Gonzalez-Mariscal, IsabelPozo-Morales, MacarenaRomero-Zerbo, Silvana YEspinosa-Jimenez, VanesaEscamilla-Sanchez, AlejandroSanchez-Salido, LourdesCobo-Vuilleumier, NadiaGauthier, Benoit RBermudez-Silva, Francisco J2023-05-032023-05-032021-10-19González-Mariscal I, Pozo-Morales M, Romero-Zerbo SY, Espinosa-Jimenez V, Escamilla-Sánchez A, Sánchez-Salido L, et al. Abnormal cannabidiol ameliorates inflammation preserving pancreatic beta cells in mouse models of experimental type 1 diabetes and beta cell damage. Biomed Pharmacother. 2022 Jan;145:112361http://hdl.handle.net/10668/22035The atypical cannabinoid Abn-CBD improves the inflammatory status in preclinical models of several pathologies, including autoimmune diseases. However, its potential for modulating inflammation in autoimmune type 1 diabetes (T1D) is unknown. Herein we investigate whether Abn-CBD can modulate the inflammatory response during T1D onset using a mouse model of T1D (non-obese diabetic- (NOD)-mice) and of beta cell damage (streptozotocin (STZ)-injected mice). Six-week-old female NOD mice were treated with Abn-CBD (0.1-1 mg/kg) or vehicle during 12 weeks and then euthanized. Eight-to-ten-week-old male C57Bl6/J mice were pre-treated with Abn-CBD (1 mg/kg of body weight) or vehicle for 1 week, following STZ challenge, and euthanized 1 week later. Blood, pancreas, pancreatic lymph nodes (PLNs) and T cells were collected and processed for analysis. Glycemia was also monitored. In NOD mice, treatment with Abn-CBD significantly reduced the severity of insulitis and reduced the pro-inflammatory profile of CD4+ T cells compared to vehicle. Concomitantly, Abn-CBD significantly reduced islet cell apoptosis and improved glucose tolerance. In STZ-injected mice, Abn-CBD decreased circulating proinflammatory cytokines and ameliorated islet inflammation reducing intra-islet phospho-NF-κB and TXNIP. Abn-CBD significantly reduced 2 folds intra-islet CD8+ T cells and reduced Th1/non-Th1 ratio in PLNs of STZ-injected mice. Islet cell apoptosis and intra-islet fibrosis were also significantly reduced in Abn-CBD pre-treated mice compared to vehicle. Altogether, Abn-CBD reduces circulating and intra-islet inflammation, preserving islets, thus delaying the progression of insulitis. Hence, Abn-CBD and related compounds emerge as new candidates to develop pharmacological strategies to treat the early stages of T1D.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Beta cellCannabinoidsInflammationInsulitisT cellsType 1 diabetesAnimalsApoptosisCytokinesDiabetes Mellitus, experimentalDiabetes mellitus, Type 1Disease progressionFemaleGlucose tolerance testInflammationInsulin-secreting cellsMaleMiceMice, Inbred C57BLMice, inbred NODResorcinolsStreptozocinresearch article34872800open accessApoptosisCitocinasCélulas secretoras de insulinaDiabetes mellitus experimentalDiabetes mellitus tipo 1EstreptozocinaResorcinoles10.1016/j.biopha.2021.1123611950-6007https://doi.org/10.1016/j.biopha.2021.112361