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.

Material 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.