Attenuation of Cigarette-Smoke-Induced Oxidative Stress, Senescence, and Inflammation by Berberine-Loaded Liquid Crystalline Nanoparticles: In Vitro Study in 16HBE and RAW264.7 Cells

Abstract

Cigarette smoke is considered a primary risk factor for chronic obstructive pulmonary disease. Numerous toxicants present in cigarette smoke are known to induce oxidative stress and airway inflammation that further exacerbate disease progression. Generally, the broncho-epithelial cells and alveolar macrophages exposed to cigarette smoke release massive amounts of oxidative stress and inflammation mediators. Chronic exposure of cigarette smoke leads to premature senescence of airway epithelial cells. This impairs cellular function and ultimately leads to the progression of chronic lung diseases. Therefore, an ideal therapeutic candidate should prevent disease progression by controlling oxidative stress, inflammation, and senescence during the initial stage of damage. In our study, we explored if berberine (an alkaloid)-loaded liquid crystalline nanoparticles (berberine-LCNs)-based treatment to human broncho-epithelial cells and macrophage inhibits oxidative stress, inflammation, and senescence induced by cigarette-smoke extract. The developed berberine-LCNs were found to have favourable physiochemical parameters, such as high entrapment efficiency and sustained in vitro release. The cellular-assay observations revealed that berberine-LCNs showed potent antioxidant activity by suppressing the generation of reactive oxygen species in both broncho-epithelial cells (16HBE) and macrophages (RAW264.7), and modulating the genes involved in inflammation and oxidative stress. Similarly, in 16HBE cells, berberine-LCNs inhibited the cigarette smoke-induced senescence as revealed by X-gal staining, gene expression of CDKN1A (p21), and immunofluorescent staining of p21. Further in-depth mechanistic investigations into antioxidative, anti-inflammatory, and antisenescence research will diversify the current findings of berberine as a promising therapeutic approach for inflammatory lung diseases caused by cigarette smoking.

Protective Effects of Diets Rich in Polyphenols in Cigarette Smoke (CS)-Induced Oxidative Damages and Associated Health Implications

“…Lungs are continuously getting exposed to oxidants, which are produced as either endogenously created (e.g., by mitochondrial electron transport during respiration or during phagocyte activation) or exogenously produced (e.g., by air pollution or cigarette smoke) [ 24 ]. ROS generation has been linked to protein, DNA, and lipid oxidation, which can cause direct lung damage or provoke a variety of cellular responses via the development of secondary metabolic reactive species [ 25 ]. ROSs have the ability to induce extracellular matrix remodeling and blood vessel remodeling, boost mucus formation, inactivate antiproteases, cause apoptosis, and regulate cell proliferation [ 26 ].…”

“…The failure in COPD repair caused by oxidative stress may explain the higher prevalence of lung cancer in COPD patients compared to smokers without airway obstruction. The failure in COPD repair caused by oxidative stress may explain the higher prevalence of lung cancer in COPD patients compared to smokers without airway obstruction [ 25 , 45 ]. The failure in COPD repair caused by oxidative stress may explain the higher prevalence of lung cancer in COPD patients compared to smokers without airway obstruction [ 46 ].…”

Evaluation of the Cytotoxic Activity and Anti-Migratory Effect of Berberine–Phytantriol Liquid Crystalline Nanoparticle Formulation on Non-Small-Cell Lung Cancer In Vitro

“…These nanocarriers have shown promising results in the delivery of potential anti-cancer agents, for example curcumin and boswellic acid, with increased bioavailability and efficacy and decreased toxicity profiles [42][43][44][45][46]. Among the nanoparticle-based formulations, liquid crystalline nanoparticles (LCNs) have been gaining interest as nano-carrier systems for anticancer and anti-inflammatory drugs, owing to their potential to improve the bioavailability and stability of the incorporated drug [47]. Monoolein-based LCNs incorporating rutin, naringenin, and berberine have already shown effectiveness in terms of their anti-cancer activity against NSCLC in vitro [48][49][50][51].…”

A kNGR Peptide-Tethered Lipid–Polymer Hybrid Nanocarrier-Based Synergistic Approach for Effective Tumor Therapy: Development, Characterization, Ex-Vivo, and In-Vivo Assessment

“…These nanosystems consist of a hydrophobic PLGA core, a lipid monolayer shell (lecithin) around the polymer core, and a PEG-linked lipid interposed in the lecithin layer, which forms the outer of the nanocarrier hydrophilic [ 13 , 14 ]. The lipid monolayer offers stability issues and outward diffusion of the encapsulated drug, providing support for attachment of specific diseased ligands, which aids in the targeted delivery of bioactives compounds [ 15 , 16 ]. The characteristics of nanoparticles may be altered by changing the material composition to customize them to specific medicinal needs.…”