Red Pepper Plant Compounds Show Promise Against Cavity-Causing Microbes

Tooth decay remains one of the most common infectious diseases on the planet, and despite decades of fluoride toothpaste, antiseptic mouthwashes, and public health campaigns, it continues to affect billions of people across every age group. The reason is deceptively simple: the mouth is a crowded ecosystem, and the microbes that cause cavities are extraordinarily good at building protective communities on tooth surfaces. Now, a team of researchers in Indonesia has reported that two secondary metabolites isolated from Piper crocatum, a climbing plant in the black pepper family long used in traditional medicine, can inhibit the growth and biofilm formation of the two organisms most closely associated with dental caries, Streptococcus mutans and Candida albicans. The study, published in BMC Complementary Medicine and Therapies, combines laboratory assays with computational simulations to build a case for these plant-derived molecules as candidates for future caries prevention.

The research was carried out by scientists at Universitas Padjadjaran, drawing on expertise from both the Department of Chemistry in the Faculty of Mathematics and Natural Sciences and the Department of Conservative Dentistry in the Faculty of Dentistry. This pairing is significant, because the study bridges two disciplines that rarely share a laboratory bench: natural products chemistry, which is devoted to isolating and characterizing molecules from plants and other organisms, and clinical dentistry, which confronts the consequences of microbial infection every day. The corresponding author, Dikdik Kurnia, and colleagues set out to test whether compounds previously isolated from Piper crocatum could act against the microbial partnership that drives tooth decay, and if so, to understand at the molecular level how they might do it.

To appreciate why the researchers focused on Streptococcus mutans and Candida albicans, it helps to understand how cavities actually form. Dental caries is not the work of a single villain but the product of complex interactions within oral biofilms, the sticky microbial communities known as plaque. S. mutans occupies a central role in this process. It metabolizes dietary sugars into lactic acid, which dissolves tooth enamel, and it produces sticky glucan polymers that help the biofilm adhere firmly to tooth surfaces. This glucan-mediated adhesion is orchestrated by enzymes called glucosyltransferases, of which glucosyltransferase B, or GtfB, is a key example. Disrupting GtfB activity would, in principle, undermine the bacterium’s ability to anchor itself and build the protective matrix that shields the community from antimicrobial agents.

Candida albicans, a fungus, adds another layer of complexity. Although it is best known as an opportunistic pathogen causing thrush and other infections, it is frequently found in cariogenic plaque, where it enhances the stability of the biofilm and contributes to tissue damage. One of its important virulence factors is secreted aspartyl proteinase 5, or Sap5, an enzyme that breaks down host proteins and helps the fungus invade and damage oral tissues. Because S. mutans and C. albicans often coexist and cooperate within plaque, an effective anti-caries agent would ideally target both organisms and both of these molecular mechanisms. That dual requirement is precisely what the Indonesian team set out to evaluate.

On the experimental side, the researchers subjected the two isolated compounds, referred to in the study as compounds 1 and 2, to a battery of in vitro tests. These included antibacterial assays against S. mutans, antifungal assays against C. albicans, and antibiofilm testing to determine whether the compounds could prevent the formation of the microbial communities that make plaque so resilient. The assays measured standard pharmacological benchmarks such as the minimum inhibitory concentration, the lowest concentration of a compound that prevents visible microbial growth, as well as the minimum bactericidal and fungicidal concentrations, which indicate the levels at which the compounds actually kill the organisms rather than merely halting their multiplication. According to the study, both compounds inhibited microbial growth and reduced biofilm formation in vitro, demonstrating activity against both the bacterium and the fungus.

Laboratory results alone, however, cannot explain how a molecule works, and this is where the computational arm of the study becomes important. The researchers performed molecular docking simulations, a technique that uses the three-dimensional structures of target proteins to predict how small molecules fit into their binding pockets and how strongly they interact with key amino acid residues. The targets were the two virulence enzymes highlighted above: GtfB from S. mutans and Sap5 from C. albicans. Docking revealed strong binding affinities between the compounds and both enzymes, suggesting a plausible structural basis for the antimicrobial effects observed in the petri dish. In other words, the computational analysis provided a mechanistic hypothesis: the plant metabolites may interfere with glucan-mediated adhesion by binding GtfB, and with proteolytic tissue damage by binding Sap5.

Docking is only the first step in a computational workflow, because a molecule that binds well in a static snapshot may still fail in the dynamic environment of a living cell. To address this, the team ran molecular dynamics simulations, which model the motion of the protein-ligand complexes over time and reveal whether the interactions remain stable under realistic physical conditions. The analysis included measures such as root-mean-square deviation and root-mean-square fluctuation, standard metrics for assessing whether a protein-ligand complex holds together or falls apart during simulation. The study reports that the compounds formed stable interactions with GtfB, reinforcing the idea that they could genuinely disrupt the enzyme’s function rather than binding transiently and drifting away. Binding energy calculations using the MMGBSA method, which estimates the free energy of binding from simulated trajectories, further supported the strength of these interactions.

The researchers also considered drug-likeness and safety profiles through in silico ADMET analysis, which predicts absorption, distribution, metabolism, excretion, and toxicity. Such predictions examined properties including plasma protein binding, blood-brain barrier permeability, cytochrome P450 interactions, half-life, and estimated lethal dose values. These computational filters matter because many natural compounds with impressive laboratory activity never progress further, either because they are too toxic, too poorly absorbed, or metabolized too quickly to be useful. While ADMET predictions are only as good as the models behind them and cannot replace actual pharmacokinetic testing, they provide an early and inexpensive way to prioritize candidates. The motivation for pursuing natural compounds in the first place, the authors note, is that they may offer safer alternatives to synthetic antimicrobials in caries prevention, an important consideration given concerns about chlorhexidine’s side effects with long-term use and the broader problem of antimicrobial resistance.

Piper crocatum itself deserves attention. Known in Indonesia as sirih merah, or red betel, the plant is a climbing vine with distinctive reddish leaves that has a long history in traditional Southeast Asian medicine, where it has been applied to wounds and used against various infections. Its leaves are rich in secondary metabolites, the chemically diverse molecules that plants produce not for basic growth but for defense, signaling, and environmental interaction. Many of these compounds, including alkaloids, flavonoids, and other phenolic substances, have documented antimicrobial properties, and plants in the Piper genus in particular have yielded bioactive molecules of considerable interest to pharmacologists. The present study fits into a wider scientific effort to mine this traditional knowledge systematically, isolating specific compounds, verifying their activity under controlled conditions, and elucidating their mechanisms of action with modern structural and computational tools.

The authors are careful about what their findings do and do not establish. The work demonstrates promising antibacterial, antifungal, and antibiofilm effects in vitro, and the computational results highlight dual targeting of GtfB and Sap5 as a plausible mechanism, but the study’s conclusion explicitly states that further in vivo studies are required to validate the findings. Moving from a laboratory assay to a clinically useful product involves many additional hurdles: confirming efficacy in animal models, establishing safe and effective concentrations in the complex environment of the human mouth, ensuring the compounds remain stable in formulations such as mouthwashes or gels, and ultimately testing in controlled clinical trials. Even so, the study adds to a growing body of evidence that plant secondary metabolites can attack oral pathogens on multiple fronts at once, inhibiting growth, preventing biofilm formation, and undermining the specific enzymes that make S. mutans and C. albicans so destructive. If future in vivo and clinical work bears out the promise of these early results, molecules from a humble red-leaved vine could one day find a place in the next generation of oral care products aimed at keeping cavities at bay.

Subject of Research: Antimicrobial and antibiofilm activity of Piper crocatum secondary metabolites against oral pathogens involved in dental caries

Article Title: Secondary metabolites from Piper crocatum as natural inhibitors of oral pathogens: in vitro and in silico insights into Streptococcus mutans and Candida albicans

Article References: Kurnia, D., Dharsono, H. D. A., Nurdin, D., Tristyaningrum, N. A., Apriyanti, E., & Azmi, S. Z. K. (2026). Secondary metabolites from Piper crocatum as natural inhibitors of oral pathogens: in vitro and in silico insights into Streptococcus mutans and Candida albicans. BMC Complementary Medicine and Therapies. https://doi.org/10.1186/s12906-026-05550-9

Image Credits: AI Generated

DOI: 10.1186/s12906-026-05550-9

Keywords: Piper crocatum, dental caries, Streptococcus mutans, Candida albicans, biofilm, glucosyltransferase B, secreted aspartyl proteinase 5, molecular docking, molecular dynamics, natural products, antimicrobial resistance, oral health