Angelica gigas NAKAI and Its Active Compound,Decursin, Inhibit Cellular Injury as an Antioxidant by the Regulation of AMP-Activated Protein Kinase and YAP Signaling

Natural products and medicinal herbs have been used to treat various human diseases by regulating cellular functions and metabolic pathways. Angelica gigas NAKAI (AG) helps regulate pathological processes in some medical fields, including gastroenterology, gynecology, and neuropsychiatry. Although some papers have reported its diverse indications, the effects of AG against arachidonic acid (AA)+ iron and carbon tetrachloride (CCl₄) have not been reported. In HepG2 cells, AA+ iron induced cellular apoptosis and mitochondrial damage, as assessed by mitochondrial membrane permeability (MMP) and the expression of apoptosis-related proteins. On the other hand, AG markedly inhibited these detrimental phenomena and reactive oxygen species (ROS) production induced by AA+ iron. AG activated the liver kinase B1 (LKB1)-dependent AMP-activated protein kinase (AMPK), which affected oxidative stress in the cells. Moreover, AG also regulated the expression of yes-associated protein (YAP) signaling as mediated by the AMPK pathways. In mice, an oral treatment of AG protected against liver toxicity induced by CCl₄, as indicated by the plasma and histochemical parameters. Among the compounds in AG, decursin had antioxidant activity and affected the AMPK pathway. In conclusion, AG has antioxidant effects in vivo and in vitro, indicating that natural products such as AG could be potential candidate for the nutraceuticals to treat various disorders by regulating mitochondrial dysfunction and cellular metabolic pathways.     

Trace element analysis of hairs in patients with dementia

The trace elements of scalp hair samples from ≥60‐year‐old dementia patients and normal persons have been studied by X‐ray absorption near‐edge spectroscopy (XANES) in fluorescent mode and wavelength‐dispersive X‐ray fluorescence spectrometry. Comparisons of hair trace element levels of age‐matched dementia patients and normal persons revealed significantly elevated amounts of calcium, chlorine and phosphorus in dementia patients relative to normal persons. The results of XANES measurements identify the chemical forms of deposited calcium and phosphorus in the hair samples of both dementia patients and normal persons to be calcium chloride (CaCl₂) and phosphate (PO₄^3?), respectively. The amount of sulfur in hairs of dementia patients was found to be not significantly different from that in normal persons. The sulfur K‐edge XANES spectra, however, show significantly higher accumulations of sulfur in the sulfate (SO₄^2?) form in hairs of Alzheimer's disease and Parkinson's disease dementia patients. This study presents the possible roles of calcium, chlorine, phosphorus and sulfur in the etiology of dementia in elderly patients.     

Cryptotanshinone against vascular dementia through inhibition of Aβ aggregation and inflammatory responses in cerebrovascular endothelial cells

Abnormal aggregation of amyloid-β (Aβ) peptides and associated inflammation and apoptosis in cerebrovascular endothelial cells are prelude to inhibition of onset of vascular dementia (VaD). Although small molecules have been widely used to mitigate the cell damage induced by aggregated species of Aβ, its molecular mechanism based on anti-amyloid properties and corresponding mitigation of cytotoxicity against cerebrovascular endothelial cells have not been elucidated. Herein, we used cryptotanshinone as the major bioactive compound from the root of Salvia miltiorrhiza Bunge to effectively inhibit Aβ fibrillation and associated cytotoxicity. Thoflavin T (ThT) and 1-Anilino-8-naphthalene sulfonate (ANS) fluorescence, Congo red, and circular dichroism (CD) analyses indicted that cryptotanshinone potentially inhibit Aβ_1-42 aggregation through elongation of nucleation phase, apparent decrease in the slope of the growth phase, and the final fluorescence intensity in a concentration-dependent manner. Also, cell viability, inflammation and capsae-3 assays showed that co-incubation of Aβ_1-42 peptide with cryptotanshinone in the aggregation buffer not only mitigated their cytotoxicity, but also reduced the levels of TNF-α, IL-1β, IL-6 and caspase-3 activity in cerebrovascular endothelial cells induced by Aβ_1-42. This study suggested that cryptotanshinone may show a great promise in the development of small molecule-based platforms for the treatment of VaD.     

Lewy body disease and dementia with Lewy bodies

In 1976 we reported our first autopsied case with diffuse Lewy body disease (DLBD), the term of which we proposed in 1984. We also proposed the term “Lewy body disease” (LBD) in1980. Subsequently, we classified LBD into three types according to the distribution pattern of Lewy bodies: a brain stem type, a transitional type and a diffuse type. Later, we added the cerebral type. As we have proposed since 1980, LBD has recently been used as a generic term to include Parkinson’s disease (PD), Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB), which was proposed in 1996 on the basis of our reports of DLBD.DLB is now known to be the second most frequent dementia following Alzheimer’s disease (AD).In this paper we introduce our studies of DLBD and LBD.