Punicalagin Activates AMPK/PGC‐1α/Nrf2 Cascade in Mice: The Potential Protective Effect against Prenatal Stress

Abstract

ScopePrenatal stress is closely associated with poor health outcomes for offspring, yet the specific mechanisms and effective interventions remain limited.Methods and ResultsIn the present study, both male and female rat offspring exposed to prenatal restraint stress (PRS) are confirmed to have impaired spatial learning and memory, accompanied by reduced AMP‐activated protein kinase (AMPK) activity and decreased protein expression of mitochondrial biogenesis and antioxidant pathways in the hippocampus. Interestingly, a deficiency in the AMPK cascade also occurs in liver, heart, and adipose tissues, suggesting that the systemic deactivation of AMPK in the offspring is potentially attributed to increased maternal glucocorticoid levels under PRS. Punicalagin (PU), a major ellagitannin in pomegranate, is found to effectively induce mitochondrial biogenesis and phase II enzymes through activation of AMPK in both HT22 and primary hippocampal neurons, thereby inhibiting glutamate‐induced cell viability and mitochondrial membrane potential loss. Meanwhile, the activation of AMPK cascade is also confirmed in mice administrated with PU for three days.ConclusionsAltogether, these results indicate that the systemic deficiency of the AMPK cascade can be the key factor that contributes to poor outcomes of PRS, and PU may be used as an effective maternal nutritional intervention.

A nascent protein labeling strategy disclosed mitochondrial proteomic responses in punicalagin intervened insulin resistance of HepG2 cells

“…3 It has been demonstrated to exhibit bioprotective effects such as reduction of oxidative stress 4 and anti-inflammatory and anti-tumor activities. 5,6 The antioxidant activity of PU is due to the high hydroxylation structure. 7,8 Gil et al 3 reported that PU contributed 50% antioxidant activities of pomegranate juice.…”

The Activation of AMPK/NRF2 Pathway in Lung Epithelial Cells Is Involved in the Protective Effects of Kinsenoside on Lipopolysaccharide-Induced Acute Lung Injury

“…AMPK is one of the crucial energy sensors which could modulate mitochondrial biogenesis through activating NRF2 in this phosphorylated status [ 35 ]. Once NRF2 is activated, it could translocate into cell nucleus and transcriptionally activate a great many antioxidant genes that are responsible for mitochondrial fusion and fission [ 25 ].…”

Ellagic Acid: A Dietary-Derived Phenolic Compound for Drug Discovery in Mild Cognitive Impairment

“…Previous findings confirmed that administration of EA prevents cognitive impairment through attenuation of the brain lipid peroxidation and prevented waning of the superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) activity in streptozotocin-induced rats ( Kumar and Bansal, 2018 ). Cao et al (2020) revealed that ellagitannin activates AMP-activated protein kinase (AMPK) to ameliorate oxidative stress by activation of NF-E2-related factor (Nrf2)-mediated phase II antioxidant enzymes. In such a manner, EA is involved not only in the management of endogenous and exogenous sources of reactive oxygen species (ROS), but also involved in antioxidant defense mechanisms.…”

“…Meanwhile, urolithin A activates mitochondrial autophagy to exert neuroprotective effects through activation of the SIRT1/mTOR signaling pathway, which aids in preventing D-galactose-induced brain aging ( Chen et al, 2019 ). Cao et al (2020) found that punicalagin regulates mitochondrial biogenesis by activating AMPK/peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) signaling, thereby preventing cognitive dysfunction. Additionally, mitochondrial respiratory dysfunction is also the main cause of ROS overproduction and treatment of EA can prevent the decrease of mitochondrial succinate dehydrogenase activity in the rat brain caused by 3-nitropropionic acid, thus protecting mitochondrial functions ( Sharma et al, 2021 ).…”