Effects of triphala and guggul aqueous extracts on inhibition of protein fibrillation and dissolution of preformed fibrils

Abstract

Herbal preparations have long been used for treatment of variety of diseases. However, a systematic and scientific evaluation of their effects and mechanisms of action have been lacking, although it is believed that synergistic complementation of the effects of the multiple chemical components in these preparations would be playing crucial regulatory roles in the different metabolic pathways which may interfere in a biological system. In this context, we investigate here protein fibrillation which is known to be an important process responsible for many neurodegenerative and other diseases. Using lysozyme as a model protein, we have studied using a combination of spectroscopic and microscopic techniques, the effects of two herbal preparations, derived from triphala and guggul, on the fibrillation process. We observed that both the extracts have the ability to inhibit protein fibrillation but triphala has much more dominating influence on fibrillation inhibition. The kinetics of fibrillation has been monitored by fluorescence spectroscopy as well as absorption spectroscopy, and the morphological changes associated with fibrillation have been monitored by transmission electron microscopy. Our experiments seem to suggest an interference (or synergy), though minor, between the effects of triphala and guggul on the fibrillation/aggregation process. We also observed that both triphala and guggul have the ability to dissolve preformed fibrils and aggregates of lysozyme, in a synergistic manner. We believe, the present indication of possible synergy between triphala and guggul can be conceptually extrapolated to the components of the individual preparations. Thus, the current work has significant therapeutic implications and will provide scientific basis to the development of new generation of phytopharmaceuticals which can be used alone or in combination with other drugs.