Corynoxine promotes TFEB/TFE3-mediated autophagy and alleviates Aβ pathology in Alzheimer's disease models.

Autophagy impairment is a key factor in Alzheimer's disease (AD) pathogenesis. TFEB (transcription factor EB) and TFE3 (transcription factor binding to IGHM enhancer 3) are nuclear transcription factors that regulate autophagy and lysosomal biogenesis. We previously showed that corynoxine (Cory), a Chinese medicine compound, protects neurons from Parkinson's disease (PD) by activating autophagy.

Protective effects of lipoic acid-niacin dimers against blue light-induced oxidative damage to retinal pigment epithelium cells.

Aim: To evaluate the protective effects of lipoic acid-niacin (N2L) dimers against blue light (BL)-induced oxidative damage to human retinal pigment epithelium (hRPE) cells

Methods: hRPE cells were divided into a control group (CG), a BL group, an N2L plus BL irradiation group, an α-lipoic acid (ALA) plus BL group, an ALA-only group, and an N2L-only group. hRPE cellular viability was detected by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) bromide assays, and apoptosis was evaluated by annexin-V-PE/7-AAD staining followed by flow cytometry. Ultrastructural changes in subcellular organelles were observed by transmission electron microscopy.

Synthesis and evaluation of multifunctional ferulic and caffeic acid dimers for Alzheimer's disease.

In this study, a series of novel ferulic and caffeic acid dimers was designed and synthesised, and their multifunctional properties against Alzheimer's disease (AD) were evaluated. Results showed that our multifunctional strategy was great supported by enhancing the inhibition of Aβ self-induced aggregation. Moreover, 7b also had potent protective effects against glutamate-induced cell death without significant cell toxicity in mouse hippocampal neuronal HT22 cells and 10c effectively scavenged diphenylpicrylhydrazyl free radicals.

Gartanin Protects Neurons against Glutamate-Induced Cell Death in HT22 Cells: Independence of Nrf-2 but Involvement of HO-1 and AMPK.

Oxidative stress mediates the pathogenesis of neurodegenerative disorders. Gartanin, a natural xanthone of mangosteen, possesses multipharmacological activities. Herein, the neuroprotection capacity of gartanin against glutamate-induced damage in HT22 cells and its possible mechanism(s) were investigated for the first time.

Natural Xanthones from Garcinia mangostana with Multifunctional Activities for the Therapy of Alzheimer's Disease.

Natural xanthones have diversity pharmacological activities. Here, a series of xanthones isolated from the pericarps of Garcinia mangostana Linn, named α-Mangostin, 8-Deoxygartanin, Gartanin, Garciniafuran, Garcinone C, Garcinone D, and γ-Mangostin were investigated. Biological screening performed in vitro and in Escherichia coli cells indicated that most of the xanthones exhibited significant inhibition of self-induced β-amyloid (Aβ) aggregation and also β-site amyloid precursor protein-cleaving enzyme 1, acted as potential antioxidants and biometal chelators.

MEF2D Mediates the Neuroprotective Effect of Methylene Blue Against Glutamate-Induced Oxidative Damage in HT22 Hippocampal Cells.

Methylene blue (MB) can ameliorate behavioral, neurochemical, and neuropathological impairments in animal models of acute and chronic neurodegenerative disorders, but the underlying mechanism remains unclear. Myocyte enhancer factor 2 (MEF2D) is known to promote neuronal survival in several models, and several survival and death signals converge on MEF2D and regulate its activity. Here, we investigated the role of MEF2D in the neuroprotective effect of MB against glutamate-induced toxicity in HT22 neuronal cells.

Fasudil hydrochloride, a potent ROCK inhibitor, inhibits corneal neovascularization after alkali burns in mice.

Purpose: To investigate the effects and mechanisms of fasudil hydrochloride (fasudil) on and in alkali burn-induced corneal neovascularization (CNV) in mice.

Methods: To observe the effect of fasudil, mice with alkali-burned corneas were treated with either fasudil eye drops or phosphate-buffered saline (PBS) four times per day for 14 consecutive days. After injury, CNV and corneal epithelial defects were measured.

Osthole, a natural coumarin improves cognitive impairments and BBB dysfunction after transient global brain ischemia in C57 BL/6J mice: involvement of Nrf2 pathway.

Oxidative stress and blood-brain barrier (BBB) disruption play important roles in cerebral ischemic pathogenesis and may represent targets for treatment. Earlier studies have shown that osthole, a main active constituent isolated from Cnidium monnieri (L.) Cusson, could be considered as an attractive therapeutic agent in the treatment of ischemic stroke.

Effect of tacrine-3-caffeic acid, a novel multifunctional anti-Alzheimer's dimer, against oxidative-stress-induced cell death in HT22 hippocampal neurons: involvement of Nrf2/HO-1 pathway.

Aims: Oxidative stress (OS) plays an important role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). This study was designed to uncover the cellular and biochemical mechanisms underlying the neuroprotective effects of tacrine-3-caffeic acid (T3CA), a novel promising multifunctional anti-Alzheimer's dimer, against OS-induced neuronal death.

Methods And Results: T3CA protected HT22 cells against high-concentration-glutamate-induced cell death in time- and concentration-dependent manners and potently attenuated glutamate-induced intracellular reactive oxygen species (ROS) production as well as mitochondrial membrane-potential (ΔΨ) disruption.

Neuroprotective polyhydroxypregnane glycosides from Cynanchum otophyllum.

Five new polyhydroxypregnane glycosides, namely cynanotosides A-E (1-5), together with two known analogues, deacetylmetaplexigenin (6) and cynotophylloside H (7), were isolated from the roots of Cynanchum otophyllum. Their structures were established by spectroscopic methods and acid hydrolysis. The neuroprotective effects of compounds 1-7 against glutamate-, hydrogen peroxide-, and homocysteic acid (HCA)-induced cell death were tested by MTT assay in a hippocampal neuronal cell line HT22.

Acrolein induces Alzheimer's disease-like pathologies in vitro and in vivo.

The pathologic mechanisms of Alzheimer's disease (AD) have not been fully uncovered. Acrolein, a ubiquitous dietary pollutant and by-product of oxidative stress, can induce cytotoxicity in neurons, which might play an important role in the etiology of AD. Here, we examined the effects of Acrolein on the AD pathologies in vitro and in vivo.

Edaravone protects HT22 neurons from H2O2-induced apoptosis by inhibiting the MAPK signaling pathway.

Aims: Oxidative stress is frequently implicated in the pathology of neurodegenerative diseases. This study aimed to investigate the effects and their underlying mechanism(s) of edaravone upon hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis in HT22 cells, a murine hippocampal neuronal model.

Methods: HT22 cells were treated with H2O2 in the presence of various concentrations of edaravone or in its absence.

Minocycline inhibits alkali burn-induced corneal neovascularization in mice.

The purpose of this study was to investigate the effects of minocycline on alkali burn-induced corneal neovascularization (CNV). A total of 105 mice treated with alkali burns were randomly divided into three groups to receive intraperitoneal injections of either phosphate buffered saline (PBS) or minocycline twice a day (60 mg/kg or 30 mg/kg) for 14 consecutive days. The area of CNV and corneal epithelial defects was measured on day 4, 7, 10, and14 after alkali burns.

Nmnat2 protects cardiomyocytes from hypertrophy via activation of SIRT6.

The discovery of sirtuins (SIRT), a family of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases, has indicated that intracellular NAD level is crucial for the hypertrophic response of cardiomyocytes. Nicotinamide mononucleotide adenylyltransferase (Nmnat) is a central enzyme in NAD biosynthesis. Here we revealed that Nmnat2 protein expression and enzyme activity were down-regulated during cardiac hypertrophy.

Sirtuin 6 protects cardiomyocytes from hypertrophy in vitro via inhibition of NF-κB-dependent transcriptional activity.

Background And Purpose: Sirtuin 6 (SIRT6) is involved in regulation of glucose and fat metabolism. However, its possible contribution to cardiac dysfunction remains to be determined. In the present study, the effect of SIRT6 on cardiac hypertrophy induced by angiotensin II (AngII) and the underlying molecular mechanisms were investigated.

The orally combined neuroprotective effects of sodium ferulate and borneol against transient global ischaemia in C57 BL/6J mice.

Objectives: This study aimed to investigate the possible modification of the neuroprotective effect of sodium ferulate, when orally co-administered with borneol, in transient global cerebral ischaemia-induced functional, histological and cellular alterations in mice.

Methods: The bilateral common carotid artery occlusion was conducted in C57 BL/6J mice for 25 min. The mice were then subjected to a water maze test over an extended recovery period, followed by an assessment of neuronal loss in the CA1 region of the hippocampus (haematoxylin and eosin staining).

Alterations in mRNA expression of BACE1, cathepsin B, and glutaminyl cyclase in mice ischemic brain.

The relationship between cerebral ischemia and Alzheimer's disease has been evaluated extensively. However, the association between cerebral ischemia and the deposition of beta-amyloid (Abeta) remains to be clarified. Here, we used mice bilateral common carotid artery ligation model to investigate the alterations in mRNA expression of Abeta precursor protein cleavage enzyme 1(BACE1), cathepsin B, and glutaminyl cyclase after transient global cerebral ischemia.

Reduced expression of GSTM2 and increased oxidative stress in spontaneously hypertensive rat.

Human essential hypertension is a complex polygenic trait with underlying genetic components that remain unknown. The spontaneously hypertensive rat (SHR) is a well-characterized experimental model for essential hypertension. By comparative proteomics, we previously identified glutathione S-transferase, mu 2 (GSTM2), a protein involved in detoxification of reactive oxygen species, which had a significant reduction in left ventricles of 16-week-old SHR compared with WKY rats.