Sinomenine ameliorates experimental autoimmune neuritis by suppressing pro-inflammatory immune components and restoring immune balance.

Sinomenine (SIN), a bioactive alkaloid derived from Sinomenium acutum, exhibits well-documented anti-inflammatory and analgesic properties with a favorable safety profile. Here, we pharmacologically characterized the preventive and therapeutic efficacy of SIN in a rat model of experimental autoimmune neuritis (EAN), an established model of immune-mediated peripheral neuropathy. Although SIN has been evaluated in several neuroinflammatory disorders, its mode of action in EAN has not been systematically addressed. Disease progression, body-weight changes, and neurological scores were monitored following preventive or therapeutic SIN administration. Immune modulation was analyzed in secondary lymphoid tissues by flow cytometry, and sciatic nerve pathology was assessed using histological staining. SIN treatment significantly attenuated clinical severity, preserved body weight, and reduced inflammatory infiltration and demyelination in sciatic nerves. At the pharmacodynamic level, SIN decreased Th1 and Th17 cell frequencies, suppressed dendritic-cell activation and costimulatory capacity, and shifted macrophage polarization toward an anti-inflammatory M2-like phenotype with reduced nitric oxide production. Collectively, these data demonstrate that SIN acts as a multi-target immunopharmacological modulator rather than a direct T-cell inhibitor, thereby limiting neuroinflammatory injury in EAN. This work provides pharmacological support for further development of SIN in immune-mediated peripheral neuropathies.