Korean red ginseng polysaccharide as a potential therapeutic agent targeting tau pathology in Alzheimer's disease.

Tau is a microtubule-associated protein that plays a critical role in the stabilization and modulation of neuronal axons. Tau pathology is stronger associated with cognitive decline in patients with Alzheimer's disease (AD) than amyloid beta (Aß) pathology. Hence, tau targeting is a promising approach for the treatment of AD. Previous studies have demonstrated that the non-saponin fraction with rich polysaccharide (NFP) from Korean red ginseng (KRG) can modulate tau aggregation and exert a therapeutic effect on AD. Therefore, we investigated the efficacy of NFP isolated from KRG on tau pathology in experimental models of AD. Our results showed that NFP from KRG ameliorated deposition and hyperphosphorylation of tau in the brain of 3xTg mice. Moreover, NFP from KRG modulated the aggregation and dissociation of tau K18 in vitro. We demonstrated the alleviatory effects of NFP from KRG on hyperphosphorylated tau and tau kinase in okadaic acid-treated HT22 cells. Furthermore, NFP from KRG mitigated Aß deposition, neurodegeneration, and neuroinflammation in 3xTg mice. We revealed the neuroprotective effects of NFP from KRG on tau-induced neuronal loss in HT22 cells. Our results indicate that NFP extracted from KRG is a novel therapeutic agent for the treatment of AD associated with tau pathology.

An Aqueous Extract of Herbal Medicine ALWPs Enhances Cognitive Performance and Inhibits LPS-Induced Neuroinflammation via FAK/NF-κB Signaling Pathways.

Recent studies have shown that Liuwei Dihuang pills (LWPs) can positively affect learning, memory and neurogenesis. However, the underlying molecular mechanisms are not understood. In the present study, we developed ALWPs, a mixture of Antler and LWPs, and investigated whether ALWPs can affect neuroinflammatory responses. We found that ALWPs (500 mg/ml) inhibited lipopolysaccharide (LPS)-induced proinflammatory cytokine IL-1ß mRNA levels in BV2 microglial cells but not primary astrocytes. ALWPs significantly reduced LPS-induced cell-surface levels of TLR4 to alter neuroinflammation. An examination of the molecular mechanisms by which ALWPs regulate the LPS-induced proinflammatory response revealed that ALWPs significantly downregulated LPS-induced levels of FAK phosphorylation, suggesting that ALWPs modulate FAK signaling to alter LPS-induced IL-1ß levels. In addition, treatment with ALWPs followed by LPS resulted in decreased levels of the transcription factor NF-κB in the nucleus compared with LPS alone. Moreover, ALWPs significantly suppressed LPS-induced BV2 microglial cell migration. To examine whether ALWPs modulate learning and memory in vivo, wild-type C57BL/6J mice were orally administered ALWPs (200 mg/kg) or PBS daily for 3 days, intraperitoneally injected (i.p.) with LPS (250 µg/kg) or PBS, and assessed in Y maze and NOR tests. We observed that oral administration of ALWPs to LPS-injected wild-type C57BL/6J mice significantly rescued short- and long-term memory. More importantly, oral administration of ALWPs to LPS-injected wild-type C57BL/6J mice significantly reduced microglial activation in the hippocampus and cortex. Taken together, our results suggest that ALWPs can suppress neuroinflammation-associated cognitive deficits and that ALWPs have potential as a drug for neuroinflammation/neurodegeneration-related diseases, including Alzheimer's disease (AD).

Epimedium koreanum Nakai inhibits PMA-induced cancer cell migration and invasion by modulating NF-κB/MMP-9 signaling in monomorphic malignant human glioma cells.

Previously, we showed that the herbal extract EYK (Epimedium koreanum Nakai) can regulate the immune response. Other studies showed that EYK has beneficial effects in human lung cancer, angiogenesis and Alzheimer's disease (AD). However, it remains unknown whether EYK can affect cancer cell migration and invasion in human brain cancer cell lines. In the present study, we found that pre- or post-treatment with EYK inhibited phorbol 12-myristate 13-acetate (PMA)-induced cancer cell migration and invasion in A172 cells, but not in U373MG or T98G cells. Additionally, pre- or post-treatment with PMA followed by EYK decreased MMP-9 activity in A172 cells. Moreover, treatment with a NF-κB inhibitor significantly decreased cell migration in A172 cells pre- or post-treated with EYK and PMA, suggesting that EYK requires NF-κB to alter cancer cell migration. Either pre- or post-treatment with EYK significantly decreased NF-κB nuclear translocation in comparison with PMA treatment. Taken together, our results suggest that EYK suppresses PMA-induced cancer cell migration in monomorphic malignant human glioma cells by downregulating the NF-κB pathway and decreasing MMP-9 activity.