基于网络药理学及分子对接技术探讨调和止动方治疗儿童抽动障碍的分子机制

doi:10.20274/j.cnki.issn.1674-3865.2025.03.016

Abstract

Abstract:

Objective To explore the potential mechanism of action of Tiaohe Zhidong prescription in the treatment of childhood tic disorders based on network pharmacology and molecular docking technology. Methods The Traditional Chinese Medicine Systems Pharmacology Database(TCMSP) was searched for the ingredients of Chinese medicine in Tiaohe Zhidong prescription to screen for the active ingredients and obtain the targets of active ingredients；the disease targets of tic disorders were obtained from CTD and OMIM databases. The intersection targets were taken. The protein?protein interaction network of the targets was established using String database. The enrichment analysis of Gene Ontology(GO) and the enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway were performed by R software, and the core ingredients and the potential targets of action were docked for verification with the aid of molecular docking software. Results In this study, a total of 23 core ingredients in Tiaohe Zhidong prescription and 34 targets of tic disorders were found, mainly involving paeoniflorin, cianidanol, corynoxeine, rhynchophylline, and IL-6, TNF, and PTGS2. The enriched pathways in KEGG mainly included dopamine and other neurotransmitters, as well as inflammatory factor signaling pathways. The molecular docking results showed that cianidanol might be the active ingredient in Tiaohe Zhidong prescription for the treatment of childhood tic disorders, and PTGS2 was the key target protein. Conclusion Tiaohe Zhidong prescription mainly exerts its therapeutic effects on childhood tic disorders through multiple mechanisms, including regulation of neurotransmitters, immune modulation, and anti?inflammation, which reflects the characteristics of traditional Chinese medicine formulations in achieving whole?body regulation through multiple components and multiple targets.

Key words: Tic disorders, Tiaohe Zhidong prescription, Network pharmacology, Molecular docking, Mechanism of action, Child

CLC Number:

R277.7

Bo QI, Yuyan CHEN, Xiaoming WANG, Shen CHENG. Exploration of molecular mechanism of Tiaohe Zhidong prescription in the treatment of childhood tic disorders based on network pharmacology and molecular docking technology[J]. Chinese Pediatrics of Integrated Traditional and Western Medicine, 2025, 17(3): 270-276.

Figures/Tables 3

Table 1

Fig. 3

Table 2

References 29

[1]	苏群燕, 冯建华. 儿童和青少年Tourette综合征治疗现状[J]. 临床儿科杂志, 2019, 37(5): 396-399.
[2]	赵利平, 胡晓红, 李中原. 儿童抽动障碍发病机制研究进展[J]. 发育医学电子杂志, 2024, 12(3): 224-228.
[3]	姜俊爽, 王雪峰, 张秀英, 等. 复方中药治疗儿童抽动障碍随机对照试验的Meta分析[J]. 中国中西医结合儿科学, 2019, 11(4): 333-339.
[4]	程申, 陈雅琴, 王庆, 等. 王晓鸣教授运用调和肝脾法治疗儿童抽动障碍经验探讨[J]. 浙江中医药大学学报, 2024, 48(6): 669-673.
[5]	宋艳玲, 陈晓玲, 王晓鸣, 等. 调和止动方联合磁珠耳穴贴治疗儿童抽动障碍脾虚肝旺型29例临床观察[J]. 中医儿科杂志, 2024, 20(4): 81-85.
[6]	和婧伟, 李梦瑶, 梁鹏晨, 等. 基于“从痰辨治” 探讨石菖蒲治疗儿童注意缺陷多动障碍作用机制的网络药理研究[J]. 中国中西医结合儿科学, 2023, 15(4): 295-301.
[7]	Zhang W, Wei L, Yu W, et al. Effect of Jian⁃Pi⁃Zhi⁃Dong Decoction on striatal glutamate and γ-aminobutyric acid levels detected using microdialysis in a rat model of Tourette syndrome[J]. Neuropsychiatr Dis Treat, 2016, 12: 1233-1242.
[8]	Wang, F, Wang WX， Song B， et al. Differences in the expression of neurotransmitters, metabolic transport, postsynaptic receptors, and signalling proteins in the dopaminergic twitch model induced by doi[J]. Acta Medica Mediterranea, 2022， 38(3): 1459-1464.
[9]	Nespoli E, Rizzo F, Boeckers T, et al. Altered dopaminergic regulation of the dorsal striatum is able to induce tic⁃like move⁃ments in juvenile rats[J]. PLoS One, 2018, 13(4): e0196515.
[10]	梁芸, 朱沁泉, 张涤. 健脾柔肝息风汤对抽动障碍模型大鼠脑组织神经元中DARPP-32、TH含量的干预作用[J]. 湖南中医药大学学报, 2022, 42(2): 235-239.
[11]	Chi S, Mok YE, Kang J, et al. Cytokine levels reflect tic symptoms more prominently during mild phases[J]. BMC Neurosci, 2023, 24(1): 57.
[12]	Tao Y, Xu P, Zhu W, et al. Changes of cytokines in children with tic disorder[J]. Front Neurol, 2022, 12: 800189.
[13]	Kutuk MO, Tufan AE, Kilicaslan F, et al. Cytokine expression profiles in children and adolescents with tic disorders[J]. Sci Rep, 2024, 14(1): 15101.
[14]	Li Y, Wang X, Yang H, et al. Profiles of proinflammatory cytokines and T cells in patients with Tourette syndrome: a meta⁃analysis[J]. Front Immunol, 2022, 13: 843247.
[15]	Zhao L, Cheng N, Sun B, et al. Regulatory effects of Ningdong granule on microglia⁃mediated neuroinflammation in a rat model of Tourette’s syndrome[J]. Biosci Trends, 2020, 14(4): 271-278.
[16]	Ke Z, Chen Y, Chen G, et al. Neuroinflammation in a rat model of Tourette syndrome[J]. Front Behav Neurosci, 2022, 16: 710116.
[17]	Leonardi L, Lorenzetti G, Carsetti R, et al. Immunological characterization of an Italian PANDAS cohort[J]. Front Pediatr, 2024, 11: 1216282.
[18]	Li E, Ruan Y, Chen Q, et al. Streptococcal infection and immune response in children with Tourette’s syndrome[J]. Childs Nerv Syst, 2015, 31(7): 1157-1163.
[19]	Wu XP, Fang RR, Ji TT. Dietary inflammatory index and its impact on severity and recurrence of Tourette syndrome in children[J]. World J Psychiatry, 2024, 14(8): 1208-1215.
[20]	贺晴,张永婷,边玉露,等.中药、复方及非药物疗法治疗抽动障碍相关信号通路作用机制的研究进展[J/OL].中药药理与临床,1-23[2024-10-02]..
[21]	金思佳, 白晓红, 修婵, 等. 基于网络药理学方法和分子对接技术探讨钩藤-菊花药对治疗抽动障碍的分子机制[J]. 山西中医药大学学报, 2023, 24(8): 866-871.
[22]	Long H, Zhang M, Wang C, et al. Rhynchophyllin attenuates neuroinflammation in Tourette syndrome rats via JAK2/STAT3 and NF-κB pathways[J]. Environ Toxicol, 2019, 34(10): 1114-1120.
[23]	刘馨鸿, 郭超, 宋冰, 等. 芍药苷抗炎作用机制研究进展[J]. 实验动物科学, 2024, 41(2): 90-95.
[24]	崔红倩, 迟宇昊, 申远. 白芍的化学成分和药理作用研究进展[J]. 新乡医学院学报, 2024, 41(3): 291-297.
[25]	谷笑彤, 白晓红, 修婵, 等. 基于网络药理学方法及分子对接技术探讨“白芍-柴胡” 药对治疗儿童抽动障碍的作用机制[J]. 山西中医药大学学报, 2024, 25(7): 781-788.
[26]	Zhang F, Li A. Dual restoring effects of gastrodin on dopamine in rat models of Tourette's syndrome[J]. Neurosci Lett, 2015, 588: 62-66.
[27]	Wang Y, Zhao L, Li AY. Gastrodin-A potential drug used for the treatment of Tourette Syndrome[J]. J Pharmacol Sci, 2021, 145(3): 289-295.
[28]	Long H, Ruan J, Zhang M, et al. Gastrodin alleviates Tourette syndrome via nrf-2/HO-1/HMGB1/NF-кB pathway[J]. J Bio⁃chem Mol Toxicol, 2019, 33(10): e22389.
[29]	Martín-Vázquez E, Cobo-Vuilleumier N, López-Noriega L, et al. The PTGS2/COX2-PGE₂ signaling cascade in inflammation: pro or anti?A case study with type 1 diabetes mellitus[J]. Int J Biol Sci, 2023, 19(13): 4157-4165.

药物	成分	Degree	药物	成分	Degree
钩藤（GT24）	Quercetin	17	钩藤（GT19）	Isorhynchophylline	7
钩藤（GT30）	Yohimbine	13	钩藤（GT6）	(E)?2?[(3R,6'S,7'S,8'aS)?6'?ethyl?2?keto?spiro[indoline?3,1'?indolizidine]?7'?yl]?3?methoxy?acrylic acid methyl ester	7
钩藤（GT9）	coryincine	12	郁金（YJ1）	Naringenin	7
钩藤（GT16）	Hirsutine	11	柴胡（CH5）	Isorhamnetin	6
钩藤（GT8）	Beta?Sitosterol	11	钩藤（GT10）	corynoxeine	6
钩藤（GT20）	kaempferol	10	钩藤（GT17）	isocorynantheic acid	6
钩藤（GT11）	Hirsuteine	9	钩藤（GT2）	(1'R,3S,4a'S,5a'S,10a'R)?1'?methyl?2?oxo?1',4a',5',5a',7',8',10',10a'?octahydrospiro[indoline?3,6'?pyrano[3,4?f]indolizine]?4'?carboxylic acid	6
钩藤（GT28）	Tetrahydroalstonine	9	钩藤（GT23）	Mitraphyllic acid	6
枳壳（ZK3）	Nobiletin	9	钩藤（GT26）	Rhynchophylline A	6
钩藤（GT21）	methyl (E)?2?[(2S,3R,12bS)?3?vinyl?1,2,3,4,6,7,12,12b?octahydroindolo[3,2?h]quinolizin?2?yl]?3?methoxy?prop?2?enoate	8	钩藤（GT3）	(1'R,3S,4a'S,5a'S,10a'R)?1'?methyl?2?oxo?1',4a',5',5a',7',8',10',10a'?octahydrospiro[indoline?3,6'?pyrano[3,4?f]indolizine]?5'?carboxylic acid	6
钩藤（GT22）	methyl (E)?2?[(2S,3Z,12bS)?3?ethylidene?2,4,6,7,12,12b?hexahydro?1H?indolo[3,2?h]quinolizin?2?yl]?3?methoxyprop?2?enoate	8	钩藤（GT4）	(2S,12bR)?methyl 2?((E)?1?oxobut?2?en?2?yl)?1,2,6,7,12,12b?hexahydroindolo[2,3?a]quinolizine?3?carboxylate	6
钩藤（CH8）	Stigmasterol	7

药物	成分	靶点	对接数值
白芍（BS1）	儿茶素（Cianidanol）	PTGS2	-6.648
白芍（BS2）	芍药苷（Paeoniflorin）	IL-6	-4.140
白芍（BS2）	芍药苷（Paeoniflorin）	TNF	-4.464
钩藤（GT10）	去氢钩藤碱（Corynoxeine）	PTGS2	-3.830
钩藤（GT25）	钩藤碱（Rhynchophylline）	PTGS2	-4.295

Exploration of molecular mechanism of Tiaohe Zhidong prescription in the treatment of childhood tic disorders based on network pharmacology and molecular docking technology

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 3

References 29

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	. Clinical practice guidelines for integrative Chinese and western medicine in children with enuresis (2025) [J]. Chinese Pediatrics of Integrated Traditional and Western Medicine, 2025, 17(3): 185-198.
[2]	Yuanjun LU, Na CHEN, Yang YANG, Man CHENG, Duojian LI, Qiuyue LI, Zhu CHEN. Differentiated treatment for central precocious puberty based on the five viscera and the theory of "Tiangui" [J]. Chinese Pediatrics of Integrated Traditional and Western Medicine, 2025, 17(3): 203-207.
[3]	Junchao LIU, Jiaojiao LIU, Hong XU. Retrospective analysis of liver⁃softening and spleen⁃strengthening therapy for children with precocious puberty of spleen⁃deficiency and liver⁃hyperactivity type [J]. Chinese Pediatrics of Integrated Traditional and Western Medicine, 2025, 17(3): 208-212.
[4]	Hongyan SHEN, Xuefeng WANG, Xinmin HAN, Bin YUAN, Siyuan HU, Xinmin LI, Lei XIONG, Ping HE, Ying ZHOU, Xuerong ZHANG, Jingwen MU. Clinical study on the treatment for children with acute tonsillitis (external wind⁃heat syndrome) with Bangbo Ruexiao granule [J]. Chinese Pediatrics of Integrated Traditional and Western Medicine, 2025, 17(3): 213-220.
[5]	Yihan XIE, Siying MEI, Xilian ZHANG. Research progress on evaluation indexes for clinical trials of infantile epileptic spasms syndrome [J]. Chinese Pediatrics of Integrated Traditional and Western Medicine, 2025, 17(3): 221-225.
[6]	Lingyan XUE, Jianying LI, Chunlan HE, Lingli ZHAO. Impact of short chain fatty acids and microbial community structure in feces on infants and young children [J]. Chinese Pediatrics of Integrated Traditional and Western Medicine, 2025, 17(3): 226-230.
[7]	Lijuan ZHENG, Fumin XUE, Jing YU. Diagnostic value of GGT combined with DBIL for biliary atresia in different age groups of children [J]. Chinese Pediatrics of Integrated Traditional and Western Medicine, 2025, 17(3): 231-236.
[8]	Haifei XIAO, Na WANG. Clinical observation of Xiaoer Dingchuan oral solution combined with western medicine treatment in the treatment of children with asthmatic bronchitis [J]. Chinese Pediatrics of Integrated Traditional and Western Medicine, 2025, 17(3): 242-245.
[9]	Huishuang CHEN, Qingling GUO, Lu DAI. Analysis of risk factors for retinopathy in very low birth weight infants [J]. Chinese Pediatrics of Integrated Traditional and Western Medicine, 2025, 17(3): 246-250.
[10]	Shengze ZHENG, Yanhong QIN, Feng ZHANG. Professor Qin Yanhong's clinical experience in differentiated treatment of functional constipation in children with the "multi⁃organ coordination" concept [J]. Chinese Pediatrics of Integrated Traditional and Western Medicine, 2025, 17(3): 251-255.
[11]	Zicheng ZHAO, Siyu WU, Pengfei YAN. Acupuncture combined with drug therapy in the treatment of childhood tic disorder based on the theory of Midnight⁃noon Ebb⁃flow [J]. Chinese Pediatrics of Integrated Traditional and Western Medicine, 2025, 17(3): 256-259.
[12]	Shiqing XU, Bin XIE, Xuefeng WANG. Professor Wang Xuefeng's experience in treating functional abdominal pain in children based on the theory of "treating middle Jiao through balancing" [J]. Chinese Pediatrics of Integrated Traditional and Western Medicine, 2025, 17(3): 260-263.
[13]	Yali CUI, Ke CHANG. Data mining of medication rules of Professor Chang Ke in the treatment of cough in children [J]. Chinese Pediatrics of Integrated Traditional and Western Medicine, 2025, 17(3): 264-269.
[14]	SHEN Hongyan, ZHANG Xiuying, TAN Chunying, SHANG Tao, MENG Bin, MU Jingwen, TIAN Zhifan, E Mingxin, WANG Xuefeng. A multi center clinical study on the adjuvant treatment with Fuxiong powder for children with Mycoplasma pneumoniae pneumonia [J]. Chinese Pediatrics of Integrated Traditional and Western Medicine, 2025, 17(2): 93-98.
[15]	WU Pan, HUANG Tingyue, ZHANG Zhanling, WANG Xuefeng. Meta analysis and GRADE evaluation of Xiaoer Feire Kechuan oral liquid in the treatment of Mycoplasma pneumoniae pneumonia [J]. Chinese Pediatrics of Integrated Traditional and Western Medicine, 2025, 17(2): 98-108.