Browsing by Author "Clarence, Dvya Delilaa"

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    Zerumbone liquid crystalline nanoparticles protect against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro
    (2024) Paudel, Keshav Raj; Clarence, Dvya Delilaa; Panth, Nisha; Manandhar, Bikash; De Rubis, Gabriele; Devkota, Hari Prasad; Gupta, Gaurav; Zacconi, Flavia C.; Williams, Kylie A.; Pont, Lisa G.; Singh, Sachin Kumar; Warkiani, Majid Ebrahimi; Adams, Jon; Macloughlin, Ronan; Oliver, Brian G.; Chellappan, Dinesh Kumar; Hansbro, Philip Michael; Dua, Kamal
    The purpose of this study was to evaluate the potential of zerumbone-loaded liquid crystalline nanoparticles (ZER-LCNs) in the protection of broncho-epithelial cells and alveolar macrophages against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro. The effect of the treatment of ZER-LCNs on in vitro cell models of cigarette smoke extract (CSE)-treated mouse RAW264.7 and human BCi-NS1.1 basal epithelial cell lines was evaluated for their anti-inflammatory, antioxidant and anti-senescence activities using colorimetric and fluorescence-based assays, fluorescence imaging, RT-qPCR and proteome profiler kit. The ZER-LCNs successfully reduced the expression of pro-inflammatory markers including Il-6, Il-1 beta and Tnf-alpha, as well as the production of nitric oxide in RAW 264.7 cells. Additionally, ZER-LCNs successfully inhibited oxidative stress through reduction of reactive oxygen species (ROS) levels and regulation of genes, namely GPX2 and GCLC in BCi-NS1.1 cells. Anti-senescence activity of ZER-LCNs was also observed in BCi-NS1.1 cells, with significant reductions in the expression of SIRT1, CDKN1A and CDKN2A. This study demonstrates strong in vitro anti-inflammatory, antioxidative and anti-senescence activities of ZER-LCNs paving the path for this formulation to be translated into a promising therapeutic agent for chronic respiratory inflammatory conditions including COPD and asthma.
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    Zerumbone-incorporated liquid crystalline nanoparticles inhibit proliferation and migration of non-small-cell lung cancer in vitro
    (2024) Manandhar, Bikash; Paudel, Keshav Raj; Clarence, Dvya Delilaa; De Rubis, Gabriele; Madheswaran, Thiagarajan; Panneerselvam, Jithendra; Zacconi, Flavia C.; Williams, Kylie A.; Pont, Lisa G.; Warkiani, Majid Ebrahimi; MacLoughlin, Ronan; Oliver, Brian Gregory; Gupta, Gaurav; Singh, Sachin Kumar; Chellappan, Dinesh Kumar; Hansbro, Philip M.; Dua, Kamal
    Lung cancer is the second most prevalent type of cancer and is responsible for the highest number of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) makes up the majority of lung cancer cases. Zerumbone (ZER) is natural compound commonly found in the roots of Zingiber zerumbet which has recently demonstrated anti-cancer activity in both in vitro and in vivo studies. Despite their medical benefits, ZER has low aqueous solubility, poor GI absorption and oral bioavailability that hinders its effectiveness. Liquid crystalline nanoparticles (LCNs) are novel drug delivery carrier that have tuneable characteristics to enhance and ease the delivery of bioactive compounds. This study aimed to formulate ZER-loaded LCNs and investigate their effectiveness against NSCLC in vitro using A549 lung cancer cells. ZER-LCNs, prepared in the study, inhibited the proliferation and migration of A549 cells. These inhibitory effects were superior to the effects of ZER alone at a concentration 10 times lower than that of free ZER, demonstrating a potent anti-cancer activity of ZER-LCNs. The underlying mechanisms of the anti-cancer effects by ZER-LCNs were associated with the transcriptional regulation of tumor suppressor genes P53 and PTEN, and metastasis-associated gene KRT18. The protein array data showed downregulation of several proliferation associated proteins such as AXL, HER1, PGRN, and BIRC5 and metastasis-associated proteins such as DKK1, CAPG, CTSS, CTSB, CTSD, and PLAU. This study provides evidence of potential for increasing the potency and effectiveness of ZER with LCN formulation and developing ZER-LCNs as a treatment strategy for mitigation and treatment of NSCLC.