Saxagliptin hydrate is a highly potent dipeptidyl peptidase-4 (DPP-4) inhibitor that regulates blood glucose by selectively inhibiting the DPP-4 enzyme, thereby elevating levels of endogenous glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)[1-2]. Saxagliptin hydrate is used to improve glycemic control in patients with type II diabetes[3], and has been shown to alleviate inflammation and oxidative stress [4].
In vitro, treatment of human papillary thyroid carcinoma cell lines K1 and TPC-1 with Saxagliptin hydrate (0.1μM) for 24h significantly enhanced cell migration and invasion capabilities[5]. Pretreatment of human dental pulp cells with Saxagliptin hydrate (500nM–1μM) for 24–48 h, followed by stimulation with LPS (100ng/ml) for 24–48h, significantly suppressed the expression and secretion of pro-inflammatory cytokines TNF-α, IL-1β, and IL-8, while reducing inflammatory responses[6].
In vivo, oral administration of Saxagliptin hydrate (10mg/kg) once daily to a high-fat diet combined with streptozotocin (STZ; 50mg/kg)-induced type 2 diabetic C57BL/6J mouse model significantly improved β-cell mass and islet morphology, regardless of whether intervention began 7 days before or 1 day after STZ injury[7]. In another study, daily oral administration of Saxagliptin hydrate (10mg/kg) for 35 days to STZ (60mg/kg/day)-induced diabetic C57BL/6J mice markedly attenuated diabetes-induced somatic chromosomal instability. Saxagliptin hydrate significantly reduced the frequency of micronucleus formation in bone marrow and reversed diabetes-induced suppression of bone marrow nucleated cell proliferation[8].
References:
[1] Thareja S, Aggarwal S, Malla P, et al. Saxagliptin hydrate: a new drug for the treatment of type 2 diabetes. Mini Rev Med Chem. 2010 Jul;10(8):759-65.
[2] Kania DS, Gonzalvo JD, Weber ZA. Saxagliptin hydrate: a clinical review in the treatment of type 2 diabetes mellitus. Clin Ther. 2011 Aug;33(8):1005-22.
[3] Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin hydrate and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013 Oct 3;369(14):1317-26.
[4] Zhang L, Qi X, Zhang G, et al. Saxagliptin hydrate protects against hypoxia-induced damage in H9c2 cells. Chem Biol Interact. 2020 Jan 5;315:108864.
[5] He L, Zhang T, Sun W, et al. The DPP-IV inhibitor Saxagliptin hydrate promotes the migration and invasion of papillary thyroid carcinoma cells via the NRF2/HO1 pathway. Med Oncol. 2020 Oct 1;37(11):97.
[6] Guo X, Chen J. The protective effects of Saxagliptin hydrate against lipopolysaccharide (LPS)-induced inflammation and damage in human dental pulp cells. Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):1288-1294.
[7] Poucher SM, Cheetham S, Francis J, et al. Effects of Saxagliptin hydrate and sitagliptin on glycaemic control and pancreatic β-cell mass in a streptozotocin-induced mouse model of type 2 diabetes. Diabetes Obes Metab. 2012 Oct;14(10):918-26.
[8] Attia SM, Ahmad SF, Nadeem A, et al. Saxagliptin hydrate, a selective dipeptidyl peptidase-4 inhibitor, alleviates somatic cell aneugenicity and clastogenicity in diabetic mice. Mutat Res Genet Toxicol Environ Mutagen. 2023 Nov-Dec;892:503707.