Abstract
Misfolded tau proteins induce accumulation of free radicals and promote neuroinflammation by activating microglia-releasing proinflammatory cytokines, leading to neuronal cell death. Traditional Chinese herbal medicines (CHMs) have been widely used in clinical practice to treat neurodegenerative diseases associated with oxidative stress and neuroinflammation. This study examined the neuroprotection effects of formulated CHMs Bai-Shao (made of Paeonia lactiflora), Gan-Cao (made of Glycyrrhiza uralensis), and Shaoyao Gancao Tang (SG-Tang, made of P. lactiflora and G. uralensis at 1 : 1 ratio) in cell model of tauopathy. Our results showed that SG-Tang displayed a greater antioxidative and antiaggregation effect than Bai-Shao and Gan-Cao and a stronger anti-inflammatory activity than Bai-Shao but similar to Gan-Cao. In inducible 293/SH-SY5Y cells expressing proaggregant human tau repeat domain (ΔK280 tauRD), SG-Tang reduced tau misfolding and reactive oxygen species (ROS) level in ΔK280 tauRD 293 cells and promoted neurite outgrowth in ΔK280 tauRD SH-SY5Y cells. Furthermore, SG-Tang displayed anti-inflammatory effects by reducing nitric oxide (NO) production in mouse BV-2 microglia and increased cell viability of ΔK280 tauRD-expressing SH-SY5Y cells inflamed by BV-2 conditioned medium. To uncover the neuroprotective mechanisms of SG-Tang, apoptosis protein array analysis of inflamed tau expressing SH-SY5Y cells was conducted and the suppression of proapoptotic proteins was confirmed. In conclusion, SG-Tang displays neuroprotection by exerting antioxidative and anti-inflammatory activities to suppress neuronal apoptosis in human tau cell models. The study results lay the base for future applications of SG-Tang on tau animal models to validate its effect of reducing tau misfolding and potential disease modification.
Highlights
Neurodegenerative diseases including Alzheimer’s disease (AD) and tauopathy are characterized by the presence of hyperphosphorylated, insoluble, and filamentous tau protein, which leads to neuronal dysfunction and loss [1]
Our results demonstrate that Shaoyao Gancao Tang (SG-Tang) could protect cells from cell death, increase neurite outgrowth, and reduce hyperphosphorylation of tau in inflamed misfolded tauexpressing ΔK280 tau repeat domain (tauRD)-DsRed cells
Since we have found SG-Tang decreased tumor necrosis factor- (TNF-)α and IL-1β in conditioned medium (CM) of BV-2, we proposed that SG-Tang may act on the inflammation-induced cell death
Summary
Neurodegenerative diseases including Alzheimer’s disease (AD) and tauopathy are characterized by the presence of hyperphosphorylated, insoluble, and filamentous tau protein, which leads to neuronal dysfunction and loss [1]. Tau is an ubiquitously distributed microtubule-associated protein that promotes and stabilizes microtubule assembly. Aside from helping microtubule assembly, tau interacts with other cytoskeleton components to play a role in axonal transport [2]. Tau is encoded by MAPT (microtubule-associated protein tau) gene located on chromosome 17q21, containing. Tau proteins exist as six different isoforms in human central nervous system (CNS). Exons 9–12 encode four C-terminal microtubule binding motifs which are imperfect copies of an 18-aminoacid tau repeat domain (tauRD). Different point mutations found in tauRD reduced the ability of tau to promote microtubule assembly [4] and accelerated aggregation of tau into filaments [5].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
