Urolithin C, a gut-microbial metabolite of Ellagic acid, is a glucose-dependent activator of insulin secretion. Urolithin C is a L-type Ca2+ channel opener and enhances Ca2+ influx. Urolithin C induces cell apoptosis through a mitochondria-mediated pathway and also stimulates reactive oxygen species (ROS) formation[1][2].
Urolithin C (20-100 μM; 1 hour; INS-1 cells) treatment enhances glucose-induced extracellular signal-regulated kinases 1/2 (ERK1/2) activation in INS-1 β-cells[1].Urolithin C significantly inhibits the proliferation of PC12 cells. Urolithin C treatment actively increases the lactate dehydrogenase (LDH) release and lipid peroxidation malondialdehyde (MDA), stimulates reactive oxygen species (ROS) formation and mitochondrial membrane depolarization, and caused calcium dyshomeostasis[2].Urolithin C treatment induces apoptosis and S phase cell cycle arrest[2]. Western Blot Analysis[1] Cell Line: INS-1 cells
The pharmacokinetics of Urolithin C (10 mg/kg; intraperitoneal administration) in male Wistar rat (140-160 g) are studied. The half-life of the terminal part is 11.3 h and the total clearance (CL/F) is 3.41 L/h/kg. The initial volume of distribution (V1/F) and the steady-state volume of distribution (Vss/F) are 0.831 L/kg and 55.6 L/kg, respectively[3].
[1]. Slimane Toubal, et al. Urolithin C Increases Glucose-Induced ERK Activation Which Contributes to Insulin Secretion. Fundam Clin Pharmacol. 2020 Feb 21. [2]. Peipei Yin, et al. Urolithin C, a gut metabolite of ellagic acid, induces apoptosis in PC12 cells through a mitochondria-mediated pathway. RSC Advances. Issue 28, 2017. [3]. Morgane Bayle, et al. Development and Validation of a Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry Method for the Determination of Urolithin C in Rat Plasma and Its Application to a Pharmacokinetic Study. J Pharm Biomed Anal. 2016 Nov 30;131:33-39.