Therapeutic Potential of Traditional Oriental Medicines in Targeting Tau Pathology: Insights from Cell-free and Cell-based Screening

Author:

Park Hyun Ha1,Kim Byeong-Hyeon1,Leem Seol Hwa1,Park Yong Ho1,Chung Hyunju2,Yoo Doo-Han34,Park Insu5,Nam Yunkwon1,Kim Sujin1,Shin Soo Jung1,Moon Minho1

Affiliation:

1. Department of Biochemistry, College of Medicine, Konyang University, 158, Gwanjeodong-ro, Seo-gu, Daejeon 35365, Republic of Korea

2. Department of Core Research Laboratory, Medical Science Research Institute, Kyung Hee University Hospital Gangdong, Seoul 05278, Republic of Korea

3. Research Institute for Dementia Science, Konyang University, 158, Gwanjeodong-ro Seo-gu, Daejeon 35365, Republic of Korea

4. Department of Occupational Therapy, Konyang University, 158, Gwanjeodong-ro, Seo-gu, Daejeon 35365, Republic of Korea

5. Department of Biomedical Engineering, Konyang University, 158, Gwanjeodong-ro, Seo-gu, Daejeon 35365, Republic of Korea

Abstract

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. 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. other: .

Publisher

Bentham Science Publishers Ltd.

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