IN SILICO AND PHARMACEUTICAL CHARACTERIZATION OF CAFESTOL IN LPS INDUCED DEPRESSION
Abstract
Depression is a complex mental disorder in which neuroinflammation may contribute to behavioral and neurobiological alterations. The present study investigated the potential anti-inflammatory and behavioral effects of cafestol and cafestol-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles in a lipopolysaccharide (LPS)-induced mouse model. Molecular docking was performed to evaluate the potential interaction of cafestol with nuclear factor kappa B (NF-κB). The nanoparticles were characterized by dynamic light scattering, zeta potential analysis, and determination of encapsulation efficiency and drug loading. Adult mice were divided into four groups: normal saline control, LPS control (0.83 mg/kg), LPS plus free cafestol (10 mg/kg), and LPS plus cafestol-loaded PLGA nanoparticles. Behavioral alterations were assessed using the light–dark box (LDB) test, while brain tissue levels of NF-κB and NOD-like receptor family pyrin domain-containing 3 (NLRP3) were measured using enzyme-linked immunosorbent assay (ELISA). Cafestol-loaded PLGA nanoparticles exhibited a mean particle size of 168.7 ± 5.2 nm, a polydispersity index of 0.162 ± 0.011, and a zeta potential of −26.8 ± 1.7 mV. Encapsulation efficiency and drug loading were 82.36 ± 2.47% and 16.72 ± 0.93%, respectively. Molecular docking indicated a potentially favorable interaction between cafestol and NF-κB. LPS administration reduced the time spent in the light compartment and increased NF-κB and NLRP3 levels. Both free cafestol and its nanoparticle formulation improved LDB performance and significantly reduced these inflammatory markers compared with the LPS group (p < 0.001). These findings suggest that cafestol may attenuate LPS-associated behavioral alterations and inflammatory responses. Further studies are required to establish its underlying mechanisms and determine whether nanoparticle encapsulation provides additional therapeutic benefits.
Keywords
- Cafestol; depression-like behavior; lipopolysaccharide; neuroinflammation; NF-κB; NLRP3; PLGA nanoparticles; molecular docking.
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