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Gut-brain axis is a dynamic, complex, and bidirectional communication network between the gut and brain. Changes in the microbiota-gut-brain axis are responsible for developing various metabolic, neurodegenerative, and neuropsychiatric disorders. According to clinical and preclinical findings, the gut microbiota is a significant regulator of the gut-brain axis. In addition to interacting with intestinal cells and the enteric nervous system, it has been discovered that microbes in the gut can modify the central nervous system through metabolic and neuroendocrine pathways. The metabolites of the gut microbiome can modulate a number of diseases by inducing epigenetic alteration through DNA methylation, histone modification, and non-coding RNA-associated gene silencing. Short-chain fatty acids, especially butyrate, are well-known histone deacetylases inhibitors. Similarly, other microbial metabolites such as folate, choline, and trimethylamine-N-oxide also regulate epigenetics mechanisms. Furthermore, various studies have revealed the potential role of microbiome dysbiosis and epigenetics in the pathophysiology of depression. Hence, in this review, we have highlighted the role of gut dysbiosis in epigenetic regulation, causal interaction between host epigenetic modification and the gut microbiome in depression and suggest microbiome and epigenome as a possible target for diagnosis, prevention, and treatment of depression.

Background:Curcumin and ellagic are the natural polyphenols having a wide range of pharmacological actions. They have been reported to have their use in various neurological disorders.Objective:This study was aimed to evaluate the effect of curcumin and ellagic acid on the activity of monoamine oxidase (MAO), the enzyme responsible for metabolism of monoamine neurotransmitters which are pivotal for neuronal development and function.Materials and Methods:The in vitro effects of these selected polyphenols on MAO activities in mitochondria isolated from rat brains were examined. Brain mitochondria were assayed for MAO type-B (MAO-B) using benzylamine as substrates. Rat brain mitochondrial MAO preparation was used to study the kinetics of enzyme inhibition using double reciprocal Lineweaver–Burk plot.Results:MAO activity was inhibited by curcumin and ellagic acid; however, higher half maximal inhibitory concentrations of curcumin (500.46 nM) and ellagic acid (412.24 nM) were required compared to the known MAO-B inhibitor selegiline. It is observed that the curcumin and ellagic acid inhibit the MAO activity with both the competitive and noncompetitive type of inhibitions.Conclusions:Curcumin and ellagic acid can be considered a possible source of MAO inhibitor used in the treatment of Parkinson's and other neurological disorders.SUMMARY Monoamine oxidase (MAO) is involved in a variety of neurological disorders including Parkinson's disease (PD)Curcumin and ellagic acid inhibit the monoamine oxidase activityEllagic acid revealed more potent MAO type-B (MAO-B) inhibitory activity than curcuminKinetic studies of MAO inhibition using different concentrations of curcumin and ellagic acid were plotted as double reciprocal Lineweaver–Burk plotThe mode of inhibition of both compounds toward MAO-B is mixed (competitive and uncompetitive) type of inhibition with both the competitive and noncompetitive type of inhibitions. Abbreviations used: MAO: Monoamine oxidase, IC50: Higher half maximal inhibitory concentrations, PD: Parkinson's disease, LB: Lewy bodies, SNpc: Substantia nigra pars compacta, ROS: Reactive oxygen species, SG: Selegiline, DMC: demethoxycurcumin, BDMC: Bisdemethoxycurcumin.

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