Scutellarin‑treated exosomes increase claudin 5, occludin and ZO1 expression in rat brain microvascular endothelial cells

Abstract

Homocysteine has been reported to be an independent risk factor for stroke. Scutellarin (Scu) dilates cerebral blood vessels and promotes anti-platelet aggregation; however, the mechanism by which Scu and Scu-treated exosomes protect against cerebrovascular disease is unclear. The aim of the present study was to investigate the mechanisms underlying the effects of Scu and Scu-treated exosomes on tight junction proteins in the blood-brain barrier. Rat brain microvascular endothelial cells (RBMVECs) were cultured and divided into five groups: Control, model, Scu, exosomes derived from RBMVECs and exosomes derived from RBMVECs after Scu administration. MTT, lactate dehydrogenase (LDH) and nitric oxide (NO) assays were performed to assess cell viability and injury. Reactive oxygen species (ROS) levels were detected using spectrophotometry and immunofluorescence. Western blotting and immunofluorescence were performed to measure cluster of differentiation (CD) 63, claudin 5, occludin and tight junction protein 1 (ZO1) expression. The results revealed that treatment with Scu and Scu-treated exosomes enhanced cell viability, reduced cell injury, increased NO levels, upregulated CD63, claudin 5, occludin and ZO1, and decreased LDH and ROS levels. These data suggest that Scu and Scu-treated exosomes protect homocysteine-induced RBMVECs via increased claudin 5, occludin and ZO1 expression.

Extracellular Vesicle Proteome of Breast Cancer Patients with and Without Cognitive Impairment Following Anthracycline-based Chemotherapy: An Exploratory Study

“…In contrast, the use of Scutellarin or Scutellarin-treated EVs was demonstrated to exert protective effect on brain microvascular endothelial cells by reducing homocysteine-mediated damage to tight junction proteins. 70 Moreover, the inhibition of glycogen synthase kinase 3β activity was shown to exhibit improved cognitive function in aged mice by upregulating claudin and restores BBB integrity. 71 It is plausible that an association exists between tight junction disruption and the breakdown of BBB, and the decreased tight junction protein expression in the plasma EVs of CI patients may be indicative of tight junction disruption via EV-related biological activities, resulting in vascular cognitive impairment in the CI patients.…”

Exosomes Interactions with the Blood–Brain Barrier: Implications for Cerebral Disorders and Therapeutics

“…These exosomes also sustained the TJs protein expression, offering dual benefits of BBB protection and antioxidant activity in vivo [146]. Moreover, exosomes treated with scutellarin were documented to protect BMECs by diminishing homocysteine-induced injury to TJ proteins and ROS-mediated oxidative stress on the BBB [147]. Collectively, these results demonstrated that exosome therapy improves BBB integrity in stroke.…”

“…There is growing evidence that exosomes specifically affect BBB integrity in various ways post-stroke [15,[145][146][147]. For example, exosomes had a protective effect on the BBB in a rat stroke model.…”

Scutellarin‐mediated autophagy activates exosome release of rat nucleus pulposus cells by positively regulating Rab8a via the PI3K/PTEN/Akt pathway

“…As a kind of natural ingredient derivative from plants, SC has exhibited multiple bioactivities and potential clinical applications for inflammation remission, cardiovascular and cerebrovascular diseases, and diabetes, and has been shown to improve the degenerative microenvironment of osteoarthritis in a series of in-vitro experiments (Luo et al, 2020). In addition, SC-treated exosomes have been reported to improve cell viability and alleviate cell injury (Zhong et al, 2019). However, at the molecular level, there remain some uncertainties regarding the mechanisms through which SC mediates exosome trafficking.…”