Mounting evidence validates Ursolic Acid directly activates SIRT1: A powerful STAC which mimic endogenous activator of SIRT1

Archives of Biochemistry and Biophysics
Nuredin BakhtiariJahanfard Kazemi

Abstract

Ursolic Acid (UA), a pentacyclic triterpenoid compound, plays a vital role in aging process. However, the role of UA in the regulation of aging and longevity is still controversial as we have previously demonstrated that UA increases SIRT1 protein level in aged-mice. Here, we reveal that UA directly activates SIRT1 in silico, in vitro and in vivo. We have identified that UA binds to outer surface of SIRT1 and leads to tight binding of substrates to enzyme in comparison with Resveratrol (RSV) and control. Furthermore, our results indicate that UA drives the structure of SIRT1 toward a closed state (an active form of enzyme). Interestingly, our experimental findings are in agreement with the molecular dynamic results. Based on our data, UA increases the affinity of enzyme for both substrates with decreasing Km value, while enhances the Vmax of enzyme. Additionally, we have determined that UA heightened SIRT1 catalytic efficiency by 2 folds compared with RSV. Thereby, to identify the endogenous activator of SIRT1, UA was administrated to aged-mice and then the tissues were isolated. According to our results, it can be concluded that UA increases SIRT1 activity and mimics Lamin A and AROS behavior in the living cells.

Citations

Jun 21, 2020·Antioxidants·Ekaterina ProshkinaAlexey Moskalev
Dec 23, 2020·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Janine Naß, Thomas Efferth
Feb 19, 2021·Frontiers in Pharmacology·Ramu ManjulaFrancisco J Alcain
Mar 12, 2021·The Journal of Nutritional Biochemistry·Zhihao QuAiling Liu

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