The HS-donor Erucin modulates SIRT1 and rescues obesity-induced vascular dysfunction in human vessels.

Eleonora Pagnotta, Laura Righetti, Sarah Costantino, Emiliano Duranti, Stefano Masi, Alessandro Mengozzi, Eugenia Piragine, Alma Martelli, Francesco Paneni, Agostino Virdis, Lara Testai, Vincenzo Calderone, Era Gorica, Federica Cappelli

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2025;189():118238

PMID: 40513389

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Abstract

Evidence highlights the potential role of hydrogen sulfide (H₂S)-donors in preventing vascular dysfunction by modulating pathways associated with oxidative stress. We investigate the H₂S-donor Erucin for its potential to reduce oxidative stress and endothelial dysfunction in obesity. Patients undergoing laparoscopic surgery were categorized by body mass index in controls and patients with obesity. Microvascular endothelial function was measured by micromyography before and after incubation with Erucin 1 µM. Mitochondrial reactive oxygen species (mtROS) were assessed by fluorescence microscopy. Expression of sirtuin 1 (SIRT1) and p66 was detected by real-time PCR. Human vascular endothelial (HUVECs) and smooth muscle cells (HASMCs) were used to study the protective effects of Erucin against H₂O₂-induced oxidative stress, with or without the sirtuin inhibitor Sirtinol. mtROS were assessed in HUVECs, and SIRT1, p66, and eNOS expression were analyzed via RT-PCR, Western blot, and ELISA. Erucin improved endothelium-dependent vasodilation in arterioles from obese patients, but not in vessels from healthy volunteers, and protected against H₂O₂-induced endothelial damage in vitro. It protected human microvessels from oxidative stress via the NO-SIRT1-p66 pathway, reducing ROS production and upregulating eNOS and SIRT1 while downregulating p66 in endothelial cells. Erucin prevented ROS production in human vascular cells and attenuated endothelial dysfunction related to oxidative stress in vessels of patients with obesity. In conclusion, therapeutic targeting of SIRT1 with Erucin offers a promising strategy to prevent and treat microvascular dysfunction associated with cardiometabolic disorders.

Address: Department of Pharmacy, University of Pisa, via Bonanno, 6, Pisa 56126, Italy; Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich and University of Zürich, Wagistrasse, 12, Schlieren, Zürich 8953, Switzerland. Electronic address: [email protected].; Department of Pharmacy, University of Pisa, via Bonanno, 6, Pisa 56126, Italy; Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, via del Borghetto, 80, Pisa 56124, Italy. Electronic address: [email protected].; Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich and University of Zürich, Wagistrasse, 12, Schlieren, Zürich 8953, Switzerland; Department of Clinical and Experimental Medicine, University of Pisa, via Roma, 67, Pisa 56126, Italy. Electronic address: [email protected].; Department of Clinical and Experimental Medicine, University of Pisa, via Roma, 67, Pisa 56126, Italy. Electronic address: [email protected].; Department of Clinical and Experimental Medicine, University of Pisa, via Roma, 67, Pisa 56126, Italy. Electronic address: [email protected].; Department of Clinical and Experimental Medicine, University of Pisa, via Roma, 67, Pisa 56126, Italy. Electronic address: [email protected].; Department of Clinical and Experimental Medicine, University of Pisa, via Roma, 67, Pisa 56126, Italy. Electronic address: [email protected].; Department of Pharmacy, University of Pisa, via Bonanno, 6, Pisa 56126, Italy; Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, via del Borghetto, 80, Pisa 56124, Italy; Interdepartmental Research Centre of Ageing Biology and Pathology, University of Pisa, via Risorgimento, 36, Pisa 56126, Italy. Electronic address: [email protected].; Council for Agricultural Research and Economics, Research Centre for Cereal and Industrial Crops (CREA-CI), via di Corticella, 133, Bologna 40128, Italy. Electronic address: [email protected].; Council for Agricultural Research and Economics, Research Centre for Cereal and Industrial Crops (CREA-CI), via di Corticella, 133, Bologna 40128, Italy. Electronic address: [email protected].; Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich and University of Zürich, Wagistrasse, 12, Schlieren, Zürich 8953, Switzerland. Electronic address: [email protected].; Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich and University of Zürich, Wagistrasse, 12, Schlieren, Zürich 8953, Switzerland. Electronic address: [email protected].; Department of Pharmacy, University of Pisa, via Bonanno, 6, Pisa 56126, Italy; Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, via del Borghetto, 80, Pisa 56124, Italy; Interdepartmental Research Centre of Ageing Biology and Pathology, University of Pisa, via Risorgimento, 36, Pisa 56126, Italy. Electronic address: [email protected].; Department of Pharmacy, University of Pisa, via Bonanno, 6, Pisa 56126, Italy; Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, via del Borghetto, 80, Pisa 56124, Italy; Interdepartmental Research Centre of Ageing Biology and Pathology, University of Pisa, via Risorgimento, 36, Pisa 56126, Italy. Electronic address: [email protected].

DOI: 10.1016/j.biopha.2025.118238