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Cell-based Assay to Study Antibody-mediated Tau Clearance by Microglia
Published on: November 9, 2018
Therapeutic Potential of Traditional Oriental Medicines in Targeting Tau Pathology: Insights from Cell-free and
Hyun Ha Park1, Byeong-Hyeon Kim1, Seol Hwa Leem1
1Department of Biochemistry, College of Medicine, Konyang University, 158, Gwanjeodong-ro, Seo-gu, Daejeon, 35365, Republic of Korea.
Background:
Traditional Oriental Medicines (TOMs) formulated using a variety of medicinal plants have a low risk of side effects. In previous studies, five TOMs, namely Dangguijakyaksan, Hwanglyeonhaedoktang, Ukgansan, Palmijihwanghwan, and Jowiseungchungtang have been commonly used to treat patients with Alzheimer's disease (AD). However, only a few studies have investigated the effects of these five TOMs on tau pathology.
Objective:
This study aimed to examine the effect of five TOMs on various tau pathologies, including post-translational modifications, aggregation and deposition, tau-induced neurotoxicity, and tau-induced neuroinflammation.
Methods:
Immunocytochemistry was used to investigate the hyperphosphorylation of tau induced by okadaic acid. In addition, the thioflavin T assay was used to assess the effects of the TOMs on the inhibition of tau K18 aggregation and the dissociation of tau K18 aggregates. Moreover, a water-soluble tetrazolium-1 assay and a quantitative reverse transcription polymerase chain reaction were used to evaluate the effects of the TOMs on tau-induced neurotoxicity and inflammatory cytokines in HT22 and BV2 cells, respectively.
Results:
The five TOMs investigated in this study significantly reduced okadaic acid-induced tau hyperphosphorylation. Hwanglyeonhaedoktang inhibited the aggregation of tau and promoted the dissociation of tau aggregates. Dangguijakyaksan and Hwanglyeonhaedoktang attenuated tau-induced neurotoxicity in HT22 cells. In addition, Dangguijakyaksan, Hwanglyeonhaedoktang, Ukgansan, and Palmijihwanghwan reduced tauinduced pro-inflammatory cytokine levels in BV2 cells.
Conclusion:
Our results suggest that five TOMs are potential therapeutic candidates for tau pathology. In particular, Hwanglyeonhaedoktang showed the greatest efficacy among the five TOMs in cell-free and cell-based screening approaches. These findings suggest that Hwanglyeonhaedoktang is suitable for treating AD patients with tau pathology.
