Abstract:
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.
