Résumé
Pancreatic β-cell function and notably glucose-induced insulin secretion play a pivotal role in glucose homeostasis. We have previously shown that natural molecules like flavonoids or ellagitannin metabolites potentiate glucose-induced insulin secretion through a mechanism implicating the activation of L-type Ca2+(CaV) channels and ERK 1/2 [1] [2] [3]. According to some studies, extracts from Angelica L. species showed similar effects on insulin secretion [4] [5]. Thus, this study aimed at isolating and studying active constituents of three pharmacopeial Angelica roots.Twenty-two coumarins were isolated from the roots of Angelica archangelica L., Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav., and Angelica pubescens Maxim through Soxhlet extraction in n-hexane, and column and preparative chromatography methods. The structures of the compounds were analysed and confirmed using UHPLC-DAD-MS and NMR methods. Pharmacological experiments were performed on the INS-1 β-cell line. Insulin release was quantified by the homogeneous time- resolved fluorescence method. The mechanism of action was studied using patch clamp and FACS techniques.Some of the studied compounds were able to modulate glucose-induced insulin secretion by acting on the membrane potential, as well as by activating voltage-gated calcium channels and increasing intracellular calcium concentrations. Overall, the results demonstrate a new pharmacological activity of coumarins present in traditionally used Angelica roots.References[1] Bardy G, Virsolvy A, Quignard JF et al. Quercetin induces insulin secretion by direct activation of L-type calcium channels in pancreatic beta cells. British Journal of Pharmacology 2013; 169: 1102–1113. doi:10.1111/bph.12194[2] Bayle M, Neasta J, Dall'Asta M et al. The ellagitannin metabolite urolithin C is a glucose-dependent regulator of insulin secretion through activation of L-type calcium channels. Br J Pharmacol 2019; 176: 4065–4078. doi:10.1111/bph.14821[3] Toubal S, Oiry C, Bayle M et al. Urolithin C increases glucose-induced ERK activation which contributes to insulin secretion. Fundam Clin Pharmacol 2020; 34: 571–580. doi:10.1111/fcp.12551[4] Leu YL, Chen YW, Yang CY et al. Extract isolated from Angelica hirsutiflora with insulin secretagogue activity. J Ethnopharmacol 2009; 123: 208–212. doi:10.1016/jjep.2009.03.027[5] Park EY, Kim EH, Kim CY et al. Angelica dahurica Extracts lmprove Glucose Tolerance through the Activation of GPR119. PLoS One 2016; 11: e0158796. doi:10.1371/journal.pone.0158796