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: .

中文翻译：

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传统东方药物针对 Tau 病理学的治疗潜力：来自无细胞和细胞筛选的见解

背景：使用多种药用植物配制的传统东方药物 (TOM) 副作用风险较低。在之前的研究中，五种 TOM，即 Dangguijakyaksan、Hwanglyeonhaedoktang、Ukgansan、Palmijihwanghwan 和 Jowiseungchungtang 常用于治疗阿尔茨海默病患者。然而，只有少数研究调查了这五种 TOM 对 tau 病理学的影响。目的：本研究旨在探讨五种 TOM 对各种 tau 病理学的影响，包括翻译后修饰、聚集和沉积、tau 诱导的神经毒性和 tau 诱导的神经炎症。方法：采用免疫细胞化学方法研究冈田酸诱导的tau蛋白过度磷酸化。此外，硫黄素 T 测定用于评估 TOM 对 tau K18 聚集的抑制和 tau K18 聚集体解离的影响。此外，使用水溶性四唑-1测定和定量逆转录聚合酶链反应分别评估TOM对HT22和BV2细胞中tau诱导的神经毒性和炎症细胞因子的影响。结果：本研究中研究的 5 个 TOM 显着降低了冈田酸诱导的 tau 过度磷酸化。 Hwanglyeonhaedoktang 抑制 tau 聚集并促进 tau 聚集体解离。 Dangguijakyaksan 和 Hwanglyeonhaedoktang 减轻了 tau 诱导的 HT22 细胞神经毒性。此外，Dangguijakyaksan、Hwanglyeonhaedoktang、Ukgansan 和 Palmijihwanghwan 降低了 BV2 细胞中 tau 诱导的促炎细胞因子水平。结论：我们的结果表明，五种 TOM 是 tau 病理学的潜在治疗候选者。特别是，Hwanglyeonhaedoktang 在无细胞和细胞筛选方法中的五种 TOM 中显示出最大的功效。这些发现表明 Hwanglyeonhaedoktang 适合治疗具有 tau 病理学的 AD 患者。其他： 。