Protective and Antioxidant Effects of Quercetin Loaded Black Cumin ‎‎(Nigella sativa L) Seed Oil-Based Nanoemulsion in Testosterone-Induced ‎Benign Prostatic Hyperplasia: An Experimental Study

Document Type : Original Articles

Authors

1 ‎Department of Veterinary Basic Sciences, Science and Research Branch, Islamic Azad ‎‎University, Tehran, Iran

2 Department of Veterinary Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran

3 Department of Veterinary Pathobiology, Science and Research Branch, Islamic Azad ‎‎University, Tehran, Iran

4 ‎Department of Veterinary Clinical Sciences, Science and Research Branch, Islamic Azad ‎‎University, Tehran, Iran

10.32592/ARI.2024.79.5.1065

Abstract

Quercetin (Qu) is a type of plant flavonoid that is beneficial in fighting prostate hyperplasia cells. ‎Meanwhile, Nigella sativa seed oil (NSO) has shown promise in relieving benign prostatic ‎hyperplasia (BPH) symptoms. This study aims to assess the effects of Qu combined with NSO-‎based nanoemulsion (Qu-NSO) against a rat model of BPH. The study involved the ‎induction of ‎BPH in rats using testosterone enanthate (5 mg/kg) subcutaneously and ‎administering different ‎treatments, ‎including Qu (25 mg/kg and 50 mg/kg), NSO, and Qu-NSO (25 mg/kg and 50 ‎mg/kg), with total volume 0.5 ml per oral to assess the effects of ‎Qu-NSO. NSO, coconut oil, ‎Tween 80, and polyethylene glycol 400 (PEG) were obtained for the ‎self-nano-emulsified drug ‎delivery system. The globule size and zeta potential of formed vesicles were measured. ‎Dihydrotestosterone (DHT), prostate-specific antigen (PSA), prostatic weight and index, oxidant ‎and antioxidant markers, and histopathology were investigated in the rat model. The average ‎globule size for Qu-NSO was ‎171.9 ± 10.9 ‎nm, with ‎a zeta potential value of ‎+17.3 mV. Qu-‎NSO declined prostate weight by 40% and prostate index by 86.71% compared to ‎the ‎testosterone group. Qu-NSO treatment ‎significantly reduced the serum levels of oxidative ‎‎contents (MDA) (p < 0.0001), while antioxidative substances (SOD and GPx activity) were ‎‎significantly more (p < 0.0001). Qu-NSO was superior to the finasteride group in decreasing ‎prostatic weight and antioxidative ‎properties, such as increasing antioxidant enzyme ‎activity.‎ ‎This study revealed that the Qu and NSO in a Qu NSO formula enhanced the Qu efficacy in ‎managing BPH.‎

Keywords

Main Subjects

References

  1. Khaki Z, Masoudifard M, Khadivar F, Shirani D, Fathipour V, Taheri M. Serum biochemical and hematological parameters in dogs with benign prostatic hyperplasia (BPH). Iran J Vet Med. 2017;11(1):55-62.
  2. Eleazu C, Eleazu K, Kalu W. Management of benign prostatic hyperplasia: Could dietary polyphenols be an alternative to existing therapies? Front Pharmacol. 2017;8:234.
  3. Plochocki A, King B. medical treatment of benign prostatic hyperplasia. Urol Clin North Am. 2022;49(2):231-8.
  4. Vrolijk MF, van Essen H, Opperhuizen A, Bast A, Janssen BJ. Haemodynamic effects of the flavonoid quercetin in rats revisited. Br J Pharmacol‎. 2020;177(8):1841-52.
  5. Reyes-Farias M, Carrasco-Pozo C. The anti-cancer effect of quercetin: molecular implications in cancer metabolism. ‎ Int J Mol Sci‎. 2019;20(13):1-19.
  6. Ma C, Xiang Q, Song G, Wang X. Quercetin and polycystic ovary syndrome. Front Pharmacol‎. 2022;13:1-20.
  7. Sul OJ, Ra SW. Quercetin prevents LPS-induced oxidative stress and inflammation by modulating NOX2/ROS/NF-kB in lung epithelial cells. Molecules. 2021;26(22).
  8. Song J, Bai J, Wang S, Liu L, Zhao Z. Effects of quercetin on autophagy and phosphatidylinositol 3-kinase/Protein kinase B/mammalian target of rapamycin signaling pathway in human prostate cancer PC-3 cells. Acta Acad Med Sin. 2020;42(5):578-84.
  9. Sreenivasulu K, Nandeesha H, Dorairajan LN, Nachiappa Ganesh R. Over expression of PI3K-AkT reduces apoptosis and increases prostate size in benign prostatic hyperplasia. Aging Male. 2020;23(5):440-6.
  10. Soltanian A, Mosallanejad B, Jalali MR, Varzi HN, Najafabadi MG. The therapeutic effects of quercetin in a canine model of low-dose lipopolysaccharide-induced sepsis compared with hydrocortisone. Iran J Vet Med. 2019;13(4):377-87.
  11. Du X, Hu M, Liu G, Qi B, Zhou S, Lu K, et al. Development and evaluation of delivery systems for quercetin: A comparative study between coarse emulsion, nano-emulsion, high internal phase emulsion, and emulsion gel. J Food Eng. 2022;314:110784.
  12. Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, et al. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed. 2013;3(5):337-52.
  13. Radwan MF, El-Moselhy MA, Alarif WM, Orif M, Alruwaili NK, Alhakamy NA. Optimization of thymoquinone-loaded self-nanoemulsion for management of indomethacin-induced ulcer. Dose Response. 2021;19(2):15593258211013655.
  14. Sadeghimanesh A, Gholipour S, Torki A, Amini-Khoei H, Lorigooini Z, Habtemariam S. Inhibitory effects of Nigella sativa seed oil on the testosterone-induced benign prostatic hyperplasia in rats. Biomedicine. 2021;11(1):19.
  15. Buya AB, Beloqui A, Memvanga PB, Préat V. Self-nano-emulsifying drug-delivery systems: From the development to the current applications and challenges in oral drug delivery. Pharmaceutics. 2020;12(12):1194.
  16. Ujilestari T, Martien R, Ariyadi B, Dono ND. Self-nanoemulsifying drug delivery system (SNEDDS) of Amomum compactum essential oil: design, formulation, and characterization. J Appl Pharm Sci. 2018;8(6):14-21.
  17. Alhakamy NA, Fahmy UA, Ahmed OA. Attenuation of benign prostatic hyperplasia by optimized tadalafil loaded pumpkin seed oil-based self nanoemulsion: In vitro and in vivo evaluation. Pharmaceutics. 2019;11(12):640.
  18. Souto EB, Cano A, Martins-Gomes C, Coutinho TE, Zielińska A, Silva AM. Microemulsions and nanoemulsions in skin drug delivery. Bioeng‎. 2022;9(4).
  19. Wang CY, Yen CC, Hsu MC, Wu YT. Self-nano emulsifying drug delivery systems for enhancing solubility, permeability, and bioavailability of sesamin. 2020;25(14).
  20. Ali MS, Pebam M, Buddhiraju HS, Dey S, Bantal V, Ganapathy N, et al. Accelerating diabetic wound healing by modulating the inflammatory environment using quercetin–rosemary oil lipid nanoemulsions with artificial intelligence‐based wound closure analysis. Adv Ther. 2024:2300345.
  21. Zandeh-Rahimi Y, Panahi N, Hesaraki S, Shirazi-Beheshtiha SH. Protective effects of phoenixin-14 peptide in the indomethacin-induced duodenal ulcer: An experimental study. Int J Pept Res Ther‎. 2022;28(1):1-7.
  22. Rashedi J, Haghjo AG, Abbasi MM, Tabrizi AD, Yaqoubi S, Sanajou D, et al. Anti-tumor effect of quercetin loaded chitosan nanoparticles on induced colon cancer in Wistar rats. Adv Pharm Bull. 2019;9(3):409-15.
  23. Kumar VD, Verma PRP, Singh SK. Morphological and in vitro antibacterial efficacy of quercetin loaded nanoparticles against food-borne microorganisms. Food Sci Techno. 2016;66:638-50.
  24. Lu X, Yang F, Chen D, Zhao Q, Chen D, Ping H, et al. Quercetin reverses docetaxel resistance in prostate cancer via androgen receptor and PI3K/Akt signaling pathways. Int J Biol Sci‎. 2020;16(7):1121-34.
  25. Csikós E, Horváth A, Ács K, Papp N, Balázs VL, Dolenc MS, et al. Treatment of Benign Prostatic Hyperplasia by Natural Drugs. Molecules‎. 2021;26(23).
  26. Wang R, Kobayashi Y, Lin Y, Rauwald HW, Fang L, Qiao H, et al. A phytosterol enriched refined extract of Brassica campestris L. pollen significantly improves benign prostatic hyperplasia (BPH) in a rat model as compared to the classical TCM pollen preparation Qianlie Kang Pule'an Tablets. ‎ Phytomedicine‎. 2015;22(1):145-52.
  27. Yang X, Yuan L, Xiong C, Yin C, Ruan J. Abacopteris penangiana exerts testosterone-induced benign prostatic hyperplasia protective effect through regulating inflammatory responses, reducing oxidative stress and anti-proliferative. J Ethnopharmacol. 2014;157:105-13.
  28. Fu W, Chen S, Zhang Z, Chen Y, You X, Li Q. Quercetin in Tonglong Qibi decoction ameliorates testosterone-induced benign prostatic hyperplasia in rats by regulating Nrf2 signalling pathways and oxidative stress. Andrologia‎. 2022;54(9):e14502.
  29. Khayatan D, Razavi SM, Arab ZN, Hosseini Y, Niknejad A, Momtaz S, et al. Superoxide dismutase: a key target for the neuroprotective effects of curcumin. Mol Cell Biochem‎. 2023;479(3):1-13.
  30. Khayatan D, Nilforoushzadeh MA, Ahmadi Ashtiani HR, Hashemian F. Effect of apple (Malus domestica) stem cells on UVB-induced damage skin with anti-inflammatory properties: an in vivo study. Adv Mater Sci Eng‎. 2022;(5):1-13.
  31. Sk SK, R. R, Nachiappa Ganesh R. Cleistanthins A and B ameliorate testosterone-induced benign prostatic hyperplasia in castrated rats by regulating apoptosis and cell differentiation. Cureus. 2022;14(12):e32141.
  32. Hiipakka RA, Zhang HZ, Dai W, Dai Q, Liao S. Structure-activity relationships for inhibition of human 5alpha-reductases by polyphenols. Biochem Pharmacol‎. 2002;63(6):1165-76.
  33. Sadeghimanesh A, Gholipour S, Torki A, Amini-Khoei H, Lorigooini Z, Habtemariam S. Inhibitory effects of Nigella sativa seed oil on the testosterone-induced benign prostatic hyperplasia in rats. 2021;11(1):19-25.
  34. Abdel-Rahman M. Effect of pumpkin seed (Cucurbita pepo L.) diets on benign prostatic hyperplasia (BPH) chemical and morphometric evaluation in rats. World J Chem. 2006;1:33-40.
  35. Tahmasebi E, Mohammadi M, Yazdanian M, Alam M, Abbasi K, Hosseini HM, et al. Antimicrobial properties of green synthesized novel TiO(2) nanoparticles using Iranian propolis extracts. J Basic Microbiol‎. 2023.
  36. Lewinski N, Colvin V, Drezek R. Cytotoxicity of nanoparticles. 2008;4(1):26-49.
  37. Li M, Zou P, Tyner K, Lee S. Physiologically based pharmacokinetic (PBPK) modeling of pharmaceutical nanoparticles. Aaps j‎. 2017;19(1):26-42.
  38. Kramer G, Mitteregger D, Marberger M. Is benign prostatic hyperplasia (BPH) an immune inflammatory disease? 2007;51(5):1202-16.
  39. Vital P, Castro P, Ittmann M. Oxidative stress promotes benign prostatic hyperplasia. ‎ Prostate‎. 2016;76(1):58-67.
  40. 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(3):249-54.
  41. Zabaiou N, Mabed D, Lobaccaro JM, Lahouel M. Oxidative stress in benign prostate hyperplasia. Andrologia‎. 2016;48(1):69-73.
  42. Sumbul S, Ahmad MA, Mohd A, Mohd A. Role of phenolic compounds in peptic ulcer: An overview. J Pharm Bioallied Sci. 2011;3(3):361-7.
Archives of Razi Institute
Volume 79, Issue 5
September and October 2024
Pages 1065-1074

Files

Share

How to cite

Statistics