Anti-aging Effects and Mechanisms of <em>Phyllanthus emblica Linn.</em> Polyphenols Extract Targeting Sirt6

The anti-aging effects and possible molecular mechanisms&nbsp;of <em>Phyllanthus emblica Linn</em>&nbsp;(PE)&nbsp;were investigated&nbsp;in this study. Results revealed that PE extracts increased antioxidant enzyme activities, T-AOC levels, and decreased MDA content in the serum and tissues of D-galactose(D-gal) mice. PE&nbsp;also improved the motor and learning memory abilities of D-gal mice.&nbsp;In addition,&nbsp;PE regulated&nbsp;the abundance of <em>Firmicutes</em>, <em>Bacteroidota</em>, and other bacteria in the&nbsp;gut microbiota&nbsp;of D-gal mice, by affecting the TCA cycle&nbsp;based on functional predictive analysis.&nbsp;The molecular docking and cellular thermal shift assay revealed that&nbsp;chebulic acid&nbsp;(CA, binding energy&nbsp;of -183.6289&nbsp;kcal/mol) might be the&nbsp;key&nbsp;active substance in PE&nbsp;extract.&nbsp;Sirt6 was an important protein that affects aging and energy metabolism. Circular dichroism spectrum&nbsp;and&nbsp;western blot analysis found&nbsp;that&nbsp;CA&nbsp;altered&nbsp;the secondary&nbsp;protein structure of Sirt6&nbsp;and&nbsp;increased its deacetylase activity.&nbsp;Co-Immunoprecipitation assay results showed that Sirt6 and Nrf2 interacted in the presence of CA.&nbsp;Finally, western blotting analysis found that PE extracts up-regulated the expression of Sirt6,&nbsp;Nrf2, and HO-1 proteins in the tissues of D-gal mice.&nbsp;Overall, the phenolic acids of&nbsp;PE&nbsp;may regulate oxidative stress through the interaction of sirt6, and affect the gut microbiota&nbsp;of mice. This study provided theoretical guidance for the potential application&nbsp;and the mechanism of health effects from&nbsp;PE.