Honokiol Stimulation Used to Prevent Hypertrophy

The ancient herbal therapy substance honokiol, which is derived from the bark, seed cones, and leaves of trees belonging to the genus Magnolia, has chemical properties that enable it to protect the heart from hypertrophy.

Honokiol is a natural biphenolic compound with anti-inflammatory, anti-oxidative, anti-tumor, and neuroprotective properties that can readily cross the blood brain barrier and the blood-cerebrospinal fluid barrier. As a result, it is a potentially potent therapeutic agent with high bioavailability.

Investigators at the University of Chicago worked with a mouse model of cardiac hypertrophy. They reported in the April 14, 2017, online edition of the journal Nature Communications that when injected into mice, honokiol reduced the excess growth of individual cardiac muscle cells, decreased ventricular wall thickness, and prevented the accumulation of interstitial fibrosis, a stiffening of cardiac muscle cells that reduces their ability to contract. The compound also protected heart muscle cells from the damage caused by oxidative stress.

The data suggested that the anti-hypertrophic effects of honkiol depended on activation of the deacetylase Sirt3 (silent mating type information regulation 2 homolog) 3. The investigators demonstrated that honkiol was present in mitochondria where it enhanced Sirt3 expression nearly twofold. They suggested that honokiol might bind to Sirt3 to further increase its activity. Increased Sirt3 activity was associated with reduced acetylation of mitochondrial Sirt3 substrates, MnSOD and oligomycin-sensitivity conferring protein (OSCP).

Manganese superoxide dismutase (MnSOD) is the primary antioxidant enzyme that protects cells from oxidative stress by catalyzing dismutation of superoxide to hydrogen peroxide and oxygen in the mitochondria of eukaryotic cells.

Honokiol treatment increased mitochondrial rate of oxygen consumption and reduced ROS (reactive oxygen species) synthesis in wild type, but not in cells that lacked the gene for Sirt3. Moreover, honokiol-treatment blocked cardiac fibroblast proliferation and differentiation to myofibroblasts in a Sirt3-dependent manner.

"Although we feel this is extremely promising, there is still much work to be done," said senior author Dr. Mahesh Gupta, professor of surgery at the University of Chicago. Honokiol is available as an herbal remedy but the purity of such preparations is undetermined. We treated the mice with injections into the peritoneal cavity, rather than by mouth, which is how this compound has traditionally been administered. We are testing to see if oral use will have a similar effect. We are working to design a clinical trial involving patients with cardiac hypertrophy and potentially other metabolic diseases, such as type II diabetes."