Molecular Pharmacology Study of Andrographolide Extracted from Andrographis Paniculata on Atherosclerosis Preventive Effect

Abstract

Ni Kadek Warditiani, Pande Made Nova Armitha Sari, Yan Ramona, Made Agus Gelgel Wirasuta.

Diet pattern resulting in hyperlipidemia is likely the main factor of atherosclerosis development. Balinese have been using Andrographis paniculata (Sambiloto) traditionally to maintain their lipid blood level and stamina. Andrographolide (AND) is its active compound. Therefore, molecular pharmacology study of AND on atherosclerosis-related diseases is urgently needed. The study aimed to develop a Thin Layer Chromatography (TLC) fingerprint method for Sambiloto standardization and to carry out the pharmacological effect of this compound on atherosclerosis prevention. This study comprised of several stages: development of the TLC fingerprint, pre-clinical research including atherosclerosis induction in an animal model, experimental treatment and prevention of atherosclerosis development in the animal model using AND, comparison of the results with those for atorvastatin treatment, and in-silico docking simulation of AND’s molecular pharmacological effect. TLC with a ratio of 9:1 (v/v) chloroform: ethanol mobile phase was found to be a suitable method for Sambiloto standardization. Rat diets composition of 5% duck yolk, 10% pork fat, Vit D3 20,000 IU, and 1% calcium induced atherosclerosis development. Daily administration of AND at 1.5 mg/kg rat body weight with atherogenic food prevented atherosclerosis development. The docking simulation showed that AND interacted well with NF-kB, ICAM-1, VCAM-1, TNFα, IFN-γ and Cyt MAP kinase P32 proteins responsible for the anti-atherosclerotic effect. Sambiloto is a potential traditional herbal medicine for use in treating and preventing hyperlipidemia from triggering atherosclerosis-related disease development. AND inhibited the ox-LDL formation and interacted well with the atherosclerosis-protein receptor targets.