databases, the intersecting targets were screened and the Venn diagram was drawn. Network topology structure analysis was performed using Cytoscape 3.8.2 software, and a "traditional Chinese medicine-active ingredient-target-disease" network diagram was drawn. The common gene targets were uploaded to the STRING database to establish a protein-protein interaction (PPI) network diagram of drug target proteins and disease target proteins. The binding energy of core targets and related compounds was obtained through molecular docking technology. A RAW264.7 cell inflammation model was established, and the effect of Sijiqing on the activity of RAW264.7 cells was detected by MTS method. The effect on NO signaling pathway was studied by Griess reagent method, and the effect of Sijiqing on inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in cell supernatant was detected by ELISA method.

Results The results of network pharmacology showed that the core components of Sijiqing were sitosterol, quercetin, kanfenol, stigmasterol, pomeolic acid acetate, etc., and the core targets were IL4, STAT, TNF, IL6, INFG, etc. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the main signaling pathways included MAPK and NF-κB. The molecular docking results showed that the binding affinities of the core components kaempferol and quercetin of Sijiqing to target molecules were less than -4 kcal/J. The results of cell experiments verified that Sijiqing could significantly reduce the expression of NO, IL-6 and TNF-α in inflammatory cells.

Conclusion Sijiqing can improve the inflammatory response of inflammatory cells through the core targets represented by IL-6 and TNF-α and key pathways such as NO.

Full-text

Please download the PDF version to read the full text: download

References

1. 娄南南, 郭晶, 马香, 等. 不同给药方案对治疗儿童咳嗽变异性哮喘的临床效果分析[J]. 数理医药学杂志, 2024, 37(6): 418-424. [Lou NN, Guo J, Ma X, et al. Clinical effect analysis of medication regimens on the treatment of cough variant asthma in children[J]. Journal of Mathematical Medicine, 2024, 37(6): 418-424.] DOI: 10.12173/j.issn.1004-5511.202403150.

2. Lin Z, Yuan L, Zhang C, et al. Association of bronchial asthma with lung cancer: a systematic review and meta-analysis[J]. Iran J Allergy Asthma Immunol, 2024, 23(4): 347-356. DOI: 10.18502/ijaai.v23i4.16209.

3. Li M, Zhong X, Xu WT. Substance P promotes the progression of bronchial asthma through activating the PI3K/AKT/NF-κB pathway mediated cellular inflammation and pyroptotic cell death in bronchial epithelialcells[J]. Cell Cycle, 2022, 21(20): 2179-2191. DOI: 10.1080/15384101.2022.2092166.

4. Al-Beltagi M, Bediwy AS, Saeed NK, et al. Diabetes-inducing effects of bronchial asthma[J]. World J Diabetes, 2025, 16(1): 97954. DOI: 10.4239/wjd.v16.i1.97954.

5. 国家药典委员会. 中国药典2020版一部[M]. 北京: 中国医药科技出版社, 2020: 104.

6. 杜伟, 黄文涛, 罗金萍, 等. 四季青水提液对慢性变应性接触性皮炎大鼠 AIM2/Caspase-1炎症小体的影响[J]. 西南大学学报（自然科学版）, 2021, 43(2): 63-69. [Du W, Huang WT, Luo JP, et al. Effect of Ilicischinensis folium water extract on the inflammatory bodies of AIM2/Caspase-1 in rats with chronic allergic contact dermatitis[J]. Journal of Southwest University (Natural Science Edition), 2021, 43(2): 63-69.] DOI: 10.13718/j.cnki.xdzk.2021.02.009.

7. 范小艳, 廖黎, 朱洁, 等. 基于网络药理学探讨四季青有效成分作用机制[J]. 中药与临床, 2021, 12(1): 15-18. [Fan XY, Liao L, Zhu J, et al. Study of mechanism of active components of Sijiqing based on network pharmacology[J]. Pharmacy and Clinics of Chinese Materia Medica, 2021, 12(1): 15-18.] DOI: 10.3969/j.issn.1674-926X.2021.01.004.

8. 张玉梅, 李春华, 盛秀涛. 中药四季青的化学成分研究[J]. 吉林中医药, 2010, 30(3): 252-253. [Zhang YM, Li CH, Sheng XT. Study on the chemical components of the traditional Chinese medicine "Sijiqing"[J]. Jilin Journal of Chinese Medicine, 2010, 30(3): 252-253.] DOI: 10.13463/j.cnki.jlzyy.2010.03.036.

9. 姚聂尘轩, 余友媛, 许存宾. 基于网络药理学和分子对接探讨虫茶中活性成分调控糖尿病的作用机制[J]. 数理医药学杂志, 2025, 38(2): 110-120. [Yao NCX, Yu YY, Xu CB. The mechanism of the active ingredients in insect tea to regulate diabetes mellitus based on network pharmacology and molecular docking[J]. Journal of Mathematical Medicine, 2025, 38(2): 110-120.] DOI: 10.12173/ j.issn.1004-4337.202409035.

10. 史永彬. 肉桂对鸡生产性能和肠道黏膜形态及肠道菌群的影响[D]. 南宁：广西大学, 2023. [Shi YB. Effects of cinnamon on the performance, intestinal mucosal morphology, and gut microbiota in chickens[D]. Nanning: Guangxi University, 2023.] DOI: 10.27034/d.cnki.ggxiu.2023.001317.

11. 谭为, 张兰兰, 李晨阳, 等. 维药狭叶薰衣草抗炎活性部位筛选研究[J]. 中国民族民间医药, 2017, 26(22): 30-34. [Tan W, Zhang LL, Li CY, et al. Study on the anti-inflammatory active fraction of lavandula augustifolia mill[J]. Chinese Journal of Ethnomedicine and Ethnopharmacy, 2017, 26(22): 30-34.] DOI: 10.3969/j.issn.1007-8517.2017.22.zgmzmjyyzz201722012.

12. 马丽, 冯程程, 徐利娟, 等. 温通活血乳膏对LPS诱导的RAW264.7巨噬细胞TNF-α、IL-6、NF-κB表达的影响[J]. 中成药, 2018, 40(9): 2058-2062. [Ma L, Feng CC, Xu LJ, et al. Effects of Wentong Huoxue Cream on the expressions of TNF-α, IL-6 and NF-κB in RAW264.7 macrophages induced by LPS[J]. Chinese Traditional Patent Medicine, 2018, 40(9): 2058-2062.] DOI: 10.3969/j.issn.1001-1528.2018.09.037.

13. Radzikowska U, Eljaszewicz A, Tan G, et al. Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19[J]. Nat Commun, 2023, 14(1): 2329. DOI: 10.1038/s41467-023-37470-4.

14. Savin IA, Zenkova MA, Sen'kova AV. Bronchial asthma, airway remodeling and lung fibrosis as successive steps of one process[J]. Int J Mol Sci, 2023, 24(22): 16042. DOI: 10.3390/ijms242216042.

15. Barosova R, Baranovicova E, Hanusrichterova J, et al. Metabolomics in animal models of bronchial asthma and its translational importance for clinics[J]. Int J Mol Sci, 2023, 25(1): 459. DOI: 10.3390/ijms25010459.

16. 程强, 曾铭, 鲁兰, 等. 四季青水煎液对铜绿假单胞菌生物被膜生成、毒力因子分泌的抑制作用及机制研究[J]. 中药药理与临床, 2019, 35(4): 111-116. [Cheng Q, Zeng M, Lu L, et al. Inhibition and mechanism of ilex chinensis Sims folium water decoction on biofilm formation and virulence of pseudomonas aeruginosa[J]. Pharmacology and Clinics of Chinese Materia Medica, 2019, 35(4): 111-116.] DOI: 10.13412/j.cnki.zyyl.2019.04.022.

17. 程强, 周杨杨, 唐炯, 等. 四季青水煎液体外抗内毒素、抗菌和体内抗炎作用[J]. 中国抗生素杂志, 2018, 43(6): 765-771. [Cheng Q, Zhou YY, Tang J, et al. The anti-endotoxin, antibacterial effects in vitro and anti-inflammatory effects in vivo of Ilicis chinensis folium water decoction[J]. Chinese Journal of Antibiotics, 2018, 43(6): 765-771.] DOI: 10.3969/j.issn.1001-8689.2018.06.020.

18. 徐新, 刘畅, 曹佳渊, 等. 加减苍耳子散通过调控SYK/PI3K/AKT信号通路治疗变应性鼻炎的作用与机制[J]. 中药药理与临床, 2025, 41(4): 28-36. [Xu X, Liu C, Cao JY, et al. Modified Cang'erzi powder treats allergic rhinitis by regulating SYK/PI3K/AKT signaling pathway[J]. Pharmacology and Clinics of Chinese Materia Medica, 2025, 41(4): 28-36.] DOI: 10.13412/j.cnki.zyyl.20241016.001.

19. Salama A, Gouida MSO, Yassen NN, et al. Immunoregulatory role of hesperidin against ovalbumin (OVA)-induced bronchial asthma and depression in rats[J]. Naunyn Schmiedebergs Arch Pharmacol, 2024, 397(5): 3363-3378. DOI: 10.1007/s00210-023-02833-7.

20. Li X, Guerra S, Ledford JG, et al. Low CC16 mRNA expression levels in bronchial epithelial cells are associated with asthma severity[J]. Am J Respir Crit Care Med, 2023, 207(4): 438-451. DOI: 10.1164/rccm.202206-1230OC.

21. Frey A, Lunding LP, Ehlers JC, et al. More than just a barrier: the immune functions of the airway epithelium in asthma pathogenesis[J]. Front Immunol, 2020, 11: 761. DOI: 10.3389/fimmu.2020.00761.

22. Kochumon S, Al-Sayyar A, Jacob T, et al. TGF-β and TNF-α interaction promotes the expression of MMP-9 through H3K36 dimethylation: implications in breast cancer metastasis[J]. Front Immunol, 2024, 15: 1430187. DOI: 10.3389/fimmu.2024.1430187.

23. 张婷婷, 刘博, 邹雪, 等. 基于网络药理学和实验验证探讨加味小柴胡汤治疗咳嗽变异性哮喘的分子机制[J]. 湖南中医药大学学报, 2024, 44(3): 419-426. [Zhang TT, Liu B, Zou X, et al. Molecular mechanism of Jiawei Xiaochaihu Decoction in treating cough-variant asthma based on network pharmacology and experimental validation[J]. Journal of Traditional Chinese Medicine University of Hunan, 2024, 44(3): 419-426.] DOI: 10.3969/j.issn.1674-070X.2024.03.010.

24. Gu YY, Zhang M, Cen H, et al. Quercetin as a potential treatment for COVID-19-induced acute kidney injury: Based on network pharmacology and molecular docking study[J]. PLoS One, 2021, 16(1): e0245209. DOI: 10.1371/journal.pone.0245209.

25. Abe Y, Suga Y, Fukushima K, et al. Advances and challenges of antibody therapeutics for severe bronchial asthma[J]. Int J Mol Sci, 2021, 23(1): 83. DOI: 10.3390/ijms23010083.

26. 邓安妮, 陈玉, 薛贝贝, 等. 基于网络药理学及动物实验探讨乌梅丸治疗支气管哮喘的作用[J]. 中成药, 2024, 46(8): 2778-2784. [Deng AN, Chen Y, Xue BB, et al. Exploration of the effect of Wumei pill in the treatment of bronchial asthma based on network pharmacology and animal experiments[J]. Chinese Traditional Patent Medicine, 2024, 46(8): 2778-2784.] DOI: 10.3969/j,issn.1001-1528.2024.08.048.

27. 候艳敏, 徐梅, 张丽娟, 等. 基于网络药理学和分子对接探究祖卡木颗粒治疗支气管哮喘的作用机制[J]. 中国药理学通报, 2024, 40(2): 363-371. [Hou YM, Xu M, Zhang LJ, et al. Mechanism and experimental validation of Zukamu granules in treatment of bronchial asthma based on network pharmacology and molecular docking[J]. Chinese Pharmacological Bulletin, 2024, 40(2): 363-371.] DOI: 10.12360/CPB202302033.

28. Yuan FJ, Liu R, Hu MY, et al. JAX2, an ethanol extract of Hyssopus cuspidatus Boriss, can prevent bronchial asthma by inhibiting MAPK/NF-κB inflflammatory signaling[J]. Phytomedicine, 2019, 57: 305-314. DOI: 201910.1016/j.phymed.2018.12.043.

29. 李川徽, 李英姿, 刘斌, 等. 基于网络药理学方法和分子对接技术探讨桔梗-苦杏仁药对治疗咳嗽变异性哮喘的作用机制[J]. 山西中医药大学学报, 2024, 25(1): 77-86. [Li CH, Li YZ, Liu B, et al. Exploration of the mechanism of couplet medicines of Jiegeng-Kuxingren in the treatment of cough variant asthma based on network pharmacology and molecular docking technology[J]. Journal of Shanxi University of Chinese Medicine, 2024, 25(1): 77-86.] DOI: 10.19763/j.cnki.2096-7403.2024.01.14.

30. 袁凤娟, 胡梦颖, 哈木拉提·哈斯木, 等. 神香草提取物防治支气管哮喘的作用机制[J]. 中成药, 2017, 39(4): 809-812. [Yuan FJ, Hu MY, Hamulati Hasimu, et al. The action mechanism of the extract of Hyssopus Officinalis L. in the prevention and treatment of bronchial asthma[J]. Chinese Traditional Patent Medicine, 2017, 39(4): 809-812.] DOI: 10.3969/j.issn.1001-1528.2017.04.031.

31. Cai ZD, Liu MM, Yuan FJ, et al. Exploration of the molecular mechanisms of Hyssopus cuspidatus boriss treatment of asthma in an mRNA-miRNA network via bioinformatics analysis[J]. Biomed Res Int, 2022: 7111901. DOI: 10.1155/2022/7111901.