Pharmacodynamic Evaluation Of Moxonidine For Immunomodulatory And Anti-Inflammatory Potentials Via NF-Κb Signaling Pathway Modulation

Abstract

Inflammation and immune dysregulation are central contributors to the pathogenesis of several chronic diseases, many of which involve hyperactivation of the NF-κBsignaling pathway. Moxonidine, a centrally acting antihypertensive agent known to modulate imidazoline and α2-adrenergic receptors, has recently shown promise in modulating metabolic and inflammatory responses. This study aimed to evaluate the pharmacodynamic potential of Moxonidine as an immunomodulatory and anti-inflammatory agent via modulation of the NF-κBsignaling pathway in a lipopolysaccharide (LPS)-induced inflammatory model in Wistar rats. Animals were divided into five groups: normal control, LPS control, Moxonidine low dose (0.1 mg/kg), Moxonidine high dose (0.5 mg/kg), and standard anti-inflammatory (Dexamethasone). Treatment was administered orally for seven days, with LPS induction on Day 5. Serum levels of TNF-α, IL-1β, and IL-6 were significantly elevated in the LPS group and attenuated dose-dependently by Moxonidine, particularly at higher doses (p < 0.01). Oxidative stress parameters also improved markedly with reduced malondialdehyde (MDA) levels and increased glutathione (GSH) and superoxide dismutase (SOD) activity. Western blot analysis confirmed a reduction in NF-κB p65 expression and restoration of IκBα levels. Histopathological examinations revealed improved tissue architecture and reduced inflammatory infiltration in liver and spleen tissues. These findings support the hypothesis that Moxonidine attenuates inflammation by downregulating the NF-κB pathway, suggesting its potential repurposing in inflammatory and autoimmune disorders beyond hypertension.