بررسی تاثیر کورکومین انکپسوله در نانوذرات پلیمرزومی بر بیان ژن افلاکس پمپ MDR1 در جدایه های کاندیدا آلبیکنس مقاوم به فلوکونازول
محورهای موضوعی : Biotechnological Journal of Environmental Microorganisms
سحر پوراصغر
1
,
آیدا بجاری
2
,
مهکامه هدایت صفا
3
,
مهدی شهریاری نور
4
,
نجمه رنجی
5
1 - گروه زیست شناسی، واحد رشت، دانشگاه آزاد اسلامی، رشت، ایران.
2 - گروه زیست شناسی، واحد رشت، دانشگاه آزاد اسلامی، رشت، ایران.
3 - university of parma, Italy
4 - گروه زیست شناسی، واحد رشت، دانشگاه آزاد اسلامی، رشت، ایران.
5 - گروه زیست شناسی، واحد رشت، دانشگاه آزاد اسلامی، رشت، ایران.
کلید واژه: : کاندیدا آلبیکنس, کورکومین, نانوذرات, MDR1, qRT-PCR,
چکیده مقاله :
کورکومین، یک ترکیب طبیعی از زردچوبه است که به عنوان یک عامل ضدباکتریایی و ضدقارچی شناخته می شود. کاندیدا آلبیکنس یکی از پاتوژن‌‌های قارچی مهم با میزان کشندگی بالا در بیماران با نقص ایمنی است. شایع ترین پاتوژن فرصت‌طلب قارچی است که مصرف پیوسته ضد قارچ‌ها در درمان آن منجر به ظهور و افزایش مقاومت چند‌دارویی شده است. در این مطالعه اثر کورکومین محبوس‌شده در نانوذرات پلیمرزومی و فلوکونازول بر بیان ژن MDR1 در جدایه‌های کاندیدا آلبیکنس مقاوم به دارو ارزیابی شد. در این مطالعه مقطعی توصیفی، 50 نمونه بالینی از زنان با عفونت ولووواژینیت از بیمارستان الزهرا (رشت) تهیه شد. بعد از تعیین هویت جدایه ها، مقاومت به فلوکونازول به روش انتشار از دیسک و براث دایلوشن بررسی شد. شش جدایه کاندیدا آلبیکنس مقاوم به فلوکونازول، تحت تیمار با فلوکونازول به تنهایی (1/2MIC) (نمونه شاهد) و در ترکیب با کورکومین محبوس‌شده در نانوذرات (نمونه تست) قرار گرفت. بعد از 24 ساعت، دو گروه سلولی جهت تخمین نرخ مرگ سلولی در محیط کشت سابوروددکستروز آگار کشت داده شد. بیان ژن MDR1 بطور کمی به روش Q-RT-PCR در سلول های تیمار‌شده و تیمار‌نشده با کورکومین مورد بررسی قرار‌گرفت. نتایج ما نشان داد که درمان ترکیبی فلوکونازول (1/2MIC) و کورکومین محبوس‌شده در نانوذرات(400µg/ml) طی 24 ساعت رشد قارچی را تا 50% کاهش داد. در سلولهای تیمار‌شده با کورکومین، آنالیز Q-RT-PCR کاهش بیان ژن MDR1 را در مقایسه با سلولهای تیمار‌نشده با کورکومین نشان داد. به نظر می رسد کورکومین بتواند از طریق کاهش بیان ژن MDR1 در جدایه‌های مقاوم به فلوکونازول، اثربخشی قلوکونازول را افزایش دهد.
Curcumin, a natural product of turmeric, is known for its antibacterial and antifungal properties. Candida albicans is a major fungal pathogen with high mortality rate, particularly in immunocompromised patients. This study aimed to evaluate the effect of curcumin encapsulated in nanoparticles (polymersomes) in combination with fluconazole on the expression of the MDRI gene in drug-resistant isolates of C. albicans. This descriptive cross-sectional study involved obtaining 50 clinical samples, from women with vulvovaginal infections at Al-Zahra hospital (Rasht, Iran). After identifying the strains, resistance to fluconazole was assessed using disc diffusion and broth dilution methods. Six fluconazole-resistant isolates of C. albicans were treated with ½ MIC fluconazole (control) alone and in combination with curcumin encapsulated in nanoparticles. After 24 hours, the two cell groups were cultured on Sabouraud dextrose agar (SDA) to estimate the cell death rate. The expression of the MDR1 gene was quantitatively investigated using the qRT-PCR method in treated and untreated isolates. Our finding indicated that combined therapy with ½ MIC fluconazole and curcumin encapsulated in nanoparticles (at a concentration of 400µg/ml) reduced fungal growth by up to 50% within during 24 hours. In treated cells, qRT-PCR analysis revealed a decrease in MDR1 gene expression compared to untreated cells. Curcumin appears to enhance the effectiveness of fluconazole in fluconazole-resistant isolates by reducing MDR1 gene expression.
Alalwan, H., Rajendran, R., Lappin, D. F., Combet, E., Shahzad, M., Robertson, D., . . . Ramage, G. (2017). The anti-adhesive effect of curcumin on Candida albicans biofilms on denture materials. Frontiers in Microbiology, 8, 258345.
Awanish Kumar, A. K., Sanjiveeni Dhamgaye, S. D., Maurya, I., Ashutosh Singh, A. S., Monika Sharma, M. S., & Rajendra Prasad, R. P. (2014). Curcumin targets cell wall integrity via calcineurin-mediated signaling in Candida albicans.
Baldesi, O., Bailly, S., Ruckly, S., Lepape, A., L'Heriteau, F., Aupee, M., . . . Berger-Carbonne, A. (2017). ICU-acquired candidaemia in France: epidemiology and temporal trends, 2004–2013–a study from the REA-RAISIN network. Journal of Infection, 75(1), 59-67.
Balouiri, M., Sadiki, M., & Ibnsouda, S. K. (2016). Methods for in vitro evaluating antimicrobial activity: A review. Journal of pharmaceutical analysis, 6(2), 71-79.
Bergin, S. A., Doorley, L. A., Rybak, J., Wolfe, K. H., Butler, G., Cuomo, C. A., & Rogers, P. D. (2023). Analysis of clinical Candida parapsilosis isolates reveals copy number variation in key fluconazole resistance genes. bioRxiv, 2023.2012. 2013.571446.
Bezerra, B. M. S., y Araújo, S. E. D. d. M., Alves-Júnior, J. d. O., Damasceno, B. P. G. d. L., & Oshiro-Junior, J. A. (2024). The Efficacy of Hybrid Vaginal Ovules for Co-Delivery of Curcumin and Miconazole against Candida albicans. Pharmaceutics, 16(3), 312.
Charles, M. P., Kali, A., & Joseph, N. M. (2015). Performance of chromogenic media for Candida in rapid presumptive identification of Candida species from clinical materials. Pharmacognosy Research, 7(Suppl 1), S69.
Chen, L., Xu, Y., Zhou, C., Zhao, J., Li, C., & Wang, R. (2010). Overexpression of CDR1 and CDR2 genes plays an important role in fluconazole resistance in Candida albicans with G487T and T916C mutations. Journal of International Medical Research, 38(2), 536-545.
Cheraghipour, K., Ezatpour, B., Masoori, L., Marzban, A., Sepahvand, A., Rouzbahani, A. K., . . . Mahmoudvand, H. (2021). Anti-Candida activity of curcumin: A systematic review. Current drug discovery technologies, 18(3), 379-390.
Garcia-Gomes, A., Curvelo, J., Soares, R. A., & Ferreira-Pereira, A. (2012). Curcumin acts synergistically with fluconazole to sensitize a clinical isolate of Candida albicans showing a MDR phenotype. Medical mycology, 50(1), 26-32.
Hajifathali, S., Lesan, S., Lotfali, E., Salimi-Sabour, E., & Khatibi, M. (2023). Investigation of the antifungal effects of curcumin against nystatin-resistant Candida albicans. Dental Research Journal, 20(1), 50.
Hu, Y., Zhang, J., Kong, W., Zhao, G., & Yang, M. (2017). Mechanisms of antifungal and anti-aflatoxigenic properties of essential oil derived from turmeric (Curcuma longa L.) on Aspergillus flavus. Food Chemistry, 220, 1-8.
Ishikane, M., Hayakawa, K., Kutsuna, S., Takeshita, N., & Ohmagari, N. (2016). Epidemiology of blood stream infection due to Candida species in a tertiary care hospital in Japan over 12 years: importance of peripheral line-associated candidemia. PLoS One, 11(10), e0165346.
Jeanmonod, R., Jeanmonod, D., Christopherson, N., & Spivey, R. (2019). Vaginal candidiasis (vulvovaginal candidiasis). StatPearls.
Kali, A., Bhuvaneshwar, D., Charles, P. M., & Seetha, K. S. (2016). Antibacterial synergy of curcumin with antibiotics against biofilm producing clinical bacterial isolates. Journal of basic and clinical pharmacy, 7(3), 93.
Khalil, O. A. K., de Faria Oliveira, O. M. M., Vellosa, J. C. R., de Quadros, A. U., Dalposso, L. M., Karam, T. K., . . . Khalil, N. M. (2012). Curcumin antifungal and antioxidant activities are increased in the presence of ascorbic acid. Food Chemistry, 133(3), 1001-1005.
Lee, Y. S., Chen, X., Widiyanto, T. W., Orihara, K., Shibata, H., & Kajiwara, S. (2022). Curcumin affects function of Hsp90 and drug efflux pump of Candida albicans. Frontiers in Cellular and Infection Microbiology, 12, 944611.
Monk, B. C., & Keniya, M. V. (2021). Roles for structural biology in the discovery of drugs and agrochemicals targeting sterol 14α-demethylases. Journal of Fungi, 7(02), 67.
Motahhary Tashi, H., & Ranji, N. (2017). Study on oprD mutation and imipenem resistance in Pseudomonas aeruginosa isolates in Gilan province. Journal of Microbial World, 10(1), 26-36.
Narayanan, V. S., Muddaiah, S., Shashidara, R., Sudheendra, U., Deepthi, N., & Samaranayake, L. (2020). Variable antifungal activity of curcumin against planktonic and biofilm phase of different candida species. Indian Journal of Dental Research, 31(1), 145-148.
Pakizehkar, S., Ranji, N., Sohi, A. N., & Sadeghizadeh, M. (2020). Polymersome‐assisted delivery of curcumin: a suitable approach to decrease cancer stemness markers and regulate miRNAs expression in HT29 colorectal cancer cells. Polymers for Advanced Technologies, 31(1), 160-177.
Paul, S., Singh, S., Sharma, D., Chakrabarti, A., Rudramurthy, S. M., & Ghosh, A. K. (2020). Dynamics of in vitro development of azole resistance in Candida tropicalis. Journal of Global Antimicrobial Resistance, 22, 553-561.
Rad, K. K., Falahati, M., Roudbary, M., Farahyar, S., & Nami, S. (2016). Overexpression of MDR-1 and CDR-2 genes in fluconazole resistance of Candida albicans isolated from patients with vulvovaginal candidiasis. Current medical mycology, 2(4), 24.
Rahbar Takrami, S., Ranji, N., & Sadeghizadeh, M. (2019). Antibacterial effects of curcumin encapsulated in nanoparticles on clinical isolates of Pseudomonas aeruginosa through downregulation of efflux pumps. Molecular biology reports, 46, 2395-2404.
Rajasekar, V., Darne, P., Prabhune, A., Kao, R. Y., Solomon, A. P., Ramage, G., . . . Neelakantan, P. (2021). A curcumin-sophorolipid nanocomplex inhibits Candida albicans filamentation and biofilm development. Colloids and Surfaces B: Biointerfaces, 200, 111617.
Ranji, N. (2014). Investigation of Survivin and hTERT gene expression in gastric adenocarcinoma cell line (AGS) treated by nano Curcumin. Cellular and Molecular Research (Iranian Journal of Biology), 27(2), 233-241.
Ranji, N., & Rahbar Takrami, S. (2017). Role of mexZ gene in ciprofloxacin resistance in Pseudomonas aeruginosa isolates in Guilan province. Studies in Medical Sciences, 27(10), 902-913. Sadiq, A., Ahmad, S., Ali, R., Ahmad, F., Ahmad, S., Zeb, A., . . . Siddique, A. N. (2016). Antibacterial and antifungal potentials of the solvents extracts from Eryngium caeruleum, Notholirion thomsonianum and Allium consanguineum. BMC complementary and alternative medicine, 16, 1-8. Sharma, P., Blackburn, R. C., Parke, C. L., McCullough, K., Marks, A., & Black, C. (2011). Angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non‐diabetic chronic kidney disease. Cochrane Database of Systematic Reviews(10). Soliman, S. S., Semreen, M. H., El-Keblawy, A. A., Abdullah, A., Uppuluri, P., & Ibrahim, A. S. (2017). Assessment of herbal drugs for promising anti-Candida activity. BMC complementary and alternative medicine, 17, 1-9. Tsopmene, U. J., Tokam Kuaté, C. R., Kayoka-Kabongo, P. N., Bisso, B. N., Metopa, A., Mofor, C. T., & Dzoyem, J. P. (2024). Antibiofilm Activity of Curcumin and Piperine and Their Synergistic Effects with Antifungals against Candida albicans Clinical Isolates. Scientifica, 2024. Vinodkumar, S., Nakkeeran, S., & Renukadevi, P. (2017). Biocontrol potentials of antimicrobial peptide producing Bacillus species: multifaceted antagonists for the management of stem rot of carnation caused by Sclerotinia sclerotiorum. Frontiers in Microbiology, 8, 254948. Zhang, H., Xu, Q., Li, S., Ying, Y., Zhang, Z., Zeng, L., . . . Huang, S. (2019). Gene Expression Analysis of Key Players Associated with Fluconazole Resistance in Candida albicans. Jundishapur Journal of Microbiology, 12(7). Zhou, Z., Wang, S., Fan, P., Meng, X., Cai, X., Wang, W., . . . Su, J. (2024). Borneol serves as an adjuvant agent to promote the cellular uptake of curcumin for enhancing its photodynamic fungicidal efficacy against Candida albicans. Journal of Photochemistry and Photobiology B: Biology, 112875.