Antinociceptive activity of Laportea species mediated by anti-inflammatory and antioxidant mechanisms: a systematic review and meta-analysis of in vivo animal studies

Laportea species (a genus of the nettle family, Urticaceae) have a history of traditional use for relieving pain. Recent preclinical evidence suggests their antinociceptive activity is mediated through modulation of inflammation and oxidative stress, yet no integrated synthesis of these mechanisms has been reported. We performed a systematic review and meta-analysis of in vivo animal studies to address this gap, by assessing the pain-relieving efficacy of Laportea species, identifying key biochemical markers of their action, and evaluating the impact of methodological considerations on pharmacological results. PubMed, Scopus, ScienceDirect, EBSCO, and Google Scholar were systematically searched for in vivo animal experiments, examining Laportea species extracts and elucidate associated anti-inflammatory and antioxidant mechanisms. Data extracted on nociceptive behavior, cytokine profiles, oxidative stress markers, and antioxidant enzyme activity. Effect sizes for treatment versus control were calculated as SMDs with 95% CI, and subgroup analyses examined the impact of dosage, extraction type, administration route, species variation, and treatment duration. There were sixteen studies included. Extracts of Laportea species significantly suppressed cytokines (IL-2, IL-1β, IFN-γ, TNF-α, IL-6) and reduced oxidative damage biomarkers (malondialdehyde, protein carbonylation, nitric oxide), enhancing anti inflammatory cytokines (IL-10 and TGF-β) and endogenous antioxidant (peroxidase, glutathione, glutathione peroxidase, superoxide dismutase, glutathione transferase, catalase, and glutathione reductase). These molecular effects correlated with reduced pain behaviors, including decreased writhing and increased pain reaction time. The strength of these effects varied depending on extraction methods, duration of treatment, administration route, tissue specificity, animal species model used, and Laportea species varieties. The antinociceptive activity of Laportea species is closely related to their anti-inflammatory and antioxidant properties, suggesting a multi-targeted mechanism of action. These findings support the potential of Laportea species extracts as phytotherapeutic agents for managing pain and related inflammatory conditions. Further translational studies are needed to clarify clinical relevance and optimize bioactive formulations.