Urolithin C, a polyphenolic intestinal microbial metabolite of ellagic acid, is a glucose-dependent activator of insulin secretion. Urolithin C is an L-type Ca2+ channel opener that enhances Ca2+ influx. Urolithin C causes apoptosis through a mitochondria-mediated pathway and stimulates the formation of reactive oxygen species (ROS).

Physicochemical Properties

Molecular Formula	C13H8O5
Molecular Weight	244.20
Exact Mass	244.037
CAS #	165393-06-6
PubChem CID	60198001
Appearance	Light brown to brown solid powder
Density	1.6±0.1 g/cm3
Boiling Point	605.4±55.0 °C at 760 mmHg
Flash Point	243.6±25.0 °C
Vapour Pressure	0.0±1.8 mmHg at 25°C
Index of Refraction	1.758
LogP	1.88
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	0
Heavy Atom Count	18
Complexity	344
Defined Atom Stereocenter Count	0
InChi Key	HHXMEXZVPJFAIJ-UHFFFAOYSA-N
InChi Code	InChI=1S/C13H8O5/c14-6-1-2-7-8-4-10(15)11(16)5-9(8)13(17)18-12(7)3-6/h1-5,14-16H
Chemical Name	3,8,9-trihydroxybenzo[c]chromen-6-one
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	L-type calcium channel
ln Vitro	In INS-1 beta cells, urolithin C (20–100 μM; 1 hour) administration increases glucose-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation [1]. Significant inhibition of PC12 cell growth was seen with urolithin C. Treatment with urolithin C produces abnormalities related to calcium homeostasis, accelerates the generation of reactive oxygen species (ROS) and mitochondrial membrane depolarization, and increases the release of lactate dehydrogenase (LDH) and lipid peroxidation malondialdehyde (MDA) [2]. Treatment with urolithin C causes S-phase cell cycle arrest and apoptosis [2]
ln Vivo	Male Wistar rats weighing 140–160 g were used to study the pharmacokinetics of urolithin C (10 mg/kg; intraperitoneally given). The terminal fraction has a half-life of 11.3 hours and a total clearance (CL/F) of 3.41 L/h/kg. The distribution's initial volume (V1/F) and steady-state volume (Vss/F) are, respectively, 0.831 L/kg and 55.6 L/kg[3].
Cell Assay	Western Blot Analysis[1] Cell Types: INS-1 cells Tested Concentrations: 20 μM, 100 μM Incubation Duration: 1 hour Experimental Results: Enhanced glucose-induced extracellular signal-regulated kinases 1/2 (ERK1/2) activation.
References	[1]. Urolithin C Increases Glucose-Induced ERK Activation Which Contributes to Insulin Secretion. Fundam Clin Pharmacol. 2020 Feb 21. [2]. Urolithin C, a gut metabolite of ellagic acid, induces apoptosis in PC12 cells through a mitochondria-mediated pathway. RSC Advances. Issue 28, 2017. [3]. 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.
Additional Infomation	Urolithin C is a member of coumarins. Urolithin C has been reported in Punica granatum with data available.

Solubility Data

Solubility (In Vitro)

DMSO : 50 mg/mL (204.75 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (8.52 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (8.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.0950 mL	20.4750 mL	40.9500 mL
	5 mM	0.8190 mL	4.0950 mL	8.1900 mL
	10 mM	0.4095 mL	2.0475 mL	4.0950 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.