Research Article
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Isorhamnetin as a promising natural bioactive flavonoid: in vitro assessment of its antifungal property

Year 2024, , 54 - 61, 25.03.2024
https://doi.org/10.31015/jaefs.2024.1.6

Abstract

Isorhamnetin (3’-methylquercetin) is an important flavonoid produced as a secondary metabolite from medicinal and aromatic plants due to its pharmacological and therapeutic properties. Thus far, the anticancer, antiallergic, antiinflammatory, antioxidant, antiviral, and antimicrobial properties of isorhamnetin have been evaluated in indirect studies conducted with isorhamnetin found in plant extracts or essential oils or direct studies performed with pure isorhamnetin. However, this is the first study in the literature on the antifungal activity of 97% pure isorhamnetin against C. tropicalis, C. albicans, C. krusei, and C. parapsilosis using two assays including agar dilution and broth microdilution methods. This study showed that isorhamnetin has a significant inhibitory effect against all Candida species used. The minimum inhibitory concentration (MIC) value of isorhamnetin against C. tropicalis, C. albicans, C. krusei, and C. parapsilosis was 1.875 mg/mL, the same for all yeast strains. These results have opened a new horizon regarding the usability of isorhamnetin as a pharmacological therapeutic antifungal agent.

Ethical Statement

Ethics committee approval is not required.

Project Number

TSA-2022-3110

References

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  • Araujo, R.C., Neves, F.A., Formagio, A.S., Kassuya, C.A., Stefanello, M.E. & Souza, V.V. (2014). Evaluation of the anti-mycobacterium tuberculosis activity and in vivo acute toxicity of Annona sylvatic. BMC Complementary and Alternative Medicine, 2014, 14-209. https://doi.org/10.1186/1472-6882-14-209
  • Benedict, K., Jackson, B.R., Chiller, T. & Beer, K.D. (2019). Estimation of Direct Healthcare Costs of Fungal Diseases in the United States. Clinical Infectious Diseases, 68 (11), 1791-1797. https://doi.org/10.1093/cid/ciy776
  • Benitez, L.L. & Carver, P.L. (2019). Adverse Effects Associated with Long-Term Administration of Azole Antifungal Agents. Drugs, 79 (8), 833-853. https://doi.org/10.1007/s40265-019-01127-8
  • Bhattacharya, D., Ghosh, D., Bhattacharya, S., Sarkar, S., Karmakar, P., Koley, H. & Gachhui, R. (2018). Antibacterial activity of polyphenolic fraction of Kombucha against Vibrio cholerae: targeting cell membrane. Letters in Applied Microbiology, 66 (2), 145-152. https://doi.org/10.1111/lam.12829.
  • Burda, S. & Oleszek, W.J. (2001). Antioxidant and antiradical activities of flavonoids. Journal of Agricultural and Food Chemistry, 49, 2774-2779. https://doi.org/10.1021/jf001413m
  • Chi, G., Zhong, W., Liu, Y., Lu, G., Lü, H., Wang, D. & Sun, F. (2016). Isorhamnetin protects mice from lipopolysaccharide-induced acute lung injury via the inhibition of inflammatory responses. Inflammation Research, 65 (1), 33-41. https://doi.org/10.1007/s00011-015-0887-9
  • Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically. 11th ed. Clinical and Laboratory Standards Institute; Wayne, PA, USA: 2018. M07Ed11.
  • Cowen, L.E., Sanglard, D., Howard, S.J., Rogers, P.D. & Perlin, D.S. (2014). Mechanisms of Antifungal Drug Resistance. Cold Spring Harbor Perspectives in Medicine, 5 (7), a019752. https://doi.org/10.1101/cshperspect.a019752
  • Ekici, M. (2023). Antibiyotik nedir? Nasıl kullanılmalıdır? Yan etkileri nelerdir?, Access: 25 December 2023, https://www.medicalpark.com.tr/antibiyotik-nedir-nasil-kullanilmalidir-yan-etkileri-nelerdir/hg-1846#:~:text=Deride%20ka%C5%9F%C4%B1nt%C4%B1%20ve%20d%C3%B6k%C3%BClmeler%2C%20nefes,antibiyotik%20zararlar%C4%B1%20aras%C4%B1nda%20yer%20al%C4%B1r.
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  • Fong, I.W. (1996). Clinical and cost considerations in the pharmacotherapy of vulvovaginal candidiasis. Pharmacoeconomics 9 (6), 497-505. https://doi.org/10.2165/00019053-199609060-00004
  • Gong, G., Guan, Y.Y., Zhang, Z.L., Rahman, K., Wang, S.J., Zhou, S., Luan, X. & Zhang, H. (2020). Isorhamnetin: A review of pharmacological effects. Biomedicine and Pharmacotherapy, 128, 110301. https://doi.org/10.1016/j.biopha.2020.110301
  • Habtamu, A. & Melaku, Y. (2018). Antibacterial and Antioxidant Compounds from the Flower Extracts of Vernonia amygdalina. Advances in Pharmacological Sciences, 2018, 4083736. https://doi.org/10.1155/2018/4083736.
  • Hu, S., Huang, L., Meng, L., Sun, H., Zhang, W. & Xu, Y. (2015). Isorhamnetin inhibits cell proliferation and induces apoptosis in breast cancer via Akt and mitogen‑activated protein kinase kinase signaling pathways. Molecular Medicine Reports, 12 (5), 6745-51. https://doi.org/10.3892/mmr.2015.4269
  • Ibarra, M., Pérez-Vizcaíno, F., Cogolludo, A., Duarte, J., Zaragozá-Arnáez, F., López-López, J.G. & Tamargo, J. (2002). Cardiovascular effects of isorhamnetin and quercetin in isolated rat and porcine vascular smooth muscle and isolated rat atria. Planta Medica, 68 (4), 307-10. https://doi.org/10.1055/s-2002-26752.
  • Ishola, I.O., Osele, M.O., Chijioke, M.C. & Adeyemi, O.O. (2019). Isorhamnetin enhanced cortico-hippocampal learning and memory capability in mice with scopolamine-induced amnesia: Role of antioxidant defense, cholinergic and BDNF signaling. Brain Research, 1712, 188-196. https://doi.org/10.1016/j.brainres.2019.02.017
  • Jaramillo, S., Lopez, S., Varela, L.M., Rodriguez-Arcos, R., Jimenez, A., Abia, R., Guillen, R. & Muriana, F.J. (2010). The flavonol isorhamnetin exhibits cytotoxic effects on human colon cancer cells. Journal of Agricultural and Food Chemistry, 58 (20), 10869-75. https://doi.org/10.1021/jf102669p
  • Jnawali, H.N., Jeon, D., Jeong, M.C., Lee, E., Jin, B., Ryoo, S., Yoo, J., Jung, I.D., Lee, S.J., Park, Y.M. & Kim, Y. (2016). Antituberculosis Activity of a Naturally Occurring Flavonoid, Isorhamnetin. Journal Of Natural Products, 79 (4), 961-9. https://doi.org/10.1021/acs.jnatprod.5b01033
  • Karakoç, Z.Ç. (2019). Epidemiology of invasive fungal infections, Klimik Dergisi, 32 (2), 118-23.
  • Khaled, R. (2020). Biological Activities of Isorhamnetin: A Review. Plantae Scientia, 3 (5), 78-81. https://doi.org/10.32439/ps.v3i5.78-81
  • Kim JE, Lee DE, Lee KW, Son JE, Seo SK, Li J, et al (2011) Isorhamnetin suppresses skin cancer by directly inhibiting MEK1 and PI3-K. Cancer Prevention Research (Philadelphia, Pa.), 4 (4), 582-591. https://doi.org/10.1158/1940-6207.capr-11-0032.
  • Knezevic, P., Aleksic, V., Simin, N., Svircev, E., Petrovic, A., & Mimica-Dukic, N. (2016). Antimicrobial activity of Eucalyptus camaldulensis essential oils and their interactions with conventional antimicrobial agents against multi-drug resistant Acinetobacter baumannii. Journal of ethnopharmacology, 178, 125–136. https://doi.org/10.1016/j.jep.2015.12.008.
  • Krcmery V, Barnes AJ (2002) Non-albicans Candida spp. causing fungaemia: pathogenicity and antifungal resistance. Journal of Hospital Infection, 50 (4), 243-60. https://doi.org/10.1053/jhin.2001.1151
  • Kuran, B. (2021). Candida Belirtileri ve Fonksiyonel Tıp Tedavisi, Access: 12 November 2023, https://www.begumkuran.com/candida-belirtileri-ve- fonksiyonel-tip-tedavisi/
  • Kuti, J.O. (2004). Antioxidant compounds from four Opuntia cactus pear fruit varieties. Food chemistry, 85, 527–33. https://doi.org/10.1016/S0308-8146(03)00184-5
  • Li, C., Yang, X., Chen, C., Cai, S., Hu, J. (2014). Isorhamnetin suppresses colon cancer cell growth through the PI3K‑Akt‑mTOR pathway. Molecular Medicine Reports, 9 (3), 935-40. https://doi.org/10.3892/mmr.2014.1886.
  • Li, W.Q., Li, J., Liu, W.X., Wu, L.J., Qin, J.Y., Lin, Z.W., Liu, X.Y., Luo, S.Y., Wu, Q.H., Xie, X.F. & Peng, C. (2022). Isorhamnetin: A Novel Natural Product Beneficial for Cardiovascular Disease. Current Pharmaceutical Design, 28 (31), 2569-2582. https://doi.org/10.2174/1381612828666220829113132
  • Mabry, T.J. & Ulubelen, A. (1980). Chemistry and utilization of phenylpropanoids including flavonoids, coumarins and ligans. Journal of Agricultural and Food Chemistry, 28, 188-196. https://doi.org/10.1021/jf60228a024
  • Man, A., Santacroce, L., Jacob, R., Mare, A., & Man, L. (2019). Antimicrobial Activity of Six Essential Oils Against a Group of Human Pathogens: A Comparative Study. Pathogens (Basel, Switzerland), 8(1), 15. https://doi.org/10.3390/pathogens8010015.
  • Memişoğlu, F. (2019). Challenges in antifungal therapy: therapeutic drug monitoring, drug-drug interactions and approach to failure after primary therapy. Klimik Dergisi, 32 (2), 177-86. Turkish.
  • Odds, F.C. (1994). Pathogenesis of Candida infections. Journal of the American Academy of Dermatology, 31 (3Pt2), S2-5 https://doi.org/10.1016/s0190-9622(08)81257-1
  • Özçetin, M., Saz, E.U., Karapınar, B., Özen, S., Aydemir, Ş. & Vardar, F. (2009). Pediatric Nosocomial Infections; Incidence, Risk Factors. Journal of Pediatric Infectious Diseases, 3, 49-53
  • Pappas, P.G., Lionakis, M.S., Arendrup, M.C., Ostrosky-Zeichner, L. & Kullberg, B.J. (2018). Invasive candidiasis. Nature Reviews Disease Primers, 11 (4), 18026. https://doi.org/10.1038/nrdp.2018.26.
  • Pengfei, L., Tiansheng, D., Xianglin, H. & Jianguo, W. (2009). Antioxidant properties of isolated isorhamnetin from the sea buckthorn marc. Plant Foods for Human Nutrition, 64 (2), 141-5. https://doi.org/10.1007/s11130-009-0116-1
  • Ramos, S. (2007). Effects of dietary flavonoids on apoptotic pathways related to cancer chemoprevention. Journal of Nutritional Biochemistry, 18 (7), 427-442. https://doi.org/10.1016/j.jnutbio.2006.11.004.
  • Ren, X., Bao, Y., Zhu, Y., Liu, S., Peng, Z., Zhang, Y. & Zhou, G. (2019). Isorhamnetin, Hispidulin, and Cirsimaritin Identified in Tamarix ramosissima Barks from Southern Xinjiang and Their Antioxidant and Antimicrobial Activities. Molecules, 24 (3), 390. https://doi.org/10.3390/molecules24030390.
  • Senizza, B., Rocchetti, G., Okur, M. A., Zengin, G., Yıldıztugay, E., Ak, G., Montesano, D., & Lucini, L. (2020). Phytochemical Profile and Biological Properties of Colchicum triphyllum (Meadow Saffron). Foods (Basel, Switzerland), 9(4), 457. https://doi.org/10.3390/foods9040457
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Year 2024, , 54 - 61, 25.03.2024
https://doi.org/10.31015/jaefs.2024.1.6

Abstract

Project Number

TSA-2022-3110

References

  • Adachi, S.I., Kondo, S., Sato, Y., Yoshizawa, F. & Yagasaki, K. (2019). Anti-hyperuricemic effect of isorhamnetin in cultured hepatocytes and model mice: structure-activity relationships of methylquercetins as inhibitors of uric acid production. Cytotechnology, 71 (1), 181-192. https://doi.org/10.1007/s10616-018-0275-8
  • Araujo, R.C., Neves, F.A., Formagio, A.S., Kassuya, C.A., Stefanello, M.E. & Souza, V.V. (2014). Evaluation of the anti-mycobacterium tuberculosis activity and in vivo acute toxicity of Annona sylvatic. BMC Complementary and Alternative Medicine, 2014, 14-209. https://doi.org/10.1186/1472-6882-14-209
  • Benedict, K., Jackson, B.R., Chiller, T. & Beer, K.D. (2019). Estimation of Direct Healthcare Costs of Fungal Diseases in the United States. Clinical Infectious Diseases, 68 (11), 1791-1797. https://doi.org/10.1093/cid/ciy776
  • Benitez, L.L. & Carver, P.L. (2019). Adverse Effects Associated with Long-Term Administration of Azole Antifungal Agents. Drugs, 79 (8), 833-853. https://doi.org/10.1007/s40265-019-01127-8
  • Bhattacharya, D., Ghosh, D., Bhattacharya, S., Sarkar, S., Karmakar, P., Koley, H. & Gachhui, R. (2018). Antibacterial activity of polyphenolic fraction of Kombucha against Vibrio cholerae: targeting cell membrane. Letters in Applied Microbiology, 66 (2), 145-152. https://doi.org/10.1111/lam.12829.
  • Burda, S. & Oleszek, W.J. (2001). Antioxidant and antiradical activities of flavonoids. Journal of Agricultural and Food Chemistry, 49, 2774-2779. https://doi.org/10.1021/jf001413m
  • Chi, G., Zhong, W., Liu, Y., Lu, G., Lü, H., Wang, D. & Sun, F. (2016). Isorhamnetin protects mice from lipopolysaccharide-induced acute lung injury via the inhibition of inflammatory responses. Inflammation Research, 65 (1), 33-41. https://doi.org/10.1007/s00011-015-0887-9
  • Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically. 11th ed. Clinical and Laboratory Standards Institute; Wayne, PA, USA: 2018. M07Ed11.
  • Cowen, L.E., Sanglard, D., Howard, S.J., Rogers, P.D. & Perlin, D.S. (2014). Mechanisms of Antifungal Drug Resistance. Cold Spring Harbor Perspectives in Medicine, 5 (7), a019752. https://doi.org/10.1101/cshperspect.a019752
  • Ekici, M. (2023). Antibiyotik nedir? Nasıl kullanılmalıdır? Yan etkileri nelerdir?, Access: 25 December 2023, https://www.medicalpark.com.tr/antibiyotik-nedir-nasil-kullanilmalidir-yan-etkileri-nelerdir/hg-1846#:~:text=Deride%20ka%C5%9F%C4%B1nt%C4%B1%20ve%20d%C3%B6k%C3%BClmeler%2C%20nefes,antibiyotik%20zararlar%C4%B1%20aras%C4%B1nda%20yer%20al%C4%B1r.
  • Eloff, J.N. (1998). A sensitive and quick microplate method to determine the minimal inhibitory concentration of plant extracts for bacteria. Planta Medica, 64 (8), 711–713. https://doi.org/10.1055/s-2006-957563
  • Fong, I.W. (1996). Clinical and cost considerations in the pharmacotherapy of vulvovaginal candidiasis. Pharmacoeconomics 9 (6), 497-505. https://doi.org/10.2165/00019053-199609060-00004
  • Gong, G., Guan, Y.Y., Zhang, Z.L., Rahman, K., Wang, S.J., Zhou, S., Luan, X. & Zhang, H. (2020). Isorhamnetin: A review of pharmacological effects. Biomedicine and Pharmacotherapy, 128, 110301. https://doi.org/10.1016/j.biopha.2020.110301
  • Habtamu, A. & Melaku, Y. (2018). Antibacterial and Antioxidant Compounds from the Flower Extracts of Vernonia amygdalina. Advances in Pharmacological Sciences, 2018, 4083736. https://doi.org/10.1155/2018/4083736.
  • Hu, S., Huang, L., Meng, L., Sun, H., Zhang, W. & Xu, Y. (2015). Isorhamnetin inhibits cell proliferation and induces apoptosis in breast cancer via Akt and mitogen‑activated protein kinase kinase signaling pathways. Molecular Medicine Reports, 12 (5), 6745-51. https://doi.org/10.3892/mmr.2015.4269
  • Ibarra, M., Pérez-Vizcaíno, F., Cogolludo, A., Duarte, J., Zaragozá-Arnáez, F., López-López, J.G. & Tamargo, J. (2002). Cardiovascular effects of isorhamnetin and quercetin in isolated rat and porcine vascular smooth muscle and isolated rat atria. Planta Medica, 68 (4), 307-10. https://doi.org/10.1055/s-2002-26752.
  • Ishola, I.O., Osele, M.O., Chijioke, M.C. & Adeyemi, O.O. (2019). Isorhamnetin enhanced cortico-hippocampal learning and memory capability in mice with scopolamine-induced amnesia: Role of antioxidant defense, cholinergic and BDNF signaling. Brain Research, 1712, 188-196. https://doi.org/10.1016/j.brainres.2019.02.017
  • Jaramillo, S., Lopez, S., Varela, L.M., Rodriguez-Arcos, R., Jimenez, A., Abia, R., Guillen, R. & Muriana, F.J. (2010). The flavonol isorhamnetin exhibits cytotoxic effects on human colon cancer cells. Journal of Agricultural and Food Chemistry, 58 (20), 10869-75. https://doi.org/10.1021/jf102669p
  • Jnawali, H.N., Jeon, D., Jeong, M.C., Lee, E., Jin, B., Ryoo, S., Yoo, J., Jung, I.D., Lee, S.J., Park, Y.M. & Kim, Y. (2016). Antituberculosis Activity of a Naturally Occurring Flavonoid, Isorhamnetin. Journal Of Natural Products, 79 (4), 961-9. https://doi.org/10.1021/acs.jnatprod.5b01033
  • Karakoç, Z.Ç. (2019). Epidemiology of invasive fungal infections, Klimik Dergisi, 32 (2), 118-23.
  • Khaled, R. (2020). Biological Activities of Isorhamnetin: A Review. Plantae Scientia, 3 (5), 78-81. https://doi.org/10.32439/ps.v3i5.78-81
  • Kim JE, Lee DE, Lee KW, Son JE, Seo SK, Li J, et al (2011) Isorhamnetin suppresses skin cancer by directly inhibiting MEK1 and PI3-K. Cancer Prevention Research (Philadelphia, Pa.), 4 (4), 582-591. https://doi.org/10.1158/1940-6207.capr-11-0032.
  • Knezevic, P., Aleksic, V., Simin, N., Svircev, E., Petrovic, A., & Mimica-Dukic, N. (2016). Antimicrobial activity of Eucalyptus camaldulensis essential oils and their interactions with conventional antimicrobial agents against multi-drug resistant Acinetobacter baumannii. Journal of ethnopharmacology, 178, 125–136. https://doi.org/10.1016/j.jep.2015.12.008.
  • Krcmery V, Barnes AJ (2002) Non-albicans Candida spp. causing fungaemia: pathogenicity and antifungal resistance. Journal of Hospital Infection, 50 (4), 243-60. https://doi.org/10.1053/jhin.2001.1151
  • Kuran, B. (2021). Candida Belirtileri ve Fonksiyonel Tıp Tedavisi, Access: 12 November 2023, https://www.begumkuran.com/candida-belirtileri-ve- fonksiyonel-tip-tedavisi/
  • Kuti, J.O. (2004). Antioxidant compounds from four Opuntia cactus pear fruit varieties. Food chemistry, 85, 527–33. https://doi.org/10.1016/S0308-8146(03)00184-5
  • Li, C., Yang, X., Chen, C., Cai, S., Hu, J. (2014). Isorhamnetin suppresses colon cancer cell growth through the PI3K‑Akt‑mTOR pathway. Molecular Medicine Reports, 9 (3), 935-40. https://doi.org/10.3892/mmr.2014.1886.
  • Li, W.Q., Li, J., Liu, W.X., Wu, L.J., Qin, J.Y., Lin, Z.W., Liu, X.Y., Luo, S.Y., Wu, Q.H., Xie, X.F. & Peng, C. (2022). Isorhamnetin: A Novel Natural Product Beneficial for Cardiovascular Disease. Current Pharmaceutical Design, 28 (31), 2569-2582. https://doi.org/10.2174/1381612828666220829113132
  • Mabry, T.J. & Ulubelen, A. (1980). Chemistry and utilization of phenylpropanoids including flavonoids, coumarins and ligans. Journal of Agricultural and Food Chemistry, 28, 188-196. https://doi.org/10.1021/jf60228a024
  • Man, A., Santacroce, L., Jacob, R., Mare, A., & Man, L. (2019). Antimicrobial Activity of Six Essential Oils Against a Group of Human Pathogens: A Comparative Study. Pathogens (Basel, Switzerland), 8(1), 15. https://doi.org/10.3390/pathogens8010015.
  • Memişoğlu, F. (2019). Challenges in antifungal therapy: therapeutic drug monitoring, drug-drug interactions and approach to failure after primary therapy. Klimik Dergisi, 32 (2), 177-86. Turkish.
  • Odds, F.C. (1994). Pathogenesis of Candida infections. Journal of the American Academy of Dermatology, 31 (3Pt2), S2-5 https://doi.org/10.1016/s0190-9622(08)81257-1
  • Özçetin, M., Saz, E.U., Karapınar, B., Özen, S., Aydemir, Ş. & Vardar, F. (2009). Pediatric Nosocomial Infections; Incidence, Risk Factors. Journal of Pediatric Infectious Diseases, 3, 49-53
  • Pappas, P.G., Lionakis, M.S., Arendrup, M.C., Ostrosky-Zeichner, L. & Kullberg, B.J. (2018). Invasive candidiasis. Nature Reviews Disease Primers, 11 (4), 18026. https://doi.org/10.1038/nrdp.2018.26.
  • Pengfei, L., Tiansheng, D., Xianglin, H. & Jianguo, W. (2009). Antioxidant properties of isolated isorhamnetin from the sea buckthorn marc. Plant Foods for Human Nutrition, 64 (2), 141-5. https://doi.org/10.1007/s11130-009-0116-1
  • Ramos, S. (2007). Effects of dietary flavonoids on apoptotic pathways related to cancer chemoprevention. Journal of Nutritional Biochemistry, 18 (7), 427-442. https://doi.org/10.1016/j.jnutbio.2006.11.004.
  • Ren, X., Bao, Y., Zhu, Y., Liu, S., Peng, Z., Zhang, Y. & Zhou, G. (2019). Isorhamnetin, Hispidulin, and Cirsimaritin Identified in Tamarix ramosissima Barks from Southern Xinjiang and Their Antioxidant and Antimicrobial Activities. Molecules, 24 (3), 390. https://doi.org/10.3390/molecules24030390.
  • Senizza, B., Rocchetti, G., Okur, M. A., Zengin, G., Yıldıztugay, E., Ak, G., Montesano, D., & Lucini, L. (2020). Phytochemical Profile and Biological Properties of Colchicum triphyllum (Meadow Saffron). Foods (Basel, Switzerland), 9(4), 457. https://doi.org/10.3390/foods9040457
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There are 49 citations in total.

Details

Primary Language English
Subjects Medicinal and Aromatic Plants
Journal Section Research Articles
Authors

Tuba Unver 0000-0002-8655-2716

Project Number TSA-2022-3110
Publication Date March 25, 2024
Submission Date November 17, 2023
Acceptance Date January 13, 2024
Published in Issue Year 2024

Cite

APA Unver, T. (2024). Isorhamnetin as a promising natural bioactive flavonoid: in vitro assessment of its antifungal property. International Journal of Agriculture Environment and Food Sciences, 8(1), 54-61. https://doi.org/10.31015/jaefs.2024.1.6

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