Canavalia brasiliensis lectin attenuates diabetes endothelial dysfunction in rats: structural basis and implication of muscarinic/insulin receptors
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Eva Pollyanna P Laranjeira1, Débora Helen M da Silva1, Francisco Glerison da Silva Nascimento1
1Superior Institute of Biomedical Sciences, State University of Ceará, 60714-903, Fortaleza, Brazil.
Abstract:
In diabetes, the endothelium acquires tendency toward vasoconstriction, inflammation, and thrombosis, and are associated with the reduced bioavailability of nitric oxide (NO). Plant lectins from the Canavalia genus elicit endothelium-dependent vasorelaxation in isolated rat aorta involving the participation of NO and the lectin domain. This study aimed to investigate ex vivo and in vivo the relaxant effect of Canavalia brasiliensis lectin (ConBr) in aorta from type 1 diabetic rats. ConBr was added at phenylephrine-contractions or acetylcholine-relaxation in isolated artery. In vivo, ConBr was injected i.v. into diabetics rats for 2 months, and aorta analyzed for histopathology, eNOS immunohistochemistry, and functional vascular response. ConBr relaxed (58 %) phenylephrine-contracted aorta of normoglycemic and diabetics. In normoglycemic, ConBr relaxant effect was inhibited by l-NAME, ODQ, 0Ca2+ and atropine, but not by TEA or by the inhibitor of PI3K/Akt (LY294002). In diabetics, ConBr effect was inhibited by l-NAME, ODQ, 0Ca2+, TEA and LY294002. In vivo, i.v. treatment with ConBr improved aorta contractility of diabetics (429.5 ± 74.7 vs. non-treated: 297.7 ± 31 mg), but unaltered acethylcholine-relaxation (52.7 ± 8.4 vs. non-treated: 55.8 ± 5.2 %). ConBr reduced aorta morphological alterations and increased eNOS expression (79 ± 3.3 vs. non-treated: 52.17 ± 2.7 %). Molecular docking of ConBr-N-glycans revealed interaction of ConBr at glycosylation points in insulin receptor. ConBr attenuates functional and morphological vascular alterations induced by diabetes, involving eNOS pathway via muscarinic and insulin receptors.
Insights
Canavalia brasiliensis lectin (ConBr) improves vascular function in diabetic rats by reducing vasoconstriction and inflammation. This plant lectin enhances nitric oxide (NO) bioavailability and restores aorta morphology and contractility.
Area of Science:
- Pharmacology
- Vascular Biology
- Diabetology
Background:
- Diabetes mellitus is characterized by endothelial dysfunction, leading to vasoconstriction, inflammation, and thrombosis, often associated with reduced nitric oxide (NO) bioavailability.
- Plant lectins from the Canavalia genus are known to induce endothelium-dependent vasorelaxation, involving NO and the lectin domain.
Purpose of the Study:
- To investigate the ex vivo and in vivo effects of Canavalia brasiliensis lectin (ConBr) on the aorta of type 1 diabetic rats.
- To elucidate the mechanisms underlying ConBr's vascular effects in diabetes, including its impact on NO pathways and receptor interactions.
Main Methods:
- Ex vivo assessment of ConBr's relaxant effect on phenylephrine-contracted and acetylcholine-relaxed isolated rat aorta from normoglycemic and diabetic rats.
- In vivo administration of ConBr to diabetic rats, followed by analysis of aorta histopathology, endothelial nitric oxide synthase (eNOS) expression, and functional vascular responses.
- Molecular docking simulations to explore ConBr's interaction with the insulin receptor.
Main Results:
- ConBr demonstrated a significant relaxant effect on phenylephrine-contracted aorta in both normoglycemic and diabetic rats.
- In diabetic rats, ConBr treatment in vivo improved aorta contractility, reduced morphological alterations, and increased eNOS expression.
- ConBr's mechanism in normoglycemic rats involved NO and muscarinic receptors, while in diabetics, it additionally involved the PI3K/Akt pathway and TEA-sensitive channels.
Conclusions:
- Canavalia brasiliensis lectin (ConBr) attenuates functional and morphological vascular alterations induced by diabetes.
- The vascular benefits of ConBr in diabetes are mediated through the eNOS pathway, potentially involving muscarinic and insulin receptors.
- ConBr shows therapeutic potential for managing vascular complications associated with diabetes.
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