Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline) is a very small protein fragment derived from another natural protein called thymosin beta 4. In the body, special enzymes break down thymosin beta 4 into smaller pieces, and one of the results of this process is Ac-SDKP [1]. This small molecule is important because it helps protect organs from scarring (fibrosis), which occurs when too much rigid tissue builds up after injury or disease. The problem is that Ac-SDKP does not last long in the body – it is quickly broken down by an enzyme called ACE (angiotensin-converting enzyme). Interestingly, ACE-blocking drugs (such as some blood pressure medications) can raise Ac-SDKP levels up to five-fold, enhancing its protective effects [1].
Initially, scientists thought that Ac-SDKP's main role was to keep blood stem cells from growing too fast. However, more recent studies show that its larger role is in tissue healing and protection. It helps to stop excessive proliferation of scar tissue in organs such as the heart, lungs, liver and kidneys. For example, it reduces the activity of certain signals that cause cells to produce too much collagen (the main protein of scars) and prevents repair cells (fibroblasts) from turning into scar-forming cells. In the case of kidney disease, Ac-SDKP shows real promise. Not only does it help the kidneys to function better, but it also reduces scarring by blocking the access of too many immune cells and alleviating the damaging processes that usually make damage worse. In short, Ac-SDKP acts as a natural „anti-scarring” and „tissue-protecting” molecule in the body. It promotes healing, reduces inflammation and may be useful in the treatment of diseases in which scarring and tissue damage play an important role.
Ac-SDKP protects the heart (based on animal studies)
Several scientific studies have described the potential of Ac-SDKP for heart health in both acute and long-term conditions. In a mouse model of heart attack, Nakagawa et al. administered Ac-SDKP at a dose of 1.6 mg/kg/day via a small subcutaneous pump and found clear benefits: heart wall tears (heart ruptures) decreased from 51.0%to 27.3%, and mortality dropped from 56.9%to 31.8%. The peptide appeared to work by calming the „first responder” immune cells that can worsen damage (M1 macrophages) without altering beneficial repair macrophages (M2) or neutrophils. It also slowed the action of an enzyme (MMP-9) that breaks down heart tissue after a heart attack, while another marker (MPO) remained unchanged, suggesting a targeted, specific action [2].
In the case of cardiac scarring caused by prolonged high blood pressure, Peng et al. showed that Ac-SDKP can reduce existing scar tissue, not just prevent it. In rats with a well-established model of hypertension, daily administration of Ac-SDKP at a dose of 400-800 µg/kg (subcutaneously) for 8 weeks reduced the amount of collagen in the heart - the main sign of scarring - in a dose-dependent manner (the higher dose was more effective). Blood pressure per se did not fall, and normal responses to angiotensin I and bradykinin were unaffected, so the benefit was not solely due to a reduction in blood pressure. Blood levels of Ac-SDKP increased 2-5-fold and key „scar-inducing” signals in the heart (TGF-β and CTGF) decreased, confirming a direct anti-scarring effect [3]. After myocardial infarction, persistent swelling and scarring can lead to heart failure. Yang et al. tested Ac-SDKP both early (to prevent damage) and later (to reverse damage). In both cases, total cardiac collagen content decreased (for example, from ~24 to ~15 µg/mg in the prevention group and from ~23 to ~14 µg/mg in the reversal group). The deleterious accumulation of immune cells also decreased: macrophages decreased by about a third in each group, and TGF-β-positive cells decreased in parallel. These benefits were achieved without lowering blood pressure or reducing the size of the heart, and pumping power was not markedly improved in the prophylaxis group. Nevertheless, the steady decrease in scarring and inflammation indicates an improvement in cardiac structure over time [4].
Ac-SDKP may also explain some of the „additional” tissue benefits observed with ACE-inhibiting drugs. Rasoul et al. compared a model of angiotensin II-induced hypertension with groups receiving captopril or Ac-SDKP (400-800 µg/kg/day). This raised blood levels several-fold and reproduced many of the protective properties similar to ACE inhibitors: less cellular hypertrophy in the heart, fewer macrophages and mast cells, lower levels of TGF-β and CTGF, and less collagen accumulation. Importantly, these benefits occurred without lowering blood pressure or reducing cardiac thickening, indicating an indirect protective effect on cardiac tissue [5]. Ac-SDKP slows scar formation in the heart at the cellular level. In cultured rat cardiac support cells (fibroblasts) in the laboratory, Rhaleb et al. tested very low doses of Ac-SDKP (0.05-100 nmol/l) and found two key effects: a reduction in cell growth (DNA copying) to normal at around 1 nmol/l and a reduction in collagen (the main „scar” protein) produced in response to endothelin-1, a potent scarring signal. Lower doses worked best for collagen; very high doses were less effective. The peptide appeared to silence a common cellular signal switch (p44/42 MAPK/ERK), and a known MAPK blocker provided the same benefit. Put simply, Ac-SDKP commands fibroblasts to slow down both proliferation and excessive scar formation, presumably by reducing the activity of a key growth pathway [6].
Furthermore, it protects the heart from damage induced by galectin-3. In studies on adult rats, Liu et al. administered galectin-3 (a protein that induces inflammation and scarring) for four weeks and observed an increased number of inflammatory cells, thicker heart walls, more pronounced scarring around vessels and between cells, higher levels of TGF-β/Smad3 signalling (a pro-scarring pathway), and weaker pumping in an echocardiographic study. The addition of Ac-SDKP (800 µg/kg/day) prevented most of these changes: the number of inflammatory cells, scarring, and heart wall thickening were reduced, and cardiac function improved. The data suggest that it protects the heart by switching off the TGF-β/Smad3 „scarring switch” and reducing inflammation [7].
Furthermore, it reduces cardiac scarring in long-standing hypertension without altering blood pressure itself. Using the classic two-kidney, one-clip model in rats, Rhaleb et al. administered Ac-SDKP (400 µg/kg/day, s.c.). Despite elevated blood pressure and cardiac hypertrophy, peptide treatment significantly decreased both inflammatory and proliferating cells in the myocardium. Importantly, it normalised interstitial collagen fraction, reducing it from approximately 10.1%in hypertensive rats to about 5.4%, a level almost identical to that of control animals (≈5.3% ). In essence, it mitigated detrimental tissue changes even when the pressure overload remained unchanged, suggesting a direct role in tissue healing [8].
Furthermore, in combination with thymosin-β4, Ac-SDKP promotes tissue repair following myocardial infarction. In a narrative review, Cavasin et al. found that thymosin-β4 promotes both cell migration and cell survival. Its derivative, Ac-SDKP, offers additional benefits by acting as an anti-fibrotic agent in arterial hypertension. In myocardial infarction models, Ac-SDKP has been shown to reverse scar formation and reduce inflammation. It also promoted angiogenesis, as demonstrated in both in vivo and ex vivo studies. Moreover, Ac-SDKP reduced the risk of cardiac rupture in mice, highlighting its therapeutic potential in cardiovascular repair. Many benefits overlap, suggesting that Ac-SDKP carries some of the healing action of thymosin-β4. However, the researcher mentioned that human trials are still needed to confirm these laboratory and animal study results [9].
In addition, Ac-SDKP reduces the activity of tissue degrading enzymes triggered by IL-1β. In adult rat cardiac fibroblasts, Rhaleb et al. showed that interleukin-1β (IL-1β), a pro-inflammatory cytokine, significantly increased the expression of matrix metalloproteinases (MMP-2, MMP-9 and MMP-13). These enzymes degrade extracellular matrix components and contribute to adverse remodelling. Ac-SDKP did not alter the basal expression of MMPs. However, it strongly inhibited the IL-1β-induced increase in the levels of these enzymes. At the same time, Ac-SDKP increased the expression of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), natural inhibitors of MMP activity. This helped to rebalance matrix turnover. Ac-SDKP also reduced the activation of two major signalling pathways that drive inflammation and proliferation: NF-κB and ERK/MAPK. Interestingly, IL-1β stimulation did not increase collagen production in this model. Ac-SDKP also had no effect on collagen synthesis. This suggests that its protective role is due to selective rebalancing of tissue remodelling, rather than a general change in collagen production. Taken together, these results indicate that Ac-SDKP may protect the myocardium from pathological remodelling by rebalancing matrix regulation [10].
Ac-SDKP protects against autoimmune cardiac damage in rats. In a model of T-cell-induced myocarditis, Nakagawa et al. treated immunized Lewis rats with Ac-SDKP and observed preservation of cardiac function, both systolic and diastolic. The treatment also reduced cardiac enlargement, reduced scar formation and preserved a healthier myocardial structure. Histological analysis showed a lower number of infiltrating immune cells, including macrophages, dendritic cells and T lymphocytes. In parallel, levels of key inflammatory mediators including cytokines (IL-1α, TNF-α, IL-2, IL-17), chemokines (CINC-1, IP-10), adhesion molecules (ICAM-1, L-selectin) and matrix metalloproteinases were significantly reduced. Interestingly, Ac-SDKP did not alter the levels of myosin-specific autoantibodies or antigen-specific T-cell responses. This indicates that its cardioprotective effect is primarily due to a reduction in immune cell recruitment and inhibition of inflammatory mediators, rather than a change in autoantibody production or T-cell activation [11].
Ac-SDKP reduces inflammation and collagen cross-linking in angiotensin II-induced hypertension. González et al. administered angiotensin II to rats for three weeks, with a separate group treated with Ac-SDKP. Blood pressure and cardiac hypertrophy remained elevated in both groups, but Ac-SDKP prevented increases in both total and cross-linked collagen. This protective effect was due to the inhibition of lysyl oxidase (LOX) mRNA and LOXL1 protein, enzymes responsible for collagen cross-linking and scar stiffening.
Furthermore, Ac-SDKP reduced TGF-β expression, inhibited NF-κB activation and limited lymphocyte infiltration. T CD4⁺ i CD8⁺ and macrophages CD68⁺ to cardiac tissue. Importantly, the influx of cells T CD4⁺ correlated with LOXL1 expression, suggesting a mechanistic link between immune cell activity and fibrosis. These findings highlight that Ac-SDKP exerts potent anti-fibrotic and anti-inflammatory effects independently of its effects on blood pressure [ 12].Furthermore, it protects the heart after myocardial infarction in mice in the early and late stages. Peng et al. administered Ac-SDKP (1.6 mg/kg/day) to C57BL/6J mice after myocardial infarction. In the first week, the treatment reduced the number of fatal wall ruptures, decreased ICAM-1 levels, reduced macrophage influx and gelatin digestion activity, inhibited p53 and reduced myocardial cell death; at the same time, the number of small blood vessels at the edge of the injury increased, suggesting better new vessel growth. At week five, hearts showed less interstitial collagen, preserved structure, lower levels of endoplasmic reticulum stress (CHOP) and maintained SERCA2 (crucial for calcium metabolism), as well as overall better function. In short, it reduces early damage and promotes healthier long-term remodelling [13].
In another study, Ac-SDKP limited cardiac scarring and improved diastolic function in diabetic cardiomyopathy. Castoldi et al. induced diabetes in rats and, two months later, began administering Ac-SDKP (1 mg/kg/day via minipumps) for eight weeks. Diabetic rats presented severe hyperglycaemia, pronounced interstitial and perivascular fibrosis, and increased cardiac TGF-β1 and phospho-Smad2/3 levels. Ac-SDKP reduced both types of fibrosis and limited TGF-β/Smad signalling, even in animals treated with the ACE inhibitor ramipril. Cardiac ultrasound showed that diabetes impaired systolic and diastolic function; insulin and ramipril restored both functions, whereas Ac-SDKP partially improved diastolic function. These data highlight antifibrotic benefits with moderate functional improvement in this model [14].
Furthermore, it protects coronary vessels from radiation-induced damage and preserves blood flow. In a rat model of chest irradiation, Sharma et al. administered Ac-SDKP subcutaneously for 18 weeks. Radiation reduced resting blood flow, killed endothelial cells, increased coronary fibrosis, and disrupted the action of tight junction proteins (claudin-1, JAM-2). This restored blood flow to normal, preserved endothelial cells, reduced fibrosis, and re-established tight junctions. In vitro studies showed that Ac-SDKP enters endothelial cells and reduces radiation-induced reactive oxygen species; in living animals, the labelled peptide concentrated in endothelial cells within hours. These results indicate vascular protection, reduced oxidative damage, and improved microvascular integrity after irradiation [15].
In addition, it reduces stress-induced scar formation in cardiac support cells. In human cardiac fibroblasts, cells were pretreated with Ac-SDKP (10 nM) and then treated with tunicamycin (0.25 µg/ml), which induces „protein stress” inside the cell factory (endoplasmic reticulum). Ac-SDKP helped to stop stressed cells from producing too much collagen. It worked by calming the cellular response to stress, reducing the activity of a stress protein called CHOP and decreasing the activity of an inflammatory switch called NF-κB. It also lowered levels of IL-6, the signal that triggers inflammation. When CHOP was genetically reduced, it continued to decrease NF-κB and type I collagen activity at both the protein and mRNA levels, confirming the same pathway [16]. Simply put: under stress conditions, this helps cells avoid excessive production of scar protein.In addition, it reduces inflammation of the vascular lining induced by TNF-α. In human coronary artery endothelial cells, TNF-α stimulation induced a significant increase in the expression of ICAM-1. This adhesion molecule plays a key role in promoting leukocyte adhesion to the blood vessel surface. Pretreatment with Ac-SDKP significantly reduced ICAM-1 levels in a dose-dependent manner. Mechanistic analysis showed that this effect was mediated by inhibition of the IKK → IκB → NF-κB signalling cascade, which is crucial for the activation of inflammatory gene expression. Interestingly, two other signalling pathways, p38 MAPK and ERK, were unaltered, indicating that Ac-SDKP selectively interacts with the NF-κB pathway to exert anti-inflammatory effects in endothelial cells [17].
Ac-SDKP helps keep the lining of blood vessels calm and reduces its „stickiness” during inflammation. Furthermore, it prevents large artery scarring in the case of angiotensin II-induced hypertension, even without lowering blood pressure itself. In rats administered angiotensin II, Ac-SDKP reduced collagen accumulation in the aorta and limited the signals (collagen type I and III mRNA) that cause scarring. It also lowered protein kinase C hyperactivity, oxidative stress, ICAM-1, and macrophage infiltration into the vessel wall. Fibrosis signals dropped (less TGF-β1 and Smad2 activity) while the natural brake on this pathway (Smad7) increased. Blood pressure and aortic thickness remained high, so these benefits to the vessel wall came from direct action on the tissues, not from changes in pressure [18].
Ac-SDKP also protects the heart from radiation damage. In rats that received targeted thoracic radiation, 18 weeks of Ac-SDKP preserved cardiac function, reduced extracellular matrix accumulation and fibrosis, reduced macrophage influx and decreased cardiac cell death. The level and release of Mac-2 (galectin-3), a macrophage protein responsible for fibrosis, also decreased. Ac-SDKP was observed inside macrophages near the cell nucleus and prevented the radiation-triggered release of Mac-2; when fibroblasts lacked Mac-2, radiation caused much weaker scarring signals [19]. It helps maintain healthier vasculature and cardiac tissue after irradiation by reducing inflammation and scar formation.
Ac-SDKP for lung health (based on animal studies)
Ac-SDKP demonstrates a more potent anti-scarring effect than thymosin-β4 in lung models. Firstly, in laboratory studies using lung cells from people with idiopathic pulmonary fibrosis (IPF), it slowed excessive cell growth and reduced two scarring signals induced by TGF-β: α-SMA and collagen. Meanwhile, in mice that were given
bleomycin to induce lung damage, thymosin-β4 helped in the early stage (day 7)
by reducing inflammation and early scarring, but did not halt fibrosis in
in later stages (14–21 days). These findings suggest that Ac-SDKP blocks the initial stages
scarring in cells and can provide more stable and long-lasting benefits
antifibrotic than its precursor, thymosin-β4 [20]. Furthermore, it inhibits pulmonary scarring
related to silica by restoring KIF3A and suppressing β-catenin signalling. Specifically, in silicosis, KIF3A levels were low in patient samples
and in the lungs of rats. After restoring KIF3A the activity of β-catenin and its downstream factors
The MRTF-A and SRF drivers decreased, thereby slowing epithelial-to-myofibroblast transition
(EMyT) associated with scarring. This consistently increased KIF3A function, and as a result
reduced β-catenin/MRTF-A/SRF signalling. However, after eliminating KIF3A, Ac-SDKP lost these
benefits, confirming that KIF3A is essential for its anti-fibrotic action [21].
In another study, Ac-SDKP in combination with VIP attenuated COPD-related changes caused by
cigarette smoking in mice. It reduced oxidative damage (lower MDA levels) and scarring
(lower hydroxyproline levels) and a key factor causing fibrosis (lower TGF-β levels).
At the same time, the amount of inflammatory cytokines (TNF-α, IL-1β, IL-6) decreased, and protection improved
antioxidant (higher SOD activity). Appropriately, lung tissue under the microscope showed
less inflammation and less structural remodelling. The combination of these substances proved beneficial
antioxidant, anti-inflammatory and anti-fibrotic in a model of injury caused by
dymem [22, 23]. Ac-SDKP also demonstrated significant results in both prevention and treatment.
bleomycin-induced lung fibrosis. In CD-1 mice, Ac-SDKP (0.6 mg/kg, i.p.) administered from day 0
or On day 7, survival was improved and bleomycin-associated weight loss was reduced. Furthermore, the lungs
showed less swelling and fewer invasive immune cells, healthier
tissue structure and less fibrosis: both collagen staining and levels decreased
soluble collagen. Mechanically, the pro-fibrotic signals IL-
17 and TGF-β, a α-SMA decreased, indicating fewer myofibroblasts. Importantly, the benefits
appeared in both early (prophylactic) and delayed (therapeutic) schedules
Furthermore, it reduces silica-induced lung fibrosis via the P-HSP27/SNAI1 pathway. U
Silicosis in rats caused an increase in P-HSP27, SNAI1, α-SMA, and collagens I/III in lung tissue.
However, Ac-SDKP — administered before exposure or after the onset of the disease — reduced all these
markers and reduced the number of positive cells for both P-HSP27 and α-SMA in imaging. What
important, administering it to healthy control individuals did not alter protein expression, suggesting that its
the action is selective towards diseased lungs [25].
Furthermore, it demonstrates strong anti-scarring effects in numerous animal studies. In a meta-analysis
covering 18 randomised trials (428 animals, 2008–2021) found that Ac-SDKP lowered
some fibrosis signals compared to untreated models: α-SMA (SMD −2.44), collagen type I
(SMD −5.36), type III collagen (SMD −3.07), TGF-β (SMD −2.88) and the surface area of pulmonary nodules
Surface-mount device
-1.80); all P<0.001. Furthermore, hydroxyproline – the chemical marker for collagen – also decreased
significant change [SMD 7.62; 95% CI 4.90–10.33; P=0.000], which is consistent with an effect on turnover
collagen. These results indicate that Ac-SDKP consistently slows fibrosis in disease models
lungs [26]. In another study, it lowered TGF-β and CTGF levels, inhibiting lung scarring associated with
silica in rats. Rats were given silica to induce fibrosis, and then
prophylactically or therapeutically Ac-SDKP (800 µg/kg/day). Compared to the control group with
In the treated lungs, a significant reduction in the level of TGF-β1 protein was observed (to ~0.244 ±
0.016) and CTGF (up to ~0.241 ± 0.017). Similarly, mRNA levels decreased, and CTGF mRNA was significantly lower compared to the model groups (P<0.05). In the group
prophylactic levels of both protein and mRNA for TGF-β1 were significantly below those at 8 weeks
silica model (P<0.05). Finally, lung histology confirmed less fibrosis [27]. Furthermore
it inhibits collagen accumulation and improves lung structure in silicosis. Rats exposed to
Silica activity received Ac-SDKP either following injury (treatment) or 48 hours prior to exposure.
(prevention). In treated groups, compared to silicosis models, the surface area of silicotic nodules
fell to.28 and.93, hydroxyproline to.89 and% 58.18, collagen type I to% 71.08 and% 58.13, and
type III collagen to 80.13% and 70.70% (at appropriate time points). In the prophylactic groups,
compared to the 8-week silicosis model, nodules reduced by 61.13%%, hydroxyproline by
60.27%, and Type I and III collagen to 40.13%and 65.77%. Correspondingly, HE and VG staining showed
milder fibrosis. This reduced both collagen content and visible scarring [28].
Additionally, it protects the lungs and bones by calming macrophage pathways in the event of exposure to
Silica. In rats and cell models, silica activated TLR4 and RANKL, causing
pneumonia and bone resorption by osteoclasts. In contrast, Ac-SDKP treatment inhibited signalling
TLR4 and RANKL protected lung elastin, reduced lung inflammation and limited activation
macrophages. At the same time, in bones, Ac-SDKP blocked osteoclast differentiation and helped
maintain bone density and microarchitecture. These results indicate dual protection: healthier lungs and
more stable bones in silica-related diseases [29]. Furthermore, it reduces scarring
lungs, inhibiting the maturation of cells that form scar tissue. TGF-β1 usually stimulates lung supporting cells
(fibroblasts) to transform into myofibroblasts and produce additional collagen. After administration
Ac-SDKP reduced the levels of α-SMA and collagen, and also the levels of TGF-β1 and its receptor.
reduced. Then, in rats with silica-induced lung injury, administration of Ac-SDKP before
or after exposure decreased TGF-β1 levels, RAS signalling and SRF activity and reduced the number
of α-SMA-positive myofibroblasts in pulmonary nodules. As a result, the accumulation decreased
collagen, which showed protection against fibrosis [30, 31]. Furthermore, Ac-SDKP protects the lining
alveolar vesicles, preventing epithelial cells from transforming into cells that form
Scars. Under the influence of damage signals, such as silica and TGF-β1, the level of markers decreases
epithelial (E-cadherin, SP-A), whereas the levels of mesenchymal markers increase and
fibrosis (vimentin, α-SMA, collagen I/III). Ac-SDKP reversed this harmful change:
Epithelial identity was preserved, fibrosis markers decreased, and the TGF-β1/ROCK1 pathway was
weakened. As a result, the delicate surface of the pulmonary alveoli remained closer to normal and
less prone to scarring [32]. Furthermore, it alleviates stress on the „protein factory” and cell death in
in lung alveoli, which in turn reduces lung scarring. When silica strikes,
Cells exhibit high ER stress signals (GRP78, phosphorylated PERK and eIF2α), CHOP and caspase-
12, and many cells die. Thanks to Ac-SDKP — much like the ER stress blocker 4-PBA — these markers
stress decreased, cell mortality decreased in cell and rat tests, and collagen in the lungs
decreased. Overall, by pacifying the PERK/eIF2α/CHOP pathway and caspase-12, Ac-
SDKP helps protect the epithelial layer and slows the progression of fibrosis [33].H2. Ac-SDKP for kidney health (based on animal studies)
Ac-SDKP protects the kidneys in lupus without lowering blood pressure. Nakagawa et al. (2017)
showed that in NZBWF1 mice susceptible to lupus, renal filters were preserved (less sclerosis
glomeruli) and reduced overall damage, without simultaneously lowering systolic
blood pressure. The onset of severe hypertension, albumin in the urine, and premature death
this was later observed with the use of Ac-SDKP, but these delays were not statistically significant
This substance also protects kidney function during salt stress. Worou et al. (2015)
The Dahl salt-sensitive rats were examined, which were treated for six weeks with a dose of 800 or 1600
µg/kg/day. Blood pressure continued to increase as a result of the salt diet, but the kidneys showed less
inflammation, less fibrosis and healthier filters. Only a higher dose reduced albumin levels in
of urine in salt-sensitive rats. For the more resistant strain (SS13BN), both doses
prevented albumin leakage and structural damage [35]. This indicates that the protective effect
was independent of blood pressure. The peptide also reduces kidney damage caused by
the immune system in the case of lupus. Liao et al. (2015) found that within 20 weeks treated
mice susceptible to lupus had better kidney function, even though levels of lupus autoantibodies did not
were altered. Kidneys contained fewer immune cells, such as macrophages, and
T cells. Inflammatory signals, such as cytokines and chemokines, were lower, and complement protein activation
(C5–9), RANTES, MCP-5 and ICAM-1 were inhibited. As a result, the filtration function was preserved
microscopic damage was reduced [36].
In another study, it prevents hypertension-related kidney damage despite
persistent high blood pressure. Rhaleb et al. (2011) demonstrated that in mice treated with salt
DOCA Ac-SDKP (800 µg/kg/day for 12 weeks) reduced renal scarring (collagen),
filtration matrix expansion and monocyte/macrophage influx, while blood pressure
remained elevated. Importantly, the urine albumin level normalised — from 41 ± 5 µg to 13 ±
3 µg per 10 g of body weight per day, approaching control level — and nephrin loss (a key
(filter slit proteins) was partially restored [37]. Consequently, Ac-SDKP protected
the filtration barrier and reduced scarring independently of blood pressure. Furthermore, it protects against scarring and
kidney dysfunction caused by diabetes. Shibuya et al. (2005) demonstrated that in diabetic db/db mice
two eight-week infusions of Ac-SDKP using minipumps resulted in approximately a three-fold
increase in plasma Ac-SDKP concentration without changes in blood sugar levels. As a result, it was prevented
glomerular oedema, excessive mesangial matrix proliferation and accumulation
extracellular matrix, and plasma creatinine concentration approached normal. Albuminuria
also decreased, although this decrease was not statistically significant. It mechanically blocked the
Smad3 before entering the cell nucleus, thereby reducing TGF-β/Smad signalling
associated with fibrosis [38]. Furthermore, Ac-SDKP reduces kidney scarring in diabetes and represents
additional benefit over ACE inhibition. Castoldi et al. (2013) induced diabetes in
rats, and then administered Ac-SDKP (1 mg/kg/day), ramipril (3 mg/kg/day), both drugs combined, or
placebo. Firstly, untreated diabetic rats exhibited high blood sugar, higher
albuminuria, renal fibrosis and reduced nephrin levels in the glomeruli. If used
Following treatment with Ac-SDKP, renal fibrosis decreased, but albuminuria did not improve. In the case of
when ramipril was used, both albuminuria and fibrosis decreased, and the level of nephrin was
restored. Importantly, the combination of Ac-SDKP with ramipril resulted in a greater reduction in fibrosis than either drug alone.
ramipril, although albuminuria did not improve further. Ac-SDKP reduces fibrosis in nephropathy
diabetic and enhances the anti-fibrotic protection of ACE inhibitors without additional benefit in
in the scope of albuminuria [39].
Interestingly, Zhang et al. (2022) developed a biologically inspired dual-network hydrogel composed of
gelatin and curcumin-zinc, coated with DOPA and functionalised with immobilised Ac-SDKP. This system
was designed to overcome the limitations of free drugs, including poor solubility,
Absorption and stability. In vivo application in partially nephrectomised rat kidneys
showed that the hydrogel consistently reduced local fibrosis, promoted angiogenesis, and
stimulated the formation of new kidney tubules. Material studies confirmed appropriate
porosity, mechanical strength and biocompatibility, which further confirms its potential
therapeutic [40]. Comparative studies also highlight distinct and stage-dependent effects
thymosin-β4 (Tβ4). Zuo et al. (2013) used models of unilateral ureteral obstruction in
wild-type mice and mice with the PAI-1 gene knocked out to assess Ac-SDKP, Tβ4, and Tβ4 in combination with
prolyl oligopeptidase (POP) inhibitor. Ac-SDKP consistently reduced fibrosis in both
genotypes, which showed lower deposition of collagen and fibronectin, fewer activated
myofibroblasts and macrophages and reduced profibrotic signalling [41]. Furthermore, Wang and
wsp. (2010) demonstrated that Ac-SDKP inhibited inflammation and fibrosis caused by obstruction. U
In rats with unilateral ureteral obstruction, 14-day treatment reduced scarring.
Cellulo-parenchymal and inflammatory changes in histological examination. The peptide reduced macrophage infiltration
renal (ED-1) and reduced the levels of MCP-1, NF-κB, α-SMA, and TGF-β1 proteins in cells
tubular and interstitial. Expression of MCP-1 and TGF-β1 genes also decreased, which
indicates that this reduced both inflammatory cell migration and matrix activation
extracellular, which are key factors causing kidney fibrosis [42]. Further
evidence comes from models of hypertension with chronic kidney damage. Liao et al.
(2010) Ac-SDKP was administered at a dose of 800 µg/kg/day to rats after 5/6 nephrectomy, prior to injury
(prevention) or after damage (reversal). Despite persistent hypertension and left ventricular hypertrophy
heart chambers, treatment reduced albuminuria, limited macrophage infiltration and lowered the level
renal collagen in both groups. Loss of nephrin in the renal glomeruli was also partially
preserved or restored, suggesting an improvement in the integrity of the filtration barrier. These findings
they emphasise that the peptide provided kidney protection in both early and advanced stages
diseases, mainly through anti-inflammatory and anti-fibrotic action, rather than through control
blood pressure [43].
In the case of salt-aldosterone hypertension, the peptide reduced scarring in both the heart and
i kidney, without affecting blood pressure. Peng et al. (2001) studied rats with one kidney removed,
and treated with aldosterone and salt for six weeks. This treatment raised blood pressure, enlarged the heart and
kidneys and increased the amount of scar tissue (collagen) along with cell proliferation markers (PCNA).
Administration of Ac-SDKP, especially at a higher dose of 800 µg/kg/day, significantly decreased the amount of collagen and
PCNA in a dose-dependent manner. Importantly, blood pressure and organ enlargement remained
unchanged, whereas a lower dose (400 µg/kg/day) provided partial benefit [44]. In
in cases of kidney diseases of immunological origin, the peptide improved kidney function and reduced
fibrosis. Omata et al. (2006) treated rats with anti-GBM nephritis, commencing 14
four days after the onset of illness, administering Ac-SDKP at a dose of 1 mg/kg/day for four weeks. In
compared to untreated animals, it lowered urinary protein levels and reduced urea concentration
in plasma creatinine and improved creatinine clearance. Tissue analysis showed less sclerosis
glomeruli and interstitial fibrosis. Mechanically, it reduced
fibronectin, collagen and TGF-β1 levels, reduced Smad2 signalling, increased Smad7 and decreased
macrophage accumulation in renal tissue [45]. In diabetes, the peptide blocked kidney scarring,
preventing blood vessel cells from turning into scar-forming cells. Nagai et al.
(2014) demonstrated that Ac-SDKP restored natural protective pathways, including let-7 microRNA and signalling
FGF receptor, which were inhibited by diabetes. As a result, it reduced fibrosis and
endothelial-to-mesenchymal transition (EndMT). Importantly, combining it with an ACE inhibitor improved
kidney protection even more than ACE inhibition itself [46].
In another study, the peptide restored healthy kidney metabolism and limited fibrosis. Srivastava et al.
(2020) compared ACE inhibitors, ARBs, Ac-SDKP and their combinations in diabetic mice. They blocked
also its natural formation using prolyl oligopeptidase inhibitor (POPi). Results
showed that Ac-SDKP mediates the action of ACE inhibitors by reprogramming
renal metabolism: SIRT3 restored, mitochondrial fatty acid oxidation improved and
a reduced the misuse of glucose. However, POPi lowered the natural levels,
accelerated fibrosis and disrupted metabolic balance. Importantly, ACE inhibitors (but not ARBs)
partially restored its level and reduced fibrosis. Both ACE inhibitors and Ac-SDKP
reduced mesenchymal transformation and decreased levels of collagen I and fibronectin in the kidneys
diabetic [47].
In cancer therapy, the Ac-SDKP analogue helped preserve blood cells during chemotherapy. Carde and
wsp. (1992) tested seraspenide in a double-blind, phase I–II crossover trial with 53
patients receiving cytarabine or ifosfamide. Compared to control periods, patients treated
seraspenide offered better protection of peripheral blood cells from chemotherapy toxicity. It was
well tolerated and did not show any adverse events. These findings suggest that the peptides
Similar to Ac-SDKP, these might protect bone marrow during cytotoxic treatment [48]. In another
investigating the peptide did not reduce blood toxicity but was safe. Cappelaere et al. (1995) investigated
84 patients with advanced squamous cell carcinoma receiving carboplatin and continuous infusion
5-fluorouracil, along with placebo or goralatide (Ac-SDKP) at a dose of 12.5 or 62.5 µg/kg/day. Over 221 chemotherapy cycles
No differences were found in the lowest blood morphology values for leukocytes, granulocytes, and platelets
of blood or haemoglobin between the groups. The duration of toxicity also remained unchanged. However
anaemia and lymphopenia were more common with goralatide. Overall, the drug
it was well tolerated, but at these doses it did not prevent blood cell loss associated with
chemotherapy [49].
In both type 1 and type 2 diabetes, the peptide improved kidney scarring and function. Nitta and
wsp. (2016) treated streptozotocin-induced type 1 diabetes CD-1 mice and db/db mice with
type 2 diabetes, using oral Ac-SDKP, imidapril (an ACE inhibitor), or both drugs in combination. Treatment
oral, both alone and in combination, reduced glomerular sclerosis and
tubulo-interstitial fibrosis. Plasma cystatin C concentration, which is elevated in diseases
nerek, returned to normal levels. All therapies restored suppressed microRNAs
anti-fibrotic (miR-29 and let-7), with the greatest improvement observed in the group
receiving combination therapy. Peptide concentration in urine was highest in the group receiving
combination therapy, which indicates an improvement in systemic exposure [50]. In the case of diseases
an immunological cause reduced protein levels in the urine, decreased inflammation, and
Fibrosis. Tan et al. (2012) administered 1.0 mg/kg/day for 8 weeks to MRL/lpr lupus mice. In
Compared to untreated lupus mice, mice receiving the peptide had less proteinuria and
improved kidney function. Kidney tissue contained fewer infiltrating T cells and macrophages. Under
mechanically, there was a decrease in NF-κB activation and TNF-α production, as well as
reduction of pro-fibrotic markers (TGF-β1, α-SMA, and fibronectin). Smad2/3 phosphorylation
was inhibited, and Smad7 increased. Importantly, complex deposition did not change
immunological and anti-dsDNA antibody levels, suggesting that the benefits were rather due to
reduction of inflammation and fibrosis than from antibody formation [51].
In cases of obesity and high salt intake, it protected the kidneys by reducing inflammation, fibrosis, and
even blood pressure. Maheshwari et al. (2018) studied Zucker lean (ZL) and Zucker obese (ZO) rats
fed for 8 weeks with a normal salt intake (0.4%) or a high salt intake (4%), with a subgroup
ZO received
1.6 mg/kg/day. High salt content worsened kidney inflammation and fibrosis in both groups, with
Obese rats showed the most severe macrophage infiltration (87.8 ± 10.8 compared with 19.14
± 1.5 cells/mm² in lean rats). Treatment reduced macrophage infiltration in obese rats
rats to 32.18 ± 2.4 cells/mm² (P<0.05) and reduced glomerular sclerosis, and
also interstitial fibrosis in both cortex and medulla (P<0.05). Systolic blood pressure in
fattened rats fed salt also fell from 164 ± 6.9 to 144.05
± 14.1 mmHg (P=0.004). Albuminuria was higher in obese rats than in lean rats, but did not significantly
significant change under the influence of salt intake or treatment [52].
Ac-SDKP for brain and nerve health (based on research)
animals
Protection in models of Parkinson's disease
This peptide helps protect dopamine-producing neurons and supports better motor function and memory in
in Parkinson's disease models. Kamarehei and Zahednasab (2025) were the first to show in experiments
cellular, that initial exposure of SH-SY5Y nerve cells to 20 nM of this peptide
protected them from 6-OHDA, a toxin commonly used to mimic Parkinson's disease. In
In rat studies, daily doses of 800 µg/kg after 6-OHDA induced brain damage led to the preservation of
more dopaminergic neurons and reduced cell death by lowering caspase-3 activity and
caspase-12. Rats treated also showed better motor coordination and improved memory
spatial awareness and fewer symptoms of anxiety and depression. From a mechanical perspective, the benefits arose from
reduction of oxidative stress, mitigation of endoplasmic reticulum (ER) stress and reduction of
inflammatory signals in the brain, which supports neuronal survival and regeneration [53].
Regeneration after spinal cord injury
It also speeds up regeneration and redirects inflammation towards healing after spinal cord injury.
vertebral. Hashemizadeh et al. (2022) administered Wistar rats 0.8 mg/kg subcutaneously once
daily for seven days, starting two or six hours after spinal cord injury
caused by the fall of a weight. Compared to untreated animals, rats subjected
treatment, they regained better walking ability, lost fewer motor neurons, and had lower levels
TNF-α (a pro-inflammatory signal) and caspase-3. Simultaneously, the mRNA level of CD206, a marker for pro-
M2-polarized macrophages. Tissue studies showed smaller areas of damage. Overall,
treatment caused a change in immune response from harmful M1 activity to
protective M2-type activity, which offered both functional and structural benefits [54].
Protection after traumatic brain injury (TBI)
Ac-SDKP helps protect the brain and aids its repair when administered soon after injury. Zhang
i wsp. (2017) induced controlled injuries to the cerebral cortex in rats and administered the compound to them (0.8
mg/kg/day) via minipump for three days, starting one hour after injury. From day 7 to day 35
the sensorimotor test results improved, and on days 33–35 spatial learning was also
better compared to the control group (p < 0.05). By the end of the study, the size decreased
damage to the cerebral cortex and loss of hippocampal neurons, while an increase in blood vessels,
the creation of new neurons and the density of dendritic spines were greater. Early treatment
It also reduced fibrin accumulation and alleviated immune cell activation. Tests
mechanistic studies revealed that blockade of TGF-β1/NF-κB signalling largely explained the effect
anti-inflammatory [55].
Benefits in a disease similar to multiple sclerosis (MS)
It also reduces brain stress and inflammation in models of multiple sclerosis. Pejman et al.
(2020) C57BL/6 mice were subjected to experimental autoimmune encephalomyelitis
vertebral (EAE). Typically, EAE increases ER stress markers (caspase-12, CHOP, PDI), stress
Oxidative stress and the influx of immune cells into the hippocampus. The treatment level of caspase-12 and
CHOP in oligodendrocytes decreased, caspase-3 activation decreased, ROS oxidation decreased, and
lipid peroxidation, antioxidant capacity improved, and IL-6/IL-1β levels were reduced.
Brain fragments confirmed smaller hippocampal damage and reduced cell infiltration
immunological, indicating a slower disease progression [56].
Ac-SDKP for liver health (based on research)
animals
Slowing down chemical-induced liver scarring
The peptide Ac-SDKP helps protect the liver from chemical damage by regulating
key gene control switch and growth pathway. Wei et al. (2022) studied rats with damage
carbon tetrachloride-induced liverCarbon tetrachlorideand observed reduced / smaller death of star-shaped cells —
The main cells forming scars in the liver. Fibrosis also decreased. Tests
Mechanistic studies showed that the treatment reduced the level of WTAP, an enzyme that adds methylation marks m⁶A Do
RNA. This alteration stabilised Ptch1 RNA and adjusted the activity of the Hedgehog pathway, a major
the factor that causes scarring. Overall, the results highlight the action
anti-fibrotic via the WTAP/m pathway⁶A/Ptch1, which regulates Hedgehog signalling [59].
Ochrona przed zwłóknieniem spowodowanym niedrożnością dróg żółciowych
Ac-SDKP also protects the liver when scars are caused by bile duct obstruction.
Zhang et al. (2012) used the bile duct ligation (BDL) model in rats and
they were subjected to continuous treatment for two weeks. Compared to untreated animals, those that
received the peptide, had inhibited TGF-β1 signalling and lower levels of markers associated with
activated stellate cells (α-SMA, FSP-1). Gene expression also decreased
Collagen (Col I, Col III) and turnover enzymes (MMP-2, TIMP-1, TIMP-2) related markers. Blood markers
liver function tests improved, and ALT, AST, bilirubin and prothrombin time neared
according to norms. Fewer mast cells were observed in tissue preparations, smaller
collagen accumulation and overall reduction in fibrosis and inflammation [60].
H3. Maintaining natural defence and repair signals
It helps the liver maintain its natural resistance during prolonged chemical damage.
Chen et al. (2010) discovered that with continuous exposure to Carbon tetrachloride the natural level of the peptide fell with time
time. Replacing it through infusion (800 µg/kg/day for eight weeks) made it possible to maintain the level
output and limit liver damage, inflammation, and fibrosis. Liver enzyme levels
in the blood, the number of inflammatory cells decreased CD45⁺, and collagen and α-SMA deposits were reduced. Pro-fibrotic signals, such as TGF-β1 and phospho-
Smad2/3 were reduced, whereas repair-associated signals, BMP-7 and phospho-Smad1/5/8,
Increased. In cell tests, it directly blocked the activation of astrocytes,
confirming the anti-fibrotic action at the cellular level [61].
H2. Ac-SDKP for skin and tissue repair (based on research in
(on animals) H3. Hydrogel skin glue that speeds up healing and
scar-reducing
A special cellulose-based skin adhesive (Dopa-OCMC-PAA, compared to OCMC-PAA) was
created to carry and release Ac-SDKP. Both versions demonstrated good swelling profiles and
distribution, high mechanical strength and safety of use with cells, but the best
Dopa-OCMC-PAA achieved results. In mice with liver haemorrhage, this glue stopped it faster.
Bleeding. In fibroblast tests, it raised the levels of enzymes responsible for remodelling
tissues (MMP-1 and MMP-3), whilst reducing the activity of collagen genes. In rabbits with thickened
scars on the ears Dopa-OCMC-PAA in combination with peptide reduced scar assessment, lowered the number
cells, improved collagen structure, and again demonstrated higher levels of MMP-1/MMP-3 with less
collagen gene activity. In conclusion, these results demonstrated improved wound healing and reduced scarring [62].
H3. Topical application improves skin survival and repair
In skin flap operations in rats (ventral and dorsal flaps), Ac-SDKP injections in
dawce 5 µg/kg dwa razy dziennie przez trzy dni zwiększyły przeżywalność zdrowej skóry. Obszar żywego
The flap increased from 50.9 ± 19.3% to 66.4 ± 7.5% in the case of the abdominal flaps and from 53.4 ± 4.2% to 74.7 ±
6,6% in the case of dorsal flaps. In the case of skin tissue damaged by UVB radiation
Topical application improved survival. Topical application also accelerated growth.
new skin, increased keratin 14 levels (a marker for skin-building cells) and increased the level of
fibronectin, demonstrating its role in the development and repair of blood vessels [63].
H3. Protecting blood formation during chemotherapy
In mice receiving the chemotherapy drug doxorubicin, Ac-SDKP was administered at a dose of 2.4
µg/day (continuously or divided) starting 48 hours before treatment lowered
mortality and protected stem cells responsible for blood formation (LTRC, CFU-S, HPP-CFC and
CFU-GM). The addition of G-CSF further accelerated the recovery of CFU-GM. Timing was of the essence
applications — to protect against short-term bone marrow damage and long-term cell loss
mother cells, it was necessary to start administration before chemotherapy [64].
H3. Stronger anti-fibrotic action thanks to improved analogues and inhibitor combinations
AceIn experiments with lung fibroblasts, the ACE-resistant form of Ac-SDKP reduced signals
scarring (TGF-β/Smad3) and collagen accumulation better than the natural form. Shortened fragment
(Ac-DKP) had only a weak effect and was slowly metabolised by ACE. In combination with inhibitors
The ACE peptide inhibited hydroxyproline (a collagen marker) more than on its own, showing stronger
action and clinical potential. In doses from 10⁻⁶ to 10⁻¹⁷ M both thymosin-β4 (Tβ4) and the peptide
reduced mast cell growth (preferably at a dose 10⁻¹⁴ M and caused unusual changes
nuclear cell cycle arrest associated. At a concentration 10⁻⁸ M they also caused
release of chemical substances from mast cells (degranulation), with the peptide showing
stronger activity (~89%) than Tβ4 (~57%). Other fragments of Tβ4 showed no activity, which
demonstrates that the effect was specific to intact Tβ4 and the peptide [65, 66].
H2. Ac-SDKP Dose
In preclinical studies, Ac-SDKP is most commonly administered subcutaneously via minipump in
a dose of around 0.8 mg/kg/day to limit fibrosis and inflammation in the heart/vessels and
In mouse studies following myocardial infarction, a dose of 1.6 mg/kg/day is sometimes used for
to provide early protection. In the brain/nerves in short cycles starting within a few
hours from injury, a dose of approximately 0.8 mg/kg/day is usually administered for 3–7 days. In studies
Cellular therapy commonly uses an initial treatment of approximately 10 nM. In liver protocols
Antifibrotic agents are often given at a dose of around 0.8 mg/kg/day during chronic injury. In
In the bleomycin model of the lungs, a dose of 0.6 mg/kg was administered intraperitoneally with repeated doses.,
starting from day 0 or day 7. For skin repair/wound dressings, topical dosage
It involved 5 µg/kg per injection twice daily for 3 days or hydrogels containing peptides
for local release. In haematology/bone marrow protection, very low doses are used
microgram, such as 2.4 µg/day in mice before chemotherapy and short courses of µg/kg/day in
early clinical trials.References
1. Wang, W., Jia, W. and Zhang, C. (2022). The role of Tβ4-POP-Ac-SDKP axis in organ fibrosis. International journal of molecular sciences, 23(21), 13282. https://doi.org/10.3390/ ijms232113282
2. Nakagawa, P., Romero, C. A., Jiang, X., D’Ambrosio, M., Bordcoch, G., Peterson, E. L., Harding, P., Yang, X. P. and Carretero, O. A. (2018). Ac-SDKP reduces mortality and risk of heart rupture after acute myocardial infarction. PLoS One, 13(1), e0190300. https://doi.org/10.1371/ journal.pone.0190300 https://pubmed.ncbi.nlm.nih.gov/29364896/
3. Peng, H., Carretero, O. A., Brigstock, D. R., Oja-Tebbe, N. and Rhaleb, N. E. (2003). Ac-SDKP reverses cardiac fibrosis in rats with renal vascular hypertension. Hypertension, 42(6), 1164–1170. https://doi.org/10.1161/01.HYP.0000100423.24330.96 https://pubmed.ncbi.nlm.nih.gov/14581293/
4. Yang, F., Yang, X. P., Liu, Y. H., Xu, J., Cingolani, O., Rhaleb, N. E. and Carretero, O. A. (2004). Ac-SDKP reverses inflammation and fibrosis in rats with myocardial infarction-induced heart failure. Hypertension, 43(2), 229-236. https://doi.org/10.1161/01.HYP.0000107777.91185.89 https:// pubmed.ncbi.nlm.nih.gov/14691195/
5. Rasoul, S., Carretero, O. A., Peng, H., Cavasin, M. A., Zhuo, J., Sanchez-Mendoza, A., Brigstock, D. R. and Rhaleb, N. E. (2004). Anti-fibrotic effect of Ac-SDKP and angiotensin-converting enzyme inhibition in hypertension. Journal of Hypertension, 22(3), 593-603. https://doi.org/ 10.1097/00004872-200403000-00023 https://pubmed.ncbi.nlm.nih.gov/15076166/
6. Rhaleb, N. E., Peng, H., Harding, P., Tayeh, M., LaPointe, M. C. and Carretero, O. A. (2001). The effect of N-acetyl-seryl-aspartyl-lysyl-proline on DNA and collagen synthesis in rat heart fibroblasts. Hypertension, 37 (3), 827-832. https://doi.org/10.1161/01.hyp.37.3.827 https://pubmed.ncbi.nlm.nih.gov/11244003/
7. Liu, Y.-H., D'Ambrosio, M., Liao, T.-D., Peng, H., Rhaleb, N.-E., Sharma, U., André, S., Gabius, H.-J. and Carretero, O. A. (2009). N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodelling and dysfunction induced by galectin-3, a lectin that regulates adhesion/growth in mammals. American Journal of Physiology-Heart and Circulatory Physiology, 296(2), H404-H412. https://doi.org/ 10.1152/ajpheart.00747.2008 https://pubmed.ncbi.nlm.nih.gov/19098114/
8. Rhaleb, N. E., Peng, H., Yang, X. P., Liu, Y. H., Mehta, D., Ezan, E. i Carretero, O. A. (2001). Long-term effects of N-acetyl-seryl-aspartyl-lysyl-proline on collagen deposition in the left ventricle of rats with hypertension induced by two-kidney, one-clip. Circulation, 103(25), 3136–3141. https://doi.org/10.1161/01.cir.103.25.3136 https://pubmed.ncbi.nlm.nih.gov/11425781/
9. Cavasin M. A. (2006). The therapeutic potential of thymosin beta4 and its derivative N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) in the treatment of the post-infarction heart. American Journal of Cardiovascular Drugs : drugs, devices, and other interventions, 6(5), 305-311. https://doi.org/ 10.2165/00129784-200606050-00003 https://pubmed.ncbi.nlm.nih.gov/17083265/
10. Rhaleb, N. E., Pokharel, S., Sharma, U. C., Peng, H., Peterson, E., Harding, P., Yang, X. P. and Carretero, O. A. (2013). N-acetyl-Ser-Asp-Lys-Pro inhibits matrix metalloproteinase activation by interleukin-1β in cardiac fibroblasts. Pflügers Archiv – European Journal of Physiology, 465(10), 1487-1495. https://doi.org/10.1007/s00424-013-1262-8 https://Analysis of the effects of pre-operative anxiety on post-operative recovery.
11. Nakagawa, P., Liu, Y., Liao, T. D., Chen, X., González, G. E., Bobbitt, K. R., Smolarek, D., Peterson, E. L., Kedl, R., Yang, X. P., Rhaleb, N. E. and Carretero, O. A. (2012). N-acetyl-seryl-aspartyl-lysyl-proline treatment prevents experimental autoimmune myocarditis in rats. American Journal of Physiology-Heart and Circulatory Physiology, 303(9), H1114–H1127. https:// doi.org/10.1152/ajpheart.00300.2011 https://pubmed.ncbi.nlm.nih.gov/22923621/
12. González, G. E., Rhaleb, N. E., Nakagawa, P., Liao, T. D., Liu, Y., Leung, P., Dai, X., Yang, X. P. and Carretero, O. A. (2014). N-acetyl-seryl-aspartyl-lysyl-proline reduces cardiac collagen cross-linking and inflammation in angiotensin II-induced hypertensive rats. Clinical Science, 126(1), 85-
13. Peng, H., Xu, J., Yang, X. P., Kassem, K. M., Rhaleb, I. A., Peterson, E. and Rhaleb, N. E. (2019). N-acetyl-seryl-aspartyl-lysyl-proline treatment protects the heart from excessive myocardial damage and heart failure in mice. Canadian Journal of Physiology and Pharmacology, 97(8), 753–765. https://doi.org/10.1139/cjpp-2019-0047 https://pubmed.ncbi.nlm.nih.gov/30998852/
14. Castoldi, G., di Gioia, C. R. T., Bombardi, C., Perego, C., Perego, L., Mancini, M., Leopizzi, M., Corradi, B., Perlini, S., Zerbini, G. and Stella, A. (2009). Prevention of myocardial fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats. Clinical Science, 118(3), 211– 220. https:// doi.org/10.1042/cs20090234 https://pubmed.ncbi.nlm.nih.gov/20310083/
15. Sharma, U. C., Sonkawade, S. D., Baird, A., Chen, M., Xu, S., Sexton, S., Singh, A. K., Groman, A., Turowski, S. G., Spernyak, J. A., Mahajan, S. D. and Pokharel, S. (2018). The effect of the novel peptide Ac-SDKP on radiation-induced coronary endothelial damage and resting myocardial blood flow. Cardio-Oncology, 4, 8 . https://doi.org/10.1186/s40959-018-0034-1 https:// pubmed.ncbi.nlm.nih.gov/31057947/
16. Suhail, H., Peng, H., Matrougui, K. and Rhaleb, N. E. (2024). Ac-SDKP attenuates stress-induced ER
production of collagen in cardiac fibroblasts by inhibiting NF-κB expression
through CHOP. Frontiers in Pharmacology, 15, 1352222.
https://doi.org/10.3389/fphar.2024.1352222 https://pubmed.ncbi.nlm.nih.gov/38495093/
17. Zhu, L., Yang, X. P., Janic, B., Rhaleb, N. E., Harding, P., Nakagawa, P., Peterson, E. L. and Carretero,
O. A. (2016). Ac-SDKP inhibits TNF-α-induced ICAM-1 expression in endothelial cells
by inhibiting IκB kinase and activating NF-κB. American Journal of Physiology-Heart and
Circulatory Physiology, 3109), H1176-H1183. https://doi.org/10.1152/ajpheart.00252.2015
https://pubmed.ncbi.nlm.nih.gov/26945075/
18. Lin, C. X., Rhaleb, N. E., Yang, X. P., Liao, T. D., D’Ambrosio, M. A. and Carretero, O. A. (2008).
Prevention of aortic fibrosis with N-acetyl-seryl-aspartyl-lysyl-proline in hypertension
induced by angiotensin II. American Journal of Physiology-Heart and Circulatory Physiology, 295(3),
H1253–H1261. https://doi.org/10.1152/ajpheart.00481.2008
https://pubmed.ncbi.nlm.nih.gov/18641275/
19. Sharma, U. C., Sonkawade, S. D., Spernyak, J. A., Sexton, S., Nguyen, J., Dahal, S., Attwood, K. M.,
Singh, A. K., van Berlo, J. H. i Pokharel, S. (2018). The small peptide Ac-SDKP inhibits radiation-induced cardiomyopathy. Circulation: Heart Failure, 11(8), e004867. https://doi.org/
10.1161/CIRCHEARTFAILURE.117.004867 https://pubmed.ncbi.nlm.nih.gov/30354563/
20. Conte, E., Iemmolo, M., Fruciano, M., Fagone, E., Gili, E., Genovese, T., Esposito, E., Cuzzocrea, S. and
Vancheri, C. (2015). The influence of thymosin β4 and its N-terminal fragment Ac-SDKP on human fibroblasts
pulmonary explants exposed to TGF-β and in a murine model of bleomycin-induced pulmonary fibrosis.
Expert Opinion on Biological Therapy, 15(Suppl 1), S211–S221. https://doi.org/
10.1517/14712598.2015.1026804 https://pubmed.ncbi.nlm.nih.gov/26098610/
21. Liu, S., Jin, R., Zheng, G., Wang, Y., Li, Q., Jin, F., Li, Y., Li, T., Mao, N., Wei, Z., Li, G., Fan, Y.,
Xu, H., Li, S. and Yang, F. (2023). Ac-SDKP promotes $\beta$-catenin inhibition via KIF3A.
through the ciliary mechanism to limit silica-induced transformation
epithelio-myofibroblastic. Biomedicine & Pharmacotherapy, 166, 115411.
https://doi.org/10.1016/j.biopha.2023.115411 https://pubmed.ncbi.nlm.nih.gov/37651800/
22. Cai, J., Chen, Q., Mehrabi Nasab, E. and Athari, S. S. (2022). Immunomodulatory effect of N-acetyl-
seryl-aspartyl-proline and intestinal vasoactive peptide on the pathophysiology of chronic obstructive
Lung diseases. Fundamental & Clinical Pharmacology, 36(6), 1005–1010. https://
doi.org/10.1111/fcp.12811 https://pubmed.ncbi.nlm.nih.gov/35763864/
23. Wang, J., Qian, Y., Gao, X., Mao, N., Geng, Y., Lin, G., Zhang, G., Li, H., Yang, F. and Xu, H. (2020).
Synthesis and identification of a new peptide, Ac-SDK (biotin) proline, which may induce action
anti-fibrotic in rats suffering from silicosis. Drug design, development and therapy, 14,
4315–4326. https://doi.org/10.2147/DDDT.S262716 https://pubmed.ncbi.nlm.nih.gov/33116418/
24. Conte, E., Fagone, E., Gili, E., Fruciano, M., Iemmolo, M., Pistorio, M. P., Impellizzeri, D., Cordaro, M.,
Cuzzocrea, S., & Vancheri, C. (2016). Preventative and therapeutic effects of the N-terminal fragment
Thymosin β4 Ac-SDKP in a bleomycin-induced lung fibrosis model. Oncotarget, 7th23),
33841–33854. https://doi.org/10.18632/oncotarget.8409 https://
pubmed.ncbi.nlm.nih.gov/27029074/
25. Cao, W., Yao, S. S., Gong, H. B., Zhu, L. Y., Miao, Z. Y. and Deng, H. J. (2022). The regulatory effect of Ac-
SDKP on the trail of phosphorylated heat shock protein 27/SNAI1 in rats with silicosis. China
Labour Hygiene Association Journal, 40(2), 90-96. https://doi.org/10.3760/ cma.j.cn121094-
20201218-00702 https://pubmed.ncbi.nlm.nih.gov/35255573/
26. Gong, H. B., Zhang, C. M., Tang, X. Y., Gong, R. B., Miao, Z. Y. and Deng, H. J. (2023). Meta-analysis
Inhibition of pulmonary fibrosis by Ac-SDKP in animal models. Zhonghua Lao Dong Wei
Sheng Zhi Ye Bing Zhi, 41 ( 4 ) , 2 6 2 – 2 7 0 . https://doi.org/10.3760/
cma.j.cn121094-20211115-00565 https://pubmed.ncbi.nlm.nih.gov/37248179/
27. Li, Q., Yang, F., Zhang, L.-J., Yan, J.-B., Chen, P., Li, D.-D., & Wu, K.-F. (2009). [Anti-fibrotic
The action of N-acetyl-seryl-aspartyl-lysyl-proline through the regulation of transforming growth factor expression
[Levels of beta-transforming growth factor and connective tissue growth factor in rats with silicosis]. Zhonghua Lao Dong Wei
Sheng Zhi Ye Bing Za Zhi, 27(7), 390–394. PMID: 20039536 https://
pubmed.ncbi.nlm.nih.gov/20039536/28. Yan, J.-B., Zhang, L.-J. i Li, Q. (2008). [Antifibrotic effect of N-acetyl-seryl-aspartyl-lysyl-
nodules in the lungs of rats with silicosis. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi, 26(7),
401–405. PMID: 19080377 https://pubmed.ncbi.nlm.nih.gov/19080377/
29. Jin, F., Geng, F., Xu, D., Li, Y., Li, T., Yang, X., Liu, S., Zhang, H., Wei, Z., Li, S., Gao, X., Cai, W.,
Mao, N., Yi, X., Liu, H., Sun, Y., Yang, F. and Xu, H. (2021). Ac-SDKP weakens macrophage activation
pulmonary and bone osteoclasts in rats exposed to silica through inhibition
TLR4 and RANKL signalling pathways. Journal of Inflammation Research, 14, 1647-1660.
https://doi.org/10.2147/ JIR.S306883 https://pubmed.ncbi.nlm.nih.gov/33948088/
30. Xu, H., Yang, F., Sun, Y., Yuan, Y., Cheng, H., Wei, Z., Li, S., Cheng, T., Brann, D. and Wang, R. (2012).
New antifibrotic drug Ac-SDKP: inhibition of myofibroblast differentiation in the lungs
silicosis rats. PLoS One, 7(7), e40301. https://doi.org/10.1371/journal.pone.0040301 https://
pubmed.ncbi.nlm.nih.gov/22802960/
31. Wang, X., Liu, Y., Xu, H., Zhang, X., Li, S., Xu, D., Gao, X., Zhang, L., Zhang, B., Wei, Z., Wang, R.,
Brann, D. & Yang, F. (2016). Acetylated α-tubulin regulated by N-acetyl-seryl-aspartyl-lysyl-
proline (Ac-SDKP) exerts an antifibrotic effect in rat pulmonary fibrosis induced by
through silica. Scientific Reports, 6, 32257. https://doi.org/10.1038/srep32257
https://pubmed.ncbi.nlm.nih.gov/27577858/
32. Deng, H., Xu, H., Zhang, X., Sun, Y., Wang, R., Brann, D. and Yang, F. (2016). Protective effect of Ac-
SDKP for lung epithelial cells by inhibiting EMT via the pathway
TGF-β1/ROCK1 in silicosis in rats. Toxicology and applied pharmacology, 294, 1-10.
https://doi.org/10.1016/ j.taap.2016.01.010 https://pubmed.ncbi.nlm.nih.gov/26785300/
33. Zhang, L., Xu, D., Li, Q., Yang, Y., Xu, H., Wei, Z., Wang, R., Zhang, W., Liu, Y., Geng, Y., Li, S., Gao,
X. and Yang, F. (2018). N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) alleviates silicosis fibrosis
by inhibiting apoptosis of pulmonary alveolar epithelial cells type II through
Endoplasmic reticulum stress mediation. Toxicology and applied pharmacology, 350, 1–
10. https://doi.org/10.1016/ j.taap.2018.04.025 https://pubmed.ncbi.nlm.nih.gov/29684394/
34. Nakagawa, P., Masjoan-Juncos, J. X., Basha, H., Janic, B., Worou, M. E., Liao, T. D., Romero, C. A.,
Peterson, E. L., & Carretero, O. A. (2017). The effect of N-acetyl-seryl-aspartyl-lysyl-proline on blood pressure.,
Kidney damage and mortality in systemic lupus erythematosus. Physiological Reports, 5(2),
e13084. https://doi.org/10.14814/phy2.13084 https://pubmed.ncbi.nlm.nih.gov/ 28126732/
35. Worou, M. E., Liao, T. D., D’Ambrosio, M., Nakagawa, P., Janic, B., Peterson, E. L., Rhaleb, N. E. et al
Carretero, O. A. (2015). Protective effect of N-acetyl-seryl-aspartyl-lysyl-proline on rat kidneys
salt-sensitive Dahl. Hypertension, 664), 816-822. https://doi.org/10.1161/
HYPERTENSION AHA.115.05970 https://pubmed.ncbi.nlm.nih.gov/26324505/
36. Liao, T. D., Nakagawa, P., Janic, B., D’Ambrosio, M., Worou, M. E., Peterson, E. L., Rhaleb, N. E.,
Yang, X. P. and Carretero, O. A. (2015). N-Acetyl-Seryl-Aspartyl-Lysyl-Proline: mechanisms of protection
The kidney in a mouse model of systemic lupus erythematosus. American Journal of Physiology-Renal
Physiology, 308 (10), F1146-F1154. https://doi.org/10.1152/ajprenal.00039.2015
https://pubmed.ncbi.nlm.nih.gov/25740596/37. Rhaleb, N. E., Pokharel, S., Sharma, U. and Carretero, O. A. (2011). Protective effect of N-acetyl-Ser-
Asp-Lys-Pro for kidneys in mice with deoxcorticosterone acetate-salt-induced hypertension.
Journal of Hypertension, 29(2), 330–338. https://doi.org/10.1097/HJH.0b013e32834103ee
pubmed.ncbi.nlm.nih.gov/21052020/
38. Shibuya, K., Kanasaki, K., Isono, M., Sato, H., Omata, M., Sugimoto, T., Araki, S., Isshiki, K.,
Kashiwagi, A., Haneda, M. and Koya, D. (2005). N-acetyl-seryl-aspartyl-lysyl-proline prevents
kidney failure and mesangial matrix expansion in db/db mice with diabetes. Diabetes, 54(3),
838–845. https://doi.org/10.2337/diabetes.54.3.838 https://pubmed.ncbi.nlm.nih.gov/15734863/
39. Castoldi, G., di Gioia, C. R. T., Bombardi, C., Preziuso, C., Leopizzi, M., Maestroni, S., Corradi, B.,
Zerbini, G. & Stella, A. (2013). Antifibrotic effect of N-acety-seryl-aspartyl-lysyl-proline on
Kidneys in rats with diabetes. American Journal of Nephrology, 37(1), 65-73.
https://doi.org/10.1159/000346116 https://pubmed.ncbi.nlm.nih.gov/23327833/
40. Zhang, R., Hu, Z., Wang, Y., Qiu, R., Wang, G., Wang, L. & Hu, B. (2022). Biomimetyczny hydrożel o
The dual network alleviates kidney fibrosis and promotes their regeneration. Journal of Materials
Chemistry B, 10 (45), 9424-9437. https://doi.org/10.1039/d2tb01939f https://
pubmed.ncbi.nlm.nih.gov/36378134/
41. Zuo, Y., Chun, B., Potthoff, S. A., Kazi, N., Brolin, T. J., Orhan, D., Yang, H.-C., Ma, L.-J., Kon, V.,
Late, T., Rhaleb, N.-E., Carretero, O. A. and Fogo, A. B. (2013). Thymosin β4 and its product
degradation, Ac-SDKP, are novel repair agents in kidney fibrosis. Kidney International,
84(6), 1166–1175. https://doi.org/10.1038/ki.2013.209 https://pubmed.ncbi.nlm.nih.gov/23739235/
42. Wang, M., Liu, R., Jia, X., Mu, S. and Xie, R. (2010). N-acetyl-seryl-aspartyl-lysyl-proline ameliorates the condition
nephritis and tubulointerstitial fibrosis in rats. International Journal of Molecular
Medicine, 26 (6), 795-801. https://doi.org/10.3892/ijmm_00000527 https://
pubmed.ncbi.nlm.nih.gov/21042772/
43. Liao, T.-D., Yang, X.-P., D’Ambrosio, M., Zhang, Y., Rhaleb, N.-E. and Carretero, O. A. (2010). N-acetyl-
seryl-aspartyl-lysyl-proline alleviates kidney damage and dysfunction in rats with hypertension
and reduced kidney mass: Blood Pressure Research Council. High blood pressure
Arterial, 552), 459-467. https://doi.org/10.1161/HYPERTENSIONAHA.109.144568
https://pubmed.ncbi.nlm.nih.gov/ 20026760/
44. Peng, H., Carretero, O. A., Raij, L., Yang, F., Kapke, A. and Rhaleb, N. E. (2001). Anti-fibrotic
The effect of N-acetyl-seryl-aspartyl-lysyl-proline on the heart and kidneys in rats with induced hypertension
aldosterone and salt. Hypertension, 37(2 Pt 2), 794-800. https://doi.org/10.1161/01.hyp.37.2.794
https:// pubmed.ncbi.nlm.nih.gov/11230375/
45. Omata, M., Taniguchi, H., Koya, D., Kanasaki, K., Sho, R., Kato, Y., Kojima, R., Haneda, M. and Inomata,
N. (2006). N-acetyl-seryl-aspartyl-lysyl-proline attenuates the progression of kidney dysfunction and fibrosis in
WKY rats with diagnosed glomerulonephritis. Journal of the American Society of
Nephrology, 17(3), 674–685. https://doi.org/10.1681/ ASN.2005040385
https://pubmed.ncbi.nlm.nih.gov/16452498/
46. Nagai, T., Kanasaki, M., Srivastava, S. P., Nakamura, Y., Ishigaki, Y., Kitada, M., Shi, S., Kanasaki, K.
Koya, D. (2014). N-acetyl-seryl-aspartyl-lysyl-proline inhibits diabetes-related kidney fibrosis and epithelial-to-mesenchymal transition. BioMed Research
International, 2014, 696475. https://doi.org/10.1155/2014/696475
https://pubmed.ncbi.nlm.nih.gov/24783220/
47. Srivastava, S. P., Goodwin, J. E., Kanasaki, K. and Koya, D. (2020). Metabolic reprogramming for
N-acetyl-seryl-aspartyl-lysyl-proline protects against diabetic kidney disease. British Journal
of Pharmacology, 177 (16), 3691-3711. https://doi.org/10.1111/bph.15087 https://
pubmed.ncbi.nlm.nih.gov/32352559/
48. Carde, P., Chastang, C., Goncalves, E., Mathieu-Tubiana, N., Vuillemin, E., Delwail, V., Corbion, O.,
Vekhoff, A., Isnard, F., Ferrero, J. M., et al. (1992). [Seraspenid (acetylSDKP): phase clinical trial
I–II concerning a haematopoietic inhibitor protecting against the toxicity of arabinoside monochemotherapy
Ifosfamide. Clinical study C R Acad Sci III, 315(13), 545–550. PMID: 1300237 https://
https://pubmed.ncbi.nlm.nih.gov/1300237/
49. Cappelaere, P., Hecquet, B., Rolland, F., Meeus, L., Domenge, C., Krakowski, I., De Gislain, C.,
Chauvergne, J., Dufour-Esquerré, F., Carde, P. (1995). [Randomised placebo-controlled study of
bone marrow protection using goralatide in patients with upper squamous cell carcinoma
of the respiratory tract and the gastrointestinal tract or oesophagus, treated with a combination of carboplatin and
Fluorouracil. Bull Cancer, 82(9), 732-737. PMID: 8535033 https://pubmed.ncbi.nlm.nih.gov/8535033/
50. Nitta, K., Shi, S., Nagai, T., Kanasaki, M., Kitada, M., Srivastava, S. P., Haneda, M., Kanasaki, K. i
Koya, D. (2016). D osage of N-acetyl-seryl-aspartyl-lysyl-proline alleviates kidney disease in
mice with type 1 and type 2 diabetes through a therapeutic regimen. BioMed Research International,
2016 , 9172157 . https://doi.org/10.1155/2016/9172157 https://
pubmed.ncbi.nlm.nih.gov/27088094/
51. Tan, H., Zhao, J., Wang, S., Zhang, L., Wang, H., Huang, B., Liang, Y., Yu, X. and Yang, N. (2012). Ac-
SDKP alleviates the progression of lupus nephritis in MRL/lpr mice. International
Immunopharmacology, 14(4), 401–409. https://doi.org/10.1016/j.intimp.2012.07.023https://
"Pubmed"
52. Maheshwari, M., Romero, C. A., Monu, S. R., Kumar, N., Liao, T. D., Peterson, E. L. and Carretero,
O. A. (2018). Renal protective effects of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) in obese rats
on a diet high in salt. American Journal of Hypertension, 31(8), 902-909. https://doi.org/
10.1093/ajh/hpy052 https://pubmed.ncbi.nlm.nih.gov/29722788/
53. Neuroprotective effect of Ac-SDKP peptide in cells
SH-SY5Y and a rat model of Parkinson's disease against oxidative stress induced
by 6-OHDA and ER stress. Neuropeptides, 112, 102534. https://doi.org/10.1016/j.npep.2025.102534
https:// pubmed.ncbi.nlm.nih.gov/40544680/
54. Hashemizadeh, S., Pourkhodadad, S., Hosseindoost, S., Pejman, S., Kamarehei, M., Badripour, A.,
Omidi, A., Pestehei, S. K., Seifalian, A. M. and Hadjighassem, M. (2022). Ac-SDKP peptide improves
Recovery of function after spinal cord injury in a preclinical model. Neuropeptides, 92, 102228.
https://doi.org/10.1016/j.npep.2022.102228 https://pubmed.ncbi.nlm.nih.gov/ 35101843/
55. Zhang, Y., Zhang, Z. G., Chopp, M., Meng, Y., Zhang, L., Mahmood, A. i Xiong, Y. (2017). Leczenie
traumatic brain injury in rats using N-acetylo-seryl-aspartyl-lizyl-prolina. Journal of Neurosurgery, 126(3), 782-795. https://doi.org/10.3171/2016.3.JNS152699 http://
https://pubmed.ncbi.nlm.nih.gov/28245754/
56. Pejman, S., Kamarehei, M., Riazi, G., Pooyan, S., & Balalaie, S. (2020). Ac-SDKP ameliorates progression
experimental autoimmune encephalomyelitis by inhibiting ER stress
oxidative stress in the hippocampus of C57BL/6 mice. Brain Research Bulletin, 154, 21–31.
https://doi.org/10.1016/j.brainresbull.2019.09.014 https://pubmed.ncbi.nlm.nih.gov/31589901/
57. Zhang, L., Chopp, M., Teng, H., Ding, G., Jiang, Q., Yang, X. P., Rhaleb, N. E. and Zhang, Z. G. (2014).
Combination therapy of N-acetyl-seryl-aspartyl-lysyl-proline and tissue plasminogen activator
provides strong neuroprotection in rats after stroke. Stroke, 45(4), 1108–1114. https://
doi.org/10.1161/STROKEAHA.113.004399 https://pubmed.ncbi.nlm.nih.gov/24549864/
58. Kim, D. H., Moon, E.-Y., Yi, J. H., Lee, H. E., Park, S. J., Ryu, Y.-K., Kim, H.-C., Lee, S. and Ryu, J.
H. (2015). Thymosin beta-4 peptide fragment enhances neurogenesis in the hippocampus and facilitates memory
spatial. Neuroscience, 310, 51-62. https://doi.org/10.1016/j.neuroscience.2015.09.017
https://pubmed.ncbi.nlm.nih.gov/26363149/
59. Wei, A., Zhao, F., Hao, A., Liu, B., & Liu, Z. (2022). N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP)
It alleviates liver fibrosis via the WTAP/m6A/Ptch1 axis through the Hedgehog pathway. Gene, 813,
146125. https://doi.org/10.1016/j.gene.2021.146125 https://pubmed.ncbi.nlm.nih.gov/34921949/
60. Zhang, L., Xu, L. M., Chen, Y. W., Ni, Q. W., Zhou, M., Qu, C. Y. and Zhang, Y. (2012).
Anti-fibrotic activity of N-acetyl-seryl-aspartyl-lysyl-proline on liver fibrosis
induced by bile duct ligation in rats. World Journal of Gastroenterology, 18(37),
5283–5288. https://doi.org/10.3748/wjg.v18.i37.5283 https://pubmed.ncbi.nlm.nih.gov/23066324/
61. Chen, Y. W., Liu, B. W., Zhang, Y. J., Chen, Y. W., Dong, G. F., Ding, X. D., Xu, L. M., Pat, B.,
Fan, J. G. and Li, D. G. (2010). Maintaining basal AcSDKP levels mitigates fibrosis
liver in rats induced by carbon tetrachloride. Journal of Hepatology, 53(3), 528-536.
https://doi.org/10.1016/ j.jhep.2010.03.027 https://pubmed.ncbi.nlm.nih.gov/20646773/
62. Ameri, Z., Shahabi, A., Farsinejad, A., Sattarzadeh Bardsiri, M., Javedani, H., Bagher, Z., Saraee, A. and
Brouki Milan, P. (2025). Adhesive cellulose-based hydrogel containing N-acetyl-seryl-
aspartyl-lysyl-proline to accelerate wound healing and prevent scar formation in
model of rabbit ears with in vivo scars. International Journal of Biological Macromolecules, 322(A pt
1), 144981. https:// doi.org/10.1016/j.ijbiomac.2025.144981
https://pubmed.ncbi.nlm.nih.gov/40480579/
63. Fromes, Y., Liu, J. M., Kovacevic, M., Bignon, J. and Wdzieczak-Bakala, J. (2006). Acetyl-tetrapeptide-
Seryna-asparaginylo-lizyno-prolina improves skin flap survival and accelerates wound healing.
Wound Repair and Regeneration, 14 (3), 306-312. https://doi.org/10.1111/ j.1743-
6109.2006.00125.x https://pubmed.ncbi.nlm.nih.gov/16808809/
64. Massé, A., Ramirez, L. H., Bindoula, G., Grillon, C., Wdzieczak-Bakala, J., Raddassi, K., Deschamps
de Paillette, E., Mencia-Huerta, J. M., Koscielny, S., Potier, P., Sainteny, F. and Carde,
P. (1998). Acetyl-N-Ser-Asp-Lys-Pro tetrapeptide (Goralatide) protects against toxicity induced
through doxorubicin: improved survival in mice and protection of bone marrow stem cells
bone and progenitor cells. Blood, 91(2), 441-449. PMID: 9427696
https://pubmed.ncbi.nlm.nih.gov/9427696/65. Ramasamy, V., Ntsekhe, M. and Sturrock, E. (2021). Study of anti-fibrotic potential
N-acetyl-seryl-aspartyl-lysyl-proline sequence peptides. Clinical and Experimental
Pharmacology and Physiology, 48(11), 1558–1565. https://doi.org/10.1111/1440-1681.13565 https://
Relevance of PNA FISH and RT-PCR in the identification of canine parvovirus 2 in clinical samples.
66. Leeanansaksiri, W., DeSimone, S. K., Huff, T., Hannappel, E. and Huff, T. F. (2004). Thymosin beta
4 and its N-terminal tetrapeptide, AcSDKP, inhibit proliferation and induce dysplastic,
non-apoptotic nuclei and mast cell degranulation. Chemistry & Biodiversity, 1(7), 1091–
1100. https://doi.org/10.1002/cbdv.200490081 https://pubmed.ncbi.nlm.nih.gov/17191900/