▎Sel Research
What is the research background of Sel?
Neuroadaptation and the Endogenous Opioid System:
The endogenous opioid system is involved in the neuroadaptation process caused by exogenous opioids. Sel, an anxiolytic synthesized based on the regulatory peptide tuftsin, can inhibit the activity of enkephalin-degrading enzymes, thus increasing the level of leucine enkephalin in the plasma (Nadorova A V, 2022). This indicates that Sel may exert its effects by regulating the endogenous opioid system.
Anxiety and mood disorders are among the most common mental health problems globally. Commonly used clinical anxiolytic drugs mainly focus on the pharmacological regulation of the activity of the brain's GABA receptor system. However, such drugs usually have a series of clinical problems such as dependence and memory impairment (Vyunova T V, 2018). There is an increasing recognition of the role of neuropeptides and bioactive lipids in the pathophysiology of mood and anxiety disorders. The heptapeptide Sel exhibits long-term anxiolytic and nootropic effects (Vyunova T V, 2018).
What is the mechanism of action of Sel?
What is the mechanism of action of Sel on anxiety and mood disorders?
Regulating the GABA Receptor System:
Anxiety and mood disorders are the most common mental health problems globally. Commonly used clinical anxiolytic drugs mainly exert their effects by regulating the activity of the GABA receptor system in the brain, but they often have problems such as dependence and memory impairment. Studies have found that the heptapeptide Sel (Thr-Lys-Pro-Arg-Pro-Gly-Pro) has a therapeutic effect on anxiety and mood disorders. Radioligand-receptor analysis methods have shown that Sel affects [3H] GABA binding as a positive allosteric modulator. The combined action of Sel with certain benzodiazepines also regulates the [3H] GABA binding activity in a specific way. This effect is not additive and is different from using either substance alone. Sel can block the regulatory activities of diazepam and olanzapine. Its binding site is apparently different from those of these drugs, but may partially overlap[1]. It is thus speculated that one of the molecular mechanisms of Sel's anxiolytic effect may be related to the subtype-selective concentration-dependent allosteric regulation of GABA receptors.
What is the mechanism of Sel in relieving the analgesia induced by morphine?
Inhibiting Morphine Withdrawal Reaction:
Some studies have shown that the peptide substance Sel can weaken the withdrawal reaction of rats to morphine at a certain dose. For example, in the morphine withdrawal model induced by naloxone, a single intraperitoneal injection of Sel (0.3mg/kg) can reduce the total index of the morphine withdrawal syndrome by 39.6%, significantly alleviate symptoms such as convulsive reactions, ptosis, and postural disorders, and increase the tactile sensitivity threshold of morphine-dependent rats by 9 times [2]. This indicates that Sel may indirectly affect the analgesic mechanism of morphine by regulating the nervous system's dependence on morphine.
Synergistic Analgesic Effect with Morphine:
In animal experiments, researchers found that Sel shows a synergistic analgesic effect when used in combination with morphine. Morphine can cause a certain degree of analgesia at a certain dose, and although Sel itself has no obvious analgesic effect, when used in combination with morphine at a specific dose (0.9mg/kg), it can increase the latency of mice's response to thermal stimuli, enhancing the analgesic effect to 29.9% of the maximum possible effect (MBE)[3]. This indicates that Sel may enhance the analgesic effect of morphine through a certain pathway.
Acting on the Enkephalin System:
Based on the study of the physiological effects of Sel and its fragments, it is speculated that Sel acts on the network of the cascade process of peptides and mediators through enkephalin. Enkephalin is a type of endogenous opioid peptide and plays an important role in pain regulation. Sel may affect the analgesic effect of morphine by regulating the activity of enkephalin-degrading enzymes and increasing the level of leucine enkephalin in the plasma [4].
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Effects of Sel (0.3 mg/kg) on the recognition of the novel object in rats subjected to forced alcoholization.
Source:PubMed[7]
What is the potential principle of Sel in treating the weakness disorder in post-COVID syndrome?
Based on Immunomodulatory Effects:
Considering the dominant role of immune disorders in the pathogenesis of COVID-19, drugs with immunomodulatory effects seem promising in the treatment of post-COVID syndrome. Sel is a peptide drug created based on the immunomodulator tafcin. In the treatment of post-COVID syndrome, Sel may relieve weakness symptoms by regulating the immune system and correcting immune dysfunction. For example, Sel may have a direct activity on immune interactions or act indirectly by reducing the post-stress response, thereby maintaining the normal state of immune function[5].
Anxiolytic and Improving Mood Disorders:
In post-COVID syndrome, patients often experience mood disorders such as anxiety and depression, accompanied by weakness and decreased performance. Studies have shown that Sel can relieve symptoms of anxiety and depression during the treatment process. Its mechanism of action may be related to Sel's regulation of the neurotransmitter system in the brain. For example, Sel may act as a positive allosteric modulator to affect [3H] GABA binding, thereby regulating the activity of the GABA receptor system and exerting an anxiolytic effect [1].
Neuroprotective Effect:
In the study, patients were divided into two groups. One group used a neuroprotective complex (cholitilin, mexidol, milgamma) and Sel, and the other group used only the neuroprotective complex. The results showed that patients using Sel had better effects in terms of weakness and decreased mental performance. This indicates that Sel may act synergistically with the neuroprotective complex to exert a neuroprotective effect, thus improving the weakness symptoms of patients [5].
Antiviral Effect:
Studies have found that Sel has antiviral properties in experimental influenza infections. Although there is currently no direct evidence that Sel has an antiviral effect against the COVID-19 virus, given its performance in influenza virus infections, Sel may have a certain impact on the COVID-19 virus through a certain mechanism, thus helping to treat the weakness disorder in post-COVID syndrome. For example, in in vivo studies, Sel induced the gene expression of interferon-α (IFN-α), which may help enhance the body's antiviral ability[6].
What are the effects of Sel?
Anxiolytic and Improving Mood Disorders:
In post-COVID syndrome, patients often experience mood disorders such as anxiety and depression, accompanied by weakness and decreased performance. Studies have shown that Sel can relieve symptoms of anxiety and depression during the treatment process. Its mechanism of action may be related to Sel's regulation of the neurotransmitter system in the brain. For example, Sel may act as a positive allosteric modulator to affect [3H] GABA binding, thereby regulating the activity of the GABA receptor system and exerting an anxiolytic effect [1].
Neuroprotective Effect:
In the study, patients were divided into two groups. One group used a neuroprotective complex (cholitilin, mexidol, milgamma) and Sel, and the other group used only the neuroprotective complex. The results showed that patients using Sel had better effects in terms of weakness and decreased mental performance. This indicates that Sel may act synergistically with the neuroprotective complex to exert a neuroprotective effect, thus improving the weakness symptoms of patients [5].
Relieving Analgesia Induced by Morphine:
Some studies have shown that Sel, an anxiolytic synthesized based on the regulatory peptide tuftsin, has an impact on morphine-induced analgesia in animal models. For example, when the morphine dose is 3.0mg/kg (intraperitoneal injection), it can cause antinociception, with a maximum possible effect (MBE) of 9%. While the Sel dose of 0.9mg/kg has no antinociceptive effect by itself, when pre-treated with morphine, it can increase the latent reaction time and cause an antinociceptive effect of 29.9% MBE[3].
Alleviating the Aversive Symptoms of Morphine Withdrawal:
The activity of the peptide tuftsin analog Sel was studied in a morphine withdrawal model induced by naloxone. A single intraperitoneal injection of Sel at an anxiolytic dose of 0.3mg/kg can reduce the total index of the morphine withdrawal syndrome by 39.6%, significantly (p＜0.0001) alleviate convulsive reactions, ptosis, and postural disorders, and increase the tactile sensitivity threshold of morphine-dependent rats by 9 times compared with the positive control group. At the same time, Sel is slightly inferior to diazepam at a dose of 2mg/kg in terms of pharmacological activity (reducing the total index of the morphine withdrawal syndrome by 49.3% and increasing the sensitivity threshold by 13 times). Therefore, like diazepam, Sel can alleviate the aversive symptoms of morphine withdrawal in opioid dependence in rats [2].
Preventing ethanol-induced memory impairment:
In rats that received 10% ethanol as their sole liquid source for up to 30 weeks, the effects of Sel, a peptide-based anxiolytic drug synthesized from the endogenous peptide tuftsin, on memory impairment and brain-derived neurotrophic factor (BDNF) levels were investigated. In object recognition tests, Sel exhibited cognitive-enhancing effects in 9-month-old rats not exposed to ethanol and prevented the development of ethanol-induced memory and attention impairments during alcohol withdrawal. In vitro experiments showed that Sel could inhibit ethanol-induced increases in BDNF levels in the hippocampus and prefrontal cortex. From the above, it can be concluded that this synaptogenic agent has a positive effect on age-related memory impairments associated with chronic alcohol dependence, and confirms that BDNF-related neurotrophic mechanisms are involved in the mechanism of action of Sel[7].
Treatment of Post-COVID-19 Syndrome:
Post-COVID-19 syndrome occurs following COVID-19 infection and may also be observed in cases of mild or asymptomatic disease. The most common symptoms of the bridge syndrome are fatigue and functional decline, followed by cognitive impairments. Given the central role of immune dysregulation in the pathogenesis of COVID-19, immunomodulatory drugs with direct immune-modulating effects or those that indirectly maintain immune function by reducing post-stress responses hold potential therapeutic promise.
Sel is a peptide drug developed based on the immunomodulator tafcin, which is effective in treating various neuroses and neurosis-like disorders. When used at a dosage of 2-3 drops four times a day for 30 consecutive days, Sel has a good therapeutic effect on patients with fatigue and cognitive impairment. Relief of anxiety and depression symptoms can also be observed[5].
Correcting cognitive and emotional disorders in patients with atopic dermatitis: A study analyzed cognitive and emotional disorders in 65 patients with atopic dermatitis (AD) and randomly divided the patients into two statistically comparable groups.
The first group of patients received standard drug therapy for atopic dermatitis (BT), while the second group received a combination of serank and BT via intranasal administration (S + BT), administered three times daily, with two drops instilled into each nostril per dose, for a total of 14 days. The control group consisted of 30 healthy individuals. Personal anxiety (LT), reactive anxiety (RT), yohimbine levels, blood β-endorphin levels, and quality of life (QOL) were assessed before treatment and 30 days after treatment initiation.
The study results showed that RT levels in AD patients were 4.2 times higher than those in the control group, LT levels were 3.2 times higher, and yekhtumia levels were 18 times higher. In the BT group, RT decreased by 1.4 times and LT decreased by 1.3 times 30 days after treatment initiation. In the C+BT group, the decreases in LT and RT were similarly significant, both by 2.4 times.
There were no significant changes in yekutumia symptoms or β-endorphin levels in the blood of patients in the BT group. In the S+BT group, Alexis emotional disorders decreased by 1.2 times, and β-endorphin levels in the blood increased by 1.9 times. The quality of life index of patients in the BT group decreased by 1.2 times 30 days after treatment initiation, while that of patients in the S+BT group decreased by 1.7 times. The conclusion is that elevated levels of personal anxiety, reactive anxiety, and yekhtumia in AD patients reduce their quality of life. The use of the regulatory peptide Sel in the comprehensive treatment of AD patients has a corrective effect on emotional and cognitive disorders, reducing levels of personal anxiety, reactive anxiety, and yekhtumia, increasing levels of β-endorphin in the blood, and improving patients' quality of life[8].
In conclusion, as a synthetic peptide drug developed based on the natural peptide clusterin, Sel has shown multi-dimensional application potential in clinical practice and research. Its core value lies in providing new solutions for diseases such as anxiety disorders, stress-related disorders, memory impairment, and immune disorders by regulating the neurotransmitter system, enhancing immune function, and improving cognitive function. Clinical studies have confirmed that Sel can effectively relieve symptoms of anxiety and depression, improve the weakness and cognitive disorders in post-COVID syndrome, and synergistically enhance the anti-inflammatory effect in the treatment of atopic dermatitis. Compared with traditional drugs, it has fewer side effects, a longer duration of action, and shows unique advantages in the fields of analgesia, anti-addiction, and neuroprotection.
About The Author
The above-mentioned materials are all researched, edited and compiled by Cocer Peptides.
Scientific Journal Author
Vyunova T V is a Russian neurochemist, chemist, biologist, and researcher. She has made significant contributions to the fields of biochemistry & molecular biology, chemistry, biophysics, pharmacology & pharmacy, and physiology. Vyunova has been associated with prestigious institutions such as the National Research Centre "Kurchatov Institute" and the Russian Academy of Sciences. Vyunova's research has also led to several patents, showcasing her innovative approach to scientific problems. Her dedication to advancing knowledge in her fields has made her a respected figure in the scientific community. Vyunova T V is listed in the reference of citation [1].
