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

Hyun Ha Park; Byeong-Hyeon Kim; Seol Hwa Leem; Yong Ho Park; Hyunju Chung; Doo-Han Yoo; Insu Park; Yunkwon Nam; Sujin Kim; Soo Jung Shin; Minho Moon

doi:10.2174/0109298673295901240311072440

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

Curr Med Chem. 2024 Mar 13. doi: 10.2174/0109298673295901240311072440. Online ahead of print.

Authors

Hyun Ha Park¹, Byeong-Hyeon Kim¹, Seol Hwa Leem¹, Yong Ho Park¹, Hyunju Chung², Doo-Han Yoo^{3

4}, Insu Park⁵, Yunkwon Nam¹, Sujin Kim¹, Soo Jung Shin¹, Minho Moon¹

Affiliations

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.

PMID: 38486385
DOI: 10.2174/0109298673295901240311072440

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.

Keywords: Neurodegenerative disease; alzheimer’s disease; dementia; screening assay.; tau; traditional oriental medicines.