In silico Study of Centella Asiatica Active Compounds as Anti-Inflammatory Agent by Decreasing Il-1 And Il-6 Activity, Promoting Il-4 Activity

Headnote

Abstract

Inflammatory is cascade process triggered by pro-inflammatory cytokines (IL-1 and IL-6) and anti-inflammatory cytokines (IL-4). Centella asiatica is known for has been studied fot its anti-inflammatory properties. The docking studies was used in the study to evaluate interaction between Centella asiatica active compound with IL-1a, IL-1ß, IL-6, and IL-4.

Based on docking results, asiaticoside and batulinic acid had binding energy for IL-1a respectively -14.4199 kcal/mol and -12.3706 kcal/mol. In IL-1ß docking, there were asiaticoside, madasiatic acid, and terminolic acid with binding energy -11.9288; -11.3074; and -11.2061 kcal/mol respectively. Asiaticoside bound into receptor active site Gln 141 of IL-1ß. Asiatic acid, madecassic acid, and asiaticoside in IL-6 docking had binding energy -9.8244; -9.7071; and -9.0171 kcal/mol respectively. The three ligand bound into IL-6 receptor active site Arg179. IL-4 reacted to madecassic acid, termolinic acid, and asiaticoside with binding energy -12.6151; -12.5650; and -11.7490 kcal/mol respectively. The three ligands bound to receptor binding site IL-4 Lys102.

Centella asiatica active compounds (asiaticoside, termolinic acid, madecassid acid, asiatic acid, batulinic acid, and madasiatic acid) interacted significantly with inflammatory cytokines (IL-1a, IL-1ß, IL-6, and IL-4). Madecassic acid, asiticoside, asiatic acid, madasiatic acid, and terminolic acid inhibit the pro-inflammatory cytokines by binding to receptor active site of IL-1ß and IL-6. Madecassic acid, terminolic acid, and asiaticoside enhance anti-inflammatory cytokines by binding to IL4 receptor binding sites.

Keywords: Anti-inflammation, Centella asiatica, In silico, IL-1a, IL-1ß, IL-6, IL-4.

1. Introduction

Cytokines is an intercellular protein produced by virtually all nucleated cell which used as signaling between cells. Cytokines act by binding to receptor membrane of targeted cell, thus trigger cascade pathway in targeted cell. This signaling pathway controls have immunomodulatory effect, controlling gene expression that leads to inflammatory cascade process.[1,2]

There had been 200 cytokines identified. These cytokines are classified into several groups, namely interleukin, growth factor, chemokines, interferon, hematopoietin, and colony stimulating factors. According to their role in inflammation process, cytokines separated into two groups, pro-inflammatory cytokines (i.e. IL-1, IL-6, TNF-a, TGF-ß) and anti-inflammatory cytokines (i.e. IL1Ra, IL- 4, IL-10, IL-13). Pro-inflammatory cytokines and antiinflammatory cytokines works balancing each other in homeostatic environment. Disturbances in these cytokines cellular system have been studied significant in development of various diseases[1,3]

Interleukin-1 (IL-1) plays significant role as pro-inflammatory cytokines as it is secreted...