Buy AICAR 50mg Online Advanced Research Peptide for AMPK Activation

Buy AICAR 50mg Online Advanced Research Peptide for AMPK Activation

In 2012, the RED-CABG trial was stopped early after interim data failed to indicate a reduction in morbidity or mortality among intermediate- to high-risk patients receiving AICAr versus placebo [15]. As a cell-permeable nucleotide, AICAr enters the cells through adenosine transporters [20] and becomes phosphorylated by adenosine kinase into AICAR [21]. AICAR or ZMP activates AMPK but it is 40- to 50- fold less potent than AMP in AMPK activation and accumulates in high concentrations in the cytoplasm [1], so that it was always likely that AICAr may have several AMPK-independent effects.

  • 5-Aminoimidazole-4-formamide ribonucleotide (AICAR) is a kind of cellular permeable nucleoside that activates AMPK to play anti-inflammatory and antioxidant stress effects (Swinnen et al., 2005; Bone et al., 2017; Kaphalia et al., 2019).
  • All animal procedures were reviewed and approved by the Animal Ethics Committee of Wenzhou Medical University.
  • The nuclear translocation of Nrf2 was increased following sodium taurocholate treatment, whereas AICAR supplementation further promoted the nuclear accumulation of Nrf2 (Figures 4A,C).
  • Moreover, the serum levels of ALT and AST in both WT and Nrf2 KO mice were augmented after L-arginine administration.

Associated Data

Interestingly, treatment with CC significantly exacerbated sodium taurocholate-induced pancreatic injury in rats, as evidenced by further increased acinar necrosis and inflammatory cell infiltration (Figure 5B). Evaluation of the pancreatitis score in pancreatic sections also revealed that CC treatment was accompanied by more severe pancreatic injury than SAP (Figure 5D). We also observed that administration of CC in rats augmented SAP-induced edema, necrosis and structural disorder in hepatic lobules with further increased liver injury scores compared with SAP rats (Figures 5C,D). In addition, the amplitude of SAP-induced elevation of serum levels of both ALT and AST, two markers of liver injury, in CC-treated rats was higher than that in the SAP groups (Figure 5E).

AICAr, AMPK, Cancer, and Leukemia

These observations confirm that AICAR treatment protects against PALI in sodium taurocholate-induced SAP rats, likely by inhibiting the inflammatory response in the liver. To verify our hypothesis, we used Nrf2 KO mice and WT mice to conduct a comparative study in an L-arginine-induced PALI model with or without AICAR treatment. We found that knockout of Nrf2 limited the ability of AICAR to reduce the severity of PALI in mice (Figures 7A–E). Most importantly, Nrf2 gene deletion markedly weakened the protective effects of AICAR to prevent SAP-induced oxidative stress and NLRP3 inflammasome activation in the liver tissues of L-arginine-induced PALI mice (Figure 7F, Figures 8B,C). AMPK can regulate a variety of physiological and pathological effects through multiple pathways to affect cell metabolism and survival (Carling, 2017; Ramirez Reyes et al., 2021).

Table 2

In human aortic endothelial cells, AICAr stimulated AMPK activity and nitric oxide (NO) production, and the effects were proved to be AMPK-dependent since the effects were inhibited by the expression of a dominant-negative (DN) AMPK mutant [60]. Similar AMPK-dependent effects on NO production were observed in response to hypoxia [61], and studies performed in the knockout of the upstream kinase LKB1 confirmed the important role of AMPK in angiogenesis [62]. When it comes to enhancing athletic performance and improving training results, many athletes and fitness enthusiasts turn to supplements and peptides to give them an edge.

Adenosine is a potent vasodilator that plays a key role in reducing ischemia/reperfusion injury, but the applications for systemic adenosine are limited owing to peripheral hemodynamic actions [13]. As shown in Figure 1, AICAr shares structural similarities with adenosine, and therefore, can increase the extracellular concentrations of adenosine by competing for the nucleoside transporter [20]. In addition, AICAR increases intracellular concentrations by inhibiting adenosine deaminase and increasing the production of adenosine rather than inosine from ATP catabolism.

It is one of the most effective means of boosting glucose uptake by muscle cells and effectively reduces both glucose levels and insulin resistance. It turns out that AICAR mimics the effects of exercise very precisely and that repeated administration of AICAR has effects similar to long-term exercise[3]. Over the last 25 years, AICAr has been used in hundreds of studies as an activator of AMPK. The results of these initial studies pointed to the important roles of AMPK, and many of them have been later confirmed by studies in transgenic mice or by using models of cells with overexpression or down-regulation of AMPK.

These findings suggest that AICAR markedly alters the nuclear accumulation of Nrf2 and inhibits NLRP3 inflammasome activation in sodium taurocholate-induced PALI rats by activating AMPK phosphorylation. Thus, we speculate that Nrf2 and NLRP3 inflammasome pathway may mediate essential parts in the protective roles of AICAR against oxidative stress and inflammation in sodium taurocholate-induced PALI rats. The initial body weight of the animals in all groups at the beginning of the study did not differ. By the end of the fourth week of the study (Day 28), there was a significant increase in body weight relative to the control group in groups 3 (HFD + vehicle), 5 (HFD + AC 7), and 6 (HFD + AC + MTX) (26.8 ± 2.0 g, 26.4 ± 1.7 g and 26.7 ± 1.9 g, respectively, versus 24.7 ± 1.1 g in the STD + vehicle group). This difference in weight remained unchanged throughout the lifetime phase of the study, i.e., the absolute weight of all the animals treated with HFD was significantly different from the weight of control animals from the fourth week of the study (Table 1). At the same time, the body weight, as well as the increase in body weight of animals from group 4, which received AICAR against the background of HFD starting from the first day, did not differ from that in group 3, which received HFD and the vehicle (Table 1 and Table 2).

In all the AICAR-treated animals, the visually assessed body fat was lower compared to untreated HFD animals. Additionally, all the animals treated with AICAR had a significantly reduced mass of adipose tissue surrounding the epididymis, relative to the animals on HFD without treatment. AICAR administered against the background of HDJ, on the contrary, improved the functional morphology of the liver—reduced the accumulation of glycogen in hepatocytes. AICAR, introduced from the first day of the study, reduced the content of lipid inclusions in the cytoplasm. Methotrexate administration had no effect on the therapeutic activity of AICAR in the study.

Of course, AICAR can also be synthesized in the lab, which is why it continues to be studied due to its potential in performance boost. Insulin was determined in the blood serum of all animals using non-competitive enzyme immunoassay with a test system (Insulin-ELISA-BEST, JSC Vector-BEST, Novosibirsk, Russia) and a Multiskan™ GO spectrophotometer (Termo Scientific, Waltham, MA, USA). The animal study was reviewed and approved by the Animal Ethics Committee of Wenzhou Medical University.

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