Synergistic and dose-dependent pharmacological effects of black shallot and nano-curcumin combination on nociceptive, pyretic, and inflammatory responses in murine models

Background Inflammation, pain, and fever are common features of chronic diseases and are often inadequately controlled by existing therapies. This study evaluated a fixed-ratio combination of black shallot extract and nano-curcumin (EBSC) for dose-dependent and synergistic antinociceptive, antipyretic, and anti-inflammatory effects in murine models. Materials and methods EBSC (100, 200, and 300 mg/kg; oral) was assessed in Swiss albino mice using the hot-plate and tail-flick tests (antinociception), Brewer’s yeast-induced pyrexia (antipyretic), and carrageenan-induced paw edema (anti-inflammatory). TRPV1, COX-2, PGE2, TNF-α, IL-6, and IL-10 levels were quantified by ELISA. Acute oral toxicity was evaluated according to OECD 423. Data were analyzed using one-way analysis of variance (ANOVA) with Tukey post hoc tests; dose-response relationships were modeled using linear and Hill fits. Results EBSC produced dose-dependent analgesic effects: hot-plate reaction latency increased from 37.92 ± 1.24 s (100 mg/kg) to 40.05 ± 1.89 s (300 mg/kg), and pain inhibition increased to 62.48 ± 1.73% (p < 0.001). Tail-flick latency also significantly prolonged. EBSC at 300 mg/kg reduced pyrexia by 1.25 ± 0.13°C (p < 0.001). Carrageenan-induced paw edema was inhibited by 46.2% at 4 h with EBSC300 (p < 0.001). Molecular markers (TRPV1, COX-2, PGE2, TNF-α, IL-6) decreased in a dose-dependent manner, whereas IL-10 levels increased. Dose-response models demonstrated strong fits (R2 > 0.98). No mortality or significant biochemical alterations were observed up to 5.000 mg/kg. Conclusions EBSC exhibits dose-dependent and synergistic antinociceptive, antipyretic, and anti-inflammatory activities with a favorable acute safety profile, supporting its potential for further development as a standardized phytopharmaceutical.