Thymosin Beta-4 Fragment (1-4) (Ac-SDKP) 500mcg (60 Capsules)

Thymosin Beta-4 Fragment (1-4) (Ac-SDKP) Overview

Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline) is a naturally occurring tetrapeptide derived from the large thymosin beta-4 protein. Research in animal models has shown Ac-SDKP to have anti-inflammatory, pro-angiogenic, and anti-scarring properties. It has been proposed as a potential therapeutic agent for a variety of conditions, including cardiovascular disease, kidney and liver fibrosis, and inflammatory bowel disease. The peptide may even offer a more natural mechanism for the treatment of high blood pressure, in part due to its association with angiotensin-converting enzyme.

Thymosin Beta-4 Fragment 1-4 Ac-SDKP Research

Mechanism of Action

At its most basic level, Ac-SDKP works by modulating the immune response. In animal models it has been shown to activate certain immune pathways responsible for bolstering anti-inflammatory responses, modulating the release of proinflammatory factors, reducing tissue infiltration by T-cells, and promoting the differentiation and migration of macrophages[1]. It is also known to suppress production of TGF-beta, which is a driver of fibrosis. This is likely the primary mechanism by which Ac-SDKP prevents the development of scar tissue.

It is important to note that Ac-SDKP is a natural derivative of thymosin beta-4 and is cleaved from TB-4, in the body, by the enzymes meprin-α and prolyl endopeptidase. TB-4 has long been known to have potent anti-inflammatory and anti-fibrotic activity[2]. Ac-SDKP can be produced synthetically and administered by orally and via injection. It is bioavailable in both forms, making it easy to administer to animal models.

Ac-SDKP: Anti-Inflammatory Effects

Research indicates that Ac-SDKP can attenuate the clinical symptoms of intestinal mucosal inflammation in animal models of inflammatory bowel disease, which are provoked by administering known intestinal irritants. While the exact cause of inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis, remains not fully understood, their prevalence is rising and appears to correlate with industrialization levels in various locations. Consequently, some speculate that irritants in food, water, or air may contribute to the development of inflammatory bowel disease in susceptible individuals. This is why Ac-SDKP has been proposed as a potential treatment and preventive for inflammatory diseases of the intestinal tract[3].

In mouse models, Ac-SDKP levels are lower in mice that lack the enzymes meprin-α and prolyl endopeptidase. Reduced levels of these enzymes have been linked to more severe inflammatory bowel disease, suggesting that the cleavage of Ac-SDKP from its parent thymosin beta-4 molecule is critical for controlling intestinal inflammation.

Research in these mouse models of inflammatory bowel disease indicates that Ac-SDKP’s activity is mediated through a reduction in MEK-ERK signaling. The MEK-ERK (Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase) signaling pathway is crucial for cellular regulation, transmitting signals from the cell surface to the nucleus to induce changes in DNA expression. MEK-ERK is involved in cell growth and proliferation, differentiation, and metabolic regulation. Increased MEK-ERK activity has been associated with inflammation, cancer development and resistance to therapy, neurodegenerative diseases, and metabolic disorders such as type 2 diabetes.

MEK-ERK signaling is also important in regulating levels of transforming growth factor beta (TGF-beta). Research in heart disease indicates that TGF-beta drives the fibrotic process, leading to scar tissue development by converting fibroblasts into myofibroblasts. Ac-SDKP suppresses the differentiation of human cardiac fibroblasts into myofibroblasts, likely by inhibiting the TGF-β/Smad/ERK1/2 signaling pathway, thereby mediating its anti-fibrotic effects[4].

Ac-SDKP: High Blood Pressure

High blood pressure has long been known to be a risk factor for heart, kidney, and vascular dysfunction. It has been linked to everything from heart attack and stroke to severe kidney disease requiring dialysis and even kidney transplant. One of medicines greatest breakthroughs was the understanding of the angiotensin-converting enzyme (ACE) pathway and the role that this enzyme plays in end organ damage secondary to high blood pressure. Doctors have long known that decreasing levels of ACE can drastically improve outcomes over and above what would be expected from the modest degradation in blood pressure seen with ACE inhibitor medications. It is now thought that high blood pressure is, in some sense, actually a marker for increased levels of angiotensin II, the protein created by ACE activity, and that it is angiotensin II that is causing much of the end organ damage. Ac-SDKP has helped to reveal this link.

Research indicates that the reason lowering ACE levels may be so effective is because it increases levels of Ac-SDKP, which directly counteracts the effects of angiotensin II. Thus, ACE inhibitors have a dual mechanism of action, not only directly decreasing levels of angiotensin II, but also increasing levels of Ac-SDKP. Specifically, Ac-SDKP has been shown to prevent and reverse the infiltration of macrophages into a number of tissues. Macrophages are directly correlated with levels of tissue scarring and are known to release several proinflammatory cytokines the lead to fibrosis and organ damage[6].

What makes Ac-SDKP truly interesting to researchers is the fact that it doesn’t just reduce rates of scarring or slow the process down, but actually reverses it. In mouse models of high blood pressure secondary to kidney dysfunction, administration of Ac-SDKP reversed left-ventricular fibrosis. It is thought that this effect may be mediated, in part, by reductions in TGF-beta[7]. What is important, however, about this effect is that scarring of the heart is a primary driver of heart failure. It is common following cardiac injury, such as is seen after heart attack or with certain viral infections. The ability to reverse scarring in the heart, and likely other tissues as well, means decreased health care expenses, reduce morbidity, and reduced mortality on a truly massive scale. When administered immediately after heart attack, in fact, Ac-SDKP reduces both death from 56.9% to 31.8% and cardiac rupture from 51.0% to 27.3% in mouse models. This activity is directly correlated with a reduction in numbers of M1 macrophages, the cells the drive fibrosis and scar formation[8].

As a function of the connection between Ace and Ac-SDKP, levels of Ac-SDKP can be monitored in order to determine if ACE inhibitor therapy is effective and to help titrate the dose of drugs that lower ACE activity. Researchers are now working to quantify this relationship so that ACE inhibitor therapy can be better tailored to the needs of specific individuals. Getting Ac-SDKP levels has high as possible, without inducing the side effects of ACE inhibitors, could help to maximize benefits in patients following a heart attack or improve the ability of doctors to prevent and treat kidney disease[9].

Ac-SDKP: Heart Health

Research in mice shows that Ac-SDKP can significantly decrease blood pressure, cardiac hypertrophy, and infiltration of activated macrophages into cardiac tissue[1]. As noted above, all of these properties lead to a reduction in cardiac scarring, improved long-term heart health, and even the reversal of existing heart disease. In one study on the long-term effects of Ac-SDKP in rats with high blood pressure, it was found that the peptide inhibited monocyte/macrophage infiltration into the left ventricle. This, in turn, prevented the normal fibrotic response that occurs in hypertension and helped to maintain heart function. Thus, it is thought that Ac-SDKP might act as a preventative for the long-term consequences of high blood pressure and help to protect cardiac function[11]. These effects are likely mediated by the effect that Ac-SDKP has on TGF-beta and the fibrotic process as mentioned above. This can be assumed because research indicates that Ac-SDKP inhibits collagen synthesis in the setting of hypertension, suggesting that its anti-inflammatory benefits help to prevent the processes of fibrosis/scar formation from getting started in the first place[12]. The reduction in scarring and cardiac remodeling are not the only ways in which Ac-SDKP benefits the heart, however.

Ac-SDKP: A Role in the Brain

Research in rat models of stroke indicates that treatment with Ac-SDKP, either alone or in combination with tissue plasminogen activator (tPA), can substantially decrease infarct volume and clinical neurological deficits without increasing the risk of bleeding. This effect is likely mediated through a reduction in several nuclear transcription factors, including NF-kappaB, TGF-beta, and plasminogen activator inhibitor-1. Together, these effects decrease microvascular fibrin extravasation and block the formation of scar tissue in the brain. The research also indicates that Ac-SDKP clearly crosses the blood-brain barrier (BBB) and can thus be administered systemically[16].

Interestingly, although Ac-SDKP crosses the BBB, MRI studies in rats provide evidence that it enhances BBB function in the setting of stroke and helps prevent disruption of this crucial layer of protection. This effect appears to reduce the deposition of fibrin into brain tissue[17].

Fibrin is a key component of blood clots and is derived from the larger fibrinogen molecule. Research shows that higher levels of fibrin are associated with an increased risk of stroke and with more severe long-term outcomes following stroke[18]. The ability of Ac-SDKP to regulate fibrin extravasation suggests it could be useful not only in the treatment of acute stroke but also in stroke prevention. Furthermore, levels of fibrin degradation products are heavily correlated with stroke severity[19][20], with higher levels predicting more severe long-term outcomes. Clearly, any intervention that can reduce fibrin activity in the brain would be beneficial for stroke treatment and prevention, making Ac-SDKP of great interest to neuroscientists.

Ac-SDKP: Summary

Ac-SDKP is a naturally occurring derivative of thymosin beta-4 that can also be produced synthetically. Research across various animal models indicates that this tetrapeptide is a potent regulator of scar formation in several organs, including the heart, liver, kidneys, and brain. Its anti-fibrotic activities have made Ac-SDKP of interest to researchers studying stroke, cardiovascular disease, and kidney disease. Additionally, Ac-SDKP has anti-inflammatory properties and helps regulate blood pressure. Its ability to modulate macrophage activity has been explored in conditions such as irritable bowel syndrome, chronic kidney disease, and in the treatment and prevention of stroke. This short peptide has demonstrated a range of beneficial effects in animal models and shows excellent oral bioavailability. Moreover, it crosses the blood-brain barrier, which enhances its versatility and ease of use.

Storage Instructions:

All of our products are manufactured using the Lyophilization (Freeze Drying) process, which ensures that our products remain 100% stable for shipping 3-4 months reconstituted (mixed with bacteriostatic water) to maintain stability. After reconstitution, the peptides will remain stable for up to 30 days.

Lyophilization is a unique dehydration process, also known as cryodesiccation, where the peptides are frozen and then subjected to low pressure. This causes the water in the peptide vial to sublimate directly from solid to gas, leaving behind a stable, crystalline white structure known as lyophilized peptide. The puffy white powder can be stored at room temperature until you're ready to reconstitute it with bacteriostatic water.

Once peptides have been received, it is imperative that they are kept cold and away from light. If the peptides will be used immediately, or in the next several days, weeks or months, short-term refrigeration under 4C (39F) is generally acceptable. Lyophilized peptides are usually stable at room temperatures for several weeks or more, so if they will be utilized within weeks or months such storage is typically adequate.

However, for longer term storage (several months to years) it is more preferable to store peptides in a freezer at -80C (-112F). When storing peptides for months or even years, freezing is optimal in order to preserve the peptide’s stability.

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