DECIPHERING THE ACTION MECHANISM OF INDONESIA HERBAL DECOCTION IN THE TREATMENT OF TYPE II DIABETES USING A NETWORK PHARMACOLOGY APPROACH

摘要

Objective: The aim of this research was to investigate action mechanism of Indonesia herbal decoctions in the treatment of Type 2 Diabetes (T2D) using network pharmacology approaches. Methods: Drug target profile analysis via Markov clustering was performed to identify the potent antidiabetic ingredients in the four herbs. Network target base identification of multicomponent synergy was applied to predict the ingredients synergetic effect. The multi-level and integrated target networks were contracted to identify the herbs major ingredients and their presumed targets. Further enrichment analysis and molecular docking were performed to validate network targets. Results: 278 ingredients from the four herbs were linked to antidiabetic drugs with an overall clustering success rate of 98.58% and 5 ingredient pairs had significant synergetic effects. Enrichment analysis demonstrates herbs candidate presumed targets were frequently involved in the significant biological process and pathways associated with progression of Type 2 diabetes (T2D) diseases. Finally, molecular docking validation revealed there was high binding site similarity between momordicoside F2 (78%), beta-sitosterol (67%) and cis-N-Feruloyltyramine (67%) with miglitol drug. In addition, the four ligands presented the higher binding affinity to Maltase-glucoamylase (MGA) receptor an enzyme responsible for the digestion of dietary starch to glucose. Conclusion: This study revealed the pharmacological mechanism of action of Indonesia herbal decoctions in the treatment of Type 2 diabetes. The herbs major presumed target played a significant biological role in the progression of Type 2 diabetes (T2D) while major herbal ingredients indicates the potential of curing Type 2 diabetes by inhibiting Maltase-glucoamylase (MGA) activity.