Ac2-26 ameliorates lung ischemia-reperfusion injury via the eNOS pathway

Gong, Jianping; Ju, Yingnan; Wang, Xueting; Zhu, Jingli; Jin, Zhousheng

doi:10.1016/j.biopha.2019.109194

Cited by 20 publications

(32 citation statements)

References 31 publications

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“…AnxA1 and its active peptide, Ac2-26, have been suggested to reduce heart and lung ischemia reperfusion injury [12,19]. We previously reported that Ac2-26 can reduce lung ischemia reperfusion injury by regulating inflammation [20]. Exogenous AnxA1 administration can inhibit the noninflammatory phagocytosis of apoptotic neurons and reduce the production of inflammatory mediators [21].…”

Section: Discussionmentioning

confidence: 99%

Ac2-26 Alleviates Brain Injury after Cardiac Arrest and Cardiopulmonary Resuscitation in Rats via the eNOS Pathway

Gong

Tai

et al. 2020

Mediators of Inflammation

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Background. Brain injury is the leading cause of death following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Ac2-26 and endothelial nitric oxide synthase (eNOS) have been shown to reduce neuroinflammation. This study is aimed at determining the mechanism by which Ac2-26 protects against inflammation during brain injury following CA and CPR. Methods. Sixty-four rats were randomized into sham, saline, Ac2-26, and Ac2-26+L-NIO (endothelial nitric oxide synthase (eNOS) inhibitor) groups. Rats received Ac2-26, Ac2-26+L-NIO, or saline after CPR. Neurologic function was assessed at baseline, 24, and 72 hours after CPR. At 72 hours after resuscitation, serum and brain tissues were collected. Results. Blood-brain barrier (BBB) permeability increased, and the number of surviving neurons and neurological function decreased in the saline group compared to the sham group. Anti-inflammatory and proinflammatory factors, neuron-specific enolase (NSE) levels, and the expression of eNOS, phosphorylated (p)-eNOS, inducible nitric oxide synthase (iNOS), and oxidative stress-related factors in the three CA groups significantly increased (P<0.05). BBB permeability decreased, and the number of surviving neurons and neurological function increased in the Ac2-26 group compared to the saline group (P<0.05). Ac2-26 increased anti-inflammatory and reduced proinflammatory markers, raised NSE levels, increased the expression of eNOS and p-eNOS, and reduced the expression of iNOS and oxidative stress-related factors compared to the saline group (P<0.05). The effect of Ac2-26 on brain injury was reversed by L-NIO (P<0.05). Conclusions. Ac2-26 reduced brain injury after CPR by inhibiting oxidative stress and neuroinflammation and protecting the BBB. The therapeutic effect of Ac2-26 on brain injury was largely dependent on the eNOS pathway.

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Section: Discussionmentioning

confidence: 99%

Ac2-26 Alleviates Brain Injury after Cardiac Arrest and Cardiopulmonary Resuscitation in Rats via the eNOS Pathway

Gong

Tai

et al. 2020

Mediators of Inflammation

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“…Then, the rats were extubated [ 11 ]. After instillation, rats in the S and A groups received saline for intravenous injection, while rats in the AA and AAB groups received Ac2-26 (1 mg/kg [ 7 , 9 , 10 ]) and Ac2-26/BOC (600 ng/kg [ 12 ]), respectively. After 24 h, all rats were anaesthetized, as previously described, and intubated.…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, the expression of formyl peptide receptor (FPR) in endothelial cells and epithelial cells significantly increases after the stimulation of endotoxins [ 8 ], and the protection of Ac2-26 is mainly dependent on the activation of FPR [ 6 , 7 ]. The previous studies conducted by the investigators also indicated that Ac2-26 protected the lungs and brain from ischaemia and reperfusion injury via reducing local inflammation [ 9 , 10 ]. These studies suggest that, as an active peptide of Annexin A1, Ac2-26 has a powerful and effective anti-inflammatory property.…”

Section: Introductionmentioning

confidence: 99%

Ac2-26 mitigated acute respiratory distress syndrome rats via formyl peptide receptor pathway

Qiu

Sun

et al. 2021

Annals of Medicine

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Background: Acute respiratory distress syndrome (ARDS) is characterized by severe local and systemic inflammation. Ac2-26, an Annexin A1 Peptide, can reduce the lung injury induced by reperfusion via the inhibition of inflammation. The present study aims to evaluate the effect and mechanism of Ac2-26 in ARDS. Methods: Thirty-two rats were anaesthetized and randomized into four groups: sham (S), ARDS (A), ARDS/Ac2-26 (AA), and ARDS/Ac2-26/BOC-2 (AAB) groups. Rats in the S group received saline for intratracheal instillation, while rats in the other three groups received endotoxin for intratracheal instillation, in order to prepare the ARDS and inject the saline, Ac2-26, and Ac2-26 combined with BOC-2. After 24 h, the PaO 2 /FiO 2 ratio was calculated. The lung tissue wet-to-dry weight ratio and the protein level in bronchoalveolar lavage fluid (BALF) were tested. Then, the cytokines in BALF and serum, and the inflammatory cells in BALF were investigated. Afterwards, the oxidative stress response and histological injury was evaluated. Subsequently, the epithelium was cultured and analyzed to estimate the effect of Ac2-26 on apoptosis. Results: Compared to the S group, all indexes worsened in the A, AA, and AAB groups. Furthermore, compared to the S group, Ac2-26 significantly improved the lung injury and alveolar-capillary permeability, and inhibited the oxidative stress response. In addition, Ac2-26 reduced the local and systemic inflammation through the regulation of pro-and anti-inflammatory cytokines, and the decrease in inflammatory cells in BALF. Moreover, Ac2-26 inhibited the epithelium apoptosis induced by LPS through the modulation of apoptosis-regulated proteins. The protective effect of Ac2-26 on ARDS was partially reversed by the FPR inhibitor, BOC-2. Conclusion: Ac2-26 reduced the lung injury induced by LPS, promoted alveolar-capillary permeability, ameliorated the local and systemic inflammation, and inhibited the oxidative stress response and apoptosis. The protection of Ac2-26 on ARDS was mainly dependent on the FPR pathway.

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“…This peptide exerts it effects by activation of the formyl peptide receptor type 1 (FPR1) and type 2 (FPR2) [18] , [19] . The anti-inflammatory effects of Ac2-26 were observed in many experimental models where inflammation is an important component including allergic conjuntivits [20] , skin allograft survival [21] , brain sepsis [22] , experimental pneumococcal pneumonia [23] , lung injury after ischemia–reperfusion [24] , chronic obstructive pulmonary disease [25] , allergic asthma and inflammation [26] , [27] and pain [28] . Table 1 summarizes the anti-inflammatory effects described for the Ac2-26 peptide.…”

Section: Introductionmentioning

confidence: 99%

“…The cytokine storm promotes an uncontrolled inflammation with directly lung failure and it inflicts multi-organ damage failure, mostly in cardiac, hepatic and renal systems. In vitro and in vivo studies demonstrated that Ac2-26 peptide was able to reduce inflammation and enrolled mediators in many models where inflammation is relevant and then it was suggested to treat several diseases as allergy, cancer, stroke, sepsis or ischemia [11] , [24] , [53] . In lungs, Ac2-26 showed protective effects in by reducing inflammation in different conditions [24] , [25] , [29] , [42] suggesting it could have an important paper during COVID-19 treatment.…”

Section: Introductionmentioning

confidence: 99%

Ac2-26 mimetic peptide of annexin A1 to treat severe COVID-19: A hypothesis

Bonavita

2020

Medical Hypotheses

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The Coronavirus Diseases-2019 (COVID-19) pandemic leads many researchers around the world to study the SARS-CoV-s2 infection and pathology to find a treatment for it. This generates a massive production of papers including pre-clinical, clinical and revisions but till now no specific treatment were identified. Meanwhile, like other coronavirus infections, COVID-19 leads to the cytokine storm syndrome resulting in hyperinflammation, exacerbated immune response and multiple organ dysfunctions indicating that drugs that modulate this response, as glucocorticoids could be a treatment option. However glucocorticoids have several side effects or usage limitations. In this sense a drug with anti-inflammatory effects and capable to reduce inflammation but with less after-effects could be a powerful tool to combat COVID-19. Thus the Ac2-26 Mimetic Peptide of Annexin A1 emerges as a possible therapy. The peptide has many anti-inflammatory effects described including the reduction of interleukin (IL)-6, one of the main mediators of cytokine storm syndrome. Therefore the hypothesis to use the Ac2-26 peptide to treat severe COVID-19 will be highlighted in this paper.

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Ac2-26 ameliorates lung ischemia-reperfusion injury via the eNOS pathway

Cited by 20 publications

References 31 publications

Ac2-26 Alleviates Brain Injury after Cardiac Arrest and Cardiopulmonary Resuscitation in Rats via the eNOS Pathway

Ac2-26 Alleviates Brain Injury after Cardiac Arrest and Cardiopulmonary Resuscitation in Rats via the eNOS Pathway

Ac2-26 mitigated acute respiratory distress syndrome rats via formyl peptide receptor pathway

Ac2-26 mimetic peptide of annexin A1 to treat severe COVID-19: A hypothesis

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