Bioactive Constituents of Piper crocatum Ruiz & Pav. and Piper betle Linn. as Antifungal and Antibiofilm Agents Against Candida albicans

Abstract: Oral infections caused by biofilm-forming fungi such as Candida albicans pose a major therapeutic challenge due to their lead to increased drug resistance, recurrent infections, and reduced efficacy of conventional antifungal agents. Piper crocatum Ruiz and Pav. and Piper betle Linn. have attracted significant attention for further research due to their rich phytochemical composition, which could potentially serve as sources of natural compounds with antifungal and antibiofilm activity. This review summarizes and critically compares the bioactive constituents, antifungal mechanisms, and antibiofilm properties of both species against one of the oral fungal pathogens, Candida albicans . Current evidence indicates that P. crocatum contains a variety of metabolites with diverse structures, such as phytosterols, amide alkaloids, neolignans, and sesquiterpenoids. Some of these compounds exhibit antifungal activity in vitro and show predictive interactions with the CYP51, ERG11, and Sap5, which are involved in ergosterol biosynthesis and the virulence of C. albicans . However, there is currently no evidence of antibiofilm activity by P. crocatum against Candida albicans . Consequently, this additional research is required in the future. In contrast, antifungal and antibiofilm evidence in P. betle is predominantly centered on hydroxychavicol, which demonstrated reproducible antifungal activity, disruption of fungal membrane integrity, interference with morphogenesis, and concentration-dependent inhibition of Candida biofilm formation. Overall, both species represent promising sources of antifungal lead compounds. However, translational development remains limited by insufficient mechanistic validation, lack of in vivo evidence, and formulation-related challenges. Keywords: Piper crocatum Ruiz and Pav, Piper betle Linn, Candida albicans , antifungal, antibiofilm