Antidiabetic Potential of Piper crocatum: A Systematic Review of In Silico, In Vitro, In Vivo, and Clinical Evidence
DOI:
https://doi.org/10.24252/djps.v8i2.61048Keywords:
Piper crocatum, Red betle, antidiabetic, antihyperglicemic, in silico, in vitro, in vivo, clinical trialsAbstract
Introduction: Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia, affecting 463 million individuals worldwide in 2019. If inadequately controlled, DM leads to progressive and serious complications. Current management relies on oral antidiabetic agents and insulin therapy, but both are associated with adverse effects, driving interest in medicinal plants as complementary or alternative therapies. Piper crocatum (red betel), a tropical species widely cultivated in Indonesia, has long been used in traditional medicine and is increasingly recognized for its antidiabetic potential. Aims: This review critically synthesizes available evidence on the pharmacological effects of Piper crocatum in diabetes management. Method: Literature was systematically retrieved from Google Scholar using keywords “(Piper crocatum) AND ((Antidiabetic) OR (Antihyperglycemic))", screened through Covidence software, and evaluated according to PRISMA guidelines. Result: From an initial 500 records, 25 studies met the inclusion criteria. Findings from in silico, in vitro, in vivo, and clinical trials consistently support the glucose-lowering activity of Piper crocatum, highlighting it as a promising natural antidiabetic candidate. Conclusion: Future research should prioritize formulation development to enable downstream translation of Piper crocatum into Obat Herbal Terstandar (OHT) and Fitofarmaka.
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Heliawati, L., Lestari, S., Hasanah, U., Ajiati, D. & Kurnia, D. 2022. Phytochemical Profile of Antibacterial Agents from Red Betel Leaf (Piper crocatum Ruiz and Pav) against Bacteria in Dental Caries. Molecules 27(9).
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Husna, F., Suyatna, F.D., Arozal, W. & Purwaningsih, E.H. 2019. Model Hewan Coba pada Penelitian Diabetes Animal Model in Diabetes Research. Mini Review Article Pharmaceutical Sciences and Research (PSR) 6(3): 131–141.
Irawan, C., Tambunan, J.A., Rachmy, S., Putri, I.D., Rosalina & Suhartini. 2024. Phytochemical Analysis of Red Betel (Piper crocatum Ruiz & Pav) Stem Extracts and its Antioxidant and Alpha-Glucosidase Inhibitory Potentials. Tropical Journal of Natural Product Research, 8(4): 7042–7048.
Kurnia, D., Lestari, S., Mayanti, T., Gartika, M. & Nurdin, D. 2024. Anti-Infection of Oral Microorganisms from Herbal Medicine of Piper crocatum Ruiz & Pav. Dove Medical Press Ltd.:
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Lister, I.N.E., Ginting, C.N., Girsang, E., Amansyah, A., Chiuman, L., Yanti, N.L.W.E., Widodo, W.S., Yusepany, D.T., Rizal, R. & Widowati, W. 2022. Piper crocatum Ameliorates APAP-Induced Hepatotoxicity through Antioxidant and Anti-Inflammatory Mechanisms. Journal of Mathematical and Fundamental Sciences 54(1): 109–120.
Maslikah, S.I., Fatchiyah, Widyananda, M.H., Rifaì, M., Warsito & Djati, M.S. 2025. Molecular Docking and Dynamic Simulation of Sesamin from Piper crocatum Ruiz & Pav as an Inhibitor Of Canonical NF-κB: Potential Anti-Inflammatory Mechanism. Journal of Pharmacy and Pharmacognosy Research 13(3): 848–856.
Maslikah, S.I. & Putra, W.E. 2024. Molecular Dynamics Simulation of Various Bioactive Compounds of Red Betel (Piper crocatum) as Anti-Inflammatory Drug-Like Candidates in Rheumatoid Arthritis Treatment. Trends in Sciences, 21(3), 7334. https://doi.org/10.48048/tis.2024.7334
Meilani, L., Hartati, R., Nor, I. & Insanu, M. 2024. Isolation and Identification Of Bioactive Flavonoid Glycosides From Syzygium jambos and Their Α-Glucosidase Inhibitory Activity. Acta Pharmaceutica Indonesia, 49(2), 60 - 69.
Alfarabi, M., Bintang, M., Suryani, Safithri, M., & Nurcholis, W. 2020. Kinetics of α -glucosidase Inhibitory Activity and Phytochemical Analysis of Piper crocatum Ruiz & Pav. Leaves Ethanol Extract. International Journal of Research in Pharmaceutical Sciences, 11(SPL4): 2032–2036.
Navirius, F.J., Pamudji, G. & Herowati, R. 2023. Effect of Red Betel Leaf Extract (Piper Crocatum) on Blood Glucose Levels and Kidney Histopathology in Streptozotosin-Nicotinamide Induced Streptozotosin-Nicotinamide Rats. Journal La Medihealtico, 4(3): 144–156.
Nor, I., Wirasutisna, K.R., Hartati, R. & Insanu, M. 2023. The α-glucosidase Inhibitory Activity of Avicularin and 4-O-methyl Gallic Acid Isolated from Syzygium myrtifolium leaves. Saudi Pharmaceutical Journal. 31(8): 101677.
Nurinsani, E.Y.Y., Andrianto, D. & Safithri, M. 2024. Acetylcholinesterase Inhibition Activity and Phytochemical Screening of Red Betel Leaf (Piper crocatum Ruiz & Pav) as Anti-dementia Agents. BIO Web of Conferences, EDP Sciences.:
Nursamsiar, N., Marwati, M. & Nur, S. 2023. The Effect of Extraction Method on Flavonoid Content and Antioxidant Activity of Red Betel and Green Betel Extracts. Tropical Journal of Natural Product Research, 7(8): 3620–3625.
Nursyarah, A.T., Safithri, M. & Andrianto, D. 2023. Red Betel Leaf Bioactive Compounds as ERα Receptor Inhibitors In Silico and MCF-7 Cell Anticancer In Vitro. HAYATI Journal of Biosciences 30(5): 789–796.
Pane, H.W., Suryantara, B. & Kristiarini, J.J. 2023. Comparison of Red Betel Leaf Decoction and Aloe Vera Decoction on Decreased Sugar Levels in Patients with Diabetes Mellitus at Setia Janji Health Center. CONTAGION: Scientific Periodical Journal of Public Health and Coastal Health, 5(2): 637–651.
Prajapati, S., Suthar, J., Hasnani, D. & Chavda, V. 2024. Adverse Drugs Reaction and Prescribing Pattern of Antidiabetic Medications in Type 2 Diabetes Patients: An Observational Ambispective Study. Clinical Diabetology, 13(3): 170–179.
Rahmatullah, M., Pangkahila, W. & Budhiarta, A.A.G. 2020. Piper crotatum leaves extract reduced fasting blood glucose and glycated albumin but has lower efficacy than metformin in diabetic rats. Indonesian Journal of Anti-Aging Medicine, 4(1): 8–11.
Kamaruzaman, S. R. S., Kasim, K. F., & Jaafar, M. N. 2020. The Effect of Harvesting Time on the Antioxidant and Antidiabetic Activity of Piper Crocatum (Sirih Merah) Extract. IOP Conference
Series: Materials Science and Engineering, IOP Publishing Ltd.
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2025-12-30
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Nor, I., Padjrin, M. A., Arsul, M. I., Julianti, N. H., Abadi, S. A., & Haris, T. (2025). Antidiabetic Potential of Piper crocatum: A Systematic Review of In Silico, In Vitro, In Vivo, and Clinical Evidence. Ad-Dawaa’ Journal of Pharmaceutical Sciences, 8(2), 235–250. https://doi.org/10.24252/djps.v8i2.61048
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