- A novel treatment has been developed for the treatment of depression
- Certain compounds present in grapes act as therapeutic agents for the treatment of depression
- Including grapes in the diet can help treat depression
New grape-derived compounds such as a dihydrocaffeic acid (DHCA) and malvidin-3'-O-glucoside (Mal-gluc) were identified that act as therapeutic agents in treating depression.
Scientists from the Icahn School of Medicine at Mount Sinai have published the study online in Nature Communications.
‘Natural compounds like dihydrocaffeic acid (DHCA) and malvidin-3'-O-glucoside (Mal-gluc) present in grapes can help reduce depression.’
The results of this study show that these natural compounds can reduce the effect of depression by targeting the underlying mechanisms of the disease.
Every year, nearly 16 million individuals in the US have a major depressive episode, reveals the U.S. Centers for Disease Control and Prevention.
Current Treatments for Depression
Conventional pharmacological treatments provide only temporary remission in less than 50 percent of patients and often lead to severe adverse effects. Therefore, there is an urgent need for novel therapeutics.
Depression is linked to a multitude of pathological processes like:
- Inflammation of the peripheral immune system,
- A set of biological structures and procedures in the lymph nodes and other tissues and
- The structures that permit neuron to pass an electrical or chemical signal to another neuron.
that are currently available are restricted to targeting the systems that aid in regulating dopamine, serotonin, and other related neurotransmitters. However, these treatments do not address inflammation and synaptic maladaptations that are now known to be associated with Major depressive disorder (MDD).
Previous studies show that grape-derived polyphenols have some ability to modulate certain aspects of depression. However, the mechanism of action is unknown.
Novel Discovery of Compounds in Grapes
The new study was led by Giulio Maria Pasinetti, Ph.D., Saunders Professor of Neurology, and a team of researchers from the Center for Integrative Molecular Neuroresilience at the Icahn School of Medicine, Mount Sinai.
The research team found that a bioactive dietary polyphenol preparation, which is in a combination of three grape-derived polyphenol products such as a select Concord grape juice, a select grape seed extract, and trans-resveratrol was extremely useful in promoting resilience against stress-induced depression in the mice.
The research team specifically found that DHCA and Mal-gluc could promote resilience in mouse models of depression by modulating inflammation and synaptic plasticity.
DHCA reduces interleukin 6 (IL-6),
a pro-inflammatory substance that is secreted by T cells and macrophages to stimulate an immune response, which is carried out by epigenetically modulating the non-coding sequence of the IL-6 gene.
Mal-gluc helps modulate histone acetylation of the Rac1 gene and later allows transcription activators to access the DNA for increased transcription in the brain, and controls the expression of genes responsible for synaptic plasticity.
The research team also demonstrated that DHCA or Mal-gluc treatment was found to be effective in reducing depression-like phenotypes in a mouse model who had an increased systemic inflammation, which was induced by transplantation of cells from the bone marrow of stress-susceptible mice.
Targeting Multiple Disease Mechanisms
"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 Jun Wang, Ph.D., Associate Professor of the Department of Neurology and first author on the paper.
For the first time, the Mount Sinai study provides novel preclinical evidence that supports the targeting of multiple disease mechanisms through DNA epigenetic modification for the treatment of depression.
This study strongly supports the need to test and identify novel compounds that target alternative pathologic mechanisms, such as inflammation and synaptic maladaptation, for individuals who are resistant to currently available treatment.
"Our approach to use a combination treatment of DHCA and Mal-gluc to simultaneously inhibit peripheral inflammation and modulate synaptic plasticity in the brain works synergistically to optimize resilience against chronic stress-induced depression-like phenotypes. The discovery of these new, natural grape-derived polyphenol compounds targeting cellular and molecular pathways associated with inflammation may provide an effective way to treat a subset of people with depression and anxiety, a condition that affects so many people," said Dr. Pasinetti.
Scientists from Rutgers, the State University of New Jersey and the University of North Texas contributed to this research.