Ginger-Degraded Collagen Hydrolysate Exhibits Antidepressant Activity in Mice

Abstract

Collagen is the most abundant protein in animals. Collagen hydrolysate has been found to have multiple functions in the skin, bones, joints, muscles, and blood vessels. Recently, it has been reported that the low molecular weight fraction of collagen hydrolysate exhibited anxiolytic activity, suggesting that collagen peptides affect brain functions. In the present study, we found that oral administration of ginger-degraded collagen hydrolysate (GDCH) significantly decreased depression-like behavior in a forced swim test, suggesting that GDCH exhibited antidepressant activity in mice. The antidepressant activity of GDCH was abolished by pre-treatment with an antagonist of the dopamine receptor, but not treatment with a serotonin receptor antagonist. GDCH significantly increased gene expression of glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) in the hippocampus, molecules that affect the differentiation and survival of neurons, relative to that in the control condition. Meanwhile, there were no changes in the gene expression of brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3, major factors related to depression-like behavior. We also found that GDCH exhibited antidepressant activity in corticosterone-administered mice in a model of stress. In addition, GDCH increased GDNF and CNTF expression in the stressed condition, suggesting that mechanisms of the antidepressant activity of GDCH were the same in unstressed and stressed conditions. These results imply that GDCH exhibits antidepressant activity in unstressed and stressed conditions in mice. The upregulation of neurotrophic genes in the hippocampus may contribute to the reduction of depression-like behavior via a dopamine signal pathway modulated by GDCH.

Prolyl‐hydroxyproline, a collagen‐derived dipeptide, enhances hippocampal cell proliferation, which leads to antidepressant‐like effects in mice

“…We previously reported that the antidepressant-like activity of GDCH disappeared following the inhibition of dopamine D 1 receptors, but not serotonin 5-HT 1A receptors. 10 Thus, the antidepressant-like activity of collagen hydrolysate and PO may be dependent on neural proliferation in the hippocampus and the facilitation of dopamine release in the prefrontal cortex.…”

“…We previously reported that ginger-degraded collagen hydrolysate (GDCH) suppressed depression-like behavior in mice. 10 Ginger protease exhibits potent activity and cleaves peptide bonds with Pro and Hyp in the second position (P 2 ). Therefore, GDCH includes abundant amounts of X-Hyp-Gly-and Gly-Pro-Y-type tripeptides.…”

“…The efficacy of antidepressant drugs is limited by a number of factors including the necessity for long‐term administration, tolerance, and side effects. We previously reported that ginger‐degraded collagen hydrolysate (GDCH) suppressed depression‐like behavior in mice . Ginger protease exhibits potent activity and cleaves peptide bonds with Pro and Hyp in the second position (P 2 ).…”

Developments for Collagen Hydrolysate in Biological, Biochemical, and Biomedical Domains: A Comprehensive Review

“…Depression and hypertension are important medical impairments that are extensively investigated with collagen hydrolysate [ 41 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 ]. Recently, a couple of efforts by the same group were presented on diminution of hypertension using novel collagen hydrolysate [ 41 , 149 ]. The group proposes that the presence of prolyl-hydroxyproline (PO) [ 41 , 149 ] and hydroxyprolyl-glycine (OG) [ 41 ] decreases the expressions of depression in a forced swim test [ 41 ].…”

“…Recently, a couple of efforts by the same group were presented on diminution of hypertension using novel collagen hydrolysate [ 41 , 149 ]. The group proposes that the presence of prolyl-hydroxyproline (PO) [ 41 , 149 ] and hydroxyprolyl-glycine (OG) [ 41 ] decreases the expressions of depression in a forced swim test [ 41 ]. Another recent research proposes a novel hydrolysate source (mung bean) for mitigation of hypertension [ 36 ].…”