Correlation Between Citrus hystrix Peel Essential Oil and its Analgesic, Antipyretic, and Anti-inflammatory Activities in an Experimental Mouse Model

Citrus hystrix DC. peel essential oil, rich in bioactive compounds, is traditionally used for pain, fever, and inflammation. This study evaluated its dose-dependent effects in mice following oral administration at 50, 100, and 150 mg/kg. The negative control group received distilled water, while positive controls included tramadol (5 mg/kg, p.o.) for analgesia, paracetamol (150 mg/kg, p.o.) for antipyresis, and indomethacin (10 mg/kg, p.o.) for inflammation. Analgesic activity was assessed via hot plate and tail-flick tests at 30, 60, and 90 minutes post-treatment. EOCHP150 significantly increased latency time in the hot plate test (p < 0.01) and achieved 72.5% inhibition in the tail-flick test. Yeast-induced pyrexia (20% Brewer’s yeast, 10 mL/kg, s.c.) was used to assess antipyretic activity, with EOCHP150 reducing rectal temperature by 4.0% at 4 hours, comparable to paracetamol. Carrageenan-induced paw edema (1% carrageenan, 50 µL, s.c.) showed a 46% inhibition in paw swelling at 4 hours with EOCHP150, accompanied by significant suppression of COX-2, PGE2, TNF-α, IL-1β, and IL-6 levels (p < 0.01). Strong correlations were observed between EOCHP dose and pharmacodynamic responses. These findings support EOCHP as a promising multi-target natural agent for the management of pain, fever, and inflammation.