Microglia, the unique and motile immune cells of the central nervous system (CNS), function as a security guard in maintaining CNS homeostasis, primarily through calcium signaling. The calcium dynamics in microglia control important functions such as phagocytosis, cytokine release, and migration. Calcium dysregulation in microglia has been linked to several CNS disorders, like Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and ischemic stroke (IS). Calcium entering through channels such as voltage-gated calcium channels (VGCCs), store-operated calcium entry (SOCE), and transient receptor potential (TRP) channels is essential for microglial activation and pro-inflammatory responses. Under pathological conditions, like the formation of amyloid-β plaques in AD, aggregation of α-synuclein in PD, and oxidative stress in MS, calcium dysregulation exacerbates neuroinflammation, mitochondrial dysfunction, and neurodegeneration. Therapeutic strategies targeting calcium signaling pathways, using calcium channel blockers and antioxidant interventions, show promise for alleviating microglial activation and slowing down disease progression. This review summarizes the underlying mechanisms of microglial calcium dysregulation and potential therapeutic benefits for restoring microglial calcium balance in CNS disorders.

Clostridioides difficile infection (CDI) remains a significant healthcare challenge, primarily due to its toxin‐mediated pathogenesis that results in severe gastrointestinal complications. This study investigates the inhibitory potential of bioactive compounds derived from Brassica oleracea L., specifically targeting the CDTa subunit of the binary toxin, using both computational and experimental approaches. Molecular docking analysis identified indolylmethyl glucosinolate (−9.1 kcal/mol) and indole‐3‐carbinol (−8.75 kcal/mol) as top candidates, demonstrating high binding affinities to the CDTa protein. Stability and dynamic behavior of the ligand–protein complexes were further assessed through 100‐ns molecular dynamics simulations, which confirmed their stable interactions. Thermodynamic evaluations using MM‐GBSA calculations revealed favorable binding free energies, supporting their potential as effective inhibitors. In parallel, the antibacterial efficacy of these compounds was validated through in vitro antibacterial assays, where indolylmethyl glucosinolate and indole‐3‐carbinol exhibited maximum inhibition zones of 23.33 ± 0.67 mm and 22.67 ± 0.33 mm, respectively, at a concentration of 100 μg/mL. In MIC and MBC assays, both compounds showed significant antibacterial activity, with indolylmethyl glucosinolate demonstrating slightly higher potency (MIC: 10.33 ± 0.72 μg/mL; MBC: 23.33 ± 1.36 μg/mL) than indole‐3‐carbinol (MIC: 11.33 ± 0.27 μg/mL; MBC: 26.67 ± 3.60 μg/mL). Additionally, PCA and DCCM revealed distinct conformational stabilization patterns and correlated motion of CDTa upon ligand binding, supporting a potential antivirulence interaction. Moreover, ADMET analysis revealed differences in their pharmacokinetic and toxicity profiles, providing further insights into their therapeutic potential. Overall, these findings suggest that B. oleracea –derived compounds exhibit a direct antibacterial activity against C. difficile while also demonstrating computationally supported inhibition of CDTa, indicating a complementary antivirulence mechanism that may contribute to their therapeutic potential in CDI.