The Antifungal Activity and Potential Mechanism of Kalopanax septemlobus against Trichophyton mentagrophytes and T. rubrum

Abstract

Kalopanax septemlobus (K. septemlobus) has been documented for therapeutic efficacy against scabies, but with fewer modern studies. In this paper, the inhibitory effects of K. semtemlobus extract and monomeric compounds on Trichophyton mentagrophytes and Trichophyton rubrum were studied, and the mechanism of action was preliminarily discussed. The chemical constituents of the ethyl acetate layer of K. semtemlobus were isolated and purified under the trace of antifungal activity (microdilution method). The structure was characterized by nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS); in vitro antifungal activity was investigated by microdilution (MIC, MFC), spore germination suppression, serum induced culture, extracellular protein determination, intracellular nucleic acid release, and PI fluorescence staining. Two compounds were isolated and elucidated, hederagenin (1) and kalopanaxsaponin A (2), respectively. The antifungal study showed that kalopanaxsaponin A had strong activity and could inhibit fungal growth from growth appreciation, transformation, and cell membrane (protein, nucleic acid leakage). The above data show that kalopanaxsaponin A has a strong antifungal effect (MIC₅₀=7.8 µg/mL), but in vivo and clinical experiments are needed to verify whether it has a curative effect. This study provides a potential compound for the development of natural antifungal drugs.

Keywords

Araliaceae - Kalopanax septemlobus - kalopanaxsaponin A - antifungal activity - Trichophyton mentagrophytes - Trichophyton rubrum

Publication History

Received: 09 December 2024

Accepted after revision: 27 June 2025

Article published online:
05 August 2025

• References

• 1 Vasyutkina EA, Adrianova IY. Genetic diversity of Kalopanax septemlobus (Thunb.) Koidz. at the northern edge of the range according to chloroplast DNA sequencing data. Russ J Genet 2021; 57: 745-749
• 2 Liu W, Ma J, Sun H, Wang X, Wang G, Yan Y, Wang Y, Li Y, Ding Y. Kalopanax septemlobus: Its phytochemistry, pharmacology and toxicity (1966–2022). Fitoterapia 2023; 168: 105561
• 3 Lee MW, Kim SU, Hahn DR. Antifungal activity of modified hederagenin glycosides from the leaves of Kalopanax pictum var. chinense . Biol Pharm Bull 2001; 24: 718-719
• 4 Kim DW, Bang KH, Rhee YH, Lee KT, Park HJ. Growth inhibitory activities of kalopanaxsaponins A and I against human pathogenic fungi. Arch Pharm Res 1998; 12: 688-691
• 5 Li Y, Shan M, Yan M, Yao H, Wang Y, Gu B, Zhu Z, Li H. Anticandidal activity of kalopanaxsaponin A: Effect on proliferation, cell morphology, and key virulence attributes of Candida albicans . Front Microbiol 2019; 10: 02844
• 6 Khalaf RA, Li Y, Shan M, Zhu Y, Yao H, Li H, Gu B, Zhu Z. Kalopanaxsaponin A induces reactive oxygen species mediated mitochondrial dysfunction and cell membrane destruction in Candida albicans . PLoS One 2020; 15: e0243066
• 7 Jeong JJ, Jang SE, Joh EH, Han MJ, Kim DH. Kalopanaxsaponin B ameliorates TNBS-induced colitis in mice. Biomol Ther 2012; 20: 457-462
• 8 Bang SY, Park GY, Park SY, Kim JH, Lee YK, Lee SJ, Kim Y. The stem bark of Kalopanax pictus exhibits anti-inflammatory effect through heme oxygenase-1 induction and NF-κB suppression. Immune Netw 2010; 10: 212-218
• 9 Kim S, Lee CH, Yeo JY, Hwang KW, Park SY. Immunostimulatory activity of stem bark of Kalopanax pictus in RAW 264.7 macrophage. J Herb Med 2022; 32: 100504
• 10 Li DW, Hyun JE, Jeong CS, Kim YS, Lee EB. Antiinflammatory activity of a-hederin methyl ester from the alkaline hydrolysate of the butanol fraction of Kalopanax pictus bark extract. Biol Pharm Bull 2003; 26: 429-433
• 11 Park C, Jeong JS, Jeong JW, Kim YJ, Jung YK, Go GB, Kim SO, Kim GY, Hong SH, Yoo YH, Choi YH. Ethanol extract of Kalopanax septemlobus leaf induces caspase-dependent apoptosis associated with activation of AMPK in human hepatocellular carcinoma cells. Int J Oncol 2016; 48: 261-270
• 12 Park C, Jeong JS, Jeong JW, Kim SO, Kim YJ, Kim GY, Hong SH, Choi YH. Ethanol extract of Kalopanax septemlobus leaf inhibits HepG2 human hepatocellular carcinoma cell proliferation via inducing cell cycle arrest at G 1 phase. Asian Pac J Trop Med 2016; 9: 344-350
• 13 Choi YJ, Yoon YJ, Choi HS, Park SR, Oh SH, Jeong SM, Suh HR, Lee BH. Effects of medicinal herb extracts and their components on steatogenic hepatotoxicity in Sk-hep1 cells. Toxicol Res 2011; 27: 211-216
• 14 Han J, Kim SH, Kang MS, Kim MS, Lee CO. Polyphenol Contents and Anti-Oxidant Effects of Castor Aralia (Kalopanax septemlobus) Leaf Extracts in Korea. I International Symposium on Medicinal, Aromatic and Nutraceutical Plants from Mountainous Areas (MAP-Mountain 2011) 2011: 105 – 111.
• 15 Seo KS, Karuppuchamy S, Papk JK, Lee CE. Investigations on the antioxidant activity of Kalopanax septemlobus root. Minerva Biotecnol 2015; 27: 179-189
• 16 Park HJ, Kim DH, Choi JW, Park JH, Han YN. A potent anti-diabetic agent from Kalopanax pictus . Arch Pharm Res 1998; 21: 24-29
• 17 Song G, Zhang M, Liu W, Liang G. Changing face of epidemiology of dermatophytoses in Chinese Mainland: A 30 years nationwide retrospective study from 1991 to 2020. Mycoses 2022; 65: 440-448
• 18 Song X, Wei YX, Lai KM, He ZD, Zhang HJ. In vivo antifungal activity of dipyrithione against Trichophyton rubrum on guinea pig dermatophytosis models. Biomed Pharmacother 2018; 108: 558-564
• 19 Fattahi A, Shirvani F, Ayatollahi A, Rezaei-Matehkolaei A, Badali H, Lotfali E, Ghasemi R, Pourpak Z, Firooz A. Multidrug‐resistant Trichophyton mentagrophytes genotype VIII in an Iranian family with generalized dermatophytosis: Report of four cases and review of literature. Int J Dermatol 2020; 60: 686-692
• 20 College JM. The Fraditional Chinese Medicine Dictionary. 2nd edition. Shanghai: Shanghai Scientific Technologic Publisher; 2006: 2163
• 21 Sun W, Zhang D, Sha Z, Zhang H, Zhang X. Studies on the saponin constituents of Kalopanax septemlobus (Thunb.) koidz. Acta Pharmaceuticca Sinica 1990; 25: 29-34
• 22 Shao CJ, Kasai R, Ohtani K, Tanaka O, Kohda H. Saponins from leaves of Kalopanax pictus (THUNB.) Nakai, harigiri: Structures of Kalophanax-Saponins JLa and JLb. Chem Pharm Bull 1990; 38: 1087-1089
• 23 Junpeng Y, Wenxue Z, Haile M, Yifen W. Studies on chemical constituents from seeds of Paeonia suffruticosa andr. Nat Prod Res Develop 2009; 21: 604-607
• 24 Zhang N, Song L, Xu Y, Pei X, Luisi BF, Liang W. The decrotonylase FoSir5 facilitates mitochondrial metabolic state switching in conidial germination of Fusarium oxysporum . Elife 2021; 10: 75583
• 25 Hwang B, Cho J, Hwang IS, Jin HG, Woo ER, Lee DG. Antifungal activity of lariciresinol derived from Sambucus williamsii and their membrane-active mechanisms in Candida albicans . Biochem Biophys Res Commun 2011; 410: 489-493
• 26 Yao H, Duan J, Wang J, Li Y. Triterpenoids and their saponins from the roots of Kalopanax septemlobus . Biochem Syst Ecol 2012; 42: 14-17
• 27 Quang TH, Ngan NTT, Minh CV, Kiem PV, Nhiem NX, Tai BH, Thao NP, Tung NH, Song SB, Kim YH. Anti-inflammatory triterpenoid saponins from the stem bark of Kalopanax pictus . J Nat Prod 2011; 74: 1908-1915
• 28 Barros MES, Santos DA, Hamdan JS. Evaluation of susceptibility of Trichophyton mentagrophytes and Trichophyton rubrum clinical isolates to antifungal drugs using a modified CLSI microdilution method (M38-A). J Med Microbiol 2007; 56: 514-518
• 29 Zeng H, Chen X, Liang J. In vitro antifungal activity and mechanism of essential oil from fennel (Foeniculum vulgare L.) on dermatophyte species. J Med Microbiol 2015; 64: 93-103
• 30 Luo N, Jin L, Yang C, Zhu Y, Ye X, Li X, Zhang B. Antifungal activity and potential mechanism of magnoflorine against Trichophyton rubrum . J Antibiot (Tokyo) 2020; 74: 206-214
• 31 Banerjee S, Johnson AD, Csiszar K, Wansley DL, McGead P. An extract of Morinda citrifolia interferes with the serum-induced formation of filamentous structures in Candida albicans and inhibits germination of Aspergillus nidulans . Am J Chin Med 2006; 34: 503-509
• 32 Liu Q. Antifungal activity of Chrysanthemum coronarium L extract on watermelon fusarium wilt and its active components. 2016. 9. 6483
• 33 Rosenberg M, Azevedo NF, Ivask A. Propidium iodide staining underestimates viability of adherent bacterial cells. Sci Rep 2019; 9: 6483
• 34 Riccardi C, Nicoletti I. Analysis of apoptosis by propidium iodide staining and flow cytometry. Nat Protoc 2006; 1: 1458-1461