And peptides could explain why
From: American Chemical Society
October
13, 2021 -- According to time-honored advice, drinking a glass of warm milk at
bedtime will encourage a good night’s rest. Milk’s sleep-enhancing properties
are commonly ascribed to tryptophan, but scientists have also discovered a
mixture of milk peptides, called casein tryptic hydrolysate (CTH), that
relieves stress and enhances sleep. Now, researchers reporting in ACS’ Journal
of Agricultural and Food Chemistry have identified specific peptides
in CTH that might someday be used in new, natural sleep remedies.
According to the U.S. Centers for
Disease Control and Prevention, one-third of U.S. adults don’t get enough
sleep. Sedatives, such as benzodiazepines and zolpidem, are commonly prescribed
for insomnia, but they can cause side effects, and people can become addicted
to them. Many sedatives work by activating the GABA receptor, a protein in the
brain that suppresses nerve signaling. Scientists have also discovered several
natural peptides, or small pieces of proteins, that bind the GABA receptor and
have anti-anxiety and sleep-enhancing effects. For example, treating a protein
in cow’s milk, called casein, with the digestive enzyme trypsin produces the
mixture of sleep-enhancing peptides known as CTH. Within this mixture, a
specific peptide known as α-casozepine (α-CZP) has been identified that could
be responsible for some of these effects. Lin Zheng, Mouming Zhao and
colleagues wondered if they could find other, perhaps more powerful,
sleep-enhancing peptides in CTH.
The researchers first compared the
effects of CTH and α-CZP in mouse sleep tests, finding that CTH showed better
sleep-enhancing properties than α-CZP alone. This result suggested that other
sleep-promoting peptides besides α-CZP exist in CTH. The team then used mass
spectrometry to identify bioactive peptides released from CTH during simulated
gastric digestion, and they virtually screened these peptides for binding to
the GABA receptor and for the ability to cross the blood-brain barrier. When
the strongest candidates were tested in mice, the best one (called YPVEPF)
increased the number of mice that fell asleep quickly by about 25% and the
sleep duration by more than 400% compared to a control group. In addition to
this promising peptide, others in CTH should be explored that might enhance
sleep through other pathways, the researchers say.
The authors acknowledge funding from
the National
Natural Science Foundation of China, the Guangdong Provincial Key R&D
Program, the Shandong Provincial Key R&D Program, and the Specific Fund
Program for Basic and Applied Basic Research of Guangdong Province.
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