Theses (MSc. Analytical & Pharmaceutical Chemistry)

Usage of plant-based compounds has been increasing recently due to their unexpected efficacy in the mitigation of certain diseases, including atherosclerosis. The aims of this study are to investigate the potential anti-inflammatory and anti-oxidative effects of 14-deoxy-11,12-didehydroandrographolide (DDAGP), an Andrographis paniculata derivative, in C57BL/6J mouse model of atherosclerosis by determining relative NF-ĸB p65 and NOX-4 expression levels, in conjunction with biochemical profiling of plasma lipid and liver enzyme levels, in Poloxamer-407 (P-407) challenged C57BL/6J mouse model. Oral administration of DDAGP, with non-toxic concentration of 15 mg/kg/day, 30 mg/kg/day and 45 mg/kg/day, measurably reduced plasma lipid components, specifically LDL-c; but only the 45 mg/kg/day dose was conducive to significant TGL level reduction. Nevertheless, DDAGP did not significantly suppress the Atherogenic Index of Plasma (AIP) and the Atherogenic Coefficient (AC), suggesting that it lacks clinically significant anti-atherogenic ability. However, treatment of P-407 challenged mice with DDAGP significantly inhibited elevation of heart homogenate levels of NK-ĸB and NOX4 in a non-dose-dependent manner. Hence, even though DDAGP may not be an effective anti-atherogenic drug, it instead possesses marked anti-inflammatory and anti-oxidative potential. In conclusion, further research along these lines is warranted, with focus on DDAGP’s efficacy in the prophylaxis and management of inflammatory diseases.

Background and Objective Atherosclerosis and the relative cardiovascular complications remain the primary contributors to the statistics of being the leading cause of death worldwide. The elucidation of molecular and cellular pathways pertaining to oxidative stress and inflammation in atherosclerosis has been elucidated via scientific studies. Phytochemical investigations on Andrographis paniculata have revealed to possesses beneficial effect against various cardiovascular disease. Andrographolide (AGP), as the major bioactive component of A. paniculata, has demonstrated to have various biological properties including anti-oxidant, and hepatoprotective in addition to anti-inflammatory properties. In this study, we aim to demonstrate the anti-atherosclerotic properties of AGP in poloxamer-407 (P-407) induced atherosclerosis in C57BL/6J mice. Methods Atherosclerosis was elicited in C57BL/6J mice using P-407 via intraperitoneal injection. On the other hand, the treatment with AGP (15, 30 and 45 mg/kg/day) was given concomitantly for 6-weeks period. Disease control and normal control were received vehicle treatment throughout the study period. At the end of the study, heart and aorta was harvested and utilised for the subsequent enzyme-linked immunosorbent assay (ELISA) and histological studies. Results The results demonstrated that the treatment of mice with AGP reversed the effects of P-407 induced atherosclerosis. The doses of AGP were in correlation with the reduction of atherosclerosis biomarkers. The high dose (45 mg/kg/day) was the most significant dose observed to reduce the progression of atherosclerosis. The Low-Density Lipoprotein (LDL), Triglycerides (TG), and atherogenic index (AI) were significantly reduced by the AGP treatment in comparison to the disease control. The histological results showed reduction in inflammation, fibrosis and hypertrophy in the heart tissues of the groups treated with AGP compared to the disease control. In addition, AGP treatment significantly reduced marker molecules of oxidative stress (NOX-4) and inflammation (p65 NF-B) in comparison to those in the disease control. Moreover, the aorta of the AGP treated groups showed normal morphological characteristics while the disease control cells were highly damaged. In addition, lipid accumulation was observed to be very clear for the disease control, while the AGP groups showed significant reduction in the lipid accumulation. Conclusion The results of our study demonstrated that AGP is very effective to reduce the symptoms of atherosclerosis through reducing of oxidative stress and inflammation. Thus, AGP is highly recommended to be considered as natural treatment to reduce or prevent the development of atherosclerosis.