Irbesartan is an angiotensin II receptor (AT1) antagonist. Irbesartan downregulates the binding of angiotensin II to the AT1 receptor, thereby participating in the modulation of various signaling pathways. Irbesartan can be used in studies related to hypertension and diabetic nephropathy in type 2 diabetes[1-4].
In vitro, gemcitabine-resistant pancreatic cancer cells (PANC-1, L3.7, MiaPaca-2, SW1990) were treated with Irbesartan (1μM) and gemcitabine (0.8μM) for 72 hours. Irbesartan significantly inhibited the expression of c-Jun, SOX9, SOX2, OCT4, FTH1, FTL, and TFRC, while reducing gemcitabine resistance and tumor stemness[5]. Irbesartan (10μM) was pre-incubated with 3T3-L1 adipocytes for 1.5 hours, followed by stimulation with Ang III (10nM) for 12 hours. Irbesartan failed to inhibit the increase in glucose uptake and the upregulation of GLUT1 expression[6].
In vivo, Irbesartan (20mg/kg/day) was orally administered to spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats for 14 days. Irbesartan significantly protected SHR rats from hypertension-induced cognitive dysfunction[7]. Irbesartan (40mg/kg/day; once daily) was administered intranasally to male APP/PS1 mice for 10 weeks. Irbesartan significantly improved the memory performance of the mice and reduced neurodegeneration, oxidative stress, and neuroinflammation[8].
References:
[1] Schupp M, Janke J, Clasen R, et al. Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptor-gamma activity. Circulation. 2004 May 4;109(17):2054-7.
[2] Ruiz E, Redondo S, Padilla E, et al. Importance of intracellular angiotensin II in vascular smooth muscle cell apoptosis: inhibition by the angiotensin AT1 receptor antagonist irbesartan. Eur J Pharmacol. 2007 Jul 19;567(3):231-9.
[3] Zhong Y, Tang R, Lu Y, et al. Irbesartan may relieve renal injury by suppressing Th22 cells chemotaxis and infiltration in Ang II-induced hypertension. Int Immunopharmacol. 2020 Oct;87:106789.
[4] Vanderheyden PM, Fierens FL, De Backer JP, et al. Distinction between surmountable and insurmountable selective AT1 receptor antagonists by use of CHO-K1 cells expressing human angiotensin II AT1 receptors. Br J Pharmacol. 1999 Feb;126(4):1057-65.
[5] Zhou T, Xie Y, Hou X, et al. Irbesartan overcomes gemcitabine resistance in pancreatic cancer by suppressing stemness and iron metabolism via inhibition of the Hippo/YAP1/c-Jun axis. J Exp Clin Cancer Res. 2023 May 4;42(1):111.
[6] Tanioka T, Maeda K, Takahashi R, et al. The Ang III/AT2R Pathway Enhances Glucose Uptake by Improving GLUT1 Expression in 3T3-L1 Adipocytes. Biol Pharm Bull. 2021;44(7):1014-1018.
[7] Hao S, He Q, Yuan Y, et al. The protective effects of Irbesartan in cognitive impairment in hypertension. Aging (Albany NY). 2024 Mar 23;16(6):5065-5076.
[8] Gouveia F, Pérez MC, Bicker J, et al. Protective effects of irbesartan against neurodegeneration in APP/PS1 mice: Unraveling its triple anti-apoptotic, anti-inflammatory and anti-oxidant action. Biomed Pharmacother. 2025 Jul;188:118167.
Irbesartan是一种血管紧张素II受体（AT1）拮抗剂。Irbesartan可下调血管紧张素II与AT1受体的结合，来参与多种信号通路的调节。Irbesartan可用于高血压和2型糖尿病肾病的相关研究[1-4]。
在体外，Irbesartan（1μM）gemcitabine（0.8μM）刺激gemcitabine耐药的胰腺癌细胞（PANC-1，L3.7，MiaPaca-2，SW1990）72小时。Irbesartan显著抑制c-Jun、SOX9、SOX2、OCT4、FTH1、FTL及TFRC的表达，同时降低gemcitabine耐药和肿瘤干性[5]。Irbesartan（10μM）预处理3T3-L1脂肪细胞1.5小时，随后以Ang III（10nM）刺激12小时。Irbesartan未能抑制葡萄糖摄取的增加及GLUT1的表达上调[6]。
在体内，Irbesartan（20mg/kg/day）口服灌胃于自发性高血压（SHR）大鼠和Wistar-Kyoto（WKY）大鼠14天。Irbesartan显著保护了SHR大鼠免受高血压诱导的认知功能障碍[7]。Irbesartan（40mg/kg/day；每日一次）鼻内给药于APP/PS1雄性小鼠10周。Irbesartan显著改善了小鼠的记忆表现，减少了神经退行性病变、氧化应激与神经炎症[8]。