Abstract
As a bioactive absorbed compound of rhubarb, Rhein is applied for the treatment of brain injury. However, the underlying pharmacological mechanisms remain unclear. In this study, we aimed to explore antineuroinflammatory functions and underlying mechanisms of Rhein in vitro. BV2 microglia cells were chosen and irritated by LPS. The influence of Rhein on cell viability was determined using MTT assay. We finely gauged the proinflammatory cytokines of TNF-α and IL-1β through tests of immunofluorescence staining, ELISA, RT-qPCR, and western blot. Additionally, mediators including IL-6, IL-12, iNOS, and IL-10 were surveyed by ELISA. Furthermore, protein levels of the underlying signaling pathways (PI3K/Akt, p38, ERK1/2, and TLR4/NF-κB) were tested adopting western blot. We found that Rhein reduced the secretion of pivotal indicators including TNF-α and IL-1β, effectively restraining their mRNA and protein expression in LPS-activated BV2 microglial cells. Besides, Rhein treatment demoted the production of IL-6, IL-12, and iNOS and promoted the excretion of IL-10. Subsequent mechanistic experiments revealed that Rhein obviously downregulated the phosphorylation levels of PI3K, Akt, p38, and ERK1/2 and simultaneously upregulated the PTEN expression. In addition, Rhein antagonized the increase of TLR4, p-IκBα, and NF-κB. In summary, Rhein suppresses neuroinflammation via multiple signaling pathways (PI3K/Akt, p38, ERK1/2, and TLR4/NF-κB) in LPS-stimulated BV2 microglia cells. This study highlights a natural agent for prevention and treatment of neuroinflammation.
Highlights
Central nervous system (CNS) controls physical and mental functions
Rhein remarkably decreased the viability of BV2 microglial cells. 160 μM of Rhein almost reduced the cell viability by 40% compared with control group
This drug remarkably upregulated the expression of the protective factor IL-10. e potential molecular mechanisms were related to the inhibition of phosphoinositide 3-kinase (PI3K)/Akt, p38, extracellular signal-regulated kinase 1/2 (ERK1/2), and Toll-like receptor 4 (TLR4)/NF-κB signaling pathways (Figure 7)
Summary
Its collapse causes neurological and neurodegenerative diseases such as traumatic brain injury (TBI), stroke, Parkinson’s diseases, multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). Most of these diseases are severe and incorrigible due to extremely limited regenerative potential of CNS [1]. CNS injury involves a series of complex pathological processes. Glial cells, and endothelial cells participate in these processes and produce immune medium. Of these cells, microglia mainly contribute to the neuroinflammation which plays an important role in brain damage [2]. CNS releases a large number of inflammatory immune factors after injury, which mediates a series of waterfall-like inflammatory responses. e responses can accelerate pathological progression and worsen subsequent prognosis [3]. erefore, to improve or reverse the pathological process through inhibiting neuroinflammatory responses becomes a coincident strategy to treat neurological diseases
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Evidence-Based Complementary and Alternative Medicine
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
