Pomegranate extract decreases oxidative stress and alleviates mitochondrial impairment by activating AMPK-Nrf2 in hypothalamic paraventricular nucleus of spontaneously hypertensive rats.

Abstract

High blood pressure, or "hypertension," is associated with high levels of oxidative stress in the paraventricular nucleus of the hypothalamus. While pomegranate extract is a known antioxidant that is thought to have antihypertensive effects, the mechanism whereby pomegranate extract lowers blood pressure and the tissue that mediates its antihypertensive effects are currently unknown. We have used a spontaneously hypertensive rat model to investigate the antihypertensive properties of pomegranate extract. We found that chronic treatment of hypertensive rats with pomegranate extract significantly reduced blood pressure and cardiac hypertrophy. Furthermore, pomegranate extract reduced oxidative stress, increased the antioxidant defense system, and decreased inflammation in the paraventricular nucleus of hypertensive rats. We determined that pomegranate extract reduced mitochondrial superoxide anion levels and increased mitochondrial function in the paraventricular nucleus of hypertensive rats by promoting mitochondrial biogenesis and improving mitochondrial dynamics and clearance. We went on to identify the AMPK-nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) pathway as a mechanism whereby pomegranate extract reduces oxidative stress in the paraventricular nucleus to relieve hypertension. Our findings demonstrate that pomegranate extract alleviates hypertension by reducing oxidative stress and improving mitochondrial function in the paraventricular nucleus, and reveal multiple novel targets for therapeutic treatment of hypertension.

• Authors: Wenyan Sun, Chunhong Yan, Bess Frost, Xin Wang, Chen Hou, Mengqi Zeng, Hongli Gao, Yuming Kang, Jiankang Liu
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 34246 (10 07 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27713551 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• NF-E2-Related Factor 2
• Nfe2l2 protein, rat
• Plant Extracts
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Animals
• Antihypertensive Agents (chemistry, pharmacology)
• Hypertension (drug therapy, metabolism, pathology)
• Lythraceae (chemistry)
• Male
• Mitochondria (metabolism, pathology)
• NF-E2-Related Factor 2 (metabolism)
• Oxidative Stress (drug effects)
• Paraventricular Hypothalamic Nucleus (metabolism, pathology)
• Plant Extracts (chemistry, pharmacology)
• Rats
• Rats, Inbred SHR