Studies on the Interaction Mechanisms of Garcinia Kolaviron Constituents with Selected Diabetes and Neurodegenerative Disease Targets

Emerging evidence has shown kolaviron, a Garcinia biflavonoid complex, as inhibitor of α-amylase, aldose reductase and acetylcholinesterase in vitro. Herein, analysis of each kolaviron constituent (GB1, GB2 and kolaflavanone) for its molecular binding signatures, interaction footprints and inhibitory potential against these proteins was performed in silico. Morelloflavone, an analog of the biflavonoids, was also assessed for its inhibitory potential and precise interaction against the proteins. Results obtained suggest all the biflavonoids as potential drug candidates in the treatment of diabetes and neurodegenerative disease; their relatively bigger size permits an efficient blockage of the enzymes’ active site, thus hindering substrate access. The biflavonoids were well accommodated and favorably occupied the active site of the proteins with high binding affinity. The numerous hydroxyl and few methoxyl groups of the biflavonoids are indispensable for their bioactivities. Kolaflavanone displayed the highest affinity to α-amylase, but lowest binding affinity to acetylcholinesterase. GB1 and GB2 showed good affinity and comparable binding conformation on the proteins. Morelloflavone formed consistent π–π interactions with all the proteins. This work is the first study to depict the unique interaction patterns of kolaviron constituents with the selected enzymes which may explain their potency and inhibitory mechanisms.