Vascular intimal hyperplasia is a hallmark event in vascular restenosis. The excessive proliferation, migration and phenotypic transformation of vascular smooth muscle cells (VSMCs) 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 VSMCs is currently unclear. In this study, we demonstrated that physalin B significantly inhibited the proliferation, migration and phenotypic transformation of VSMCs induced by PDGF-BB. Physalin B also reduced inflammation and oxidative stress in VSMCs 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 VSMCs 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.

中文翻译：

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Physalin B 通过激活 Nrf2 通路抑制 PDGF-BB 诱导的 VSMC 增殖、迁移和表型转化

血管内膜增生是血管再狭窄的标志性事件。血管平滑肌细胞（VSMCs）的过度增殖、迁移和表型转化在血管内膜增生的病理机制中起重要作用。Physalin B 是一种从Physalis中分离出来的醇化物（茄科）具有广泛的生物活性。然而，physalin B 对 VSMCs 的影响目前尚不清楚。在本研究中，我们证明physalin B 显着抑制PDGF-BB 诱导的VSMCs 的增殖、迁移和表型转化。Physalin B 还减少了由 PDGF-BB 诱导的 VSMC 中的炎症和氧化应激。机理研究表明，physalin B 主要通过激活 Nrf2 发挥作用。Nrf2激活后，physalin B通过增强抗氧化基因HO-1的表达来减轻氧化应激; 另一方面，physalin B 抑制 NF-κB 通路以减轻炎症反应。这两种作用最终降低了 PDGF-BB 诱导的 VSMC 的增殖、迁移和表型转化。此外，在小鼠颈动脉结扎模型中，physalin B 可防止内膜增生，抑制增生内膜细胞的增殖、迁移和表型转化。总之，我们提供了重要的证据表明physalin B 通过激活Nrf2 介导的信号转导消除了PDGF-BB 诱导的VSMC 增殖、迁移、表型转化和内膜增生。因此，physalin B 可能是预防或治疗再狭窄的潜在治疗剂。