Objective  To investigate the effects and mechanisms of schinifoline on chronic inflammatory pain in mice.

Methods  C57BL/6 mice were randomly divided into five groups: normal control group, model group, indomethacin group (5 mg/kg), and low-dose (10 mg/kg) and high-dose (40 mg/kg) groups of schinifoline, with 6 mice in each group. Except for the normal control group, all other groups of mice were induced with chronic inflammatory pain mouse models by injecting complete Freund's adjuvant into the left posterior foot. After 3 days of induction, oral administration was started according to the corresponding groups for 3 consecutive days. The normal control group and model group were given equal volumes of physiological saline. After drug administration, paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were measured to evaluate pain levels; levels of serum algesic factors and inflammatory cytokines were detected using commercial kits; the serum metabolite profiles were characterized via metabolomics, followed by differential metabolite and pathway analysis; Western Blot was used to detect protein expression of pathway-related molecules in the left paw tissue.

Results  Compared with the normal control group, the model group exhibited significantly decreased PWT and PWL (P<0.05), with markedly elevated levels of serum algesic factors and inflammatory cytokines (P<0.05). Compared with the model group, schinifoline-treated groups showed significant reversal in PWT, PWL, and the levels of serum algesic factors and inflammatory cytokines (P<0.05). The serum metabolomics revealed that arachidonic acid metabolism might be the main regulatory pathway of schinifoline. Compared with the normal control group, the model group showed significantly increased expression of cyclooxygenase-2 (COX-2) and lipoxygenase-5 (LOX-5) and decreased expression of cytochrome P450 4A (CYP4A)  in left paw tissue (P<0.05). Compared with the model group, schinifoline groups exhibited significant reversal in the expression of COX-2, LOX-5, and CYP4A (P<0.05).

Conclusion  Schinifoline has a significant analgesic effect in mice with chronic inflammatory pain, and its mechanism may be related to its inhibition of arachidonic acid metabolism.

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