Helicteres ovata is a native Brazilian species belonging to a genus traditionally used for the treatment of inflammatory and pain-related disorders. However, its pharmacological studies remain scarce. This study investigated the phytochemical profile, inorganic composition, antinociceptive activity, and safety of a 60% hydroethanolic extract of Helicteres ovata in murine models of paclitaxel-induced neuropathic pain. Phytochemical dereplication was performed using UPLC-ESI-TOF-MS/MS, and elemental analysis via ICP-MS. Antinociceptive effects were evaluated using hot plate and von Frey assays in paclitaxel-sensitized mice. Opioid and cannabinoid pathways involvement was assessed using naltrexone and AM251, respectively. TNF-α and CXCL-1 modulation was determined in central and peripheral tissues. Histological and morphometric analyses were conducted on the sciatic nerve and dorsal root ganglia. Cytotoxicity was assessed via the Artemia salina lethality assay, and acute oral toxicity was evaluated in BALB/c mice (2000 mg/kg). The extract contained flavonoids, xanthones, phenolic acids, and essential minerals including potassium, magnesium, and phosphorus. It reduced mechanical allodynia and thermal hyperalgesia in a dose-dependent manner. Its antinociceptive effect was attenuated by naltrexone and AM251, indicating opioid and cannabinoid pathways involvment. The extract modulated pro-inflammatory cytokine and preserved neural morphology. Moderate cytotoxicity was observed at 48 h in A. salina, but no adverse effects were detected in acute toxicity model. Helicteres ovata extract exhibits significant antiallodynic effect in chemotherapy-induced neuropathic pain, mediated by inflammatory and neuromodulatory pathways. It is well tolerated in vivo and holds promise as a phytotherapeutic candidate for neuropathic pain management.
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