From Ethnobotany to Immunometabolism: Network Pharmacology Analysis of Nigerian Medicinal Plants as Modulators of Immune-Metabolic Pathways in Obesity and Type 2 Diabetes

Abstract Background: Nigeria bears a disproportionate burden of metabolic disease, with diabetes affecting an estimated 6.8-7.5% of adults and obesity prevalence among women reaching 15.7%. Despite the rich ethnobotanical tradition of using indigenous plants to manage these conditions, the molecular mechanisms by which Nigerian plant-derived phytochemicals modulate immunometabolic pathways remain poorly characterised. Objectives: This narrative review synthesises current evidence on the immunometabolic mechanisms of key phytochemicals derived from Nigerian medicinal plants, with specific focus on how these compounds regulate macrophage polarisation, inflammatory cytokine signalling, insulin sensitivity, and metabolic reprogramming in obesity and type 2 diabetes (T2D). Methods: A comprehensive narrative review was conducted using PubMed, Scopus, Google Scholar, Web of Science, and African Journals Online (AJOL). Studies reporting in vitro, in vivo, or in silico evidence for the immunometabolic activity of phytochemicals from Nigerian medicinal plants were included. Key immunometabolic targets - NF-kB, PPARgamma, AMPK, mTOR, HIF-1alpha, and macrophage M1/M2 polarisation markers - were used as mechanistic anchors for evidence synthesis. Results: Multiple phytochemicals abundant in Nigerian plants - including rutin, quercetin, luteolin, chlorogenic acid, vitexin, kolaviron, nimbolide, and 6-gingerol - demonstrate modulatory activity at immunometabolic nodes. These compounds converge on shared targets: suppression of NF-kB-driven M1 macrophage polarisation, activation of AMPK-mediated anti-inflammatory signalling, PPARgamma agonism to promote insulin sensitisation, and attenuation of HIF-1alpha-driven glycolytic reprogramming. Mechanistically, this represents a phytochemical-mediated shift from pro-inflammatory M1 immunometabolism toward an anti-inflammatory, insulin-sensitising M2 phenotype. Conclusions: Nigerian medicinal plants represent an underexplored reservoir of immunometabolic modulators. Their principal phytochemicals act on mechanistic targets directly relevant to the pathophysiology of obesity-linked T2D. Integrating ethnobotanical knowledge with network pharmacology and immunometabolic biology offers a compelling framework for rational drug discovery from Nigerian biodiversity. Future experimental validation using macrophage culture models and high-fat-diet animal systems is warranted.