Theses (MSc. Molecular Medicine)

Zerumbone (ZER) is an 11-membered crystalline sesquiterpene from the rhizome of Zingiber zerumbet, which carries many beneficial properties, including anti-inflammatory and antioxidant properties. In chronic obstructive pulmonary disease (COPD), zerumbone targets several inflammatory and oxidative mediators released by broncho-epithelial cells and alveolar macrophages in various pathways resulting in the suppression of the disease progression. However, zerumbone has many several drawbacks such as low bioavailability, poor gastrointestinal (GI) absorption and non-specific targeting of tissues and organs, all of which limits the development of ZER as potential new drug formulation for the treatment of COPD. Liquid crystalline nanoparticles (LCN) are novel drug delivery carrier that have tuneable characteristics to enhance and ease the delivery of bioactive compounds. Loading ZER into LCNs can potentially overcome the drawbacks of free ZER on its own. In this study, ZERLCNs were investigated for their ability to inhibit cigarette smoke extract induced inflammation, oxidative stress and senescence (the main characteristics of COPD) through in vitro study in human healthy bronchoepithelial cell line (BCiNS1.1) and mice macrophage (RAW264.7). The study compared the biological activity of ZER-LCNs with pure ZER powder. The results from this study indicated that ZER-LCNs had advantageous physicochemical parameters including a sustained in vitro release as well as a high entrapment efficiency. Additionally, the in vitro cellular studies showed that the ZER-LCNs had potent anti-inflammatory and antioxidant properties in both the BCi-NS1.1 and RAW 264.7 by regulating the genes and cytokines produced during inflammation and oxidative stress. The broncho-epithelial cells treated with ZER-LCNs inhibited the senescence induced by cigarette smoke extract by regulating the gene and protein expression of p21 and p16 (a marker of senescence). The research found that ZER-LCNs have superior biological activity compared to free ZER against cigarette smoke extract induced oxidative stress, inflammation, and senescence. This suggests the unique tuneable characteristics of ZER-LCNs and promising potential development for widescale pharmaceutical use. Additional in-depth studies involving animal model or clinical study on the mechanistic effect of ZER-LCN for its anti-inflammatory, antioxidative and antisenescence properties is required to validate its potential to treat COPD. Keywords: Zerumbone, liquid crystalline nanoparticles, monoolein, P407, anti-inflammatory, antioxidant, entrapment efficiency, drug release.

Diabetes mellitus (DM) is a chronic metabolic disorder, characterised by constant elevated levels of glucose in the blood. Currently, type 2 diabetes mellitus (T2DM) emerged as global burden disease. Despite the significant progress in treating diabetes by hypoglycaemic drugs, search for new drugs continues as the present synthetic drugs have several limitations. The herbal drugs with antidiabetic activity are attracting scientists' attention. Commonly, the aims of using herbs are to enhance insulin sensitivity and secretion. Madecassoside (MAD) and catalpol (CAT) are antioxidant herbal compounds. This study aimed to investigate the effect of MAD and CAT on insulin sensitivity and release in INS-1E cells. INS-1E cells were cultured in high glucose medium for 48 h. Subsequently, the medium was removed then MAD and CAT were added for 24 h. Then glucose stimulated insulin secretion (GSIS) and insulin signalling proteins were investigated. Results showed that 30 μM MAD and 40 μM CAT significantly increased the insulin concentration 26.4 ± 0.1 (P<0.01) and 26.1 ± 0.2 μg/L (P <0.05), respectively. Furthermore, these compounds improved insulin resistance through a significant enhancement of Phospho- (Tyr608) insulin receptor substrate-1 (IRS1), Akt, phospho-Ser473 Akt and GLUT2 expressions. In conclusion, 30 μM MAD and 40 μM CAT markedly increased the sensitivity of the cells to glucose and insulin.