A natural compound extracted from magnolia bark protects the heart from hypertrophy, which is often caused by chronic high blood pressure and can lead to heart failure, researchers report in the April 14 online journal Nature.
When injected into mice, honokiol (hoh-NOH’-kee-ohl) reduces the overgrowth of individual cardiomyocytes, reduces ventricular wall thickness and prevents the accumulation of interstitial fibrosis, a type of cardiomyocyte of sclerosis, reducing their ability to contract. It also protects cardiomyocytes from damage caused by oxidative stress, which damages DNA.
Researchers at the University of Chicago School of Medicine also describe how the centuries-old remedy, widely used in Asia, protects the heart.They found that the compound activates SIRT3, a protective protein associated with anti-aging, stress resistance and metabolic regulation.
“Honokiol effectively prevented the induction and progression of cardiac hypertrophy in mice by increasing SIRT3 levels,” said study author Mahesh Gupta, PhD, director of the Cardiac Cell Biology Research Program at the University of Chicago.”It even reduced pre-existing cardiac hypertrophy. This has the potential to play an important role in the prevention and treatment of heart failure.”
“To our knowledge, this is the first report describing a pharmacological activator of SIRT3,” he added.”So far, calorie restriction combined with endurance exercise has been the only way to increase SIRT3 levels. Very few people have been able to follow such a strict regimen.”
As one of the sirtuin protein family, SIRT3 is mainly active in mitochondria, the main energy source of cells.It plays a central role in energy metabolism and preventing acetylation, a process that can alter protein function.In the absence of SIRT3, mitochondrial proteins become hyperacetylated, which impairs function.
Human studies have shown that sedentary patients over the age of 60 have a nearly 40% reduction in SIRT3.Mice lacking the SIRT3 gene had 40 percent lower levels of ATP, a major source of energy, than mice with the gene.
The researchers tested multiple compounds, looking for one that could activate SIRT3.They found that honokiol reduced mitochondrial protein acetylation.When they tested it in the heart muscle cells of mice, they found that small amounts and honokiol nearly doubled SIRT3 levels within 24 hours.
Other studies have shown that honokiol, acting through SIRT3, can reduce or prevent hypertrophic growth of cardiomyocytes, prevent generalized hypertrophy in mice, and even reduce existing damage from established hypertrophy.
It also blocked the production of fibroblasts — cells that interfere with heart muscle function — and reduced the production of myofibroblasts, cells that speed wound healing but impair heart function.The researchers did not find any apparent toxicity.
To confirm this mechanism, the researchers performed the same experiment on mice lacking the SIRT3 gene.In these studies, Magnolia officinalis had no effect.
They also identified and Magnolia officinalis binds directly to SIRT3.This combination appears to increase SIRT3 activity.
The authors write that the results suggest that pharmacological activation of SIRT3 by honokiol may be “a potential therapeutic strategy to prevent adverse cardiac remodeling and other diseases associated with abnormal cell growth and organ fibrosis.”
and Magnolia officinalis are available as herbal medicines, but the purity of such preparations has not been established.”We gave the mice an intraperitoneal injection,” emphasises Gupta, “instead of orally, which is how this compound has traditionally been administered. We’re testing whether oral administration would have a similar effect.”
Despite the caveats, “We are very excited,” Gupta said.”We are working to design a clinical trial involving patients with cardiac hypertrophy and potentially other metabolic diseases such as type 2 diabetes.”
Materials provided by the University of Chicago Medical Center.Note: Content may be edited for style and length.
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Post time: May-09-2022
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