Silybin induces endothelium-dependent vasodilation via TRPV4 channels in mouse mesenteric arteries. 2022

Xin Wen, and Yidi Peng, and Bohao Zheng, and Shaying Yang, and Jing Han, and Fan Yu, and Tingting Zhou, and Li Geng, and Zhiming Yu, and Lei Feng
Wuxi School of Medicine, Jiangnan University, Wuxi, China.

Silybin is a flavonolignan extracted from the seeds of Silybum marianum that has been used as a dietary supplement for treating hepatic diseases and components of metabolic syndrome such as diabetes, obesity and hypertension. Transient receptor potential vanilloid 4 (TRPV4) channels are Ca2+-permeable, nonselective cation channels that regulate vascular endothelial function and blood flow. However, the relationship between silybin and TRPV4 channels in small mesenteric arteries remains unknown. In our study, we carried out a molecular docking experiment by using Discovery Studio v3.5 to predict the binding of silybin to TRPV4. Activation of TRPV4 with silybin was detected via intracellular Ca2+ concentration ([Ca2+]i) measurement and patch clamp experiments. The molecular docking results showed that silybin was likely to bind to the ankyrin repeat domain of TPRV4. [Ca2+]i measurements in mesenteric arterial endothelial cells (MAECs) and TRPV4-overexpressing HEK293 (TRPV4-HEK293) cells demonstrated that silybin induced Ca2+ influx by activating TRPV4 channels. The patch clamp experiments indicated that in TRPV4-HEK293 cells, silybin induced TRPV4-mediated cation currents. In addition, in high-salt-induced hypertensive mice, oral administration of silybin decreased systolic blood pressure (SBP) and significantly improved the arterial dilatory response to acetylcholine. Our findings provide the first evidence that silybin could induce mesenteric endothelium-dependent vasodilation and reduce blood pressure in high-salt-induced hypertensive mice via TRPV4 channels, thereby revealing the potential effect of silybin on preventing endothelial dysfunction-related cardiovascular diseases.

UI MeSH Term Description Entries
D006973 Hypertension Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more. Blood Pressure, High,Blood Pressures, High,High Blood Pressure,High Blood Pressures
D008638 Mesenteric Arteries Arteries which arise from the abdominal aorta and distribute to most of the intestines. Arteries, Mesenteric,Artery, Mesenteric,Mesenteric Artery
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077385 Silybin The major active component of silymarin flavonoids extracted from seeds of the MILK THISTLE, Silybum marianum; it is used in the treatment of HEPATITIS; LIVER CIRRHOSIS; and CHEMICAL AND DRUG INDUCED LIVER INJURY, and has antineoplastic activity; silybins A and B are diastereomers. 2,3-Dehydrosilybin,Alepa-forte,Ardeyhepan,Cefasilymarin,Durasilymarin,Hepa-Merz Sil,Hepa-loges,HepaBesch,Hepar-Pasc,Heparsyx,Heplant,Lagosa,Legalon Forte,Silibin,Silibinin,Silibinin A,Silibinin B,Silybin A,Silybin B,Silybinin,2,3 Dehydrosilybin,Alepa forte,Hepa Merz Sil,Hepa loges,Hepar Pasc
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014664 Vasodilation The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE. Vasodilatation,Vasorelaxation,Vascular Endothelium-Dependent Relaxation,Endothelium-Dependent Relaxation, Vascular,Relaxation, Vascular Endothelium-Dependent,Vascular Endothelium Dependent Relaxation
D042783 Endothelial Cells Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer. Capillary Endothelial Cells,Lymphatic Endothelial Cells,Vascular Endothelial Cells,Capillary Endothelial Cell,Cell, Capillary Endothelial,Cell, Endothelial,Cell, Lymphatic Endothelial,Cell, Vascular Endothelial,Cells, Capillary Endothelial,Cells, Endothelial,Cells, Lymphatic Endothelial,Cells, Vascular Endothelial,Endothelial Cell,Endothelial Cell, Capillary,Endothelial Cell, Lymphatic,Endothelial Cell, Vascular,Endothelial Cells, Capillary,Endothelial Cells, Lymphatic,Endothelial Cells, Vascular,Lymphatic Endothelial Cell,Vascular Endothelial Cell
D050051 Transient Receptor Potential Channels A broad group of eukaryotic six-transmembrane cation channels that are classified by sequence homology because their functional involvement with SENSATION is varied. They have only weak voltage sensitivity and ion selectivity. They are named after a DROSOPHILA mutant that displayed transient receptor potentials in response to light. A 25-amino-acid motif containing a TRP box (EWKFAR) just C-terminal to S6 is found in TRPC, TRPV and TRPM subgroups. ANKYRIN REPEATS are found in TRPC, TRPV & TRPN subgroups. Some are functionally associated with TYROSINE KINASE or TYPE C PHOSPHOLIPASES. TRP Cation Channel,Transient Receptor Potential Cation Channel,Transient Receptor Potential Channel,TRP Cation Channels,TRP Membrane Proteins,Transient Receptor Potential Cation Channels,Cation Channel, TRP,Cation Channels, TRP,Channel, TRP Cation,Channels, TRP Cation,Membrane Proteins, TRP,Proteins, TRP Membrane
D050916 TRPV Cation Channels A subgroup of TRP cation channels named after the vanilloid receptor. They are very sensitive to TEMPERATURE; hot spicy food, and CAPSAICIN. They contain a TRP domain (a five-turn amphipathic helix with an invariant TRYPTOPHAN) and ANKYRIN repeats. Selectivity for CALCIUM over SODIUM ranges from 3 to 100 fold. Capsaicin Receptor,Vanilloid Receptor,Capsaicin Receptors,Vanilloid Receptors,Cation Channels, TRPV,Channels, TRPV Cation,Receptor, Capsaicin,Receptor, Vanilloid,Receptors, Capsaicin,Receptors, Vanilloid

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