基于网络药理学与分子对接技术探讨西洋参-牛膝药对治疗干燥综合征的作用机制

doi:10.5246/jcps.2025.10.069

中国药学(英文版) ›› 2025, Vol. 34 ›› Issue (10): 932-942.DOI: 10.5246/jcps.2025.10.069

基于网络药理学与分子对接技术探讨西洋参-牛膝药对治疗干燥综合征的作用机制

李浩天¹, 刘签兴², 夏聪敏², 呼思乐³, 刘燕君³^,^*(), 姜泉²^,^*()

^1. 中文单位
^2. 中文单位
^3. 镇江学院医药化工研究所镇江功能化学重点实验室, 江苏镇江 212028

收稿日期:2025-04-12 修回日期:2025-05-16 接受日期:2025-06-06 出版日期:2025-11-03 发布日期:2025-11-03
通讯作者: 刘燕君, 姜泉

Unveiling the mechanisms of Bidentate Achyranthes and American Ginseng therapy in Sjögren’s Syndrome: insights from network pharmacology and molecular docking

Haotian Li¹, Qianxing Liu², Congmin Xia², Sile Hu³, Yanjun Liu³^,^*(), Quan Jiang²^,^*()

¹ 英文单位China
² 英文单位China
³ Zhenjiang Key Laboratory of Functional Chemistry, Institute of Medicine & Chemical Engineering, Zhenjiang College, Zhenjiang 212028, Jiangsu, China

Received:2025-04-12 Revised:2025-05-16 Accepted:2025-06-06 Online:2025-11-03 Published:2025-11-03
Contact: Yanjun Liu, Quan Jiang
Supported by:
Research on the Knowledge Graph System of “Disease Syndrome Formula (Medicine)” for Rheumatology, Science and Technology Innovation Project of the Chinese Academy of Traditional Chinese Medicine (Grant No. C12021A01507). The self-selected project of the Basic Research Business Fee of the Institute of Traditional Chinese Medicine Basic Theory, Chinese Academy of Traditional Chinese Medicine, is based on knowledge graphs and deep learning to trace the academic ideas of Lu Zhizheng in the treatment of rheumatism during three periods (Grant No. YZX-202317). Central High-level Chinese Medicine Hospital Clinical Research and Results Translation Capacity Enhancement Program (Grant No. HLCMHPP20230120) High Level Chinese Medical Hospital Promotion Project (Grant No. HLCMHPP2023087).

摘要/Abstract

摘要：

干燥综合征(SS)是风湿病免疫系统中一种较难治愈的疾病。最近的研究表明, 线粒体功能障碍(MDF)引起的免疫微环境失衡是SS发病的关键。中医药在治疗SS上疗效较为显著。本研究通过挖掘国医大师路志正治疗SS的病例, 发现牛膝和西洋参是治疗干燥综合征的高频药对。通过网络药理学分析, 牛膝和西洋参治疗干燥综合征的关键基因与cGAS STING信号通路的上游和下游基因有关。牛膝和西洋参可能通过mtDNA-cGAS-STING信号轴纠正MDF, 改善颌下腺免疫微环境的失衡, 从而治疗和缓解SS。

关键词: 网络药理学, 路志正, 分子对接, cGAS-STING通路

Abstract:

Sjögren’s syndrome (SS) is a challenging condition within the realm of rheumatologic immune disorders. Recent studies have indicated that the imbalance in the immune microenvironment, exacerbated by mitochondrial dysfunction (MDF), plays a critical role in the pathogenesis of SS. The efficacy of traditional Chinese medicine (TCM) in treating SS has been noteworthy. In the present study, we compiled medical cases of SS treated by Lu Zhizheng, a renowned master of Chinese medicine, and identified bidentate achyranthes and American ginseng as high-frequency medicinal pairs utilized in the treatment of desiccation syndrome through data mining. Network pharmacology analysis revealed that key genes associated with these medicinal pairs were linked to both upstream and downstream components of the cGAS-STING signaling pathway. Our findings suggested that bidentate achyranthes and American ginseng might correct MDF through the mtDNA-cGAS-STING signaling axis, thereby restoring the balance of the immune microenvironment in the submandibular gland. This mechanism potentially led to the treatment and alleviation of symptoms associated with SS.

Key words: Network pharmacology, Lu Zhizheng, Molecular docking, cGAS-STING pathway

Supporting:

李浩天, 刘签兴, 夏聪敏, 呼思乐, 刘燕君, 姜泉. 基于网络药理学与分子对接技术探讨西洋参-牛膝药对治疗干燥综合征的作用机制[J]. 中国药学(英文版), 2025, 34(10): 932-942.

Haotian Li, Qianxing Liu, Congmin Xia, Sile Hu, Yanjun Liu, Quan Jiang. Unveiling the mechanisms of Bidentate Achyranthes and American Ginseng therapy in Sjögren’s Syndrome: insights from network pharmacology and molecular docking[J]. Journal of Chinese Pharmaceutical Sciences, 2025, 34(10): 932-942.

图/表 7

Figure 1. Disease target Venn diagram.

Figure 2. Drug-molecular-target network diagram.

Figure 3. PPI network.

Figure 4. The GO enrichment analysis.

Figure 5. The KEGG enrichment analysis.

Figure 6. Binding energies of the 4 active ingredients and 5 hub targets. Darker red indicates, stronger binding energy between the active ingredients and the hub target.

Figure 7. Molecular docking patterns. (A) BAX and QUERCETIN; (B) BAX and BERBERINE; (C) CASP3 and QUERCETIN; (D) CASP3 and BERBERINE.

参考文献 27

[1]	Borchers, A.T.; Naguwa, S.M.; Keen, C.L.; Gershwin, M.E. Immunopathogenesis of Sjögren’s syndrome. Clin. Rev. Allergy Immunol. 2003, 25, 89–104.
[2]	Zhang, H.; Liu, C.H.; Wu, B. Advances in the epidemiology of primary Sjögren’s syndrome. Modern Prevent. Med. 2020, 47, 3056–3058, 3063.
[3]	Zeng, X.F.; Yan, S.M. Progress of diagnosis and treatment of primary dry syndrome in the elderly. Pract. Geriatr. 2008, 2, 14–17
[4]	Zhong, H.; Liu, S.Y.; Wang, Y.H.; Xu, D.; Li, M.T.; Zhao, Y.; Zeng, X.F. Primary Sjögren’s syndrome is associated with increased risk of malignancies besides lymphoma: a systematic review and meta-analysis. Autoimmun. Rev. 2022, 21, 103084.
[5]	Seror, R.; Nocturne, G.; Mariette, X. Current and future therapies for primary Sjögren syndrome. Nat. Rev. Rheumatol. 2021, 17, 475–486.
[6]	Zhan, Q.P.; Zhang, J.N.; Lin, Y.B.; Chen, W.J.; Fan, X.Z.; Zhang, D.F. Pathogenesis and treatment of Sjögren’s syndrome: review and update. Front. Immunol. 2023, 14, 1127417.
[7]	Imgenberg-Kreuz, J.; Sandling, J.K.; Almlöf, J.C.; Nordlund, J.; Signér, L.; Norheim, K.B.; Omdal, R.; Rönnblom, L.; Eloranta, M.L.; Syvänen, A.C.; Nordmark, G. Genome-wide DNA methylation analysis in multiple tissues in primary Sjögren’s syndrome reveals regulatory effects at interferon-induced genes. Ann. Rheum. Dis. 2016, 75, 2029–2036.
[8]	Ramos-Casals, M.; Brito-Zerón, P.; Bombardieri, S.; Bootsma, H.; De Vita, S.; Dörner, T.; Fisher, B.A.; Gottenberg, J.E.; Hernandez-Molina, G.; Kocher, A.; Kostov, B.; Kruize, A.A.; Mandl, T.; Ng, W.F.; Retamozo, S.; Seror, R.; Shoenfeld, Y.; Sisó-Almirall, A.; Tzioufas, A.G.; Vitali, C.; Bowman, S.; Mariette, X.; Group, E.S S.T.F. EULAR recommendations for the management of Sjögren’s syndrome with topical and systemic therapies. Ann. Rheum. Dis. 2020, 79, 3–18.
[9]	Liu,Y.J.; Liu, Z.X.; Xia, M.C.; Li, H.T.; Jiang, Q. Exploring the invisible knowledge of Lu Zhizheng’s medication for dry syndrome and the academic idea of "Gu Run Dry, Na Huan Chang" based on data mining and knowledge mapping. J. Basic Chin. Med. 2024, 30, 1534–1539.
[10]	Ru, J.L.; Li, P.; Wang, J.N.; Zhou, W.; Li, B.H.; Huang, C.; Li, P.D.; Guo, Z.H.; Tao, W.Y.; Yang, Y.F.; Xu, X.; Li, Y.; Wang, Y.H.; Yang, L. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J. Cheminform. 2014, 6, 13.
[11]	Kim, S. Getting the most out of PubChem for virtual screening. Expert Opin. Drug Discov. 2016, 11, 843–855.
[12]	Daina, A.; Michielin, O.; Zoete, V. Swiss Target Prediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res. 2019, 47, W357–W364.
[13]	Stelzer, G.; Rosen, N.; Plaschkes, I.; Zimmerman, S.; Twik, M.; Fishilevich, S.; Stein, T.I.; Nudel, R.; Lieder, I.; Mazor, Y.; Kaplan, S.; Dahary, D.; Warshawsky, D.; Guan-Golan, Y.; Kohn, A.; Rappaport, N.; Safran, M.; Lancet, D. The GeneCards suite: from gene data mining to disease genome sequence analyses. Curr. Protoc. Bioinformatics. 2016, 54, 1.30.1–1.30.1.30.33.
[14]	Amberger, J.S.; Bocchini, C.A.; Schiettecatte, F.; Scott, A.F.; Hamosh, A. OMIM.org: Online Mendelian Inheritance in Man (OMIM^®), an online catalog of human genes and genetic disorders. Nucleic Acids Res. 2015, 43, D789–D798.
[15]	Szklarczyk, D.; Gable, A.L.; Nastou, K.C.; Lyon, D.; Kirsch, R.; Pyysalo, S. Doncheva, N.T.; Legeay, M.; Fang, T.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 2021, 49, D605–D612.
[16]	Sherman, B.T.; Hao, M.; Qiu, J.; Jiao, X.L.; Baseler, M.W.; Lane, H.C.; Imamichi, T.; Chang, W.Z. DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res. 2022, 50, W216–W221.
[17]	Burley, S.; Bhikadiya, C.; Bi, C.X.; Bittrich, S.; Chao, H.; Chen, L.; Craig, P.; Crichlow, G.; Dalenberg, K.; Duarte, J.M.; Dutta, S.; Fayazi, M.; Feng, Z.K.; Flatt, J.; Ganesan, S.J.; Ghosh, S.; Goodsell, D.; Green, R.K.; Guranovic, V.; Henry, J.; Hudson, B.; Khokhriakov, I.; Lawson, C.; Liang, Y.H.; Lowe, R.; Peisach, E.; Persikova, I.; Piehl, D.W.; Rose, Y.; Sali, A.; Segura, J.; Sekharan, M.; Shao, C.; Vallat, B.K.; Voigt, M.; Webb, B.M.; Westbrook, J.; Whetstone, S.; Young, J.Y.; Zalevsky, A.; Zardecki, C. RCSB protein data bank (RCSB.org): delivery of experimentally-determined PDB structures alongside one million computed structure models of proteins from artificial intelligence/machine learning. Nucleic Acids Res. 2022, 51, D488–D508.
[18]	Luo, J.; Xu, Y.; Zhou, X.Y. Li, M.T.; Hou, X.J.; Wang, H.L.; Chen, H.; Zhang, Q.; Geng, Y.; Zhao, Y.; Zhao, M.S.; Wang, J.B.; Wang, Y.; Zhang, X.X.; Tao, Q.W. Expert consensus on clinical diseases responding specifically to traditional Chinese medicine: Sjögren’s Syndrome. Chin. J. Exper. Tradit. Med. Formul. 2023, 29, 73–79.
[19]	Xu, H.D.; Jiang, Q.; Cheng, Z.Y.; Zhou, X.Y.; Li, K.S.; Li, D.; Liu, R.H.; Wu, S.Y.; Tang, X.P. Research progress on treatment of primary Sjögren’s syndrome from the deficiency of both qi and yin. China J. Tradit. Chin. Med. Pharmacy. 2023, 38, 2720–2723.
[20]	Peng, Y.; Zhang, Z.; Chen, N.H.; Research progress on the protective effect of American ginseng on neurodegenerative diseases. J. Neuropharmacol. 2018, 8, 57.
[21]	Feng, C.Y.; Qi, M.X.; Huang, X.R. Tang, S.W.; Pan, J.; Ding, Y. Mitochondrial ultrastructure analysis of ecdysterone protection against oxidative damage in human lens epithelial cells. China J. Chin. Ophthalmol. 2014, 24, 22–24.
[22]	Mohanty, A.; Tiwari-Pandey, R.; Pandey, N.R. Mitochondria: the indispensable players in innate immunity and guardians of the inflammatory response. J. Cell Commun. Signal. 2019, 13, 303–318.
[23]	Glancy, B. Visualizing mitochondrial form and function within the cell. Trends Mol. Med. 2020, 26, 58–70.
[24]	Kopach, O.; Pivneva, T.; Fedirko, N.; Voitenko, N. Mitochondrial malfunction mediates impaired cholinergic Ca²⁺ signalling and submandibular salivary gland dysfunction in diabetes. Neuropharmacology. 2024, 243, 109789.
[25]	Ning, X.H.; Wang, Y.T.; Jing, M.; Sha, M.Y.; Lv, M.Z.; Gao, P.F.; Zhang, R.; Huang, X.J.; Feng, J.M.; Jiang, Z.F. Apoptotic caspases suppress type I interferon production via the cleavage of cGAS, MAVS, and IRF3. Mol. Cell. 2019, 74, 19–31.e7.
[26]	Li, Y.X.; Cui, S.F.; Meng, W.; Hu, H.Y.; Wang, C. Mitochondrial DNA and cGAS-STING Innate Immune Signaling Pathway: Latest Research Progress. J. Sichuan Univ. (Medical Sciences). 2021, 52, 387–395.
[27]	Xu, J.B.; Chen, C.Y.; Yin, J.H.; Fu, J.Y.; Yang, X.J.; Wang, B.L.; Yu, C.Q.; Zheng, L.Y.; Zhang, Z.Y. Lactate-induced mtDNA accumulation activates cGAS-STING signaling and the inflammatory response in Sjögren’s syndrome. Int. J. Med. Sci. 2023, 20, 1256–1271.

基于网络药理学与分子对接技术探讨西洋参-牛膝药对治疗干燥综合征的作用机制

Unveiling the mechanisms of Bidentate Achyranthes and American Ginseng therapy in Sjögren’s Syndrome: insights from network pharmacology and molecular docking

RichHTML

可视化

摘要/Abstract

引用本文

使用本文

图/表 7

参考文献 27

相关文章 15

编辑推荐

Metrics

本文评价

[1]	邓茜, 彭紫凝, 毛丹宁, 黄元波, 刘念, 晏蔚田, 彭江云. 基于生物信息与网络药理学探究飞龙掌血治疗骨关节炎的作用机制[J]. 中国药学(英文版), 2025, 34(9): 860-872.
[2]	王毅, 熊玉瑶. 基于网络药理学和分子对接探究土茯苓-薏苡仁药对治疗痛风及高尿酸血症的作用机制[J]. 中国药学(英文版), 2025, 34(8): 741-754.
[3]	郑宜鋆, 王哲元, 王满才, 肖琪, 邓弘扬, 李戟玭, 张岭漪, 张有成. 基于分子动力学模拟探讨泽漆对淋巴结转移阳性胃癌的潜在干预作用[J]. 中国药学(英文版), 2025, 34(7): 644-663.
[4]	张晓琴, 秦湫红, 李晓杰, 杨建刚, 麻纪斌, 任建平. 基于生物信息学探究细胞衰老参与多发性硬化关键基因的筛选及验证[J]. 中国药学(英文版), 2025, 34(6): 530-542.
[5]	李跃文, 张勤生, 胡素芹. 基于数据挖掘探讨中药复方专利治疗急性阑尾炎的组方规律及机制[J]. 中国药学(英文版), 2025, 34(6): 566-580.
[6]	张玉倩, 牛海英, 张晓炜, 解伟伟, 张恺玥, 张兰桐, 靳怡然. 基于网络药理学研究桑黄酮G治疗糖尿病性脑病作用机制研究[J]. 中国药学(英文版), 2025, 34(3): 251-259.
[7]	朱晓东, 邸学士, 孙劲晖. 基于网络药理学及分子对接技术探讨柴胡-黄芪治疗酒精性肝纤维化的作用机制[J]. 中国药学(英文版), 2025, 34(2): 163-174.
[8]	杨帆, 李蕊, 刘雯婷, 孙舰, 赵承孝, 冯秀娥, 李青山. 多酚化合物LM49对角叉菜胶诱导足肿胀小鼠的抗炎作用及机制研究[J]. 中国药学(英文版), 2025, 34(1): 41-54.
[9]	尚平, 刘琳, 方毅. 基于网络药理学和分子对接探讨六味地黄丸治疗卵巢早衰的作用机制[J]. 中国药学(英文版), 2024, 33(9): 805-818.
[10]	朱美玲, 张基荣, 张秋荣, 林羽, 李小艳, 许文, 徐伟. 基于网络药理学和化学计量学对中成药质量控制方法研究: 以活络散为例[J]. 中国药学(英文版), 2024, 33(9): 819-836.
[11]	李霞, 程贝贝, 谭骏岚, 万佳婧, 王宇红, 戴爱国. 黄芪主成分槲皮素通过MAPK通路调控PASMCs铁死亡抗低氧性肺动脉高压的研究[J]. 中国药学(英文版), 2024, 33(8): 714-729.
[12]	魏晓玉, 于路航, 李梦茹, 徐强. 网络药理学研究揭示连花清瘟-辛夷散联合治疗新冠后嗅觉损伤的潜在作用机制[J]. 中国药学(英文版), 2024, 33(7): 631-646.
[13]	张啸, 钟叶, 胡永生, 王博龙. 《肿瘤良方大全》中肝癌用药规律挖掘及其核心药对机制分析[J]. 中国药学(英文版), 2024, 33(7): 647-658.
[14]	韩世盛, 王怡. 桃红四物汤改善动静脉内瘘失功的潜在机制: 一项网络药理学、分子对接以及分子动力学模拟研究[J]. 中国药学(英文版), 2024, 33(6): 511-524.
[15]	李双, 孙璐瑶, 尤斯涵, 张佳燚, 殷宏艳, 曹津萌, 刘心星, 郭春燕, 刘喜富. 基于网络药理学探讨桃红四物汤治疗阿尔茨海默症的主要有效成分及其作用机制[J]. 中国药学(英文版), 2024, 33(6): 525-542.