Telmisattan is a novel, orally active angiotensin II receptor type 1 (AT1) antagonist (IC50=9.2nM). Telmisattan lowers aldosterone by blocking AT1 and partially agonizes PPARγ to improve metabolism, Telmisattan activates the ACE2/Ang(1-7)/MasR anti-inflammatory pathway to alleviate tissue injury. Telmisattan can be used in research on essential hypertension, metabolic syndrome, and COVID-19[1-4].
In vitro, Telmisattan (10, 50, 100μM) was applied to human hepatocellular carcinoma cell lines HLF, HLE, HepG2, HuH-7, and PLC/PRF/5 for 24-48h. Telmisattan dose-dependently inhibited the proliferation of poorly differentiated HLF, HLE, and HepG2 cells. In HLF cells, Telmisattan additionally induced G0/G1 cell cycle arrest, downregulated cyclin D1, cyclin E, CDK4, CDK6, and CDK2 expression, activated AMPK phosphorylation, suppressed mTOR and p70S6K phosphorylation, and induced apoptosis[5]. Telmisattan (10μM) was used to pretreat mouse microglial BV2 cells for 2h, followed by LPS (100ng/ml) stimulation for 1h, with a separate Telmisattan-alone group (10μM; 3h). Telmisattan alone downregulated the expression of Ccrl2, Dusp2, Dusp5, Csfl, Bcl11b, and 11 miRNAs including miR-874 and miR-574 in uninjured BV2 cells, and upregulated Hist1h, Hist2h, Hist4h, Ang4, Slc25a51, and Usp17le (Dub3) genes. Telmisattan pretreatment significantly suppressed the LPS-induced upregulation of pro-injury genes such as IL-1β, IL-6, TNFα, IkBα, NF-κB, miR-221, miR-155, TLR2, and Adamts1, and reversed the LPS-induced downregulation of protective genes like snoRNA, Eid2b, Hist1h4m, and Hist1h2bh[6].
In vivo, Telmisattan (40mg/kg/day) was administered via drinking water to K14-IL-17Aind/+ mice with keratinocyte-specific IL-17A overexpression (a psoriasis-like skin disease model) and IL-17Aind/+ control mice for 4 consecutive weeks. Telmisattan significantly reduced systolic blood pressure in both K14-IL-17Aind/+ and control mice; Telmisattan failed to lower the elevated peripheral ROS/RNS levels or the increased plasma levels of IL-17A, G-CSF, IL-6, and IL-1β in K14-IL-17Aind/+ mice[7]. Telmisattan (2g/kg mixed into solid-formula diet) was given to C57BL/6J mice with ocular hypertension glaucoma model for 12 weeks, with the right eye serving as the contralateral uninjected control. Telmisattan reduced the loss of optic nerve retinal ganglion cell axons and the increase in axonal degeneration percentage caused by elevated intraocular pressure[8].
References:
[1] Imenshahidi M, Roohbakhsh A, Hosseinzadeh H. Effects of telmisartan on metabolic syndrome components: a comprehensive review. Biomed Pharmacother. 2024 Feb;171:116169.
[2] McClellan KJ, Markham A. Telmisartan. Drugs. 1998 Dec;56(6):1039-44; discussion 1045-6.
[3] Akhrass PR, McFarlane SI. Telmisartan and cardioprotection. Vasc Health Risk Manag. 2011;7:677-83.
[4] Moen MD. Telmisartan/amlodipine: single-pill combination in hypertension. Am J Cardiovasc Drugs. 2010;10(6):401-12.
[5] Oura K, Tadokoro T, Fujihara S, et al. Telmisartan inhibits hepatocellular carcinoma cell proliferation in vitro by inducing cell cycle arrest. Oncol Rep. 2017 Nov;38(5):2825-2835.
[6] Elkahloun AG, Rodriguez Y, Alaiyed S, et al. Telmisartan Protects a Microglia Cell Line from LPS Injury Beyond AT1 Receptor Blockade or PPARγ Activation. Mol Neurobiol. 2019 May;56(5):3193-3210.
[7] Wild J, Schüler R, Knopp T, et al. Telmisartan Lowers Elevated Blood Pressure in Psoriatic Mice without Attenuating Vascular Dysfunction and Inflammation. Int J Mol Sci. 2019 Aug 30;20(17):4261.
[8] Hazlewood RJ, Kuchtey J, Wu HJ, et al. Telmisartan Reduces Axon Degeneration in Mice With Experimental Glaucoma. Invest Ophthalmol Vis Sci. 2020 May 11;61(5):51.