Advanced Search

Journal of Traditional Chinese Medicine >

2025 , Vol. 45 >Issue 1: 89 - 99

DOI: https://doi.org/10.19852/j.cnki.jtcm.20240423.002

Network pharmacology and animal experiments revealed the protective effects of Guilong prescription (归龙方) on chronic prostatitis and its possible mechanisms

  • Peixuan ZHU ,
  • Zeqi SU ,
  • Qiongyin FAN ,
  • Cai ZHANG ,
  • Ting WANG
Expand
  • 1 School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
    2 Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
    3 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsycho-pharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China

Received date: 2023-12-12

  Accepted date: 2024-03-14

  Online published: 2024-04-23

Supported by

National Major Scientific and the Technological Special Project: Establishment of a Clinically Oriented Preclinical Research and Development Technology Platform for New Chinese Medicines based on Famous Doctors' Prescriptions(2017ZX09301011);"Decoding Traditional Chinese Medicine" Project of Beijing University of Chinese Medicine: New Drugs Research and Development of Chinese Medicine based on Famous Doctors and Famous Prescriptions(90010961020020);the Horizontal Project: Preclinical Pharmacology and Pharmacodynamic Research of a New Chinese Medicine — Guilong Granules(2016110031007799)

Fold

Abstract

OBJECTIVE: To investigate the protective effects of Guilong prescription (归龙方, GL) on chronic prostatitis (CP) and unravel the underlying mechanisms of its pharmacological effects.

METHODS: The composition of GL was determined via linear ion trap/electrostatic field orbital trap tandem high-resolution mass spectrometry, and the identified compounds were performed network pharmacological analysis to predict possible pathways of the effects of GL on CP. A CP rat model was established by carrageenan, and rats were randomly assigned into a Control group, Sham group, CP group, GL low dose (3.5 g/kg) group, GL medium dose (7 g/kg) group, and GL high dose (14 g/kg) group. Hematoxylin-eosin staining of the prostate, and prostate blood -perfusion measured by laser speckle contrast analysis were used to evaluate the efficacy of GL. Expression of intercellular cell adhesion molecule-1 (ICAM-1) and induce nitric oxide synthase (iNOS) were determined by immunohistochemistry, and the content of interferon-γ (IFN-γ), interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-10 (IL-10), chemokine ligand 1 (CXCL1) and tumor necrosis factor-α (TNF-α) were determined by electro-chemiluminescence assays. The expression of p38 mitogen-activated protein kinase (p38 MAPK), phosphatidylinositol 3-kinase (PI3K), ribosome-associated complex-alpha serine/threonine-protein kinase (Akt), nuclear factor-κ-gene binding p65 (NF-κB p65), inhibitor of NF-κB-α (IκBα), glycogen synthase kinase-3β (GSK-3β), and their phosphorylated forms were tested by Western blot.

RESULTS: In GL, a total of 48 compounds were identified, including 14 flavonoids, 14 alkaloids, 11 carboxylic acids, 4 lactones, 2 glycosides, 2 terpenoids and 1 aldehyde. Network pharmacological analysis suggested that the mechanism of GL may be related to PI3K-Akt signaling pathway and cytokine expression. After treatment with GL, inflammatory pathological changes in the prostate of rats were significantly improved, and blood perfusion of the prostate was significantly decreased. GL reduced the expression of IFN-γ, CXCL1, TNF-α, IL-1β, iNOS, ICAM-1, p38 MAPK, p-p38 MAPK, PI3K, p-PI3K, NF-κB, p-NF-κB, IκBα, p-IκBα, GSK-3β, p-GSK-3β, p-Akt in CP rats, and increased the expression of IL-4 and IL-10 in CP rats.

CONCLUSION: The chemical compositions of GL were first identified. GL can improve pathological changes in the prostate and recover the prostate blood perfusion of CP rats. The possible mechanisms of GL on CP involve increasing the expression of anti-inflammatory cytokines IL-4 and IL-10, inhibiting pro-inflammatory cytokines TNF-α, IL-1β, and IFN-γ, and down regulating the expression of CXCL1, iNOS, and ICAM-1 via inhibiting PI3K-Akt and NF-κB signaling pathway.

Key words： Prostatitis; cytokines; anti-inflammatory agents; carrageenan; Guilong prescription; network pharmacology

Cite this article

Peixuan ZHU , Zeqi SU , Qiongyin FAN , Cai ZHANG , Ting WANG . Network pharmacology and animal experiments revealed the protective effects of Guilong prescription (归龙方) on chronic prostatitis and its possible mechanisms[J]. Journal of Traditional Chinese Medicine, 2025 , 45(1) : 89 -99 . DOI: 10.19852/j.cnki.jtcm.20240423.002

References

1. Krieger JN, Nyberg L Jr, Nickel JC. NIH consensus definition and classification of prostatitis. JAMA 1999; 282: 236-7.
2. Magistro G, Wagenlehner FME, Pilatz A. Chronic prostatitis/chronic pelvic pain syndrome. Urologie 2023; 62: 590-6.
3. Suskind AM, Berry SH, Ewing BA, et al. The prevalence and overlap of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome in men: results of the RAND Interstitial Cystitis Epidemiology male study. J Urol 2013; 189: 141-5.
4. Pena VN, Engel N, Gabrielson AT, et al. Diagnostic and management strategies for patients with chronic prostatitis and chronic pelvic pain syndrome. Drugs Aging 2021; 38: 845-86.
5. 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 Mens Health 2020; 14: 1557988320903200.
6. Qin Z, Zhang C, Guo J, et al. Oral pharmacological treatments for chronic prostatitis/chronic pelvic pain syndrome: a systematic review and network Meta-analysis of randomised controlled trials. EClinicalMedicine 2022; 48: 101457.
7. Nickel JC. Chronic prostatitis/chronic pelvic pain syndrome: it is time to change our management and research strategy. BJU Int 2020; 125: 479-80.
8. Xue Y, Duan Y, Gong X, et al. Traditional Chinese Medicine on treating chronic prostatitis/chronic pelvic pain syndrome: a systematic review and Meta-analysis. Medicine (Baltimore) 2019; 98: e16136.
9. Franco JV, Turk T, Jung JH, et al. Pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome. Cochrane Database Syst Rev 2019; 10: CD012552.
10. Zhang ZJ (Eastern Han dynasty). Jin Gui Yao Lüe. Beijing: XueYuan Publishing House, 2007: 116.
11. Li H, Hung A, Yang AWH. Herbal formula (Danggui Beimu Kushen Wan) for prostate disorders: a systematic review of classical literature. Integr Med Res 2019; 8: 240-6.
12. Li H, Hung A, Yang AWH. A classic herbal formula Danggui Beimu Kushen Wan for chronic prostatitis: from traditional knowledge to scientific exploration. Evid Based Complement Alternat Med 2018; 2018: 1612948.
13. Yang X, Yuan L, Chen J, et al. Multitargeted protective effect of Abacopteris penangiana against carrageenan-induced chronic prostatitis in rats. J Ethnopharmacol 2014; 151: 343-51.
14. Hajighorbani M, Ahmadi-Hamedani M, Shahab E, et al. Evaluation of the protective effect of pentoxifylline on carrageenan-induced chronic non-bacterial prostatitis in rats. Inflammopharmacology 2017; 25: 343-50.
15. Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm 2016; 7: 27-31.
16. Zhang C, Wang X, Wang C, et al. Qingwenzhike prescription alleviates acute lung injury induced by LPS via inhibiting TLR4/NF-kB pathway and NLRP 3 inflammasome activation. Front Pharmacol 2021; 12: 790072.
17. Wu Y, Zhang F, Yang K, et al. SymMap: an integrative database of Traditional Chinese Medicine enhanced by symptom mapping. Nucleic Acids Res 2019; 47: D1110-7.
18. Stelzer G, Rosen N, Plaschkes I, et al. The Gene Cards Suite: from gene data mining to disease genome sequence analyses. Curr Protoc Bioinformatics 2016; 54: 1.30. 1-33.
19. Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 2019; 10: 1523.
20. He H, Luo H, Xu H, et al. Preclinical models and evaluation criteria of prostatitis. Front Immunol 2023; 14: 1183895.
21. Epstein JI, Netto GJ. Biopsy interpretation of the prostate. Fifth edition ed.Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2015: 9.
22. Cho IR, Keener TS, Nghiem HV, et al. Prostate blood flow characteristics in the chronic prostatitis/pelvic pain syndrome. J Urol 2000; 163: 1130-3.
23. Meng LQ, Yang FY, Wang MS, et al. Quercetin protects against chronic prostatitis in rat model through NF-kappa B and MAPK signaling pathways. Prostate 2018; 78: 790-800.
24. de Lima NM, Ferreira EO, Fernandes MY, et al. Neuroinflammatory response to experimental stroke is inhibited by boldine. Behav Pharmacol 2017; 28: 223-37.
25. Wang HQ, Hu J, Yan HY, et al. Corydaline inhibits enterovirus 71 replication by regulating COX-2 expression. J Asian Nat Prod Res 2017; 19: 1124-33.
26. Li Y, Zhang L, Zhang P, Hao Z. Dehydrocorydaline protects against sepsis-induced myocardial injury through modulating the TRAF6/NF-κB pathway. Frontiers in Pharmacology 2021; 12: 709604.
27. Jiang D, Rasul A, Batool R, et al. Potential anticancer properties and mechanisms of action of formononetin. Biomed Res Int 2019; 2019: 5854315.
28. Chen MH, Gu YY, Zhang AL, et al. Biological effects and mechanisms of matrine and other constituents of Sophora flavescens in colorectal cancer. Pharmacol Res 2021; 171: 105778.
29. Tarabasz D, Kukula-Koch W. Palmatine: a review of pharmacological properties and pharmacokinetics. Phytother Res 2020; 34: 33-50.
30. Yang G, Zeng R, Song X, et al. Sophocarpine alleviates injury-induced intima hyperplasia of carotid arteries by suppressing inflammation in a rat model. J Clin Med 2021; 10: 5449.
31. Hao Q, Wu Y, Vadgama JV, Wang P. Phytochemicals in inhibition of prostate cancer: evidence from molecular mechanisms studies. Biomolecules 2022; 12: 1306.
32. Peng X, Guo H, Chen J, et al. The effect of pirfenidone on rat chronic prostatitis/chronic pelvic pain syndrome and its mechanisms. Prostate 2020; 80: 917-25.
33. Schwartz ES, La JH, Young EE, et al. Chronic prostatitis induces bladder hypersensitivity and sensitizes bladder afferents in the mouse. J Urol 2016; 196: 892-901.
34. Chen L, Zhang M, Liang C. Chronic prostatitis and pelvic pain syndrome: another autoimmune disease? Arch Immunol Ther Exp (Warsz) 2021; 69: 24.
35. Hayden MS, Ghosh S. Regulation of NF-κB by TNF family cytokines. Semin Immunol 2014; 26: 253-66.
36. Shidid S, Bluth MH, Smith-Norowitz TA. The role of inflammasomes in mediating urological disease: a short literature review. J Inflamm Res 2022; 15: 4359-65.
37. Motrich RD, Breser ML, Molina RI, et al. Patients with chronic prostatitis/chronic pelvic pain syndrome show T helper type 1 (Th1) and Th17 self-reactive immune responses specific to prostate and seminal antigens and diminished semen quality. BJU Int 2020; 126: 379-87.
38. Hu Q, Lyon CJ, Fletcher JK, et al. Extracellular vesicle activities regulating macrophage- and tissue-mediated injury and repair responses. Acta Pharm Sin B 2021; 11: 1493-512.
39. Soundararajan L, Dharmarajan A, Samji P. Regulation of pleiotropic physiological roles of nitric oxide signaling. Cell Signal 2023; 101: 110496.
40. ückert S, Kedia GT, Tsikas D, et al. Emerging drugs to target lower urinary tract symptomatology (LUTS)/benign prostatic hyperplasia (BPH): focus on the prostate. World J Urol 2020; 38: 1423-35.
41. Korbecki J, Barczak K, Gutowska I, et al. CXCL1: gene, promoter, regulation of expression, mRNA stability, regulation of activity in the intercellular space. Int J Mol Sci 2022; 23: 792.
42. Bui TM, Wiesolek HL, Sumagin R. ICAM-1: a master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis. J Leukoc Biol 2020; 108: 787-99.
43. Heeb LEM, Egholm C, Boyman O. Evolution and function of interleukin-4 receptor signaling in adaptive immunity and neutrophils. Genes Immun 2020; 21: 143-9.
44. Saraiva M, Vieira P, O'Garra A. Biology and therapeutic potential of interleukin-10. J Exp Med 2020; 217: e20190418.
45. Kameritsch P, Renkawitz J. Principles of leukocyte migration strategies. Trends Cell Biol 2020; 30: 818-32.
46. Song W, Sun Y, Liang XC, et al. Jinmaitong ameliorates diabetes-induced peripheral neuropathy in rats through Wnt/β-catenin signaling pathway. J Ethnopharmacol 2021; 266: 113461.
Options
Outlines

/

〈 〉