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

Abstract

Depression has been a mental health issue worldwide. We previously reported that ginger‐degraded collagen hydrolysate (GDCH) suppressed depression‐like behavior in mice. Furthermore, prolyl‐hydroxyproline (PO) and hydroxyprolyl‐glycine (OG) were detected in the circulating blood after the oral administration of GDCH. In the present study, PO, but not OG, was detected in the cerebrospinal fluid of rats after the oral administration of GDCH, suggesting that PO is transported from blood to the brain. We then investigated the effects of PO and OG on the depression‐like behavior of mice. The oral administration of PO significantly decreased depression‐like behavior in the forced swim test. OG had no antidepressant‐like effect. In addition, proline and hydroxyproline, components of PO, also had no antidepressant‐like effect after their oral administration. PO significantly increased the gene expression of brain‐derived neurotrophic factor and nerve growth factor in the hippocampus, and promoted the proliferation of neural progenitor cells in vivo and in vitro. PO also increased the dopamine concentration in the prefrontal cortex. Thus, PO‐dependent regulation of neurotrophic function and neurotransmitter may be the mechanism for antidepressant‐like behavior. Together, these results demonstrate that PO is an antidepressant bioactive peptide accompanying the proliferation of hippocampal neural progenitor cells.

Long-term intake of ginger protease-degraded collagen hydrolysate reduces blood lipid levels and adipocyte size in mice

“…A. Minaguchi et al., 2017 ; Nakatani et al., 2009 ; Nishikimi et al., 2018 ; Nogimura et al., 2020 ; Nomura et al., 2019 ; Ohara et al., 2010 ; Shigemura et al., 2009 ; Taga et al., 2018a , Taga et al., 2018b ), it is possible that these Hyp-containing oligopeptides are responsible for the effects of GDCH on lipid metabolism. Direct evaluation of collagen-derived oligopeptides for TG storage using adipocytes and for CHO synthesis/catabolism using hepatocytes is currently being planned in order to investigate the key ingredient(s) of the lipid-lowering effects by GDCH.…”

“…A. Minaguchi et al., 2017 ; Nakatani et al., 2009 ; Nomura et al., 2019 ; Ohara et al., 2010 ; Taga et al., 2018a , Taga et al., 2018b ), improvement of skin conditions ( Shimizu et al., 2015 ) and antidepressant effects ( Nogimura et al., 2020 ).…”

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

“…Most of the osteoarthritis (OA) studies are conducted on rats/mice. Nogimura et al finds the antidepressant effects of collagen dipeptide (prolyl-hydroxyproline) in male ddY mice [ 41 ]. Sonklin et al also performs an antihypertensive analysis on spontaneously hypertensive rats [ 36 ].…”

“…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 ].…”