Study Notes on Anti-Infection of Oral Microorganisms from Herbal Medicine of Piper crocatum Ruiz & Pav

Review of Anti-Infection of Oral Microorganisms from Herbal Medicine of Piper crocatum Ruiz & Pav

Authors

  • Dikdik Kurnia, Seftiana Lestari, Tri Mayanti, Meirina Gartika, Denny Nurdin

  • Affiliations:

    • Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Padjadjaran, Sumedang, Indonesia

    • Department of Pediatric Dentistry, Faculty of Medicine, University of Padjadjaran, Bandung, Indonesia

    • Departement of Conservative Dentistry, Faculty of Dentistry, Universitas Padjadjaran, Bandung, Indonesia

  • Correspondence: Dikdik Kurnia, Email: dikdik.kurnia@unpad.ac.id

Abstract

  • The WHO Global Status Report on Oral Health 2022 highlights that oral diseases caused by oral pathogenic microorganisms affect nearly 3.5 billion people globally.

  • Key microorganisms implicated:

    • Streptococcus mutans

    • Streptococcus sanguinis

    • Enterococcus faecalis

    • Candida albicans

  • Use of synthetic anti-infective drugs is common, but these drugs can cause side effects and resistance.

  • There is a growing interest in safe anti-infective alternatives derived from herbal sources.

  • Piper crocatum (Red Betel leaf) is proposed as a potential herbal anti-infective agent.

  • Objectives of the review:

    • Discuss the mechanisms through which various microorganisms can cause health problems.

    • Explain the mechanisms of synthetic oral anti-infectives against microbial growth.

    • Evaluate the potential of Piper crocatum as a herbal anti-infective treatment.

  • The study underscores the need for continued research into natural components for effective treatment options for oral infections.

Keywords

  • Piper crocatum

  • Anti-infection

  • Antibacterial

  • Antifungal

  • Oral pathogens

Introduction

  • Oral infections can arise from various pathogenic microorganisms, including bacteria, fungi, and viruses.

  • Notable pathogenic bacteria causing oral issues include:

    • S. mutans (associated with dental caries)

    • S. sanguinis

    • E. faecalis

  • Prevalence of dental caries:

    • 2017: By country, prevalence ranged from 20% to over 50%.

    • 2018: Indonesia's prevalence reached 88.8% (root caries at 56.6%); children aged 5-9 years had a prevalence of up to 92.6%.

  • Fungal infections, particularly from C. albicans (candidiasis), occur with a prevalence of approximately 20-25% in Indonesia, affecting multiple areas: hair, skin, nails, mucous membranes, and the esophagus.

  • Concerns are rising regarding the side effects of synthetic anti-infectives, including resistance against antibiotics like ampicillin, amoxicillin, penicillin, and various others. These can lead to significant resistance rates:

    • In adults, highest resistance against amoxicillin (14.8%) and lincomycin (28.7%).

    • In children, highest resistance against penicillin (27.6%) and vancomycin (42.5%).

  • Reports suggest C. albicans shows considerable resistance to antifungal agents such as nystatin and fluconazole.

  • Focus on Indonesia's diverse flora is promising for discovering active compounds with potential oral anti-infective properties.

Anti-Infection: Definitions and Concepts

  • Anti-infective: A general term for drugs inhibiting or killing infectious microorganisms (viruses, bacteria, fungi, parasites).

  • Antibacterial agents: Substances that inhibit or kill bacteria, classified as:

    • Bacteriostatic: Inhibit bacterial growth.

    • Bactericidal: Kill bacteria.

  • Mechanisms for inhibiting bacteria include targeting:

    • DNA synthesis

    • Protein biosynthesis

    • Bacterial cell wall synthesis (e.g., penicillins, glycopeptides).

  • Drug resistance mechanisms:

    • Degradation/modification through enzymes (e.g., β-lactamase).

    • Resistance is depicted through antibiotic persistence against specific classes.

    • β-Lactamase: Degrades β-lactam antibiotics via nucleophilic attacks.

Fungal Infections

  • Fungal infections often arise from predispositional environmental factors or immune compromise.

  • Types of fungal infections:

    • Systemic mycoses (e.g., candidiasis, aspergillosis)

    • Dermatophytes (e.g., infections affecting skin, hair, nails)

    • Mucocutaneous infections (mostly caused by Candida).

  • Antifungals: Classified into groups based on their target:

    • Systemic antifungals: Amphotericin B, fluconazole, etc.

    • Topical antifungals: Griseofulvin, clotrimazole, etc.

  • Azole antifungals target ergosterol biosynthesis in fungi, disrupting membrane integrity.

Potential of Piper crocatum as an Anti-Infective

  • Piper crocatum (Red Betel): Traditionally used for:

    • Treating toothaches

    • Vaginal fungal infections

    • Ulcers, diabetes, sore eyes, respiratory issues

  • Exhibits multiple bioactivities:

    • Antifungal, antibacterial, antioxidant, antihyperglycemic, anti-inflammatory properties.

  • Phytochemical composition includes:

    • Flavonoids, essential oils, alkaloids, saponins, tannins, terpenoids, and phenolic compounds—potentially responsible for bioactivity.

  • Research has isolated various bioactive compounds with noted effects like:

    • β-sitosterol (IC50 values across various solvent extracts)

    • Several neolignan compounds (identified in studies from 2014 to 2023).

Anti-Infection Activity of Red Betel Extract

  • Strong potential against various microorganisms:

    • Bacterial infections

    • Fungal infections (e.g., demonstrating activity against C. albicans).

  • Notable studies and results:

    • Molecular docking studies illustrate binding energy comparisons of secondary metabolites against C. albicans receptors, showcasing substantial inhibitory potential.

Anti-Fungal Activity of Red Betel Extract

  • Secondary metabolites in Red Betel exhibit antifungal properties, confirmed through experimental results.

  • Molecular docking studies assess binding capacities of several compounds interacting with virulence factors, emphasizing their potential effectiveness.

  • Highlighted compounds:

    • Biclo [3.2.1] neologies and other identified compounds with activity against various fungi.

Antibacterial Activity of Red Betel Extract

  • Numerous studies affirm the antibacterial efficacy of Red Betel extracts against both gram-positive and gram-negative bacteria:

    • Reports highlight significant inhibition against Staphylococcus epidermidis, E. coli, and others, emphasizing the extract's broad-spectrum capabilities.

  • Different fractions of Red Betel extract have shown varying degrees of inhibition in various concentrations.

Pathogenic Bacteria Causing Oral Infections

Streptococcus mutans

  • Key pathogenic role in causing dental caries.

  • Characteristics and environmental adaptability promoting pathogenicity.

Streptococcus sanguinis

  • Important for biofilm formation and oral health, generally working to inhibit the growth of S. mutans.

Enterococcus faecalis

  • Notable for its role in root canal infections due to its ability to survive hostile conditions.

  • Involved in multiple virulence factors enhancing its pathogenicity.

Candida albicans

  • Opportunistically pathogenic fungus associated with multiple oral infections (e.g., candidiasis).

  • Biofilm formation mechanisms and systemic virulence factors elaborated.

Conclusion

  • Piper crocatum exhibits notable anti-infective properties, meriting further exploration as a medicinal agent for combatting oral infections against bacteria and fungi.

  • The bioactive components' varying concentrations and structures play a pivotal role in their inhibitory effects on identified oral pathogens.