Physalin B inhibits PDGF-BB-induced VSMC proliferation, migration and phenotypic transformation by activating the Nrf2 pathway
- 20 September 2021
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Food & Function
- Vol. 12 (21), 10950-10966
- https://doi.org/10.1039/d1fo01926k
Abstract
Vascular intimal hyperplasia is a hallmark event in vascular restenosis. The excessive proliferation, migration and phenotypic transformation of vascular smooth muscle cells (VSMC) play important roles in the pathological mechanism of vascular intimal hyperplasia. Physalin B is an alcoholate isolated from physalis (Solanaceae) that has a wide range of biological activities. However, the effect of physalin B on VSMC is currently unclear. In this study, we demonstrated that physalin B significantly inhibited the proliferation, migration and phenotypic transformation of VSMC induced by PDGF-BB. Physalin B also reduced inflammation and oxidative stress in VSMC induced by PDGF-BB. Mechanistic studies showed that physalin B plays a role mainly by activating Nrf2. After Nrf2 activation, physalin B mitigates oxidative stress by enhancing the expression of the antioxidant gene HO-1; on the other hand, physalin B inhibits the NF-κB pathway to alleviate the inflammatory response. These two effects ultimately reduce the proliferation, migration and phenotypic transformation of VSMC induced by PDGF-BB. In addition, in the mouse carotid artery ligation model, physalin B prevented intimal hyperplasia and inhibited the proliferation, migration and phenotypic transformation of cells in the hyperplastic intima. In conclusion, we provided significant evidence that physalin B abrogates PDGF-BB-induced VSMC proliferation, migration, phenotypic transformation and intimal hyperplasia by activating Nrf2-mediated signal transduction. Therefore, physalin B may be a potential therapeutic agent for preventing or treating restenosis.Keywords
Funding Information
- National Natural Science Foundation of China (81900364)
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