Functional and Transcriptomic Insights Into Amlodipine's Anti-Inflammatory Effects

Muhammed Yusuf^1,2*

• ¹Faculty of Pharmacy, Anadolu University, Eskişehir, Türkiye
• ²Kocaeli Universitesi, Körfez, Türkiye

Background and Purpose: Amlodipine, a clinically used L-type calcium channel blocker with vasodilatory properties, may also influence neuroinflammation. This work explored whether Amlodipine can mitigate the pro-inflammatory transition of microglia and examined its effects on their morphology, function, and gene expression. Experimental Approach: Primary microglial cultures from neonatal Sprague Dawley rats and brain slices prepared from C57BL/6 mice were used. Microglia were activated by ischemia or lipopolysaccharide (LPS) and treated with Amlodipine (5–20 μM). Morphological changes, phagocytic activity, Iba1 expression, and TNF-α production were evaluated. RNA from monocultures was processed for next-generation sequencing to define transcriptomic alterations. Key Results: LPS stimulation promoted a pro-inflammatory phenotype, modifying cytokine and complement gene expression, upregulating ionotropic purinergic and TRP channels, while reducing voltage-and ligand-gated calcium channels, ryanodine, and IP3 receptors. It also increased SERCA pump expression. Amlodipine reduced amoeboid transformation and phagocytosis, altering 110 genes, most in the opposite direction of LPS effects. Notably, differentially expressed genes included 20 linked to immune activity, 7 to cell adhesion, and 2 to autophagy. Conclusion and Implications: Beyond its vascular effects, Amlodipine suppresses microglial activation through Ca²-dependent transcriptional regulation of immune pathways. These findings suggest potential therapeutic applications of Amlodipine in neuroinflammatory conditions.