COP-22 Alleviates D-Galactose-Induced Brain Aging by Attenuating Oxidative Stress, Inflammation, and Apoptosis in Mice.

Aging is a natural and inevitable process of organisms. With the intensification of population aging, research on aging has become a hot topic of global attention. The most obvious manifestation of human aging is the aging of brain function, which has been linked to the development of neurodegenerative diseases. In this study, COP-22, a mono-carbonyl curcumin derivative, was evaluated for its anti-aging ability, especially its ability to resist brain aging induced by D-galactose (D-gal) in mice. For brain protection, COP-22 could resist D-gal-induced oxidative stress by increasing the activity of antioxidative defense enzymes and enhancing antioxidant capacity in the brain tissue; COP-22 could improve the dysfunction of the cholinergic system by decreasing the increased activity of acetylcholinesterase and increasing the reduced content of acetylcholine induced by D-gal; and COP-22 could protect nerve cells of the brain. Further, western blot was used to determine related proteins of the brain. We found that COP-22 could effectively protect against brain injury (SIRT1, p53, p21, and p16) by inhibiting oxidative stress (Nrf2 and HO-1), inflammation (IL-6 and TNF-α), and apoptosis (Bax and caspase-3) in D-gal-induced aging mice. Additionally, COP-22 demonstrated the ability to reduce oxidative stress in serum and liver caused by D-gal, as well as relieve the damages in the liver and kidney induced by D-gal. These results indicated that COP-22 had potential anti-aging activity and could be used in the therapy of aging and aging-associated diseases like Alzheimer disease.

Discovery of a 4-Hydroxy-3'-Trifluoromethoxy-Substituted Resveratrol Derivative as an Anti-Aging Agent.

With the intensification of population aging, aging-related diseases are attracting more and more attention, thus, the study of aging mechanisms and anti-aging drugs is becoming increasingly urgent. Resveratrol is a potential candidate as an anti-aging agent, but its low bioavailability limits its application in vivo. In this work, a 4-hydroxy-3'-trifluoromethoxy-substituted resveratrol derivative (4-6), owing to its superior cell accumulation, could inhibit NO production in an inflammatory cell model, inhibit oxidative cytotoxicity, and reduce ROS accumulation and the population of apoptotic cells in an oxidative stress cell model. In D-galactose (D-gal)-stimulated aging mice, 4-6 could reverse liver and kidney damage; protect the serum, brain, and liver against oxidative stress; and increase the body's immunity in the spleen. Further D-gal-induced brain aging studies showed that 4-6 could improve the pathological changes in the hippocampus and the dysfunction of the cholinergic system. Moreover, protein expression related to aging, oxidative stress, and apoptosis in the brain tissue homogenate measured via Western blotting also showed that 4-6 could ameliorate brain aging by protecting against oxidative stress and reducing apoptosis. This work revealed that meta-trifluoromethoxy substituted 4-6 deserved to be further investigated as an effective anti-aging candidate drug.