The molecular mechanisms of anti-inflammatory impact of three minor phytocannabinoids, eugenol and psilocybin and the protective effect of two major phyatocannabinoids, three minor phytocannabinoids, eugenol and psilocybin on high glucose-high lipid induced ß-cell loss, dysfunctionality and dedifferentiation

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Ghasemi Gojani, Esmaeel
University of Lethbridge. Faculty of Arts and Science
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Lethbridge, Alta. : University of Lethbridge, Dept. of Biological Sciences
Type 2 Diabetes, a growing disorder worldwide, particularly in advanced countries, is closely associated with dysregulated inflammation. In our current research, we aimed to explore the molecular mechanisms behind the potential anti-inflammatory effects of major and minor phytocannabinoids, eugenol and psilocybin. We investigated their impact on mitigating proinflammatory responses in human macrophages, as well as their potential to counteract high glucose-high lipid-induced (HG-HL) loss and dedifferentiation of beta-cells, along with impaired glucose-stimulated insulin secretion. Our findings suggest that the anti-inflammatory effects of THCV, CBC, and CBN are likely mediated through the involvement of CB1R and PPARγ receptors. Furthermore, we identified PANX-1, TXNIP, and ADAR1 as potential contributors to the mitigation of Nlrp3 inflammasome and the anti-inflammatory effects exerted by these three minor phytocannabinoids. We also observed that THC, CBD, THCV, CBC, and CBN could inhibit HG-HL-induced loss of beta-cells, possibly by reducing apoptosis and pyroptosis. Additionally, all five phytocannabinoids displayed varying degrees of inhibitory effects on HG-HL-induced -cell dedifferentiation. Moreover, we found evidence suggesting that eugenol exerts its anti-inflammatory effects, at least in part, by mitigating NFκB activity. Eugenol also demonstrated the ability to inhibit apoptosis and dedifferentiation in HG-HL-induced beta-cell. As for psilocybin, it showed potential inhibitory effects on cytokine storm through the suppression of NFκB, STAT3, and STAT1 transcription factors. Psilocybin also exhibited a suppressive impact on beta-cell loss and dedifferentiation. In summary, our research sheds light on the molecular mechanisms underlying the anti-inflammatory properties of eugenol and psilocybin, as well as major and minor phytocannabinoids. These findings have implications for understanding the potential therapeutic benefits of these compounds in mitigating inflammation and preserving beta-cell function in the context of Type 2 Diabetes.
Inflammation , Diabetes , Phytocannabinoids , Eugenol , Psilocybin