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Mixture of Corni Fructus and Schisandrae Fructus improves testosterone-induced benign prostatic hyperplasia through regulating 5α-reductase 2 and androgen receptor

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BACKGROUND/OBJECTIVES: Benign prostatic hyperplasia (BPH) characterized by an enlarged prostate gland is common in elderly men. Corni Fructus (CF) and Schisandrae Fructus (SF) are known to have various pharmacological effects, including antioxidant and anti-inflammatory activities. In this study, we evaluated the inhibitory efficacy of CF, SF, and their mixture (MIX) on the development of BPH using an in vivo model of testosterone-induced BPH. MATERIALS/METHODS: Six-week-old male Sprague-Dawley rats were randomly divided into seven groups. To induce BPH, testosterone propionate (TP) was injected to rats except for those in the control group. Finasteride, saw palmetto (SP), CF, SF, and MIX were orally administered along with TP injection. At the end of treatment, histological changes in the prostate and the level of various biomarkers related to BPH were evaluated. RESULTS: Our results showed that BPH induced by TP led to prostate weight and histological changes. Treatment with MIX effectively improved TP-induced BPH by reducing prostate index, lumen area, epithelial thickness, and expression of BPH biomarkers such as 5α-reductase type 2, prostate-specific antigen, androgen receptor, and proliferating cell nuclear antigen compared to treatment with CF or SF alone. Moreover, MIX further reduced levels of elevated serum testosterone, dihydrotestosterone, and prostate-specific antigen in BPH compared to the SP, a positive control. BPH was also improved more by MIX than by CF or SF alone. CONCLUSIONS: Based on the results, MIX is a potential natural therapeutic candidate for BPH by regulating 5α-reductase and AR signaling pathway.

Abstract

BACKGROUND/OBJECTIVES: Benign prostatic hyperplasia (BPH) characterized by an enlarged prostate gland is common in elderly men. Corni Fructus (CF) and Schisandrae Fructus (SF) are known to have various pharmacological effects, including antioxidant and anti-inflammatory activities. In this study, we evaluated the inhibitory efficacy of CF, SF, and their mixture (MIX) on the development of BPH using an in vivo model of testosterone-induced BPH. MATERIALS/METHODS: Six-week-old male Sprague-Dawley rats were randomly divided into seven groups. To induce BPH, testosterone propionate (TP) was injected to rats except for those in the control group. Finasteride, saw palmetto (SP), CF, SF, and MIX were orally administered along with TP injection. At the end of treatment, histological changes in the prostate and the level of various biomarkers related to BPH were evaluated. RESULTS: Our results showed that BPH induced by TP led to prostate weight and histological changes. Treatment with MIX effectively improved TP-induced BPH by reducing prostate index, lumen area, epithelial thickness, and expression of BPH biomarkers such as 5α-reductase type 2, prostate-specific antigen, androgen receptor, and proliferating cell nuclear antigen compared to treatment with CF or SF alone. Moreover, MIX further reduced levels of elevated serum testosterone, dihydrotestosterone, and prostate-specific antigen in BPH compared to the SP, a positive control. BPH was also improved more by MIX than by CF or SF alone. CONCLUSIONS: Based on the results, MIX is a potential natural therapeutic candidate for BPH by regulating 5α-reductase and AR signaling pathway.

참고문헌 (53)

  1. Sharma M, "Phytotherapeutic agents for benign prostatic hyperplasia : an overview", Mini Rev Med Chem, 17, pp.1346~1363 (2017)
  2. Vickman RE, "The role of the androgen receptor in prostate development and benign prostatic hyperplasia : a review", Asian J Urol, 7, pp.191~202 (2020)
  3. Vasanwala FF, "Benign prostatic hyperplasia and male lower urinary symptoms : a guide for family physicians", Asian J Urol, 4, pp.181~184 (2017)
  4. Mobley D, "Benign prostatic hyperplasia and urinary symptoms : evaluation and treatment", Postgrad Med, 127, pp.301~307 (2015)
  5. Madersbacher S, "Pathophysiology of benign prostatic hyperplasia and benign prostatic enlargement : a mini-review", Gerontology, 65, pp.458~464 (2019)
  6. Zhu YS, "5alpha-reductase isozymes and androgen actions in the prostate", Ann N Y Acad Sci, 1155, pp.43~56 (2009)
  7. Cózar JM, "The role of prostate-specific antigen in light of new scientific evidence: an update in 2020", Actas Urol Esp(Engl Ed), 45, pp.21~29 (2021)
  8. Kizilay F, "The place of androgen receptor gene mutation analysis in the molecular diagnosis of prostate cancer and genotype-phenotype relationship", Turk J Med Sci, 44, pp.261~266 (2014)
  9. La Vignera S, "Pharmacological treatment of lower urinary tract symptoms in benign prostatic hyperplasia : consequences on sexual function and possible endocrine effects", Expert Opin Pharmacother, 22, pp.179~189 (2021)
  10. De Nunzio C, "Combination therapies for improved management of lower urinary tract symptoms", benign prostatic hyperplasia, 2016, pp.52, 501~517
  11. Gupta S, "Evolving novel chemical entities for management of benign prostatic hyperplasia", Mini Rev Med Chem, 17, pp.593~602 (2017)
  12. Garg G, "Management of benign prostate hyperplasia : an overview of alphaadrenergic antagonist", Biol Pharm Bull, 29, pp.1554~1558 (2006)
  13. Azzouni F, "Role of 5α-reductase inhibitors in benign prostatic diseases", Prostate Cancer Prostatic Dis, 15, pp.222~230 (2012)
  14. Abdulmaged M. Traish, "The Dark Side of 5α-Reductase Inhibitors’ Therapy: Sexual Dysfunction, High Gleason Grade Prostate Cancer and Depression", Investigative and Clinical Urology, 55(6), pp.367~379 (2014), 대한비뇨의학회
  15. Gao X, "Active components and pharmacological effects of Cornus officinalis : literature review", Front Pharmacol, 12, pp.633447~ (2021)
  16. Dong Y, "Corni Fructus : a review of chemical constituents and pharmacological activities", Chin Med, 13, pp.34~ (2018)
  17. Kopustinskiene DM, "Antioxidant effects of Schisandra chinensis fruits and their active constituents", Antioxidants, 10, pp.620~ (2021)
  18. Rybnikář M, "Schisandra chinensis and its phytotherapeutical applications", Ceska Slov Farm, 68, pp.95~118 (2019)
  19. Huang J, "Ethnopharmacology, phytochemistry, and pharmacology of Cornus officinalis Sieb. et Zucc", J Ethnopharmacol, 213, pp.280~301 (2018)
  20. Zhou Y, "Pharmacodynamic effects and molecular mechanisms of lignans from Schisandra chinensis Turcz. (Baill.), a current review", Eur J Pharmacol, 892, pp.173796~ (2021)
  21. Mitsunari K, "Pharmacological effects and potential clinical usefulness of polyphenols in benign prostatic hyperplasia", Molecules, 26, pp.450~ (2021)
  22. Castelli T, "Metabolic syndrome and prostatic disease: potentially role of polyphenols in preventive strategies. A review", Int Braz J Urol, 42, pp.422~430 (2016)
  23. Minciullo PL, "Oxidative stress in benign prostatic hyperplasia : a systematic review", Urol Int, 94, pp.249~254 (2015)
  24. Bostanci Y, "Correlation between benign prostatic hyperplasia and inflammation", Curr Opin Urol, 23, pp.5~10 (2013)
  25. 황보현, "Corni Fructus attenuates testosterone-induced benign prostatic hyperplasia by suppressing 5α-reductase and androgen receptor expression in rats", Nutrition Research and Practice, 12(5), pp.378~386 (2018), 한국영양학회
  26. Wei F, "Stepwise frontal analysis coupled with cell membrane chromatography for affinity screening and characterization analysis of bioactive constituent from the mature fruits of schisandra chinensis", J Chromatogr B Analyt Technol Biomed Life Sci, 1161, pp.122443~ (2020)
  27. Bandiera Solange, "Hepatic and renal damage by alcohol and cigarette smoking in rats", 한국독성학회지, 37(2), pp.209~219 (2021), 한국독성학회[DOI]
  28. Bhat A, "Are all procedures for benign prostatic hyperplasia created equal? A systematic review on post-procedural PSA dynamics and its correlation with relief of bladder outlet obstruction", World J Urol, 40, pp.889~905 (2022)
  29. Gravina GL, "Phenotypic characterization of human prostatic stromal cells in primary cultures derived from human tissue samples", Int J Oncol, 42, pp.2116~2122 (2013)
  30. Zhou Y, "Proliferation and phenotypic changes of stromal cells in response to varying estrogen", androgen levels in castrated rats, 2009, pp.11, 451~459
  31. Rodriguez-Nieves JA, "Prostatic fibrosis, lower urinary tract symptoms, and BPH", Nat Rev Urol, 10, pp.546~550 (2013)
  32. Song KH, "Extracts of Phyllostachys pubescens leaves represses human steroid 5-α reductase type 2 promoter activity in BHP-1 cells and ameliorates testosterone-induced benign prostatic hyperplasia in rat model", Nutrients, 13, pp.884~ (2021)
  33. 김대근, "Quisqualis indica extract ameliorates low urinary tract symptoms in testosterone propionate-induced benign prostatic hyperplasia rats", Laboratory Animal Research, 36(3), pp.208~217 (2020), 한국실험동물학회[DOI]
  34. Kim HJ, "Psoralea corylifolia L. extract ameliorates benign prostatic hyperplasia by regulating prostate cell proliferation and apoptosis", J Ethnopharmacol, 273, pp.113844~ (2021)
  35. Hong GL, "The therapeutic effects of Stauntonia hexaphylla in benign prostate hyperplasia are mediated by the regulation of androgen receptors and 5α-reductase type 2", J Ethnopharmacol, 250, pp.112446~ (2020)
  36. Choi YJ, "Effect of Paecilomyces tenuipes extract on testosteroneinduced benign prostatic hyperplasia in Sprague-Dawley rats", Int J Environ Res Public Health, 16, pp.3764~ (2019)
  37. Lee G, "Cynanchum wilfordii ameliorates testosteroneinduced benign prostatic hyperplasia by regulating 5α-reductase and androgen receptor activities in a rat model", Nutrients, 9, pp.1070~ (2017)
  38. Karunasagara S, "Protective effects of combination of Stauntonia hexaphylla and Cornus officinalis on testosterone-induced benign prostatic hyperplasia through inhibition of 5α-reductase type 2 and induced cell apoptosis", PLoS One, 15, pp.e0236879~ (2020)
  39. Uroko RI, "Combined ethanol extract of Funtumia africana and Abutilon mauritianium leaves improves the lipid profile and kidney function indices of benign prostatic hyperplasia in rats", Acta Sci Pol Technol Aliment, 19, pp.395~404 (2020)
  40. Cai H, "Rapid simultaneous identification and determination of the multiple compounds in crude Fructus Corni and its processed products by HPLC-MS", MS with multiple reaction monitoring mode, 2013, pp.51, 273~278
  41. Liu H, "Comprehensive chemical analysis of Schisandra chinensis by HPLC-DAD-MS combined with chemometrics", Phytomedicine, 20, pp.1135~1143 (2013)
  42. Kim DU, "Loganin attenuates the severity of acute kidney injury induced by cisplatin through the inhibition of ERK activation in mice", Int J Mol Sci, 22, pp.1421~ (2021)
  43. Cheng YC, "Loganin ameliorates painful diabetic neuropathy by modulating oxidative stress, inflammation and insulin sensitivity in streptozotocin-nicotinamide-induced diabetic rats", Cells, 10, pp.2688~ (2021)
  44. Nasser MI, "Inhibitory effects of Schisandrin B on human prostate cancer cells", Oncol Rep, 41, pp.677~685 (2019)
  45. Mahapokai W, "Models for studying benign prostatic hyperplasia", Prostate Cancer Prostatic Dis, 3, pp.28~33 (2000)
  46. Zhang J, "Animal models of benign prostatic hyperplasia", Prostate Cancer Prostatic Dis, 24, pp.49~57 (2021)
  47. Soni KK, "Protective effect of DA-9401in finasteride-induced apoptosis in rat testis : inositol requiring kinase 1 and c-Jun N-terminal kinase pathway", Drug Des Devel Ther, 11, pp.2969~2979 (2017)
  48. Messner EA, "The androgen receptor in prostate cancer : effect of structure, ligands and spliced variants on therapy", Biomedicines, 8, pp.422~ (2020)
  49. Chughtai B, "Benign prostatic hyperplasia", Nat Rev Dis Primers, 2, pp.16031~ (2016)
  50. Soulitzis N, "Expression analysis of peptide growth factors VEGF, FGF2, TGFB1, EGF and IGF1 in prostate cancer and benign prostatic hyperplasia", Int J Oncol, 29, pp.305~314 (2006)
  51. Minutoli L, "Apoptotic pathways linked to endocrine system as potential therapeutic targets for benign prostatic hyperplasia", Int J Mol Sci, 17, pp.1311~ (2016)
  52. Jin BR, "Anti-proliferative effects of standardized Cornus officinalis on benign prostatic epithelial cells via the PCNA", E2F1-dependent cell cycle pathway, 2020, pp.21, 9567~
  53. Choo SH, "Effects of Schisandra chinensis extract on the relaxation of isolated human prostate tissue and smooth muscle cell", J Ethnopharmacol, 156, pp.271~276 (2014)

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