The acetylcholinesterase inhibitors donepezil and rivastigmine have been used as therapeutic drugs for Alzheimer’s disease (AD), but their effects on LPS- and Aβ-induced neuroinflammatory responses and the underlying molecular pathways have not been studied in detail in vitro and in vivo. In the present study, we found that 10 or 50 μM donepezil significantly decreased the LPS-induced increases in the mRNA levels of a number of proinflammatory cytokines in BV2 microglial cells, whereas 50 μM rivastigmine significantly diminished only LPS-stimulated IL-6 mRNA levels. In subsequent experiments in primary astrocytes, donepezil suppressed only LPS-stimulated iNOS mRNA levels. To identify the molecular mechanisms by which donepezil regulates LPS-induced neuroinflammation, we examined whether donepezil alters LPS-stimulated proinflammatory responses by modulating LPS-induced downstream signaling and the NLRP3 inflammasome. Importantly, we found that donepezil suppressed LPS-induced AKT/MAPK signaling, the NLRP3 inflammasome, and transcription factor NF-kB/STAT3 phosphorylation to reduce neuroinflammatory responses. In LPS-treated wild-type mice, a model of neuroinflammatory disease, donepezil significantly attenuated LPS-induced microglial activation, microglial density/morphology, and proinflammatory cytokine COX-2 and IL-6 levels. In a mouse model of AD (5xFAD mice), donepezil significantly reduced Aβ-induced microglial and astrocytic activation, density, and morphology. Taken together, our findings indicate that donepezil significantly downregulates LPS- and Aβ-evoked neuroinflammatory responses in vitro and in vivo and may be a therapeutic agent for neuroinflammation-associated diseases such as AD.

Hardy kiwifruits (Actinidia arguta) contain various bioactive compounds such as vitamin C and phenolics and can withstand cold temperatures. Changes in soluble solid, vitamin C, total phenolic, and total flavonoid content, and antioxidant capacity of three cultivars of hardy kiwifruits (A. arguta 9 A. deliciosa cv. Mansu, A. arguta cv. Haeyeon, and A. arguta cv. Chiak) were comparatively evaluated for 8 weeks of storage at 1 ± 0.5 °C. After the 8 weeks of storage, soluble solid content of three cultivars increased, whereas their vitamin C content decreased. Throughout this storage period, total phenolic and flavonoid content of cv. Mansu and cv. Haeyeon remained the same, while antioxidant capacity of these two cultivars also remained similar but with slightly more variations. Cv. Chiak, however, showed a decrease in total phenolic and flavonoid content and antioxidant capacity. These results suggest that cold storage of the hardy kiwifruits maintains levels of bioactive compounds.

Hardy kiwifruits (Actinidia arguta) have a smaller non-edible portion than other kiwifruits such as gold kiwifruit (A. chinensis) and green kiwifruit (A. deliciosa) due to their smooth and edible skins. Although hardy kiwifruits are smaller than most common commercial kiwifruits such as A. deliciosa cv. Hayward and A. chinensis cv. Hort16A [1, 2], hardy kiwifruits are gaining popularity in the market. Hardy kiwifruits can withstand cold and frosty environments (up to −30°C) and are commonly cultivated in mountainous areas with cold climates [3]. Hardy kiwifruits are a good source of vitamin C [2, 4] and have a higher total phenolic content than green kiwifruit cv. Hayward [5]. Recently, new cultivars of hardy kiwifruits have been developed and registered in breeding programs in Republic of Korea [6].Reactive oxygen species (ROS) occur normally or abnormally during oxygen metabolism in the body. ROS are mostly eliminated by antioxidant defense mechanisms including phenolics, vitamin C, and antioxidant enzymes. However, due to imbalance of excessive ROS production, oxidative stress results in neuronal cell damage, causing oxidative modification of proteins, DNA, and lipids, eventually leading to neurological disorders such as Alzheimer's disease [7]. Antioxidants such as phenolics and vitamin C in foods are known to reduce oxidative stress by scavenging ROS and possibly preventing apoptosis of neuronal cells against oxidative stress [7,8]. Protection of neurons in the brain using antioxidants can delay or prevent neurodegeneration caused by excessive and chronic oxidative stress.Hardy kiwifruits have been reported to show beneficial health effects such as antioxidant, anti-cancer, antihypercholesterolemia, and neuroprotective effects [9][10][11][12]. It was previously reported that hardy kiwifruit cultivars showed anti-inflammatory effects, although their phenolic profile was not presented [9]. Various kiwifruits Hardy kiwifruits (Actinidia arguta Planch.) have high amounts of antioxidants, including ascorbic acid (vitamin C) and phenolics. The anti-cholinesterase activity and neuroprotective effects of three different cultivars of hardy kiwifruits, cv. Mansu (A. arguta × A. deliciosa), cv. Haeyeon (A. arguta), and cv. Chiak (A. arguta), on PC-12 and SH-SY5Y cells were evaluated. Extraction of phenolics and vitamin C was carried out using 80% (v/v) aqueous ethanol and metaphosphoric acid assisted with homogenization, respectively. Hardy kiwifruit of cv. Mansu showed higher total phenolic, total flavonoid, and vitamin C contents and antioxidant capacity compared to the other two cultivars of hardy kiwifruits, cv. Haeyeon and cv. Chiak. Analysis of high-performance liquid chromatography results revealed the presence of procyanidin B2, (−)-epicatechin, neochlorogenic acid, cryptochlorogenic acid, rutin, hyperoside, isoquercitrin, and astragalin in hardy kiwifruits. The three cultivars of hardy kiwifruits had a wide range of vitamin C content of 55.2−130.0 mg/100 g fresh weight. All three cultivars of hardy kiwifruits ...

Neurodegenerative disorders in the elderly are characterized by gradual loss of memory and cognitive function. Oxidative stress caused by reactive oxygen species is associated with progressive neuronal cell damage and death in Alzheimer's disease, one of the most common neurodegenerative disorders. An edible brown seaweed, Ecklonia cava, contains a variety of biologically active compounds such as phlorotannins. In this study, we comparatively evaluated the total phenolic content, antioxidant capacity, and neuroprotective effects of the phlorotannin-rich extract from E. cava (PEEC). The total phenolic content of PEEC and dieckol was 810.8 mg gallic acid equivalents (GAE)/g and 996.6 mg GAE/g, respectively. Antioxidant capacity of PEEC was 1,233.8 mg vitamin C equivalents (VCE)/g and 392.1 mg VCE/g determined using ABTS and DPPH assays, respectively, while those of dieckol were 2,238.4 mg VCE/g and 817.7 mg VCE/g. High-performance liquid chromatography results revealed 48.08 ± 0.67 mg dieckol/g of PEEC. PEEC had neuroprotective effects in pheochromocytoma (PC-12) and human neuroblastoma (SH-SY5Y) cells against H 2 O 2 -and AAPH-induced oxidative damage, partly due to reduced intracellular oxidative stress. PEEC treatment inhibited acetylcholinesterase and butyrylcholinesterase in a dose-dependent manner. Taken together, these findings suggest that PEEC is a good source of antioxidants and neuroprotective materials.

The FDA-approved EGFR/HER2 inhibitor varlitinib inhibits tumor growth and is used in cancer treatment. However, the neuroinflammatory response associated with EGFR/HER2 and its underlying mechanism have not been elucidated. This study evaluates the impact of varlitinib on LPS- and tau-mediated neuroinflammatory responses for the first time. In BV2 microglial cells, varlitinib reduced LPS-stimulated il-1β and/or inos mRNA levels and downstream AKT/FAK/NF-kB signaling. Importantly, varlitinib significantly diminished LPS-mediated microglial nlrp3 inflammasome activation in BV2 microglial cells. In primary astrocytes, varlitinib downregulated LPS-evoked astroglial il-1β mRNA levels, AKT signaling, and nlrp3 inflammasome activation. In LPS-treated wild-type mice, varlitinib significantly reduced LPS-stimulated glial activation and IL-1β/NLRP3 inflammasome formation. Moreover, varlitinib significantly reduced micro- and astroglial activation and tau hyperphosphorylation in 3-month-old tau-overexpressing PS19 mice by downregulating tau kinase DYRK1A levels. However, in 6-month-old tau-overexpressing PS19 mice, varlitinib only significantly diminished astroglial activation and tau phosphorylation at Thr212/Ser214. Taken together, our findings suggest that varlitinib has therapeutic potential for LPS- and tau-induced neuroinflammatory responses and the early stages of tau pathology.