Licochalcone A Protects Vaginal Epithelial Cells Against Candida Albicans Infection Via the TLR4/NF-κB Signaling Pathway

Overview

Journal J Microbiol

Specialty Microbiology

Date 2024 May 31

PMID 38819759

Authors

Wei Li

Yujun Yin

Taoqiong Li

Yiqun Wang

Wenyin Shi

Affiliations

Soon will be listed here.

Abstract

Vulvovaginal candidiasis (VVC) is a prevalent condition affecting a significant portion of women worldwide. Licochalcone A (LA), a natural compound with diverse biological activities, holds promise as a protective agent against Candida albicans (C. albicans) infection. This study aims to investigate the potential of LA to safeguard vaginal epithelial cells (VECs) from C. albicans infection and elucidate the underlying molecular mechanisms. To simulate VVC in vitro, VK2-E6E7 cells were infected with C. albicans. Candida albicans biofilm formation, C. albicans adhesion to VK2-E6E7 cells, and C. albicans-induced cell damage and inflammatory responses were assessed by XTT reduction assay, fluorescence assay, LDH assay, and ELISA. CCK-8 assay was performed to evaluate the cytotoxic effects of LA on VK2-E6E7 cells. Western blotting assay was performed to detect protein expression. LA dose-dependently hindered C. albicans biofilm formation and adhesion to VK2-E6E7 cells. Furthermore, LA mitigated cell damage, inhibited the Bax/Bcl-2 ratio, and attenuated the secretion of pro-inflammatory cytokines in C. albicans-induced VK2-E6E7 cells. The investigation into LA's impact on the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway revealed that LA downregulated TLR4 expression and inhibited NF-κB activation in C. albicans-infected VK2-E6E7 cells. Furthermore, TLR4 overexpression partially abated LA-mediated protection, further highlighting the role of the TLR4/NF-κB pathway. LA holds the potential to safeguard VECs against C. albicans infection, potentially offering therapeutic avenues for VVC management.

References

Alfian A, Watchaputi K, Sooklim C, Soontorngun N . Production of new antimicrobial palm oil-derived sophorolipids by the yeast Starmerella riodocensis sp. nov. against Candida albicans hyphal and biofilm formation. Microb Cell Fact. 2022; 21(1):163. PMC: 9382743. DOI: 10.1186/s12934-022-01852-y. View

Cai M, Xu Y, Deng B, Chen J, Chen T, Zeng K . Radix Glycyrrhizae extract and licochalcone a exert an anti-inflammatory action by direct suppression of toll like receptor 4. J Ethnopharmacol. 2022; 302(Pt A):115869. DOI: 10.1016/j.jep.2022.115869. View

Chaillot J, Tebbji F, Garcia C, Wurtele H, Pelletier R, Sellam A . pH-Dependant Antifungal Activity of Valproic Acid against the Human Fungal Pathogen . Front Microbiol. 2017; 8:1956. PMC: 5640775. DOI: 10.3389/fmicb.2017.01956. View

Chen Z, Luo T, Huang F, Yang F, Luo W, Chen G . Kangbainian Lotion Ameliorates Vulvovaginal Candidiasis in Mice by Inhibiting the Growth of Fluconazole-Resistant and the Dectin-1 Signaling Pathway Activation. Front Pharmacol. 2022; 12:816290. PMC: 8819624. DOI: 10.3389/fphar.2021.816290. View

Chu X, Ci X, Wei M, Yang X, Cao Q, Guan M . Licochalcone a inhibits lipopolysaccharide-induced inflammatory response in vitro and in vivo. J Agric Food Chem. 2012; 60(15):3947-54. DOI: 10.1021/jf2051587. View

El-Saber Batiha G, Magdy Beshbishy A, El-Mleeh A, Abdel-Daim M, Devkota H . Traditional Uses, Bioactive Chemical Constituents, and Pharmacological and Toxicological Activities of L. (Fabaceae). Biomolecules. 2020; 10(3). PMC: 7175350. DOI: 10.3390/biom10030352. View

Feng X, Zhang H, Hu K, Shi G, Wu D, Shao J . Longdan Xiegan decoction ameliorates vulvovaginal candidiasis by inhibiting the NLRP3 inflammasome via the Toll-like receptor /MyD88 pathway. J Ethnopharmacol. 2023; 318(Pt A):116869. DOI: 10.1016/j.jep.2023.116869. View

Furusawa J, Funakoshi-Tago M, Mashino T, Tago K, Inoue H, Sonoda Y . Glycyrrhiza inflata-derived chalcones, Licochalcone A, Licochalcone B and Licochalcone D, inhibit phosphorylation of NF-kappaB p65 in LPS signaling pathway. Int Immunopharmacol. 2009; 9(4):499-507. DOI: 10.1016/j.intimp.2009.01.031. View

Gao Y, Liang G, Wang Q, She X, Shi D, Shen Y . Different Host Immunological Response to C. albicans by Human Oral and Vaginal Epithelial Cells. Mycopathologia. 2019; 184(1):1-12. DOI: 10.1007/s11046-018-0301-6. View

10.

Gaziano R, Sabbatini S, Roselletti E, Perito S, Monari C . -Based Probiotics as Novel Antimicrobial Agents to Prevent and Treat Vaginal Infections. Front Microbiol. 2020; 11:718. PMC: 7186379. DOI: 10.3389/fmicb.2020.00718. View

11.

Helmy Y, Kassem I, Rajashekara G . Immuno-modulatory effect of probiotic E. coli Nissle 1917 in polarized human colonic cells against Campylobacter jejuni infection. Gut Microbes. 2020; 13(1):1-16. PMC: 7781529. DOI: 10.1080/19490976.2020.1857514. View

12.

Hou X, Yang S, Zheng Y . Licochalcone A attenuates abdominal aortic aneurysm induced by angiotensin II via regulating the miR-181b/SIRT1/HO-1 signaling. J Cell Physiol. 2018; 234(5):7560-7568. DOI: 10.1002/jcp.27517. View

13.

Hu J, Liu J . Licochalcone A Attenuates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting NF-κB Activation. Inflammation. 2015; 39(2):569-74. DOI: 10.1007/s10753-015-0281-3. View

14.

Jacobsen I . The Role of Host and Fungal Factors in the Commensal-to-Pathogen Transition of . Curr Clin Microbiol Rep. 2023; 10(2):55-65. PMC: 10154278. DOI: 10.1007/s40588-023-00190-w. View

15.

Li P, Yu C, Zeng F, Fu X, Yuan X, Wang Q . Licochalcone A Attenuates Chronic Neuropathic Pain in Rats by Inhibiting Microglia Activation and Inflammation. Neurochem Res. 2021; 46(5):1112-1118. DOI: 10.1007/s11064-021-03244-x. View

16.

Li D, Zhang T, Yang H, Yang W, Zhang C, Gao G . Effect of Vitamin D on the Proliferation and Barrier of Atrophic Vaginal Epithelial Cells. Molecules. 2023; 28(18). PMC: 10535479. DOI: 10.3390/molecules28186605. View

17.

Liu J, Geng F, Sun H, Wang X, Zhang H, Yang Q . Candida albicans induces TLR2/MyD88/NF-κB signaling and inflammation in oral lichen planus-derived keratinocytes. J Infect Dev Ctries. 2020; 12(9):780-786. DOI: 10.3855/jidc.8062. View

18.

Lopes J, Lionakis M . Pathogenesis and virulence of . Virulence. 2021; 13(1):89-121. PMC: 9728475. DOI: 10.1080/21505594.2021.2019950. View

19.

Luan T, Liu X, Mao P, Wang X, Rui C, Yan L . The Role of 17β-Estrogen in Candida albicans Adhesion on Human Vaginal Epithelial Cells via FAK Phosphorylation. Mycopathologia. 2020; 185(3):425-438. DOI: 10.1007/s11046-020-00440-1. View

20.

Messier C, Grenier D . Effect of licorice compounds licochalcone A, glabridin and glycyrrhizic acid on growth and virulence properties of Candida albicans. Mycoses. 2011; 54(6):e801-6. DOI: 10.1111/j.1439-0507.2011.02028.x. View