Ampelopsin attenuates brain aging of D-gal-induced rats through miR-34a-mediated SIRT1/mTOR signal pathway

Abstract

The underlying molecular mechanisms for aging-related neurodegenerative diseases such as Alzheimer's disease (AD) are not fully understood. Currently, growing evidences have revealed that microRNAs (miRNAs) are involved in aging and aging-related diseases. The up-regulation of miR-34a has been reported to be associated with aging-related diseases, and thus it should be a promising therapeutic target. Ampelopsin, also called dihydromyricetin (DHM), a natural flavonoid from Chinese herb Ampelopsis grossedentata, has been reported to possess multiple pharmacological functions including anti-inflammatory, anti-oxidative and anti-cancer functions. Meanwhile, it has also gained tremendous attention against neurodegenerative diseases as an anti-aging compound. In the present study, the model rats with D-gal-induced brain aging revealed an obvious expression of miR-34a; in contrast, it could be significantly suppressed upon DHM treatment. In addition, target genes associated with miR-34a in the presence of DHM treatment were also explored. DHM supplementation inhibited D-gal-induced apoptosis and rescued impaired autophagy of neurons in hippocampus tissue. Moreover, DHM activated autophagy through up-regulated SIRT1 and down-regulated mTOR signal pathways due to the down-regulated miR-34a. In conclusion, DHM can execute the prevention and treatment of D-gal-induced brain aging by miR-34a-mediated SIRT1-mTOR signal pathway.

Swimming attenuates d-galactose-induced brain aging via suppressing miR-34a-mediated autophagy impairment and abnormal mitochondrial dynamics

“…We evaluated the spatial learning and memory of D-gal-induced aging rats by MWM test. Consistent with our previous reports (18), the escape latency of the rats on the first day of swimming training in the groups except D-gal aging model group was longer than that on other days and then decreased gradually during 4 days swimming training. In the MWM task, on the day 5, the escape latency of the rats in D-gal-induced aging model group was significantly longer than that in the normal control group.…”

“…Moreover, dysfunctional autophagy associated with the extension of age provides the chance for the accumulation of damaged or abnormal mitochondria (35). These findings reveal a clear correlation between dysfunctional autophagy and senescence, suggesting that the appropriate activation of autophagy could be a valuable strategy for the prevention and treatment of aging-related diseases (18). Currently, the functional status of autophagy during the aging process and the effect of swimming intervention on functional status of autophagy in hippocampal tissue have not been fully understood yet.…”

“…Morris water maze test. After swimming training for 6 consecutive weeks, the Morris water maze (MWM) was used to evaluate hippocampus-dependent spatial learning and memory capacity of D-galinduced aging rats as previously reported (18). MWM consisted of a circular pool (150 cm in diameter) filled with water.…”

“…The deficiency or dysfunction of autophagy has been reported during normal aging process both in invertebrates and higher organisms. Recently, the functional status of autophagy during the aging process has attracted increasing attention, but the relationship between functional status of autophagy and aging remains unclear (12,18). Some studies have reported that the impairment of autophagy can induce premature senescence in primary human fibroblasts and rapamycin as an autophagy activator can extend the life span of mice (15,17).…”

Protective effect of dihydromyricetin on LPS-induced acute lung injury

“…Some previous studies about the molecular mechanisms underlying DHM‐mediated pharmacological effects had already confirmed several signaling pathways that were identified in our present study. For example, DHM has been reported to exert the role of anti‐tumor activity by regulating the p53 pathway (KEGG ID: 04115), NF‐κB pathway (KEGG ID: 04064), and mTOR pathway (KEGG ID: 04150) in human hepatocellular, ovarian, and gastric cancer cells; neuroprotective activity by regulating the PI3K‐Akt pathway (KEGG ID: 04151) and mTOR pathway; anti‐inflammatory activity by regulating NF‐κB pathway and MAPK pathway (KEGG ID: 04010); and other pharmacological activities such as cardioprotective effect by regulating HIF‐1 signaling pathway (KEGG ID: 04066) and PI3K‐Akt pathway (KEGG ID: 04151) . These data provide preliminary evidence for the validation of predicted molecular targets of DHM using a bioinformatics approach.…”