Integrative Analysis of the Pharmacological Activities of Lumbricus rubellus: Evidence from Preclinical and Clinical Research
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Submitted
20 November 2024
Published
30 November 2025
Keywords:
-
Lumbricus rubellus, Lumbrokinase, Neuroprotective effect, Fibrinolytic mechanism, Antimicrobial activity
Abstract
Lumbricus rubellus, commonly known as the red earthworm, has long been used in traditional medicine and contains diverse bioactive compounds with therapeutic potential. However, comprehensive and systematic evaluation of its pharmacological mechanisms remains limited. This review systematically analyzes the pharmacological activities of L. rubellus based on in vivo and clinical trial evidence to provide an integrated scientific understanding of its therapeutic potential. A systematic literature search was performed in PubMed, ScienceDirect, Wiley Online Library, Cochrane Library, and Google Scholar for studies published between 2013 and 2022. The review followed PRISMA 2020 guidelines, applying the PICOS framework for eligibility determination. Study quality was assessed using the ARRIVE checklist for in vivo studies and the JADAD scale for clinical trials. Twelve studies met the inclusion criteria, comprising nine in vivo and three clinical trials. Lumbricus rubellus demonstrated multiple pharmacological effects, including fibrinolytic, antibacterial, hepatoprotective, neuroprotective, and anticancer activities. These effects are mainly attributed to proteins such as lumbrokinase and coelomic fluid metabolites that exhibit antithrombotic, anti-inflammatory, and cytoprotective actions. This review highlights strong evidence supporting the diverse pharmacological activities of L. rubellus and its potential as a natural source for developing novel therapeutic agents. Further standardized clinical investigations are required to confirm its efficacy and safety.
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References
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3. Medina-Sauza RM, Álvarez-Jiménez M, Delhal A, Reverchon F, Blouin M, Guerrero-Analco JA, et al. Earthworms building up soil microbiota, a review. Front Environ Sci. 2019;7:81. DOI: 10.3389/fenvs.2019.00081
4. Zhang Q, Liu H, Zhang Y, Ruan H. The complete mitochondrial genome of Lumbricus rubellus (Oligochaeta, Lumbricidae) and its phylogenetic analysis. Mitochondrial DNA B Resour. 2019;4(2):2677–8. DOI: 10.1080/23802359.2019.1644242; PMCID: PMC7706552; PMID: 33365679
5. Venkatachalam S, Chrostyraj JRSS, Don Bosco RB, Yesudhason BV. Antimicrobial peptides from earthworms: Emerging candidates for novel therapeutic applications. Toxicon. 2025;264:108458. DOI: 10.1016/j.toxicon.2025.108458; PMID: 40499792
6. Zhu Z, Deng X, Xie W, Li H, Li Y, Deng Z. Pharmacological effects of bioactive agents in earthworm extract: A comprehensive review. Animal Model Exp Med. 2024;7(5):653-72. DOI: 10.1002/ame2.12465; PMCID: PMC11528390; PMID: 38957072
7. Dharmawati IGAA, Mahadewa TGB, Widyadharma IPE. Antibacterial Activity of Lumbricus Rubellus Earthworm Extract Against Porphyromonas Gingivalis as the Bacterial Cause of Periodontitis. Open Access Maced J Med Sci. 2019;7(6):1032-6. DOI: 10.3889/oamjms.2019.222; PMCID: PMC6454178; PMID: 30976356
8. Foekh NP, Sukrama IDM, Lestari AAW. The ability of earthworm Lumbricus rubellus extract in slowing down the activation of NFkB and TNF-α in lipopolysaccharide-induced Rattus norvegicus. Bali Med J. 2019;8(2):347-52. DOI: 10.15562/bmj.v8i2.1405
9. Sara M, Ilyas F, Hasballah K, Nurjannah N, Harapan H, Mudatsir M. Lumbricus rubellus earthworm as an antibacterial: A systematic review. J Appl Pharm Sci. 2023;13(12):79-86. DOI: 10.7324/JAPS.2023.128228
10. Sara M, Ilyas F, Hasballah K, Nurjannah N, Mudatsir M. The Effects of Lumbricus rubellus Extract on Staphylococcus aureus Colonization and IL-31 Levels in Children with Atopic Dermatitis. Medicina. 2023;59(11):2007. DOI: 10.3390/medicina59112007; PMCID: PMC10672803; PMID: 38004056
11. Ivaldi D, Burgos M, Oltra G, Liquitay CE, Garegnani L. Adherence to PRISMA 2020 statement assessed through the expanded checklist in systematic reviews of interventions: A meta-epidemiological study. Cochrane Evid Synth Methods. 2024;2(5):e12074. DOI: 10.1002/cesm.12074; PMCID: PMC11795886; PMID: 40476264
12. Amir-Behghadami M, Janati A. Population, Intervention, Comparison, Outcomes and Study (PICOS) design as a framework to formulate eligibility criteria in systematic reviews. Emerg Med J. 2020;37(6):387. DOI: 10.1136/emermed-2020-209567; PMID: 32253195
13. Wang L, Hu D, Xu J, Hu J, Wang Y. Complex in vitro Model: A Transformative Model in Drug Development and Precision Medicine. Clin Transl Sci. 2023;17(2):e13695. DOI: 10.1111/cts.13695; PMCID: PMC10828975; PMID: 38062923
14. Su Q, Cheng G, Huang J. A review of research on eligibility criteria for clinical trials. Clin Exp Med. 2023;23(6):1867-79. DOI: 10.1007/s10238-022-00975-1; PMCID: PMC9815064; PMID: 36602707
15. Gusenbauer M, Haddaway NR. Which academic search systems are suitable for systematic reviews or meta-analyses? Evaluating retrieval qualities of Google Scholar, PubMed, and 26 other resources. Res Synth Methods. 2020;11(2):181-217. DOI: 10.1002/jrsm.1378; PMCID: PMC7079055; PMID: 31614060
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Hardiana I, Wahyudin E, Aswad M, Agustina R. Integrative Analysis of the Pharmacological Activities of Lumbricus rubellus: Evidence from Preclinical and Clinical Research. Borneo J Pharm [Internet]. 2025Nov.30 [cited 2025Dec.6];8(4):313-25. Available from: https://journal.umpr.ac.id/index.php/bjop/article/view/8741
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