Piper guineense (Swhan and Thon) Inhibits Lanosterol-14α-demethylase in Multi-Drug Resistant Non-albicans Candida Species: In vitro and In silico Studies

Olumide Oluyele, Damilola Alex Omoboyowa, Ayomide Esther Aderogba, Koffi Adusa Osei

Abstract


Candida species are globally recognized for invasive infections with poor prognosis. Burgeoning quest for the discovery of novel therapeutics has increased the scientific scrutiny of several medicinal plants. This study assessed the efficacy of Piper guineense crude extract and fractions against selected multi-drug resistant non- albicans Candida species. Both the crude and fractionated extracts of P. guineense elicited marked anti-candidal activity. Overall, the crude extract showed better efficacy over the fractions with the highest inhibition zone (25.0mm) recorded against Candida tropicalis; amongst the fractions, n-hexane fraction (F2) produced the highest inhibition zone (23mm) against Candida glabrata. The MIC ranged from 25mg/ml to 50mg/ml; while the MBC ranged between 100 mg/ml to 200 mg/ml. HPLC analysis revealed the presence of 14 compounds in the extract, with prominent members being quercetin, ellagic acid, persin, catechin, p-coumaric acid, and lutein. The binding affinity and free binding energy results reveal that most of these bioactive compounds were better than the standard drug (Fluconazole). Conclusively, P. guineense extracts demonstrated impressive anti-candidal properties against the tested multi-drug resistant non-albicans Candida species and could have potential as new drug lead for the treatment of infections resulting from these pathogens.

Received on, 17 October 2024

Accepted on, 15 January 2025

Published on, 15 March 2025


Keywords


P. guineense, non-albicans Candida, Lanosterol- 14α-demethylase, Antimicrobial resistance

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References


Denning DW. Global incidence and mortality of severe fungal disease. Lancet Infect Dis. 2024 Jul;24(7):e428–38.

Pappas PG, Lionakis MS, Arendrup MC, Ostrosky-Zeichner L, Kullberg BJ. Invasive candidiasis. Nat Rev Dis Primers. 2018 May 11;4(1):18026.

Netea MG, Joosten LAB, van der Meer JWM, Kullberg BJ, van de Veerdonk FL. Immune defence against Candida fungal infections. Nat Rev Immunol. 2015 Oct 21;15(10):630–42.

Mayer FL, Wilson D, Hube B. Candida albicans pathogenicity mechanisms. Virulence. 2013 Feb 15;4(2):119–28.

Pfaller MA. Antifungal drug resistance: Mechanisms, epidemiology, and consequences for treatment. American Journal of Medicine. 2012;125(1 SUPPL.).

Oluyele O, Oladunmoye MK, Ogundare AO, Onifade AK, Okunnuga NA. Microbial spectrum and susceptibility profile of opportunistic pathogens isolated from cancer patients attending a tertiary healthcare centre in Akure, Nigeria. Microbes, Infection and Chemotherapy. 2023;3.

Dhanya K, Kizhakkayil J, Syamkumar S, Sasikumar B. Isolation and Amplification of Genomic DNA from Recalcitrant Dried Berries of Black Pepper (Piper nigrum L.)—A Medicinal Spice. Mol Biotechnol. 2007 Sep 13;37(2):165–8.

Oluyele O, Oladunmoye MK, Ogundare AO. Toxicity Studies on Essential Oil from Phoenix dactylifera (L.) Seed in Wistar Rats. Biologics. 2022;2(1).

Singh VK, Singh P, Patel AMA, Yadav KKM. Piperine: delightful surprise to the biological world, made by plant “pepper” and a great bioavailability enhancer for our drugs and supplements. World J Pharm Res. 2014;3(6).

Matsuda H, Ninomiya K, Morikawa T, Yasuda D, Yamaguchi I, Yoshikawa M. Protective effects of amide constituents from the fruit of Piper chaba on d-galactosamine/TNF-α-induced cell death in mouse hepatocytes. Bioorg Med Chem Lett. 2008 Mar;18(6):2038–42.

Damanhouri ZA. A Review on Therapeutic Potential of Piper nigrum L. (Black Pepper): The King of Spices. Med Aromat Plants (Los Angel). 2014;03(03).

Mathew PJ, Mathew PM, Kumar V. Graph clustering of Piper guineense L. (black pepper). Vol. 18. Euphytica; 2020. 257–264 p.

Ahmad N, Fazal H, Abbasi BH, Farooq S, Ali M, Khan MA. Biological role of Piper nigrum L. (Black pepper): A review. Asian Pac J Trop Biomed. 2012 Jan;2(3):S1945–53.

Hernández-Pabón JC, Tabares B, Gil Ó, Lugo-Sánchez C, Santana A, Barón A, et al. Candida Non-albicans and Non-auris Causing Invasive Candidiasis in a Fourth-Level Hospital in Colombia: Epidemiology, Antifungal Susceptibility, and Genetic Diversity. Journal of Fungi. 2024 Apr 30;10(5):326.

Jannati B, Pourdad A, Izadjoo A, Zarrinfar H, Najafzadeh Mj, Fata A. The prevalence of Non-albicans Candida and Candida mixed-species in vulvovaginal candidiasis in Iran. Clin Exp Obstet Gynecol. 2024;51(3):77.

Galocha M, Pais P, Cavalheiro M, Pereira D, Viana R, Teixeira MC. Divergent approaches to virulence in C. Albicans and C. Glabrata: Two sides of the same coin. Int J Mol Sci. 2019;20(9).

Ceballos Garzon A, Amado D, Robert E, Parra Giraldo CM, Le Pape P. Impact of calmodulin inhibition by fluphenazine on susceptibility, biofilm formation and pathogenicity of caspofungin-resistant Candida glabrata. Journal of Antimicrobial Chemotherapy. 2020;75(5).

Oluyele O, Oladunmoye M. Susceptibility Patterns of Staphylococcus aureus Isolated from Wounds Swabs to Extracts of Vernonia amygdalina. J Adv Med Pharm Sci. 2017;13(4).

Pham DC, Truong DH, Tran QH, Ho QT, Nguyen TAD, Nguyen TNH, et al. Fractionation, identification of chemical constituents, and biological properties of cashew (Anacardium occidentale L.) leaf extracts. Food Sci Nutr. 2023;11(12).

Khan S, Mirza KJ, Anwar F, Abdin MZ. Development of RAPD markers for authentication of Piper nigrum (L.) . Environmental International Journals of Science Technology . 2010;5:47–56.

Omoboyowa DA. Exploring molecular docking with E-pharmacophore and QSAR models to predict potent inhibitors of 14-α-demethylase protease from Moringa spp. Pharmacological Research - Modern Chinese Medicine. 2022;4.

Mgbeahuruike EE, Holm Y, Vuorela H, Amandikwa C, Fyhrquist P. An ethnobotanical survey and antifungal activity of Piper guineense used for the treatment of fungal infections in West-African traditional medicine. J Ethnopharmacol. 2019;229.

Mgbeahuruike EE, Fyhrquist P, Vuorela H, Julkunen-Tiitto R, Holm Y. Alkaloid-Rich Crude Extracts, Fractions and Piperamide Alkaloids of Piper guineense Possess Promising Antibacterial Effects. Antibiotics. 2018 Nov 9;7(4):98.

Ogunmefun OT, Akharaiyi FC, Adegunle SJ. Phytochemical and Antimicrobial Properties of Piper guineense (Shumach and Thonn) on Selected Human Pathogens. J Chem Pharm Res. 2020;9(11):180–6.

Chitlange SS, Payal BS, Sanjay D, Nipanikar S, Dheeraj N. Development and validation of RPHPLC method for quantification of piperine from single herb formulation containing Piper guineense extract. . International Journals of Pharmacological Science Revised. 2020;6(2):16–21.

Gao M, Wang H, Zhu L. Quercetin Assists Fluconazole to Inhibit Biofilm Formations of Fluconazole-Resistant Candida Albicans in In Vitro and in Vivo Antifungal Managements of Vulvovaginal Candidiasis. Cellular Physiology and Biochemistry. 2016;40(3–4).

Oliveira VM, Carraro E, Auler ME, Khalil NM. Quercetin and rutin as potential agents antifungal against Cryptococcus spp. Brazilian Journal of Biology. 2016 May 6;76(4):1029–34.

Singh BN, Upreti DK, Singh BR, Pandey G, Verma S, Roy S, et al. Quercetin Sensitizes Fluconazole-Resistant Candida albicans To Induce Apoptotic Cell Death by Modulating Quorum Sensing. Antimicrob Agents Chemother. 2015 Apr;59(4):2153–68.

Nejatbakhsh S, Ilkhanizadeh-Qomi M, Razzaghi-Abyaneh M, Jahanshiri Z. The Effects of Ellagic Acid on Growth and Biofilm Formation of Candida albicans. Journal of Medical Microbiology and Infectious Diseases. 2020 Jan 1;8(1):14–8.

G V, K MA, M KC, M RM, R S, H S, et al. REVIEW OF PLANTS USED AS KSHAR OF FAMILY PIPERACEAE. International Journal of Ayurvedic Medicine. 2010 Oct 9;1(2).

Sinsinwar S, Vadivel V. Catechin isolated from cashew nut shell exhibits antibacterial activity against clinical isolates of MRSA through ROS-mediated oxidative stress. Appl Microbiol Biotechnol. 2020;104(19).

Kusmiati, Ningsih EB, Ramadhani I, Amir M. Antibacterial and antioxidant activity test of crude lutein extracted from sunflower (Helianthus annuus L.). In: AIP Conference Proceedings. 2021.

Oladimeji AO, Karigidi KO, Yeye EO, Omoboyowa DA. Phytochemical composition, antioxidant and antimicrobial activities of essential oils extracted from Emilia coccinea (Sims) G. Don using in-vitro and in-silico approaches. Vegetos. 2024 Aug 28;

Monk BC, Sagatova AA, Hosseini P, Ruma YN, Wilson RK, Keniya M V. Fungal Lanosterol 14α-demethylase: A target for next-generation antifungal design. Vol. 1868, Biochimica et Biophysica Acta - Proteins and Proteomics. 2020.

Rosam K, Monk BC, Lackner M. Sterol 14α-Demethylase Ligand-Binding Pocket-Mediated Acquired and Intrinsic Azole Resistance in Fungal Pathogens. Journal of Fungi. 2020 Dec 22;7(1):1.

Rampogu S, Baek A, Zeb A, Lee KW. Exploration for novel inhibitors showing back-to-front approach against VEGFR-2 kinase domain (4AG8) employing molecular docking mechanism and molecular dynamics simulations. BMC Cancer. 2018 Dec 7;18(1):264.




DOI: https://dx.doi.org/10.21622/AMPDR.2025.05.1.1060

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Copyright (c) 2025 Olumide Oluyele, Damilola Alex Omoboyowa, Ayomide Esther Aderogba, Koffi Adusa Osei

Advances in Medical, Pharmaceutical and Dental Research
E-ISSN: 2812-4898
P-ISSN: 2812-488X 

Published by:

Academy Publishing Center (APC)
Arab Academy for Science, Technology and Maritime Transport (AASTMT)
Alexandria, Egypt
ampdr@aast.edu