Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Integrating Network Pharmacology and Experimental Verification to Investigate the Mechanisms of Shuangshi Tonglin Capsule to Treat Chronic Prostatitis

Author(s): Qian Mao, Xinyue Zhang, Chuan Wang, Jiping Liu, Ziqiang Wang, Bin Wang, Peng Mao, Hao Wei* and Baoan Wang*

Volume 26, Issue 10, 2023

Published on: 07 December, 2022

Page: [1856 - 1865] Pages: 10

DOI: 10.2174/1386207326666221024144543

Price: $65

Abstract

Background and Objective: Chronic prostatitis (CP) is one of the most common diseases in young and middle-aged men but lacks effective treatment. Shuangshi Tonglin Capsule (SSTLC) is a clinical drug for the treatment of chronic prostatitis. However, the underlying molecular mechanisms of SSTLC in treating CP are still unclear. In this study, we researched the underlying mechanisms of SSTLC in treating chronic prostatitis.

Methods: The ingredients of SSTLC were received from the TCMSP and BATMAN databases, and the CP targets were collected based on GeneCards and OMIM. Then, the PPI network and the “drug-ingredient-target” network map were constructed. GO and KEGG enrichment analyses by using DAVID. Molecular docking was performed by using AutoDock 4.2 and PyMol. And using animal experiments to verify the potential effect of SSTLC in CP.

Results: SSTLC contained 10 herbs, 158 chemical ingredients and 277 targets, 2002, diseaserelated targets were obtained. Network analysis outcomes indicated that VEGFA, TNF, MAPK1, EGFR, and MAPK8 are the key targets of SSTLC in treating chronic prostatitis. Furthermore, molecular docking revealed that quercetin, luteolin, and kaempferol exhibited a strong binding effect. Animal experimental indicated that SSTLC can reduce the pathological damage to prostate tissue. And, we found that high-dose SSTLC significantly reduced the level of TNF-α and downregulated the expression of EGFR, p-p38 and p-ERK1/2 (P<0.05).

Conclusion: This study determined the pharmacological effects of SSTLC and the potential mechanism of action on SSTLC to treat CP, it provides a new idea for traditional Chinese medicine to treat chronic prostatitis.

Keywords: Chronic prostatitis, shuangshi tonglin capsule, network pharmacology, EGFR, MAPK, SSTLC.

[1]
Zhang, J.; Liang, C.; Shang, X.; Li, H. Chronic prostatitis/chronic pelvic pain syndrome: A disease or symptom? current perspectives on diagnosis, treatment, and prognosis. Am. J. Men Health, 2020, 14(1), 1557988320903200.
[http://dx.doi.org/10.1177/1557988320903200] [PMID: 32005088]
[2]
Magri, V.; Marras, E.; Restelli, A.; Wagenlehner, F.M.; Perletti, G. Multimodal therapy for category III chronic prostatitis/chronic pelvic pain syndrome in UPOINTS phenotyped patients. Exp. Ther. Med., 2015, 9(3), 658-666.
[http://dx.doi.org/10.3892/etm.2014.2152] [PMID: 25667610]
[3]
Pontari, M.A. Etiologic theories of chronic prostatitis/chronic pelvic pain syndrome. Curr. Urol. Rep., 2007, 8(4), 307-312.
[http://dx.doi.org/10.1007/s11934-007-0077-6] [PMID: 18519015]
[4]
Passavanti, M.B.; Pota, V.; Sansone, P.; Aurilio, C.; De Nardis, L.; Pace, M.C. Chronic pelvic pain: Assessment, evaluation, and objectivation. Pain Res. Treat., 2017, 2017, 1-15.
[http://dx.doi.org/10.1155/2017/9472925] [PMID: 29359045]
[5]
Aktar, N.; Moudud, A.; Chen, T.; Gao, X.; Min, H.; Tang, M.; Zhou, X. Recent advances in pharmacological interventions of chronic prostatitis/chronic pelvic pain syndrome. Curr. Pharm. Des., 2021, 27(25), 2861-2871.
[http://dx.doi.org/10.2174/1381612827666210322125054] [PMID: 33749554]
[6]
Hu, M.; Wazir, J.; Ullah, R.; Wang, W.; Cui, X.; Tang, M.; Zhou, X. Phytotherapy and physical therapy in the management of chronic prostatitis–chronic pelvic pain syndrome. Int. Urol. Nephrol., 2019, 51(7), 1081-1088.
[http://dx.doi.org/10.1007/s11255-019-02161-x] [PMID: 31054003]
[7]
Jin, C.; Chen, Z.; Zhang, J. Meta-analysis of the efficacy of Ningmitai capsule on the treatment of chronic prostatitis in China. Medicine (Baltimore), 2018, 97(33), e11840.
[http://dx.doi.org/10.1097/MD.0000000000011840] [PMID: 30113475]
[8]
Xue, Y.; Duan, Y.; Gong, X.; Zheng, W.; Li, Y. Traditional Chinese medicine on treating chronic prostatitis/chronic pelvic pain syndrome. Medicine (Baltimore), 2019, 98(26), e16136.
[http://dx.doi.org/10.1097/MD.0000000000016136] [PMID: 31261537]
[9]
Khattak, A.S.; Raison, N.; Hawazie, A.; Khan, A.; Brunckhorst, O.; Ahmed, K. Contemporary management of chronic prostatitis. Cureus, 2021, 13(12), e20243.
[PMID: 35004057]
[10]
Dashdondov, O.; Wazir, J.; Sukhbaatar, G.; Mikrani, R.; Dorjsuren, B.; Aktar, N.; Zhou, X. Herbal nutraceutical treatment of chronic prostatitis–chronic pelvic pain syndrome: A literature review. Int. Urol. Nephrol., 2021, 53(8), 1515-1528.
[http://dx.doi.org/10.1007/s11255-021-02868-w] [PMID: 33907984]
[11]
Zhang, X.H.; Liu, N.S.; Mao, J.Y.; Yi, H. Clinical study of Shuangshi Tonglin capsules combined with roxithromycin in treatment of type IIIA prostatitis. Drugs Clin., 2021, 36(08), 1664-1668.
[12]
Jin, S.; He, J.H.; Jiang, H.; Zhang, J.; Mao, P. Shuangshi Tonglin capsule in the treatment of chronic prostatitis. Shaanxi J. Tradit. Chin. Med., 2016, 37(02), 216-218.
[13]
Liu, W.Z.; Jiao, S.M.; Wang, B.A. Effect of Shuangshi Tonglin capsules on non-bacterial prostatitis. Clin. Res. Pract., 2019, 4(13), 5-7.
[14]
Guojun, Y.; Yonglin, W.; Xinxin, H.; Qian, Z.; Hui, X.; Jun, C.; De, J.; Chunqin, M.; Tulin, L. A modern technology applied in traditional chinese medicine: Progress and future of the nanotechnology in TCM. Dose-Resp., 2019, 17(3), 1559325819872854.
[15]
Liu, J.; Liu, L.; Zhang, G.; Peng, X. Poria cocos polysaccharides attenuate chronic nonbacterial prostatitis by targeting the gut microbiota: Comparative study of Poria cocos polysaccharides and finasteride in treating chronic prostatitis. Int. J. Biol. Macromol., 2021, 189, 346-355.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.08.139] [PMID: 34428489]
[16]
Zheng, C.; Pei, T.; Huang, C.; Chen, X.; Bai, Y.; Xue, J.; Wu, Z.; Mu, J.; Li, Y.; Wang, Y. A novel systems pharmacology platform to dissect action mechanisms of traditional Chinese medicines for bovine viral diarrhea disease. Eur. J. Pharm. Sci., 2016, 94, 33-45.
[http://dx.doi.org/10.1016/j.ejps.2016.05.018] [PMID: 27208435]
[17]
Meng, L.Q.; Yang, F.Y.; Wang, M.S.; Shi, B.K.; Chen, D.X.; Chen, D.; Zhou, Q.; He, Q.B.; Ma, L.X.; Cheng, W.L.; Xing, N.Z. Quercetin protects against chronic prostatitis in rat model through NF-κB and MAPK signaling pathways. Prostate, 2018, 78(11), 790-800.
[http://dx.doi.org/10.1002/pros.23536] [PMID: 29654614]
[18]
Chen, D.; Bi, A.; Dong, X.; Jiang, Y.; Rui, B.; Liu, J.; Yin, Z.; Luo, L. Luteolin exhibits anti-inflammatory effects by blocking the activity of heat shock protein 90 in macrophages. Biochem. Biophys. Res. Commun., 2014, 443(1), 326-332.
[http://dx.doi.org/10.1016/j.bbrc.2013.11.122] [PMID: 24321097]
[19]
Tu, Y.C.; Lian, T.W.; Yen, J.H.; Chen, Z.T.; Wu, M.J. Antiatherogenic effects of kaempferol and rhamnocitrin. J. Agric. Food Chem., 2007, 55(24), 9969-9976.
[PMID: 17973448]
[20]
Basu, A.; Das, A.S.; Sharma, M.; Pathak, M.P.; Chattopadhyay, P.; Biswas, K.; Mukhopadhyay, R. STAT3 and NF-κB are common targets for kaempferol-mediated attenuation of COX-2 expression in IL-6-induced macrophages and carrageenan-induced mouse paw edema. Biochem. Biophys. Rep., 2017, 12, 54-61.
[http://dx.doi.org/10.1016/j.bbrep.2017.08.005] [PMID: 28955792]
[21]
Cho, J.; Lee, H.K. Wogonin inhibits excitotoxic and oxidative neuronal damage in primary cultured rat cortical cells. Eur. J. Pharmacol., 2004, 485(1-3), 105-110.
[http://dx.doi.org/10.1016/j.ejphar.2003.11.064] [PMID: 14757129]
[22]
Nakamura, N.; Hayasaka, S.; Zhang, X.Y.; Nagaki, Y.; Matsumoto, M.; Hayasaka, Y.; Terasawa, K. Effects of baicalin, baicalein, and wogonin on interleukin-6 and interleukin-8 expression, and nuclear factor-κb binding activities induced by interleukin-1β in human retinal pigment epithelial cell line. Exp. Eye Res., 2003, 77(2), 195-202.
[http://dx.doi.org/10.1016/S0014-4835(03)00116-7] [PMID: 12873450]
[23]
Byrne, A.M.; Bouchier-Hayes, D.J.; Harmey, J.H. Angiogenic and cell survival functions of Vascular Endothelial Growth Factor (VEGF). J. Cell. Mol. Med., 2005, 9(4), 777-794.
[http://dx.doi.org/10.1111/j.1582-4934.2005.tb00379.x] [PMID: 16364190]
[24]
Fatima, L.A.; Campello, R.S.; Santos, R.S.; Freitas, H.S.; Frank, A.P.; Machado, U.F.; Clegg, D.J. Estrogen receptor 1 (ESR1) regulates VEGFA in adipose tissue. Sci. Rep., 2017, 7(1), 16716.
[http://dx.doi.org/10.1038/s41598-017-16686-7] [PMID: 29196658]
[25]
Slevin, S.M.; Egan, L.J. New insights into the mechanisms of action of anti-tumor necrosis factor-α monoclonal antibodies in inflammatory bowel disease. Inflamm. Bowel Dis., 2015, 21(12), 2909-2920.
[http://dx.doi.org/10.1097/MIB.0000000000000533] [PMID: 26348448]
[26]
Huang, T.R.; Li, W.; Peng, B. Correlation of inflammatory mediators in prostatic secretion with chronic prostatitis and chronic pelvic pain syndrome. Andrologia., 2018, 50(2)
[http://dx.doi.org/10.1111/and.12860] [PMID: 28762547]
[27]
Barroso-Chinea, P.; Luis-Ravelo, D.; Fumagallo-Reading, F.; Castro-Hernandez, J.; Salas-Hernandez, J.; Rodriguez-Nuñez, J.; Febles-Casquero, A.; Cruz-Muros, I.; Afonso-Oramas, D.; Abreu-Gonzalez, P.; Moratalla, R.; Millan, M.J.; Gonzalez-Hernandez, T. DRD3 (dopamine receptor D3) but not DRD2 activates autophagy through MTORC1 inhibition preserving protein synthesis. Autophagy, 2020, 16(7), 1279-1295.
[http://dx.doi.org/10.1080/15548627.2019.1668606] [PMID: 31538542]
[28]
Zhang, Q.; Liu, J.; Zhang, M.; Wei, S.; Li, R.; Gao, Y.; Peng, W.; Wu, C. Apoptosis induction of fibroblast-like synoviocytes is an important molecular-mechanism for herbal medicine along with its active components in treating rheumatoid arthritis. Biomolecules, 2019, 9(12), 795.
[http://dx.doi.org/10.3390/biom9120795] [PMID: 31795133]
[29]
Hanafusa, H.; Torii, S.; Yasunaga, T.; Nishida, E. Sprouty1 and Sprouty2 provide a control mechanism for the Ras/MAPK signalling pathway. Nat. Cell Biol., 2002, 4(11), 850-858.
[http://dx.doi.org/10.1038/ncb867] [PMID: 12402043]
[30]
Zhang, Y.; Wang, L.; Zhang, M.; Jin, M.; Bai, C.; Wang, X. Potential mechanism of interleukin-8 production from lung cancer cells: An involvement of EGF-EGFR-PI3K-Akt-Erk pathway. J. Cell. Physiol., 2012, 227(1), 35-43.
[http://dx.doi.org/10.1002/jcp.22722] [PMID: 21412767]
[31]
Elkamhawy, A.; Hassan, A.H.E.; Paik, S.; Sup Lee, Y.; Lee, H.H.; Shin, J.S.; Lee, K.T.; Roh, E.J. EGFR inhibitors from cancer to inflammation: Discovery of 4-fluoro-N-(4-(3-(trifluoromethyl) phenoxy)pyrimidin-5-yl)benzamide as a novel anti-inflammatory EGFR inhibitor. Bioorg. Chem., 2019, 86, 112-118.
[http://dx.doi.org/10.1016/j.bioorg.2019.01.017] [PMID: 30685642]
[32]
Yang, F.; Meng, L.; Han, P.; Chen, D.; Wang, M.; Jiang, Y.; Wu, Y.; Wu, Y.; Xing, N. New therapy with XLQ® to suppress chronic prosta-titis through its anti‐inflammatory and antioxidative activities. J. Cell. Physiol., 2019, 234(10), 17570-17577.
[http://dx.doi.org/10.1002/jcp.28380] [PMID: 30790289]
[33]
Roh, Y.S.; Park, S.; Kim, J.W.; Lim, C.W.; Seki, E.; Kim, B. Tolllike receptor 7-mediated type I interferon signaling prevents cholestasis- and hepatotoxin-induced liver fibrosis. Hepatology, 2014, 60(1), 237-249.
[http://dx.doi.org/10.1002/hep.26981] [PMID: 24375615]
[34]
Menon, M.B.; Gaestel, M. TPL2 meets p38MAPK: Emergence of a novel positive feedback loop in inflammation. Biochem. J., 2016, 473(19), 2995-2999.
[http://dx.doi.org/10.1042/BCJ20160672C] [PMID: 27679858]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy