Marine algae as emerging therapeutic alternatives for depression: A review

Abstract

Depression is a complex heterogeneous brain disorder characterized by a range of symptoms, resulting in psychomotor and cognitive disabilities and suicidal thoughts. Its prevalence has reached an alarming level affecting millions of people globally. Despite advances in current pharmacological treatments, the heterogenicity of clinical response and incidences of adverse effects have shifted research focus to identification of new natural substances with minimal or no adverse effects as therapeutic alternatives. Marine algae-derived extracts and their constituents are considered potential sources of secondary metabolites with diverse beneficial effects. Marine algae with enormous health benefits are emerging as a natural source for discovering new alternative antidepressants. Its medicinal properties exhibited shielding efficacy against neuroinflammation, oxidative stress, and mitochondrial dysfunction, which are indicated to underlie the pathogenesis of many neurological disorders. Marine algae have been found to ameliorate depressive-like symptoms and behaviors in preclinical and clinical studies by restoring monoaminergic neurotransmission, hypothalamic-pituitary-adrenal axis function, neuroplasticity, and continuous neurogenesis in the dentate gyrus of the hippocampus via modulating brain-derived neurotrophic factors and antineuroinflammatory activity. Although antidepressant effects of marine algae have not been validated in comparison with currently available synthetic antidepressants, they have been reported to have effects on the pathophysiology of depression, thus suggesting their potential as novel antidepressants. In this review, we analyzed the currently available research on the potential benefits of marine algae on depression, including their effects on the pathophysiology of depression, potential clinical relevance of their antidepressant effects in preclinical and clinical studies, and the underlying mechanisms of these effects.

Keywords: Antidepressants; Complementary medicine; Depression; Microalgae; Neuroinflammation; Neuronal plasticity; Seaweed.

Figure 1

The hypothesis of modulation of monoaminergic transmitters in the pathophysiology of depression. (a) Normal neurotransmission in the monoamine system and (b) Potential disruptions of precursors, enzymes, storage and release of monoamines, monoamine receptors, and exocytosis, leading to a deficiency in neurotransmission. Solid arrows show the course of monoamine synthesis, transportation of monoamine neurotransmitters in the synaptic vesicles, and the release of neurotransmitters into the synaptic cleft. Dashed arrows show the reuptake of monoamine neurotransmitters from the synaptic cleft into the presynaptic neuron for recycling or to be broken down by monoamine oxidase

Figure 2

The hypothesis of dysregulation of HPA axis in the pathogenesis of depression. Chronic stress is perceived by the cerebral cortex and amygdala, and transmitted to the hypothalamus (indicated by dashed arrows). Activated PVN releases CRH and AVP into the hypothalamo-hypophyseal portal system. Corticotrophin-releasing hormone and AVP stimulate the corticotropes of the anterior pituitary gland to secrete ACTH into the bloodstream, acting on the zona fasciculata of the adrenal cortex to secrete glucocorticoids. Arrows with plus sign indicate a positive feedback mechanism towards the synthesis and secretion of glucocorticoids into the bloodstream in response to chronic stress. Dotted lines indicate the reduced expression of GR in the prefrontal cortex, hippocampus, PVN, and anterior pituitary gland due to GR-mediated negative feedback loss. The schematic diagram was adapted and modified from Lew et al. (11)

Figure 3

The hypothesis of neuroplasticity involving BDNF in the pathogenesis of depression. Chronic stress leads to a decrease in hippocampal BDNF expression, causing a reduction in the binding of BDNF to TrkB receptors needed for activation of the BDNF-TrkB signaling pathway (indicated by solid arrows). This results in compromised neuroplasticity, and reduced neuronal survival rate, dendritic growth, spine density, synaptogenesis, and maturation of neurons

Figure 4

The hypothesis of neuroinflammation in the pathogenesis of depression. (a) Chronic stress or inflammation leads to the expression of proinflammatory markers in the periphery. Dashed arrows indicate transportation of the markers through the BBB into CNS to activate microglia. (b) Activated microglia produce proinflammatory cytokines and mediators via activation of NF-κB. The neuroinflammatory response enhances HPA axis hyperactivity, IDO activity, and release of CRH, ACTH, and eventually glucocorticoids. Simultaneously, up-regulated proinflammatory cytokines and mediators also enhance IDO activity, inhibit the synthesis of serotonin from tryptophan (indicated by a dotted arrow) and increase the production of KYN and QUIN

Figure 5

Antidepressant-like effects of marine algae against chronic stress and LPS-induced neuroinflammation in preclinical studies