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
Keshav Raj Paudel,
Nisha Panth,
Bikash Manandhar,
Sachin Kumar Singh,
Gaurav Gupta,
Peter R. Wich,
Srinivas Nammi,
Ronan MacLoughlin,
Jon Adams,
Majid Ebrahimi Warkiani,
Dinesh Kumar Chellappan,
Brian G. Oliver,
Philip M. Hansbro,
Kamal Dua
Affiliations
Keshav Raj Paudel
Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW 2007, Australia
Nisha Panth
Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW 2007, Australia
Bikash Manandhar
Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia
Sachin Kumar Singh
Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia
Gaurav Gupta
School of Pharmacy, Suresh Gyan Vihar University, Jaipur 302017, Rajasthan, India
Peter R. Wich
School of Chemical Engineering, University of New South Wales, Sydney, NSW 2052, Australia
Srinivas Nammi
School of Science, Western Sydney University, Penrith, NSW 2751, Australia
Ronan MacLoughlin
IDA Business Park, H91 HE94 Galway, Connacht, Ireland
Jon Adams
Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia
Majid Ebrahimi Warkiani
School of Biomedical Engineering, University of Technology Sydney, Sydney, NSW 2007, Australia
Dinesh Kumar Chellappan
Department of Life Sciences, School of Pharmacy, International Medical University, Kuala Lumpur 57000, SGR, Malaysia
Brian G. Oliver
Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW 2037, Australia
Philip M. Hansbro
Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW 2007, Australia
Kamal Dua
Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia
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.
