Delta-Sleep-Inducing Peptide (DSIP): Research & Benefits

Delta sleep-inducing peptide (DSIP, TrpAlaGlyGlyAspAlaSerGlyGlu) has been known since the late 1970s. It was discovered that it is a part that assists rabbits in achieving slow-wave rem sleep, and it was also shown to have an effect on sleep in other animal species and humans.

While further research was not able to conclusively prove that this regulatory neuropeptide promotes sleep, it did reveal a variety of other sleep-related benefits. This spectrum included a number of physiological and pathological processes, such as modulation of pain, circadian cycles, stress response, and alcohol and drug abuse. 

Mechanism of Action of Delta-Sleep-Inducing Peptide (DSIP) 

The several ways in which DSIP protects against stress may be connected to its capacity to control the energy mechanism of the mitochondria. Mitochondria are the most essential cellular location for the generation of reactive oxygen species (ROS), regardless of whether the condition is normal or disordered. Mitochondria are the target of abnormalities that are generated by stress and that lead to cell death through the activation of apoptosis and necrosis pathways.

The mechanisms that occur in mitochondria may be related to the ability of DSIP to counteract disturbances produced by stress. Our data provide additional evidence for this idea since they demonstrate that DSIP has an impact on the activity of a number of mitochondrial enzymes in rat brain preparations (MAO-A, hexokinase, creatine kinase, malate dehydrogenase) and decreases lipid peroxidation, particularly under stressful settings. [4]

Research Evidence of Delta-Sleep-Inducing Peptide (DSIP) 

Experiments on animals have proven that delta-sleep-inducing-peptide (DSIP) is a neuropeptide that induces sleep in a way that is distinct to each species. Five different human experiments were carried out in which single and repeated doses of DSIP were given through an intravenous injection. The trials were done under double-blind settings. P

sychophysiological testing and polygraphic recordings were used to evaluate how the levels of DSIP affected the patient. DSIP was found to be compatible. It was discovered that slow injection was quite important. It was shown that the latency of sleep induction was one hour, but the duration might persist for as long as 20 hours.

The somnogenic characteristics, which were initially revealed in a study on animals, were confirmed. It was shown that there were specific effects on chronobiological controls. Those who had insomnia received four consecutive injections, and this led to a complete restoration of their disordered sleep patterns.

DSIP led to greater alertness and better performance when in the active, awake state. Psychotherapists conducted psychological tests and evaluations that demonstrated that DSIP altered ego processes in a way that improved stress tolerance and coping capacities.

From a neurophysiological standpoint, the various activities of DSIP can be seen as a sort of "programming" behavior that is achieved by modulating "local vigilances." Although the somatogenic effects of DSIP appear to be a possible treatment for insomnia, further research is necessary to explore additional therapeutic options in the field of psychiatry [2].

Research Applications of Delta-Sleep-Inducing Peptide (DSIP) 

It has been observed that the ICV infusion of extracorporeal dialysates from the blood of donor rabbits that were in a state of electrically induced sleep causes recipient rabbits to enter delta (slow-wave) sleep. This effect seems to be caused by a nano-peptide called delta sleep-inducing peptide (DSIP), which was isolated from these dialysates.

Additional trials have demonstrated that this effect can be reproduced in rats and cats, even when the drug is given through the veins or under the skin rather than through the brain. In humans, intravenous infusions of DSIP in the morning or at night increased total sleep time. In both rats and humans, plasma DSIP showed a circadian rhythm, with levels peaking in the late afternoon and dropping to their lowest point in the early morning.

However, there was no relationship between the levels of plasma DSIP and the stage of sleep. This circadian rhythm is eliminated by constant exposure to light.[5]

DSIP has been found to have positive effects in humans with insomnia, narcolepsy, opiate addiction, alcoholism, and chronic, severe pain episodes. Recent studies on chronic psychophysiological insomniacs have reported that after six days of DSIP treatment, insomnia was completely eliminated, and there were improvements in sleep, mood during the day, circadian regularity of sleep, and cognitive and psychomotor performance. Monti and colleagues have been unable to reproduce these results, hence the clinical value of DSIP has yet to be established.

DSIP has been shown to impact sleep and also influence a range of physiological processes in both people and animals. Graf and colleagues have suggested that, in addition to helping with sleep, DSIP may also have a chronopharmacologic effect as a natural programming drug. They claim that the programming effects may be caused by changes in cerebral neurotransmitters and plasma proteins that are generated by DSIP.

Uridine and SPS-B are chemicals that promote sleep. A number of active components can be found in sleep-promoting substances (SPS), which are recovered from the aqueous dialysates of brain stems of rats that have been deprived of sleep for 24 hours. [3]

Future Perspective for DSIP

Delta-sleep-inducing peptide (DSIP) has the potential to be used as a treatment for sleep disorders such as insomnia, especially if further research can clarify how it works and develop ways to safely deliver it across the blood-brain barrier. There are also potential applications in areas such as stress management and neurodegenerative disease research due to its potential role in neuroprotection and neuroendocrine regulation. However, there are still significant challenges in fully understanding how it is naturally synthesized and released, as well as identifying its specific receptor, which could limit its immediate clinical translation. 

Therapeutic potential for sleep disorders: DSIP has the potential to be a good treatment for insomnia because its main role is to induce deep sleep. This is especially true if the route of delivery is improved so that it can pass the blood-brain barrier more effectively.

Looking into other possible positions: In addition to sleep regulation, research may investigate the possible role of DSIP in other physiological processes, including as stress response, pain perception, and cognitive function. This could lead to new therapeutic applications for linked conditions.

Studies on the mechanism of action: More research is necessary to completely understand how DSIP interacts with its receptor(s) and the downstream signaling pathways involved in its effects of delta sleep-inducing peptide. This knowledge could help design medicines that are more targeted for slow-wave sleep.

Creating ways to deliver: It is essential to overcome the problem of getting delta-sleep-inducing peptide over the blood-brain barrier in order for it to be used in clinical settings. This may require the development of new drug delivery methods, such as nanoparticles or intranasal administration.

Genetic and molecular investigations: By identifying the gene responsible for the production of DSIP and understanding how it is regulated by the central nervous system, we may be able to gain insight into the complicated systems that control sleep-wake cycles and the potential genetic variables that contribute to sleep disorders. 

Possible restrictions: There is not enough clinical data available. At this time, there have not been enough substantial clinical trials on DSIP, which means that further study is required to determine how effective and safe it is for humans. Unclear receptor identification: The specific receptor that DSIP uses to produce its actions is not completely understood, which could slow down the process of developing new drugs. Possible negative effects: DSIP is currently thought to have few side effects, however, more clinical trials are needed to fully evaluate its safety. In general, DSIP has a lot of potential as a new treatment for sleep disorders, but more research is needed to better understand how it works, come up with effective ways to give it, and determine how effective and safe it is in clinical settings. 

References

1. https://pubchem.ncbi.nlm.nih.gov/compound/68816#section=2D-Structure

2. Biochemical Pharmacology of Sleep by Rafael de Jesus Cabeza, ... J. Christian Gillin, in Sleep Disorders Medicine.

3. Kovalzon V., Fessenko G., Ashmarin I. and Koroleva S. (2003) Peptide interaction and rodent sleep. Behav. Pharmacol. 14, S82.

4. Lysenko A. V. and Mendzheritsky A. M. (1995) Characteristics and mechanisms of realizing biological effects of the peptide-inducing delta-sleep. Uspekhi Sovremennoy Biologii 115, 729–739. (In Russian).

5. Monnier M. and Schoenenberger G. A. (1983) The peptidergic modulation of sleep with the delta sleep-inducing peptide as a prototype, in Functions of the Nervous System. (Monnier M., ed.), Vol. 4, pp. 161–219. Elsevier, Amsterdam