Purple sweet potato color alleviates D-galactose-induced brain aging in old mice by promoting survival of neurons via PI3K pathway and inhibiting cytochrome C-mediated apoptosis.
Purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, protects brain function against oxidative stress induced by D-galactose (D-gal) (Sigma-Aldrich, St. Louis, MO, USA). Our data showed that PSPC enhanced open-field activity, decreased step-through latency, and improved spatial learning and memory ability in D-gal-treated old mice by decreasing advanced glycation end-products' (AGEs) formation and the AGE receptor (RAGE) expression, and by elevating Cu,Zn-superoxide dismutase (Cu,Zn-SOD) (Sigma-Aldrich) and catalase (CAT) expression and activity. Cleavage of caspase-3 and increased terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end-labeling (TUNEL)-positive cells in D-gal-treated old mice were inhibited by PSPC, which might be attributed to its antioxidant property. PSPC also suppressed the activation of c-Jun NH(2)-terminal kinase (JNK) and the release of cytochrome c from mitochondria that counteracted the onset of neuronal apoptosis in D-gal-treated old mice. Furthermore, it was demonstrated that phosphoinositide 3-kinase (PI3K) activation was required for PSPC to promote the neuronal survival accompanied with phosphorylation and activation of Akt and p44/42 mitogen-activated protein kinase (MAPK) by using PI3K inhibitor LY294002 (Cell Signaling Technology, Inc., Beverly, MA, USA), implicating a neuronal survival mechanism. The present results suggest that neuronal survival promoted by PSPC may be a potentially effective method to enhance resistance of neurons to age-related disease.
Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou, China.
Jun
J
Lu
Dong-mei
DM
Wu
Yuan-lin
YL
Zheng
Bin
B
Hu
Zi-feng
ZF
Zhang
D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D045304:Cytochromes c / Q000502:physiology*; D005690:Galactose / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051034:Inhibitor of Apoptosis Proteins / Q000502:physiology*; D027723:Ipomoea batatas / Q000737:chemistry / Q000502:physiology*; D008297:Male; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D058539:Phosphatidylinositol 3-Kinase / Q000502:physiology*; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D051034:Inhibitor of Apoptosis Proteins; D010936:Plant Extracts; D045304:Cytochromes c; D058539:Phosphatidylinositol 3-Kinase; D005690:Galactose