In a study to be published in Nature Communications, scientists describe an extensive analysis of novel grape-derived compounds, dihydrocaffeic acid (DHCA) and malvidin-3'-O-glucoside (Mal-gluc),which might be developed as therapeutic agents for the treatment of depression. The study results indicate that these natural compounds may attenuate depression by targeting newly discovered underlying mechanisms of the disease.
According to the U.S. Centers for Disease Control and Prevention, each year approximately 16 million individuals in the United States have a major depressive episode. Conventional pharmacological treatments are estimated to produce temporary remission in less than 50 percent of patients, and they are often associated with severe adverse effects. Thus, there is an urgent need for a wider spectrum of novel therapeutics.
Depression is associated with a multitude of pathological processes, including inflammation of the peripheral immune system, a set of biological structures and processes in the lymph nodes and other tissues that protect against disease and abnormalities involving synapses, the structures that permit neurons to pass an electrical or chemical signal to other neurons. However, currently available antidepressants are largely restricted to targeting the systems that regulate serotonin, dopamine, and other related neurotransmitters, and these treatments do not specifically address inflammation and synaptic maladaptations that are now known to be associated with MDD.
Previous research has found that grape-derived polyphenols have some efficacy in modulating aspects of depression, yet the mechanisms of action had largely remained unknown until now. The new study found that a bioactive dietary polyphenol preparation--a combination of three grape-derived polyphenol products, including a select Concord grape juice, a select grape seed extract, and trans-resveratrol--was effective in promoting resilience against stress-induced depression in mice.
Specifically, researchers found that DHCA and Mal-gluc can promote resilience in mouse models of depression by modulating inflammation and synaptic plasticity, respectively. DHCA reduces interleukin 6 (IL-6), a pro-inflammatory substance secreted by T cells and macrophages to stimulate immune response, by epigenetically modulating the non-coding sequence of the IL-6 gene. Mal-gluc modulates histone acetylation of the Rac1 gene and allows transcription activators to access the DNA for increased transcription in the brain, which influences the expression of genes responsible for synaptic plasticity.
Researchers also demonstrated that DHCA/Mal-gluc treatment was effective in attenuating depression-like phenotypes in a mouse model of increased systemic inflammation induced by transplantation of cells from the bone marrow of stress-susceptible mice.
"Our research shows that combination treatment with the two compounds can promote resilience against stress-mediated depression-like phenotypes by modulating systemic inflammatory responses and brain synaptic plasticity in a mouse model of depression," says first author on the paper.
Grape-Derived Compounds Capable of Promoting Resilience Against Stress-Induced Depression
- 931 views