Apocynin, a naturally occurring acetophenone, is a potent inhibitor of the complex NADPH-oxidase with an IC50 value of 10μM[1]. Apocynin prevents translocation of p47phox subunit to the plasma membrane[2]. Apocynin can inhibit the generation of eNOS-dependent superoxide in diabetic cardiomyopathy, reduce the activation of NLRP3 and TGFβ/Smad signaling in diabetic nephropathy, and serve as a model compound for developing new therapeutic drugs for cardiovascular diseases[3].
In vitro, Apocynin treatment (300µM; 6h) increased the accumulation of nitrite in the extracellular culture medium of N11 mouse glial cells, and enhanced the activity of nitric oxide synthase (NOS) in the cell lysates[4]. Treatment of rat vascular smooth muscle cells with 100μM Apocynin for 15 minutes significantly inhibited the phosphorylation of Akt and extracellular signal-regulated kinase 1/2, and weakened the activation of p38 mitogen-activated protein kinase and Akt and extracellular signal-regulated kinase 1/2 induced by reactive oxygen species (ROS), as well as the production of superoxide anions[5].
In vivo, Apocynin treatment via intraperitoneal injection of 10mg/kg/day for 4 consecutive days can alleviate the morphological and histological changes in the lungs of rats induced by lipopolysaccharide (LPS), reduce pulmonary edema, lower pulmonary permeability, and decrease the MPO activity induced by LPS in the bronchoalveolar fluid and lung homogenate of rats, as well as TNF-α and IL-1β in the plasma[6]. Intravenous injection of 2.5mg/kg of Apocynin for 30 minutes before experimental stroke can improve neurological function, reduce infarct volume, and decrease the incidence of cerebral hemorrhage in the mouse model[7]. In SAMP6 mice, after 3 months of treatment with Apocynin via intraperitoneal injection (0.1mg/kg/day), both bone mineral density and total bone mass increased, and the activity of osteoblasts significantly enhanced in shin bones of mice[8].
References:
[1] Stefanska J, Pawliczak R. Apocynin: molecular aptitudes[J]. Mediators of inflammation, 2008, 2008(1): 106507.
[2] Savla S R, Laddha A P, Kulkarni Y A. Pharmacology of apocynin: a natural acetophenone[J]. Drug metabolism reviews, 2021, 53(4): 542-562.
[3] Bhatia A, Thakur S, Kohal R, et al. A comprehensive update on phytochemistry and medicinal developments of apocynin[J]. Fitoterapia, 2025: 106558.
[4] Riganti C, Costamagna C, Doublier S, et al. The NADPH oxidase inhibitor apocynin induces nitric oxide synthesis via oxidative stress[J]. Toxicology and applied pharmacology, 2008, 228(3): 277-285.
[5] Heumüller S, Wind S, Barbosa-Sicard E, et al. Apocynin is not an inhibitor of vascular NADPH oxidases but an antioxidant[J]. Hypertension, 2008, 51(2): 211-217.
[6] Kouki A, Ferjani W, Ghanem-Boughanmi N, et al. The NADPH oxidase inhibitors apocynin and diphenyleneiodonium protect rats from LPS-induced pulmonary inflammation[J]. Antioxidants, 2023, 12(3): 770.
[7] Tang X N, Cairns B, Cairns N, et al. Apocynin improves outcome in experimental stroke with a narrow dose range[J]. Neuroscience, 2008, 154(2): 556-562.
[8] Sun J, Ming L, Shang F, et al. Apocynin suppression of NADPH oxidase reverses the aging process in mesenchymal stem cells to promote osteogenesis and increase bone mass[J]. Scientific Reports, 2015, 5(1): 18572.
Apocynin是一种天然存在的苯乙酮类化合物，可作为NADPH氧化酶复合物的强效抑制剂，IC50值为10μM[1]。Apocynin可以阻止p47phox亚基向质膜转位[2]。Apocynin能抑制糖尿病心肌病中eNOS依赖性超氧化物的产生，降低糖尿病肾病中NLRP3和TGFβ/Smad信号通路的激活，是心血管疾病新药开发的模型化合物[3]。
在体外，300μM浓度的Apocynin处理N11小鼠胶质细胞6小时后，可增加细胞培养液中亚硝酸盐的积累，并提升细胞裂解物中一氧化氮合酶（NOS）活性[4]。100μM浓度的Apocynin处理大鼠血管平滑肌细胞15分钟，能显著抑制Akt和细胞外信号调节激酶1/2的磷酸化，减弱活性氧（ROS）诱导的p38丝裂原活化蛋白激酶、Akt及ERK1/2激活，同时减少超氧阴离子生成[5]。
在体内，大鼠连续4天腹腔注射10mg/kg/day剂量的Apocynin，可缓解脂多糖(LPS)诱导的肺组织形态学改变，减轻肺水肿、降低肺通透性，并减少支气管肺泡灌洗液和肺匀浆中MPO活性及血浆TNF-α、IL-1β水平[6]。实验性脑卒中前30分钟静脉注射2.5mg/kg剂量的Apocynin，能改善小鼠神经功能、缩小梗死体积并降低脑出血发生率[7]。在 SAMP6 小鼠中，通过腹腔注射Apocynin（0.1mg/kg/day）治疗3个月后，小鼠胫骨的骨物质密度和总骨量均有所增加，成骨细胞的活性也显著增强[8]。