Evaluating the efficacy and safety of Lumbricus rubellus extract as a natural antipyretic agent

Year 2026, Volume: 30 Issue: 1, 341 - 356, 11.01.2026

Iyan Hardiana , Elly Wahyudin , Muhammad Aswad , Rina Agustina

https://doi.org/10.12991/jrespharm.1845195

Abstract

Fever, a complex physiological response, is regulated by inflammatory mediators like IL-1, IL-6, and TNF-
α. Conventional antipyretics, while effective, are associated with adverse effects, prompting interest in natural
alternatives such as Lumbricus rubellus extract. This study evaluates the efficacy, safety, and antipyretic mechanism
of Lumbricus rubellus extract through in silico, in vitro, and in vivo methodologies. The extract was standardized for
specific and non-specific parameters. Molecular docking assessed interactions with prostaglandin E2 synthesis
receptors. ADMET predictions and acute oral toxicity studies were performed using Sprague Dawley rats. Antipyretic
efficacy was determined using brewer's yeast-induced pyrexia models. The extract showed high binding affinity with
mPGES-1 (docking score: -4.8), indicating potential antipyretic activity. ADMET analysis predicted favorable
pharmacokinetic properties with minimal toxicity. In vivo studies revealed significant dose-dependent reductions in
rectal temperature, with the 200 mg dose outperforming acetaminophen (0.54 °C vs. 0.42 °C reduction). Toxicity studies
showed no adverse effects at doses up to 2000 mg/kg, classifying the extract as safe per OECD guidelines. The
antipyretic action of Lumbricus rubellus is attributed to its bioactive compound, lombricine, which inhibits PGE2
synthesis. The extract also met safety standards for microbial contamination and heavy metal content, reinforcing its
therapeutic potential. Lumbricus rubellus extract demonstrates promising antipyretic efficacy and safety, positioning it
as a viable natural alternative to conventional antipyretics. Further clinical studies are warranted to confirm its
application in humans.

Keywords

Lumbricus rubellus , antipyretic activity , prostaglandin E2 inhibition , toxicity evaluation , molecular docking

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