ABSTRACT
Previous studies have shown that peptides isolated from C-phycocyanin (C-PC) possess various functions including antioxidant and anticancer activities. However, there is little research on C-PC peptides applied for the neuroprotective effect against a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) model. In this study, twelve novel peptides from C-PC were isolated, purified and identified, and the anti-PD effect of the synthesized peptides was evaluated in a zebrafish PD model. As a result, three of these peptides (MAAAHR, MPQPPAK, and MTAAAR) significantly reversed the loss of dopamine neurons and cerebral vessels, and reduced the locomotor impairment in PD zebrafish. In addition, three novel peptides could inhibit the MPTP-induced decrease of antioxidant enzymes (SOD, CAT, and GSH-Px) and increase the ROS and protein carbonylation content. In addition, they can also alleviate apoptosis of brain regions and acetylcholinesterase (AChE) activity in zebrafish. Further studies elucidated the potential molecular mechanism of peptides' anti-PD effects in the larvae. The results showed that C-PC peptides could modulate multiple genes associated with oxidative stress, autophagy and apoptosis signaling pathways, and thereby alleviate the occurrence of PD symptoms. Overall, our results highlight the neuroprotective effects of three novel peptides and provide valuable mechanistic insights and a promising drug target for the treatment of PD.
Subject(s)
Neuroprotective Agents , Parkinson Disease , Animals , Mice , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Zebrafish/metabolism , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/adverse effects , Phycocyanin/pharmacology , Phycocyanin/therapeutic use , Antioxidants/metabolism , Acetylcholinesterase , Peptides/pharmacology , Peptides/therapeutic use , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Disease Models, Animal , Mice, Inbred C57BLABSTRACT
C-phycocyanin from Spirulina platensis has pharmacological effects such as anti-oxidation, anti-cancer, anti-inflammatory and anti-atherosclerosis activities as well as liver and kidney protection. However, there is little research on C-phycocyanin applied in the field of reproductive medicine, and it is therefore the focus of the current study. In this study, a GC-1 spg cell model and male mouse reproductive injury model were constructed by TNF α + Smac mimetic + zVAD-fmk (TSZ) and cyclophosphamide (Cy), respectively. It has been proved that C-phycocyanin can increase cell viability and reduce cell death in GC-1 spg cells induced by TSZ. C-phycocyanin could protect the reproductive system of male mice from cyclophosphamide, improve spermatogenesis, sperm quality and fertility, increase the release of testosterone, stabilize the feedback regulation mechanism, and ensure the spermatogenic ability of mice. It could also improve the ability of anti-oxidation. In addition, C-phycocyanin could play a protective role by down-regulating RIPK1, RIPK3, and p-MLKL to inhibit the necroptotic signaling pathway. These results suggest that C-phycocyanin could protect GC-1 spg cells and the reproductive system of male mice from TSZ and cyclophosphamide, and the protective mechanism may be achieved by inhibiting the signal pathway of necroptosis. Therefore, C-phycocyanin could serve as a promising reproductive system protective agent. C-phycocyanin may enter public life as a health product in the future.