Antioxidant Biomolecules and Their Potential for the Treatment of Difficult-to-Treat Depression and Conventional Treatment-Resistant Depression

María Eugenia Riveros,Alba Ávila,Koen Schruers,Fernando Ezquer

doi:10.3390/antiox11030540

María Eugenia Riveros, Alba Ávila + Show 2 more

Open Access

https://doi.org/10.3390/antiox11030540

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Abstract

Major depression is a devastating disease affecting an increasing number of people from a young age worldwide, a situation that is expected to be worsened by the COVID-19 pandemic. New approaches for the treatment of this disease are urgently needed since available treatments are not effective for all patients, take a long time to produce an effect, and are not well-tolerated in many cases; moreover, they are not safe for all patients. There is solid evidence showing that the antioxidant capacity is lower and the oxidative damage is higher in the brains of depressed patients as compared with healthy controls. Mitochondrial disfunction is associated with depression and other neuropsychiatric disorders, and this dysfunction can be an important source of oxidative damage. Additionally, neuroinflammation that is commonly present in the brain of depressive patients highly contributes to the generation of reactive oxygen species (ROS). There is evidence showing that pro-inflammatory diets can increase depression risk; on the contrary, an anti-inflammatory diet such as the Mediterranean diet can decrease it. Therefore, it is interesting to evaluate the possible role of plant-derived antioxidants in depression treatment and prevention as well as other biomolecules with high antioxidant and anti-inflammatory potential such as the molecules paracrinely secreted by mesenchymal stem cells. In this review, we evaluated the preclinical and clinical evidence showing the potential effects of different antioxidant and anti-inflammatory biomolecules as antidepressants, with a focus on difficult-to-treat depression and conventional treatment-resistant depression.

Highlights

From 1990 to 2017, cases of major depressive disorder (MDD) increased worldwide by nearly 50% [1]
The role of diet in depression risk has been deeply explored, showing that antiinflammatory and antioxidant diets may prevent and/or help in the treatment of depressive disorders, which has led to the exploration of antioxidant and anti-inflammatory molecules derived from plants for the treatment of MDD
We will review: (i) some plant molecules with antioxidant action that are proposed as potential antidepressants, and (ii) molecules produced by the anti-inflammatory and antioxidant mesenchymal stem cells that could act as new therapeutic options for the treatment of this devastating disease

Summary

Introduction

From 1990 to 2017, cases of major depressive disorder (MDD) increased worldwide by nearly 50% [1]. It is urgent to improve the present capacity for diagnosis and treatment of this disease since no reliable biomarkers are available, nor is there a guide to predict the response to treatment and the course of the disease [7]. In this sense, a critical limitation is that regardless of the increasing research efforts, the pathophysiology of depression is still not completely understood. The role of diet in depression risk has been deeply explored, showing that antiinflammatory and antioxidant diets may prevent and/or help in the treatment of depressive disorders, which has led to the exploration of antioxidant and anti-inflammatory molecules derived from plants for the treatment of MDD. We will review: (i) some plant molecules with antioxidant action that are proposed as potential antidepressants, and (ii) molecules produced by the anti-inflammatory and antioxidant mesenchymal stem cells that could act as new therapeutic options for the treatment of this devastating disease

Current Treatments for MDD and Treatment Challenges

Oxidative Damage in the Brain and Its Association with MDD

Plant-Derived Antioxidant Molecules in MDD Treatment

Findings

Conclusions