PDF herunterladen
CC BY 4.0 · Pharmaceutical Fronts 2023; 05(02): e64-e76
DOI: 10.1055/s-0043-1768477
Original Article

In Vivo and in Silico Assessment of Ameliorative Effects of Xylopia aethiopica on Testosterone Propionate-Induced Benign Prostatic Hyperplasia

Udu A. Ibiam
1   Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Ebonyi State, Nigeria
,
Daniel E. Uti
2   Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, Federal University of Health Sciences, Otukpo, Benue State Nigeria
,
Chris C. Ejeogo
1   Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Ebonyi State, Nigeria
,
Obasi U. Orji
1   Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Ebonyi State, Nigeria
,
Patrick M. Aja
1   Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Ebonyi State, Nigeria
,
Ezeaani N. Nwamaka
1   Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Ebonyi State, Nigeria
,
Esther U. Alum
1   Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Ebonyi State, Nigeria
,
Chukwuma Chukwu
3   Department of Chemistry, Alex Ekwueme Federal University, Ndufu-Alike Ikwo, Abakaliki, Ebonyi State, Nigeria
,
Chinyere Aloke
4   Department of Chemistry/Biochemistry and Molecular Biology, Alex Ekwueme Federal University, Ndufu-Alike Ikwo, Abakaliki, Ebonyi State, Nigeria
,
Kate E. Chinedum
1   Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Ebonyi State, Nigeria
,
Peter Agu
1   Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Ebonyi State, Nigeria
,
Valentine Nwobodo
1   Department of Biochemistry, Faculty of Science, Ebonyi State University, Abakaliki, Ebonyi State, Nigeria
› Institutsangaben
Funding The authors wish to acknowledge the support given to this research by the Ebonyi State University Tertiary Education Trust-fund Institutional Based Seed Research grants, 2020 (Reference Number: EBSU/TETfund/IBR/2020/001).
› Weitere Informationen
Auch verfügbar auf
  Lizenzen und Reprints

Abstract

Xylopia aethiopica (XAE) is a commonly used herbal medicine and contains rich active ingredients for a variety of biological activities. The study aimed to explore the role of XAE in the management of benign prostatic hyperplasia (BPH). In the study, testosterone propionate-induced BPH in albino rats was established and treated with different concentrations of ethanol extract of XAE leaf. After treatment, the rats were sacrificed, and the body and prostate weights were recorded. The prostate-specific antigen (PSA) and acid phosphatase (ACP) levels in the blood samples were also determined. Gas chromatography-mass spectrometry was conducted to assess the active chemical compounds. Docking analysis was performed to screen chemical compounds by evaluating their binding affinity with two pro-BPH protein targets (cellular prostatic ACP and PSA). Our data showed the presence of 44 chemical compounds in XAE leaf extract. The body and prostate weights, as well as the levels of PSA and ACP, were significantly increased in BPH induction, and the changing trend was significantly reversed by additional XAE treatment. Interestingly, PSA and ACP levels in XAE-treated groups were reduced to almost the same levels as those in the healthy control. Docking analysis identified four top-posed compounds: β-amyrin, α-amyrin, α-amyrenone, and lupenone with stronger binding energies to prostatic ACP being −9.8, −8.3, −8.4, and −8.6, respectively, compared with the standard drug finasteride (−8.3). Furthermore, the two-dimensional analysis revealed strong interactions through hydrogen bonding, covalent interactions, and several van der Waal forces between the lead compounds and the target proteins. Notably, there was a recurrence interaction between similar residues Asn-1062, Lys-1250, Lys-1059, and Phe-1060 on the protein targets and the lead compounds. The study first revealed the role of XAE in BPH therapy and will help in drug design based on the lead compounds discovered in this work.

Keywords

benign prostatic hyperplasia - Xylopia aethiopica - acid phosphatase - prostate-specific antigen - docking analysis


Publikationsverlauf

Eingereicht: 04. Oktober 2022

Angenommen: 03. April 2023

Artikel online veröffentlicht:
24. Mai 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Wang W, Guo Y, Zhang D, Tian Y, Zhang X. The prevalence of benign prostatic hyperplasia in mainland China: evidence from epidemiological surveys. Sci Rep 2015; 5 (01) 13546
    CrossrefPubMedSuche in Google Scholar
  • 2 Chughtai B, Forde JC, Thomas DD. et al. Benign prostatic hyperplasia. Nat Rev Dis Primers 2016; 2: 16031
    CrossrefPubMedSuche in Google Scholar
  • 3 Miller J, Tarter TH. Combination therapy with dutasteride and tamsulosin for the treatment of symptomatic enlarged prostate. Clin Interv Aging 2009; 4: 251-258
    PubMedSuche in Google Scholar
  • 4 Abdollah F, Briganti A, Suardi N. et al. Metabolic syndrome and benign prostatic hyperplasia: evidence of a potential relationship, hypothesized etiology, and prevention. Korean J Urol 2011; 52 (08) 507-516
    CrossrefPubMedSuche in Google Scholar
  • 5 Liu CC, Huang SP, Li WM. et al. Relationship between serum testosterone and measures of benign prostatic hyperplasia in aging men. Urology 2007; 70 (04) 677-680
    CrossrefPubMedSuche in Google Scholar
  • 6 Roehrborn CG. Male lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Med Clin North Am 2011; 95 (01) 87-100
    CrossrefPubMedSuche in Google Scholar
  • 7 Nickel JC. BPH: costs and treatment outcomes. Am J Manag Care 2006; 12 (5, Suppl): S141-S148
    PubMedSuche in Google Scholar
  • 8 Barkin J, Guimarães M, Jacobi G, Pushkar D, Taylor S, van Vierssen Trip OB. Alpha-blocker therapy can be withdrawn in the majority of men following initial combination therapy with the dual 5alpha-reductase inhibitor dutasteride. Eur Urol 2003; 44 (04) 461-466
    CrossrefPubMedSuche in Google Scholar
  • 9 Wei JT, Calhoun E, Jacobsen SJ. Urologic diseases in America project: benign prostatic hyperplasia. J Urol 2005; 173 (04) 1256-1261
    CrossrefPubMedSuche in Google Scholar
  • 10 Roehrborn CG, Rosen RC. Medical therapy options for aging men with benign prostatic hyperplasia: focus on alfuzosin 10  mg once daily. Clin Interv Aging 2008; 3 (03) 511-524
    CrossrefPubMedSuche in Google Scholar
  • 11 Cannarella R, Condorelli RA, Barbagallo F, La Vignera S, Calogero AE. Endocrinology of the aging prostate: current concepts. Front Endocrinol (Lausanne) 2021; 12: 554078
    CrossrefPubMedSuche in Google Scholar
  • 12 Ozoemena FN. . A Catechism of Prostate Disease: Men and Diseases of the Prostate. 1st ed. Enugu: Ezu Books Ltd; 2003
  • 13 Wennberg JE, Roos N, Sola L, Schori A, Jaffe R. Use of claims data systems to evaluate health care outcomes. Mortality and reoperation following prostatectomy. JAMA 1987; 257 (07) 933-936
    CrossrefPubMedSuche in Google Scholar
  • 14 Andriole G, Bruchovsky N, Chung LW. et al. Dihydrotestosterone and the prostate: the scientific rationale for 5alpha-reductase inhibitors in the treatment of benign prostatic hyperplasia. J Urol 2004; 172 (4, Pt 1): 1399-1403
    CrossrefPubMedSuche in Google Scholar
  • 15 Kumar VL, Wahane VD. Current status of 5alpha-reductase inhibitors in the treatment of benign hyperplasia of prostate. Indian J Med Sci 2008; 62 (04) 167-175
    CrossrefPubMedSuche in Google Scholar
  • 16 Dhingra N, Bhagwat D. Benign prostatic hyperplasia: an overview of existing treatment. Indian J Pharmacol 2011; 43 (01) 6-12
    CrossrefPubMedSuche in Google Scholar
  • 17 Earnest EO, Moke GE. Xylopia aethiopica: a review of its ethnomedicinal, chemical and pharmacological properties. Am J Pharm Tech Res 2014; 4 (06) 22-37
    Suche in Google Scholar
  • 18 Yin X, Chávez León MASC, Osae R, Linus LO, Qi LW, Alolga RN. Xylopia aethiopica seeds from two countries in West Africa exhibit differences in their proteomes, mineral content and bioactive phytochemical composition. Molecules 2019; 24 (10) 1979
    Suche in Google Scholar
  • 19 Minciullo PL, Inferrera A, Navarra M, Calapai G, Magno C, Gangemi S. Oxidative stress in benign prostatic hyperplasia: a systematic review. Urol Int 2015; 94 (03) 249-254
    Suche in Google Scholar
  • 20 Zhang YJ, Gan RY, Li S. et al. Antioxidant phytochemicals for the prevention and treatment of chronic diseases. Molecules 2015; 20 (12) 21138-21156
    CrossrefPubMedSuche in Google Scholar
  • 21 Lezoul NEH, Belkadi M, Habibi F, Guillén F. Extraction processes with several solvents on total bioactive compounds in different organs of three medicinal plants. Molecules 2020; 25 (20) 4672
    CrossrefPubMedSuche in Google Scholar
  • 22 Vijay DT, Rajendra PB. Estimation of total phenol, tanin, alkaloid and flavanoid in Hibiscus Tiliacous Linn. wood extracts. J Pharmacogn Phytochem 2014; 2 (04) 41-47
    Suche in Google Scholar
  • 23 Harborne JB. . Phytochemical Methods: A Guide to Modern Techniques of Plant Analysis. 3rd ed. London: Chapman and Hall; 2005
  • 24 Evans WC. . Trease and Evans Pharmacognosy. 15th ed. London: WB Saunders; 2002
  • 25 Association of Officials of Analytical Chemists. Official Methods of Analysis. 16th ed. Washington: AOAC International; 1995
  • 26 Lorke D. A new approach to practical acute toxicity testing. Arch Toxicol 1983; 54 (04) 275-287
    CrossrefPubMedSuche in Google Scholar
  • 27 Nilsson O, Peter A, Andersson I, Nilsson K, Grundström B, Karlsson B. Antigenic determinants of prostate-specific antigen (PSA) and development of assays specific for different forms of PSA. Br J Cancer 1997; 75 (06) 789-797
    CrossrefPubMedSuche in Google Scholar
  • 28 Allen SM. An enzyme linked immunosorbent assay (ELISA) for detection of seminal fluid using a monoclonal antibody to prostatic acid phosphatase. J Immunoassay 1995; 16 (03) 297-308
    CrossrefPubMedSuche in Google Scholar
  • 29 Talib VH, Khurana SR. . Handbook Medical Laboratory Technology. 2nd ed. New Delhi: CBS Publishers and Distributors; 1999:97
  • 30 Pettersen EF, Goddard TD, Huang CC. et al. UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem 2004; 25 (13) 1605-1612
    CrossrefPubMedSuche in Google Scholar
  • 31 Dallakyan S, Olson AJ. Small-molecule library screening by docking with PyRx. Methods Mol Biol 2015; 1263: 243-250
    CrossrefPubMedSuche in Google Scholar
  • 32 Fhu CW, Ali A. Fatty acid synthase: an emerging target in cancer. Molecules 2020; 25 (17) 3935
    CrossrefPubMedSuche in Google Scholar
  • 33 Bisson JF, Hidalgo S, Rozan P, Messaoudi M. Therapeutic effect of ACTICOA powder, a cocoa polyphenolic extract, on experimentally induced prostate hyperplasia in Wistar-Unilever rats. J Med Food 2007; 10 (04) 628-635
    CrossrefPubMedSuche in Google Scholar
  • 34 Udensi UK, Tchounwou PB. Oxidative stress in prostate hyperplasia and carcinogenesis. J Exp Clin Cancer Res 2016; 35 (01) 139
    CrossrefPubMedSuche in Google Scholar
  • 35 Benavente-García O, Castillo J, Marin FR, Ortuño A, Del Río JA. Uses and properties of citrus flavonoids. J Agric Food Chem 1997; 45 (12) 4505-4515
    CrossrefSuche in Google Scholar
  • 36 Close DC, McArthur C. Rethinking the role of many plant phenolics – protection from photodamage not herbivores?. Oikos 2002; 99 (01) 166-172
    CrossrefSuche in Google Scholar
  • 37 Prasad S, Kalra N, Singh M, Shukla Y. Protective effects of lupeol and mango extract against androgen induced oxidative stress in Swiss albino mice. Asian J Androl 2008; 10 (02) 313-318
    CrossrefPubMedSuche in Google Scholar
  • 38 Salah N, Miller NJ, Paganga G, Tijburg L, Bolwell GP, Rice-Evans C. Polyphenolic flavanols as scavengers of aqueous phase radicals and as chain-breaking antioxidants. Arch Biochem Biophys 1995; 322 (02) 339-346
    CrossrefPubMedSuche in Google Scholar
  • 39 Jucá MM, Cysne Filho FMS, de Almeida JC. et al. Flavonoids: biological activities and therapeutic potential. Nat Prod Res 2020; 34 (05) 692-705
    CrossrefPubMedSuche in Google Scholar
  • 40 Buck AC. Phytotherapy for the prostate. Br J Urol 1996; 78 (03) 325-336
    CrossrefPubMedSuche in Google Scholar
  • 41 Jang H, Bae WJ, Kim SJ. et al. The effect of anthocyanin on the prostate in an andropause animal model: rapid prostatic cell death by apoptosis is partially prevented by anthocyanin supplementation. World J Mens Health 2013; 31 (03) 239-246
    CrossrefPubMedSuche in Google Scholar
  • 42 Bespalov VG, Alexandrov VA, Semenov AL. et al. Old rats are more susceptible to induction of benign prostatic hyperplasia (BPH) at comparative to young mature. Curr Aging Sci 2021; 14 (02) 124-132
    CrossrefPubMedSuche in Google Scholar
  • 43 Takizawa I, Nishiyama T, Hara N, Isahaya E, Hoshii T, Takahashi K. Serum prostate-specific antigen levels reflect the androgen milieu in patients with localized prostate cancer receiving androgen deprivation therapy: tumor malignant potential and androgen milieu. Prostate 2010; 70 (13) 1395-1401
    CrossrefPubMedSuche in Google Scholar
  • 44 Carson III C, Rittmaster R. The role of dihydrotestosterone in benign prostatic hyperplasia. Urology 2003; 61 (4, Suppl 1): 2-7
    CrossrefPubMedSuche in Google Scholar
  • 45 Shojaii A, Motaghinejad M, Norouzi S, Motevalian M. Evaluation of anti-inflammatory and analgesic activity of the extract and fractions of Astragalus hamosus in animal models. Iran J Pharm Res 2015; 14 (01) 263-269
    PubMedSuche in Google Scholar
  • 46 Akinyemi RA, Huthman IO, Adesanya OA, Akpan HB, Adefule AK. Effect of the methanolic extract of Trichosathes cucumerina seed (Snake gourd/tomatoes) on experimentally increased prostate specific Antigen PSA in adult wister rats. J Med Health Sci 2012; 1 (01) 10-17
    Suche in Google Scholar
  • 47 Kong HY, Byun J. Emerging roles of human prostatic acid phosphatase. Biomol Ther (Seoul) 2013; 21 (01) 10-20
    CrossrefPubMedSuche in Google Scholar
  • 48 Yeh HF, Li TF, Tsai CH. et al. The effects of a Chinese herbal medicine (VGHBPH0) on patients with benign prostatic hyperplasia: a pilot study. J Chin Med Assoc 2020; 83 (10) 967-971
    CrossrefPubMedSuche in Google Scholar
  • 49 Emeka EJI, Ogidigo JO. Prostate specific antigen (PSA), antioxidant and hematological parameters in prostate rats feel fed macrocarpon leaves. Asian J Biologic Sci 2015; 8 (01) 30-41
    Suche in Google Scholar
  • 50 Lin MF, Garcia-Arenas R, Chao YC, Lai MM, Patel PC, Xia XZ. Regulation of prostatic acid phosphatase expression and secretion by androgen in LNCaP human prostate carcinoma cells. Arch Biochem Biophys 1993; 300 (01) 384-390
    CrossrefPubMedSuche in Google Scholar