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In the fields of medicine and biology, the inflammatory response is a complex defensive reaction of the body to various injurious stimuli. Excessive or uncontrolled inflammatory responses can cause damage to the body and lead to a series of diseases. Vilon, as a substance with unique structural and functional characteristics, has demonstrated distinctive roles and application potential in anti-inflammatory effects.
Figure 1 Antioxidative mechanisms.
Sources and Structural Basis of Vilon
Vilon is a bioactive peptide with the full name L-Lys-L-Glu. It was synthesized based on the drug Thymogen, which contains the dipeptide L-Glu-L-Trp with immune-modulating activity. In 1991, Morozov and Khavinson isolated Naturalthymic factors (NTFs) from calf thymus, and subsequently developed the drug Thymalin based on NTFs, which is clinically used for the prevention and treatment of immunodeficiency disorders. Later, using reverse-phase liquid chromatography, Thymogen containing the key dipeptide was isolated from Thymalin, and Vilon was further synthesized based on this. This stepwise derivation process from natural substances laid the foundation for Vilon's unique anti-inflammatory activity. It is composed of a specific amino acid sequence, with L-Lys (lysine) and L-Glu (glutamic acid) connected by a peptide bond. This structure enables Vilon to interact with cell surface receptors or intracellular molecules, thereby initiating a series of anti-inflammatory responses.
Vilon's regulatory effects on inflammatory cells and inflammatory factors
Effects on macrophages: Macrophages are key cells in the inflammatory response. During inflammation, macrophages are activated and secrete various pro-inflammatory factors and inflammatory mediators. Vilon significantly influences the secretion of pro-inflammatory factors IL-1β and TNF-α, as well as the inflammatory mediator NO, by mouse peritoneal macrophages involved in the inflammatory response. Using LPS-activated mouse primary cultured peritoneal macrophages as a positive control, when mouse peritoneal macrophages were co-stimulated with Vilon at concentrations of 0.1 μg/mL, 1 μg/mL, and 10 μg/mL, and LPS at 1 μg/mL, Vilon exhibited a marked promotional effect on the secretion of IL-1β and NO by LPS-activated mouse peritoneal macrophages, with a dose-dependent relationship. This indicates that as the concentration of Vilon increases, its ability to promote the secretion of these inflammatory-related substances by macrophages also increases. Additionally, Vilon also promoted the expression of IL-1β, TNF-α, and iNOS mRNA.
This suggests that Vilon can regulate the synthesis of inflammatory factors at the gene transcription level, thereby influencing the progression of the inflammatory response. Although Vilon appears to promote the secretion of inflammatory factors, this promotional effect may serve as a regulatory mechanism within the complex network of inflammatory responses. For example, moderate secretion of inflammatory factors helps initiate the body's immune defense mechanisms to eliminate pathogens and other harmful stimuli, and Vilon may precisely regulate the secretion levels of these inflammatory factors to maintain them at a level that facilitates normal inflammatory progression without causing excessive damage to the body.
Potential effects on other immune cells: In addition to macrophages, Vilon, as a multifunctional immune regulatory factor, may also influence other immune cells, indirectly participating in the anti-inflammatory process. For example, it can promote the proliferation, activation, and differentiation of thymocytes. The thymus is a crucial site for the maturation of T lymphocytes, and Vilon's effects on thymocytes may influence the number and function of T lymphocytes. T lymphocytes play an important role in immune regulation during inflammatory responses, with different subtypes of T lymphocytes regulating the intensity and duration of inflammation through mechanisms such as cytokine secretion. By influencing thymocytes, Vilon may indirectly modulate T lymphocyte function, directing it toward an anti-inflammatory orientation. Additionally, Vilon can enhance the humoral immune response of splenic cells. The spleen is an important immune organ in the body, and splenic cells participate in various immune processes, including antibody production. Enhancing the humoral immune response of splenic cells helps the body better respond to pathogen infections and alleviate inflammation caused by the prolonged presence of pathogens. Vilon also promotes the chemotaxis and phagocytosis of neutrophils. Neutrophils are among the first immune cells to arrive at the site of inflammation. Enhanced chemotaxis and phagocytic capabilities help to more quickly clear pathogens and inflammatory debris, thereby alleviating inflammation.
Application Prospects of Vilon in Inflammation-Related Diseases
Chronic inflammatory diseases: Many chronic diseases are closely associated with persistent inflammatory responses. In liver diseases, chronic inflammation is a key component in the progression of cirrhosis. Vilon's anti-inflammatory properties make it a potential therapeutic agent for chronic liver inflammatory diseases such as cirrhosis. By regulating the secretion of inflammatory factors and mediators by inflammatory cells, it can reduce inflammatory damage to the liver and slow the progression of cirrhosis. In chronic inflammatory bowel diseases (such as ulcerative colitis and Crohn's disease), the intestines are in a prolonged inflammatory state, leading to damage to the intestinal mucosa and impairing digestive and absorptive functions. Vilon can regulate the function of intestinal immune cells, promote stability in the intestinal microenvironment, reduce inflammatory damage to the intestinal mucosa, and thereby improve patients' symptoms. Additionally, in autoimmune diseases such as rheumatoid arthritis, the immune system mistakenly attacks the body's own tissues, triggering chronic inflammation and causing joint pain, swelling, and functional impairment. Vilon may regulate immune cell function, correct immune system abnormalities, reduce inflammatory responses in joint areas, and alleviate patients' discomfort.
Figure 2 Cytokines in liver disease.
Acute inflammatory response: In acute inflammatory responses triggered by infection or trauma, Vilon also has potential application value. For example, in severe bacterial infections leading to systemic inflammatory response syndrome (SIRS), the inflammatory response is overly activated, potentially causing multi-organ dysfunction. Vilon can regulate the function of inflammatory cells to prevent the excessive release of inflammatory factors, reduce inflammation-induced organ damage, and improve patient survival rates. In post-traumatic inflammatory responses, Vilon can promote the function of immune cells at the wound site, accelerating wound healing. It can promote the chemotaxis and phagocytosis of neutrophils, clearing pathogens and necrotic tissue from the wound site, while regulating the secretion of appropriate levels of inflammatory factors by macrophages to promote tissue repair and regeneration.
Diabetes-related inflammation: Diabetes patients often have chronic low-grade inflammation, which is closely related to diabetes complications.
In elderly type 1 diabetes patients, Vilon, as part of comprehensive treatment, not only optimizes coagulation and hemostasis but also stabilizes the immune system. Vilon can regulate the number and function of immune cells, reduce the levels of inflammation-related cytokines, alleviate the inflammatory state in diabetes patients, and thereby reduce the risk of diabetes complications. Diabetic retinopathy is one of the common microvascular complications of diabetes, and inflammation plays a significant role in its pathogenesis. Vilon may slow the progression of diabetic retinopathy by reducing inflammatory responses in the eye.
Mechanisms of Vilon's Anti-inflammatory Effects
Intracellular signal pathway regulation: Vilon may regulate inflammatory responses by influencing intracellular signal pathways. There are multiple signal pathways related to inflammation within cells, such as the NF-κB signal pathway. NF-κB is a key transcription factor that is activated under inflammatory stimuli, enters the cell nucleus, and initiates the transcription of a series of inflammatory factor genes. Vilon may reduce the synthesis and secretion of inflammatory factors by inhibiting the activation of the NF-κB signal pathway. For example, Vilon may bind to receptors on the cell surface, activate downstream signal transduction molecules, and inhibit NF-κB activity through modifications such as phosphorylation, preventing it from entering the cell nucleus and initiating the transcription of inflammatory factors. The MAPK signaling pathway is another important pathway in inflammatory responses, including branches such as ERK, JNK, and p38 MAPK. Vilon may regulate these branches to influence the expression of inflammation-related genes. Inhibiting the phosphorylation of p38 MAPK reduces the synthesis of inflammatory factors such as TNF-α and IL-1β.
Immune regulatory mechanisms: As mentioned earlier, Vilon has regulatory effects on various immune cells, which is one of its important anti-inflammatory mechanisms. By promoting the proliferation, differentiation, and activation of thymocytes, Vilon can regulate the development and function of T lymphocytes. Different subtypes of T lymphocytes play distinct roles in inflammatory responses: Th1 cells primarily mediate cellular immunity, Th2 cells primarily mediate humoral immunity, Th17 cells are closely associated with inflammation and autoimmune diseases, and Tregs cells exhibit immunosuppressive effects. Vilon regulates the balance of these T lymphocyte subtypes, directing the body's immune response toward an anti-inflammatory direction. Promoting the differentiation and function of Tregs cells, inhibiting excessive immune responses and inflammation. Vilon's promotional effect on humoral immune responses in spleen cells helps the body produce more effective antibodies to eliminate pathogens and reduce inflammation caused by pathogen infections. Additionally, Vilon's regulatory effects on neutrophils and macrophages directly influence immune defense and inflammatory regulation capabilities at the site of inflammation.
Gene expression regulation: Vilon's regulation of gene expression related to inflammatory factors and inflammatory mediators is a key foundation of its anti-inflammatory effects. Through techniques such as RT-PCR, it has been found that Vilon can promote or inhibit the mRNA expression of specific genes. It can promote the expression of IL-1β, TNF-α, and iNOS mRNA, but this promotional effect may be a fine-tuned regulation of the inflammatory response under specific inflammatory microenvironments. Vilon may interact with intracellular transcription factors or other regulatory elements to influence the initiation, rate, and termination of gene transcription. It can also regulate the synthesis of inflammatory-related proteins by affecting mRNA stability and translation efficiency. This multi-level regulation of gene expression enables Vilon to play a role at different stages of the inflammatory response, maintaining inflammatory balance.
Conclusion
As an anti-inflammatory substance, Vilon is beneficial for the treatment of inflammatory-related diseases.
Sources
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[2] Kronborg T M, Ytting H, Hobolth L, et al. Novel Anti-inflammatory Treatments in Cirrhosis. A Literature-Based Study[J]. Frontiers in Medicine, 2021,8:718896.DOI:10.3389/fmed.2021.718896.
[3] Kuznik B I, Isakova N V, Kliuchereva N N, et al. [Effect of vilon on the immunity status and coagulation hemostasis in patients of different age with diabetes mellitus].[J]. Advances in Gerontology = Uspekhi Gerontologii, 2007,20 2:106-115.
[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://api.semanticscholar.org/CorpusID:221168647.
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