Research Focusing on How Qinge Pill Functions in Managing Stress Urinary Incontinence, Utilizing Network Pharmacology

Authors

  • Bo Ma Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210017, China
  • Jia Shen Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210017, China
  • Ming Yang Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210017, China
  • Qiao Du Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210017, China
  • Hesong Ye Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210017, China

DOI:

https://doi.org/10.53469/jcmp.2024.06(06).29

Keywords:

Qing-e pill, Stress urinary incontinence, Network pharmacology, Mechanism of action, Signaling pathway

Abstract

Objective: Investigating how Qing-e pill aids in managing stress urinary incontinence through network pharmacology. Methods: Utilizing the TCM system's pharmacological database and analytical framework (TCMSP), along with literature exploration, the active components and their respective targets for Qing-e pill were identified, leading to the creation of a network of compound TCM - active ingredients - targets. The focus of SUI was identified using the GeneCards and OMIM databases. The active ingredient SUI-target network model was developed and examined using the Cytoscape 3.10.1 software. The protein interaction network (PPI) was created using the STRING database, incorporating gene ontology functional annotation (GO) and Tokyo Genome Encyclopedia (KEGG) pathway enrichment analysis on key targets through DAVID online, with molecular docking performed using Surflex software. Results: Screening yielded 86 active components, 461 possible targets, 2551 SUI targets, and 187 typical targets for Qing-e pill and SUI. The outcomes of network analysis revealed Qing-e pill's primary targets for SUI treatment were AKT1, IL6, JUN, TNF, HSP90AA1, ESR1, CTNNB1, EGFR, among others. The primary biological mechanisms encompassed reactions to lipopolysaccharide, molecules originating from bacteria, metal ions, growth of epithelial cells, and the control of membrane potential, among others. KEGG enrichment primarily aims to utilize the AGE-RAGE signaling pathway in treating a range of conditions, including diabetes complications, prostate cancer, fluid shear stress, atherosclerosis, lipid and atherosclerosis, IL-17 signaling pathway, and more. Conclusion: Initially, network pharmacology shed light on the foundational materials and operational methods of Qing-e pill in treating SUI, offering a theoretical foundation for their clinical use.

References

Han Lu, Qu Xueling. Pelvic Floor Disorders. Shenyang: Liaoning Science and Technology Press, 2020: 57-61.

Liu Tao. Basic Practice of Nursing for Common Clinical Diseases. Harbin: Heilongjiang Science and Technology Press, 2020: 278-280.

Guo Yinglu, Yan Yanqun, Ye Zhangqun. Guidelines for the Diagnosis and Treatment of Urological and Andrological Diseases in China 2022. Beijing: Science Press, 2022: 565-576

Shi Xuemin. Acupuncture[M]. Beijing: China Traditional Chinese Medicine Press, 2017.03.

Wei Junying, Zheng Zhipan, Zhang Biao, et al. Exploring the Traditional Chinese Medicine Origins of Female Stress Urinary Incontinence. Traditional Chinese Medicine Research, 2009, 22(2): 14-15.

Liu Ling, Weng Zebin, Wang Heng, et al. Pharmacokinetic-Pharmacodynamic Correlation Study of Effective Ingredients in Qing-e Pill[J]. China Journal of Chinese Materia Medica, 2016, 41(23): 4436-4441.

MA Chenyao, SONG Shanshan, WANG Yiqing, et al. Integrative network pharmacology study on the active ingredients and antidepressant mechanism of Qing-e Pill based on UHPLC-Q-TOF-MS[J]. Chinese Pharmacological Bulletin, 2023, 39(11): 2170-2176.

Song Shanshan, Sun Hong, Jing Wen, et al. Exploring the antidepressant mechanism of Qing-e Pill on CUMS rats based on the estrogen receptor pathway. Chinese Journal of Experimental Traditional Medical Formulae, 2020, 26(04): 9-15.

Ru J, Li P, Wang J, et al. TCMSP: a database of system spharmacology for drug discovery from herbal medicines[J].1Uniprot Consortium Cheminform, 2014, 6:13.

UniProt: the universal protein knowledgebase in 2021[J]. Nucleic Acids Res, 2021, 49(D1):D480-D489.

Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks [J]. Genome Res, 2003, 13(11):2498-2504.

Szklarczyk D, Gable AL, Nastou KC, et al. The STRINGdatabase in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurementsets[J]. Nucleic Acids Res, 2021, 49(D1):D605-D612.

B.T. Sherman, M. Hao, J. Qiu, et al. DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update) [J]. Nucleic Acids Research.23 March 2022.

Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID Bioinformatics Resources[J]. Nature Protoc. 2009:4(1):44-57.

Lim R, Liong ML, Leong WS, et al. The impact of stress urinary incontinence on individual components of quality of life in malaysian women[J]. Urol, 2018, 112(1):38-45.

Ahlund S, Rothstein E, Radestad I, et al. Urinary incontinence after uncomplicated spontaneous vaginal birth in primiparous women during the first year after birth[J]. Int Urogynecol J, 2020, 31(7):1409-1416

Siddiqui NY, Wiseman JB, Cella D, et al. Mental health, sleep and physical function in treatment seeking women with urinary incontinence[J].J Urol, 2018, 200(4):848-855.

Edited by Wang Dachun. Translation and annotations of Jingyue Quanshu. Beijing: Renmin University of China Press, 2016: 1584-1885.

Wu XiongZhi. Research on Wu's Treatise on Febrile Diseases and Miscellaneous Diseases. Shenyang: Liaoning Science and Technology Press, 2016

Shen Jia. Discussion on the Application of the Method of Grasping the Singular in Traditional Chinese Gynecology [J]. Classic Traditional Chinese Medicine Research, 2020, 3(1): 1-8.

Sun Xingyan, Sun Fengyi, eds. The Divine Farmer's Materia Medica. Taiyuan: Shanxi Science and Technology Press, 2018.02:31

Miao Xiyong. Commentary on the Divine Farmer's Materia Medica. Beijing: Ancient Chinese Medicine Literature Press, 2017.7: 336-338.

Gao Hongwei, Li Yuping, Li Shouchao. Research Progress on the Chemical Components and Pharmacological Effects of Eucommia ulmoides [J]. Traditional Chinese Medicine Information, 2021, 38(6): 73-81.

Fan Bingbing, Zhong Renzhong, Ma Zhuang, et al. Advances in the Pharmacological Research of Psoralea corylifolia [J]. Chinese Journal of Traditional Chinese Medicine, 2024, 42(04): 84-87.

Yang Run, Zhang Liyan, Wang Liang, et al. Preliminary study on the anti-hyperlipidemia activity of walnut kernel and network pharmacology analysis. Journal of Guizhou University of Traditional Chinese Medicine, 2021, 43(4): 37-42.

Hu Ming, Li Mingqiang. Research Progress on the Pharmacological Effects and Medicinal Preparations of Allicin [J]. Modern Medicine & Health, 2017, 33(18): 2799-2802.

Yang Rongping, Xue Bingjie, Sun Guanyun, et al. Effects of different extraction sites of compound Qing-e pill on hydrocortisone-induced yang deficiency syndrome[J]. Chongqing Traditional Chinese Medicine Research, 2011, 2:31-33.

Sun Guanyun, Wang Xingqin, Xue Bingjie, et al. Study on estrogen-like effects of different extract parts of Compound Qing-e Pill[J]. Chongqing Journal of Chinese Herbal Medicine, 2011, 2: 37-40.

L.Yang, Q. Chen, F. Wang, et al. Antiosteo porotic compounds from seeds of Cuscuta chinensis[J]. Ethnopharmacol, 135(2011)553-560.

Liu H, Huang Y, Yang J, et al. Involvement of estrogen receptor activation in kaempferol-3-O-glucoside's protection against aging-related cognition impairment and microglial inflammation[J]. Exp Cell Res.2023 Dec 15;433(2):113849.

L.Yu, C. Chen, L. F. Wang, et al. Neuroprotective effect of kaempferol glycosides against brain injury and neuroinflammation by inhibiting the activation of NF-kappa B and STAT3 in transient focal stroke, PLoS One 8 (2013), e55839.

X. Chen, C. Cheng, X. Zuo, et al. Astragalin alleviates cerebral ischemia-reperfusion injury by improving anti-oxidant and anti-inflammatory activities andinhibiting apoptosis pathway in rats, BMC Complement Med Ther 20(2020)120.

D. Liu, Y. Gu, W. Wang, et al. Astragalin alleviates ischemia/reperfusioninduced brain injury via suppression of endoplasmic reticulum stress. Mol. Med. Rep. 22(2020)4070-4078.

Simandi Z, Horvath A, Cuaranta-Monroy I, et al. RXR heterodimers orchestrate transcriptional control of neurogenesis and cell fate specification[J]. Mol Cell Endocrinol, 2018, 471(8):51-62.

Dong W, Zhang Y. Retinoic acid receptor alpha expression exerts an anti-apoptosis effect on PC12 cells following oxygen-glucose deprivation[J]. Exp Ther Med, 2018, 16(4):3525-3533.

Chen P, Li L, Gao Y, et al. Beta-carotene provides neuro protection after experimental traumatic brain injury via the Nrf2-ARE pathway[J]. Integr Neurosci, 2019, 18(2) :153-161.

Yang Yuhua, Luo Baolong. Mi Ke Bao, vitamin B1 acupoint injection treatment of 34 cases of diabetic neurogenic bladder[J]. Chinese Clinical Doctor, 2007(08):57.

Boido CC, Tasso B, Boido V, et al. Cytisine derivatives as ligands for neuronal nicotine receptors and with various pharmacological activities[J]. Farmaco.2003 Mar;58(3):265-77.

Vakhitova YV, Farafontova EI, Zainullina LF, et al.Search of (-)-Cytisine Derivatives as Potential Inhibitors of NF-κB and STAT1[J].Bioorg Khim.2015 May-Jun;41(3):336-45.

Akbar A, Liu K, Michos ED, et al. Racial differences in urinary incontinence prevalence and associated bother: the Multi-Ethnic Study of Atherosclerosis[J]. Am J Obstet Gynecol.2021 Jan;224(1):80.e1-80.e9.

Gille A, Bodor ET, Ahmed K, et al. Nicotinic acid: pharmacological effects and mechanisms of action[J]. Annu Rev Pharmacol Toxicol.2008;48:79-106.

ROTWEIN P. Variation in Akt protein kinases in human populations[J]. American Journal of Physiology- Regulatory, Integrative and Comparative Physiology, 2017, 313(6):R687-R692

Erta M, Quintana A, Hidalgo J. Interleukin-6, a major cytokine in the central nervous system[J]. Int J Biol Sci (2012) 8(9):1254-66.

Cafferty WB, Gardiner NJ, Das P, et al. Conditioning injury-induced spinal axon regeneration fails in interleukin-6 knock-out mice[J]. Neurosci (2004) 24(18): 4432-43.

Langevin H M, Churchill D L, Cipolla M J. Mechanical signaling through connective tissue: a mechanism for the therapeutic effect of acupuncture[J]. Faseb Journal Official Publication of the Federation of American Societies for Experimental Biology, 2001, 15(12):2275

Yoshikawa S, Sumino Y, Kwon J, et al. Effects of multiple simulated birth traumas on urethral continence function in rats[J]. Am J Physiol Renal Physiol, 2017, 313(5):F1089-F1096.

Ou JR, Tan MS, Xie AM, et al. Heat shock protein 90 in Alzheimer’s disease[J]. Biomed Res Int. 2014; 2014:796869.

Bohush A, Bieganowski P, Filipek A. Hsp90 and its co-chaperones in neurodegenerative diseases[J]. Int J Mol Sci, 2019, 20(20):4976.

Astillero-Lopez V, Villar-Conde S, Gonzalez-Rodriguez M, et al. Proteomic analysis identifies HSP90AA1, PTK2B, and ANXA2 in the human entorhinal cortex in Alzheimer's disease: Potential role in synaptic homeostasis and Aβ pathology through microglial and astroglial cells[J]. Brain Pathol, 2024 Jan 22:e13235.

Shinohara M, Sumino Y, Sato F, et al. Tumor necrosis factoralpha inhibits differentiation of myogenic cells in human urethral rhabdosphincter [J]. Int J Urol, 2017, 24(6):461-467.

Sakakibara R, Takahashi O, Nishimura H, et al. The relationship between bladder, periarterial and somatic neuropathy in diabetes[J]. Intern Med, 2018, 57(15):2165-2168.

Downloads

Published

2024-06-30

How to Cite

Ma, B., Shen, J., Yang, M., Du, Q., & Ye, H. (2024). Research Focusing on How Qinge Pill Functions in Managing Stress Urinary Incontinence, Utilizing Network Pharmacology. Journal of Contemporary Medical Practice, 6(6), 160–167. https://doi.org/10.53469/jcmp.2024.06(06).29