Alda 1 is an aldehyde dehydrogenase 2 (ALDH2) activator [1]. Alda 1 specifically activating the ALDH2 enzyme in mitochondria, enhances the enzyme's ability to metabolize toxic aldehydes such as acetaldehyde, thereby reducing cellular damage caused by these substances [2-3]. Alda 1 is primarily used to study diseases associated with abnormal acetaldehyde metabolism [4].
In human pulmonary alveolar epithelial cells, Alda 1 (20μM; 1h) pretreatment can alleviate lung ischemia-reperfusion injury [5]. In SH-SY5Y cells, pretreatment with Alda 1 (20 μM; 24 h) restored ALDH2 activity and content, increased mitochondrial membrane potential, and reduced reactive oxygen species in cells [6].
In C57BL/6J mice, after Alda 1 (5mg/kg; ip; single injection) administration elevated hepatic ALDH activity, which was blocked by the specific ALDH2 inhibitor, daidzin [7]. In liver ischemia-reperfusion injury (IRI) mice model, Alda 1 (30mg/kg; ip; single injection) mediated ALDH2 activation may improve hepatic IRI by scavenging reactive aldehydes and enhancing autophagy [8]. In hyperoxia mice model, Alda 1 (8mg/kg; sc; 48h) pretreatment attenuates hyperoxia-induced immune cell infiltration [9].
References:
[1]. Stachowicz A, Olszanecki R, Suski M, et al. Proteomic analysis of mitochondria-enriched fraction isolated from the frontal cortex and hippocampus of apolipoprotein E knockout mice treated with Alda-1, an activator of mitochondrial aldehyde dehydrogenase (ALDH2)[J]. International Journal of Molecular Sciences, 2017, 18(2): 435.
[2]. Stachowicz A, Głombik K, Olszanecki R, et al. The impact of mitochondrial aldehyde dehydrogenase (ALDH2) activation by Alda-1 on the behavioral and biochemical disturbances in animal model of depression[J]. Brain, Behavior, and Immunity, 2016, 51: 144-153.
[3]. Ikeda T, Takahashi T, Tsujita M, et al. Effects of Alda-1, an aldehyde dehydrogenase-2 agonist, on hypoglycemic neuronal death[J]. PLoS One, 2015, 10(6): e0128844.
[4]. Stachowicz A, Olszanecki R, Suski M, et al. Mitochondrial aldehyde dehydrogenase activation by Alda‐1 inhibits atherosclerosis and attenuates hepatic steatosis in apolipoprotein E‐knockout mice[J]. Journal of the American Heart Association, 2014, 3(6): e001329.
[5]. Ding J, Zhang Q, Luo Q, et al. Alda-1 attenuates lung ischemia-reperfusion injury by reducing 4-hydroxy-2-nonenal in alveolar epithelial cells[J]. Critical care medicine, 2016, 44(7): e544-e552.
[6]. Deza-Ponzio R, Albrecht P A, Fernandez-Hubeid L E, et al. ALDH2 inhibition by lead and ethanol elicits redox imbalance and mitochondrial dysfunction in SH-SY5Y human neuroblastoma cell line: Reversion by Alda-1[J]. Neurotoxicology, 2023, 97: 12-24.
[7]. Zhong W, Zhang W, Li Q, et al. Pharmacological activation of aldehyde dehydrogenase 2 by Alda-1 reverses alcohol-induced hepatic steatosis and cell death in mice[J]. Journal of hepatology, 2015, 62(6): 1375-1381.
[8]. Li M, Xu M, Li J, et al. Alda‐1 Ameliorates Liver Ischemia‐Reperfusion Injury by Activating Aldehyde Dehydrogenase 2 and Enhancing Autophagy in Mice[J]. Journal of Immunology Research, 2018, 2018(1): 9807139.
[9]. Sidramagowda Patil S, Hernández-Cuervo H, Fukumoto J, et al. Alda-1 attenuates hyperoxia-induced acute lung injury in mice[J]. Frontiers in pharmacology, 2021, 11: 597942.
Alda 1是一种醛脱氢酶2（ALDH2）激活剂 [1]。Alda 1特异性激活线粒体中的ALDH2酶，增强该酶代谢乙醛等毒性醛类物质的能力，从而减轻这些物质对细胞造成的损伤 [2-3]。Alda 1主要用于研究与乙醛代谢异常相关的疾病 [4]。
在人肺泡上皮细胞中，Alda 1（20μM；1h）预处理可减轻肺缺血-再灌注损伤 [5]。在SH-SY5Y细胞中，Alda 1（20μM；24h）预处理可恢复ALDH2活性和含量，提高线粒体膜电位，并降低细胞中的活性氧 [6]。
在C57BL/6J小鼠中，给予Alda 1（5mg/kg；ip；单次注射）后，肝脏ALDH活性升高，而该活性可被特异性ALDH2抑制剂大豆苷元阻断 [7]。在肝脏缺血-再灌注损伤（IRI）小鼠模型中，Alda 1（30mg/kg；ip；单次注射）介导的ALDH2激活可能通过清除活性醛和增强自噬来改善肝脏IRI [8]。在高氧小鼠模型中，Alda 1（8mg/kg；sc；48h）预处理可减轻高氧诱导的免疫细胞浸润 [9]。