Vilon

Vilon Research

What is the research background of Vilon?

1. The Urgent Need for Research on Aging and Diseases

With the acceleration of the global population aging process, a series of issues related to aging, such as cellular senescence, decline in tissue function, and the high incidence of geriatric diseases, have become urgent medical problems to be solved. Cellular senescence is accompanied by the gradual loss of the ability to maintain homeostasis and repair damaged tissues, making it particularly crucial to find substances that can delay the process of cellular senescence and enhance tissue repair function.

At the same time, major diseases such as cancer, diabetes, cardiovascular diseases, and liver diseases seriously threaten human health. Traditional treatment methods have certain limitations in dealing with these diseases, and there is an urgent need to develop new treatment methods and drugs. For example, elderly cancer patients have poor tolerance to radiotherapy and chemotherapy, and the treatment effect is not satisfactory. It is urgent to find safe and effective adjuvant treatment methods. In such a difficult situation, scientists have turned their attention to bioactive peptides, hoping to find a breakthrough point, and the research on Vilon came into being.

2. The Vigorous Development of Research on Bioactive Peptides

Peptide substances widely exist in living organisms and participate in many key physiological processes, such as cell signaling, immune regulation, and metabolic regulation. In recent years, with the rapid development of technologies such as molecular biology and biochemistry, significant progress has been made in the research on bioactive peptides. 

Scientists can more precisely synthesize, isolate, and identify various peptides, and deeply explore their mechanisms of action. A large number of studies have shown that peptides with different structures have diverse biological activities, bringing new hope for solving health and disease problems. In this process, researchers have studied a large number of peptides through methods such as high-throughput screening and functional verification. Vilon, as a dipeptide with a unique structure and potential functions, has gradually come into people's view.

3. In-depth Exploration of the Mechanisms of Tissue Repair and Regeneration

Tissue repair and regeneration are important processes for maintaining the normal physiological functions of organisms and responding to injuries. However, there are still many gaps in the current understanding of this process, and how to promote more efficient tissue repair and regeneration has become the focus of research. Stem cells play a core role in tissue repair and regeneration, and the research on their activation, proliferation, and differentiation mechanisms has received much attention.

In addition, factors such as the synthesis and degradation of the extracellular matrix and intercellular signaling also have an important impact on tissue repair. In the process of exploring the mechanisms of tissue repair and regeneration, researchers have found that some peptides can regulate these key processes. Based on this, the research on peptides with the potential to regulate tissue repair and regeneration has been continuously deepened. Vilon has become a key research object in this field due to its potential effects in supporting stem cell activation and proliferation and regulating fibroblast activity.

What is the mechanism of action of Vilon?

1. Effects on Chromosomes and Gene Expression

Promoting the Unwinding of Heterochromatin: Studies have shown that Vilon can induce the unwinding (deheterochromatization) of the total heterochromatin in the cultured lymphocytes of the elderly^[1]. This means that it can activate the synthesis process of ribosomal genes caused by the deheterochromatization of the nucleolar organizing region and release the genes that are inhibited due to the condensation of the euchromatin region to form facultative heterochromatin. At the same time, Vilon does not cause the unwinding of the constitutive heterochromatin around the centromere. The results show that Vilon will gradually activate facultative heterochromatin (deheterochromatization) with age ^[1].

2. Roles in Disease Treatment

Comprehensive Treatment for Cancer Patients: In the treatment of elderly cancer patients, Vilon is included in the treatment plan as an immunomodulator. Preliminary research results show that the application of Vilon can improve the 2-year survival rate of patients, prevent postoperative complications, distant complications, recurrence, and tumor spread, and improve the quality of life after active treatment^[2].

Antitumor Effect: In vitro experiments, Vilon has a dose-dependent inhibitory effect on the growth of three types of tumor cells, namely human colorectal cancer LOVO, human gastric cancer MKN45, and human liver cancer QGY7703, but has no obvious inhibitory effect on human normal white blood cells ^[3]. In vivo tumor inhibition experiments show that Vilon has an inhibitory effect on the growth of mouse liver cancer H22, and the effective dose is 15mg・Kg-1. When the high dose of 30mg・Kg-1 is used, the tumor inhibition rate of the transplanted tumor liver cancer H22 in mice reaches more than 60%^[3].

Effects on Diabetic Patients: In elderly type I diabetic patients, Vilon, as part of the comprehensive treatment, can optimize the coagulation and hemostasis function, manifested as an increase in the content of natural anticoagulants (antithrombin III and protein C) and the stimulation of fibrinolysis ^[4]. At the same time, in most cases, Vilon can also reduce the insulin dose required to stabilize carbohydrate metabolism. In addition, it can also reduce the content of T helper cells, T-dependent and non-T-dependent NK cells, normalize the levels of active T lymphocytes, B lymphocytes, and IgA, and has a stabilizing effect on the immune system and hemostasis function ^[4].

3. Effects on Cell and Organ Functions

Stimulating Hepatocyte Regeneration: In a rat model of liver cirrhosis induced by carbon tetrachloride poisoning, Vilon has a certain effect on the recovery of the functional activity of hepatocytes and the regeneration of the liver in rats with liver cirrhosis. Two weeks after the application of the drug, the activity of glucose-6-phosphatase (G6P) in the liver of rats with liver cirrhosis decreases, and Vilon can increase it. In the untreated rats, the content of total glycogen and its components and the activity of G6P are still at the pre-cirrhosis level. Throughout the experiment, the activities of glycogen phosphorylase (GP) and glycogen synthase (GS) in the liver of rats with liver cirrhosis in both groups have no difference from the control values. Vilon has a weak stimulating effect on the regeneration of the liver in rats with liver cirrhosis, manifested as the total protein content and ploidy level in the hepatocytes of the second group of rats being 4.7% and 11.5% higher than those of the first group respectively ^[5].

Effects on Radiosensitive Organs: Vilon stimulates the proliferative activity of thymocytes and enhances the proliferative potential of intestinal stem cells, thereby stimulating the post-radiation recovery of key organs. For example, studies on intact rats and rats that received a single whole-body gamma-ray irradiation (6Gy) have found that Vilon has an effect on the functional morphology of the thymus, spleen, and duodenum^[6].

4. Roles at the Molecular Level

Possible Mechanism of Binding to the Membrane: Molecular dynamics trajectory studies have shown that both Vilon (lysylglutamic acid dipeptide) and thymopoietin (Glu-Trp) contain intramolecular salt bridges in their structures, reducing their conformational flexibility. Due to the aliphatic side chain of Lys, Vilon is relatively more flexible. A possible mechanism for the ligand-receptor binding of the dipeptide to the excitable membrane has been proposed, that is, binding through the nitrogen and oxygen atoms that form the salt bridge^[7].

Effects on Protein Expression in the Nucleolar Organizing Region: Vilon stimulates and inhibits the expression of AIDS proteins in the nucleolar organizing regions of the serum tissue and epithelial cell nuclei, respectively forming or reducing the formation, assembly, and transport of ribosomes to the cytoplasm, thus determining the intensity of protein synthesis in these cells. In addition, this peptide also promotes the transformation of thymocytes into proliferating blast cells ^[8].

What are the applications of Vilon?

1. Anti-aging

Vilon is considered a potential anti-aging peptide that can delay cellular senescence by improving gastrointestinal function, enhancing enzyme activity, and promoting nutrient absorption. In addition, Vilon has also been found to be able to improve the expression of skin collagen and reduce the signs of skin aging. Studies have found that the peptide KE (Lys-Glu, Vilon) can increase the expression area of collagen 1 in the culture of senescent skin fibroblasts by 83%; it also increases the expression area of sirtuin 6 in the culture of young and old skin fibroblasts by 1.6 and 2.6 times respectively ^[11].

2. Tissue Repair and Regeneration

Vilon shows significant potential in tissue repair and regeneration. It can support the activation and proliferation of stem cells, accelerate wound healing and tissue repair. Studies have also found that Vilon may promote the repair of the skin, intestines, and other tissues by regulating fibroblast activity. Studies have shown that the synthetic dipeptide Vilon was added to the explant culture medium from rats of different ages. The results showed that Vilon could induce tissue morphological stability, activate the regeneration and functional activity of cells, and had a stronger effect on the explants of elderly rats, suggesting that Vilon has potential in tissue repair^[9].

3. Cardiovascular and Renal Protection

Vilon also has a positive impact on cardiovascular and renal health. It can improve cardiovascular function by changing the gene expression pattern and enhance microvascular permeability in kidney diseases, promoting the optimization of blood coagulation.

4. Applications in Cancer Treatment

Comprehensive Treatment for Elderly Cancer Patients: In the treatment of elderly cancer patients, Vilon is included in the treatment plan as an immunomodulator. For example, in the comprehensive treatment of elderly patients with rectal cancer and colon cancer, preliminary research results show that the application of Vilon can improve the 2-year survival rate of patients, prevent postoperative complications, distant complications, recurrence, and tumor spread^[2].

Patient Stratification for Multiple Cancers: The Variation of information fused Layers of Networks algorithm (ViLoN) adopted by Vilon is a new network-based method that can be used to integrate multiple molecular maps. In terms of patient stratification, this method has been verified on various combinations of data types (gene expression, methylation, copy number), and has a significant improvement effect on patient stratification, and has consistent competitiveness in all cases. In smaller cohorts (rectal adenocarcinoma: 90 cases, esophageal cancer: 180 cases), incorporating prior functional knowledge (KEGG, GO) is crucial for achieving good results^[10].

5. Applications in the Treatment of Liver Diseases

Effects on the Liver of Rats with Liver Cirrhosis: The effects of the dipeptide preparation "Vilon" on the recovery of the functional activity of hepatocytes and the regeneration of the liver in rats with liver cirrhosis were studied. Rats with liver cirrhosis induced by carbon tetrachloride poisoning for 4 months were given Vilon (1.7 micrograms/kg) and injected daily for 5 days. The results showed that two weeks after the application of the drug, the activity of glucose-6-phosphatase (G6P), which was reduced by 1.2 times in liver cirrhosis, increased under the action of Vilon. Vilon has a weak stimulating effect on the regeneration of the liver in rats with liver cirrhosis, manifested as the total protein content and ploidy level in the hepatocytes of the second group of rats being 4.7% and 11.5% higher than those of the first group respectively ^[5].

6. Applications in the Treatment of Diabetes

Effects on Elderly Diabetic Patients: Vilon, as a thymic mimetic, is used as an adjuvant drug in the comprehensive treatment of elderly type I diabetic patients. The results show that the application of Vilon optimizes the coagulation and hemostasis function, manifested as an increase in the content of natural anticoagulants (antithrombin III and protein C) and the stimulation of fibrinolysis. In most cases, Vilon reduces the insulin dose required to stabilize carbohydrate metabolism. At the same time, Vilon also reduces the content of T helper cells, T-dependent and non-T-dependent NK cells, and normalizes the levels of active T lymphocytes, B lymphocytes, and IgA, indicating that Vilon has a stabilizing effect on the immune system and hemostasis function ^[4].

7. Applications in the Treatment of Radiation Injury

Effects on Radiosensitive Organs: The effects of vilon and epithalon on the functional morphology of the thymus, spleen, and duodenum of intact rats and rats that received a single whole-body γ-ray irradiation of 6Gy were studied. The results show that vilon stimulates the proliferative activity of thymocytes and enhances the proliferative potential of intestinal stem cells, thereby stimulating the post-radiation recovery of key organs^[6].

In conclusion, as a special dipeptide, Vilon can improve gastrointestinal function, delay aging, assist in tissue repair and regeneration, and maintain cardiovascular and renal health. It also has a positive effect in the treatment of cancer, liver diseases, diabetes, and radiation injuries.

Relevant Citations

[1]   Lezhava T, Khavison V, Monaselidze J, et al. Bioregulator Vilon-induced reactivation of chromatin in cultured lymphocytes from  old people[J]. Biogerontology, 2004,5(2):73-79.DOI:10.1023/B:BGEN.0000025070.90330.7f.

[2]  Ias'Kevich L S, Krutilina N I, Kostetskaia T V, et al. Application of peptide bioregulator in complex treatment of elderly cancer patients.[J]. Advances in Gerontology = Uspekhi Gerontologii, 2005,16:97-100. https://pubmed.ncbi.nlm.nih.gov/16075684/.

[3]  Jun-hui C. Antitumor activity of Vilon dipeptide Lys-Glu[J]. Chinese Pharmacological Bulletin, 2007. https://api.semanticscholar.org/CorpusID:86988257.

[4]  Bi K, Nv I, Nn K, et al. Effect of vilon on the immunity status and coagulation hemostasis in patients of different age with diabetes mellitus[J]. Advances in Gerontology, 2007,20:106. https://pubmed.ncbi.nlm.nih.gov/18306698/.

[5]  Kudriavtseva M V, Bezborodkina N N, Sek E N, et al. Effect of "vilon" on cirrhotically changed rat liver. Liver regeneration, and status of glycogen-forming function of hepatocytes.[J]. Tsitologiia, 2000,42(8):758-764. https://pubmed.ncbi.nlm.nih.gov/11033862/.

[6]  Khavinson V K, Yuzhakov V V, Kvetnoi I M, et al. Immunohistochemical and morphometric analysis of effects of vilon and epithalon on functional morphology of radiosensitive organs[J]. Bulletin of Experimental Biology and Medicine, 2001,131(3):285-292.DOI:10.1023/A:1017676104877.

[7]  Shchegolev B F, Rogachevskii I V, Khavinson V K, et al. Molecular Mechanics Study of the Steric Structure of the Dipeptides Vilon and Thymogen[J]. Russian Journal of General Chemistry, 2003,73(12):1909-1913.DOI:10.1023/B:RUGC.0000025152.01400.52.

[8]  Raikhlin N T, Bukaeva I A, Smirnova E A, et al. Expression of argyrophilic proteins in the nucleolar organizer regions of human thymocytes and thymic epitheliocytes under conditions of coculturing with Vilon and Epithalon peptides[J]. Bulletin of Experimental Biology and Medicine, 2004,137(6):588-591.DOI:10.1023/B:BEBM.0000042720.40439.16.

[9]  Kniaz'Kin I V, Iuzhakov V V, Chalisova N I, et al. Functional morphology of organotypic culture of spleens from rats of various  ages exposed to vilon[J]. Advances in Gerontology, 2002,9:110-115. https://pubmed.ncbi.nlm.nih.gov/12096432/.

[10] Kańduła M M, Aldoshin A D, Singh S, et al. ViLoN-a multi-layer network approach to data integration demonstrated for patient  stratification[J]. Nucleic Acids Research, 2023,51(1):e6.DOI:10.1093/nar/gkac988.

[11]Fridman N V, Linkova N S, Polyakova V O, et al. Molecular Aspects of the Geroprotective Effect of Peptide KE in Human Skin Fibroblasts[J]. Advances in Gerontology, 2018,8(3):235-238.DOI:10.1134/S2079057018030050.