The global prevalence of nonalcoholic fatty liver disease (NAFLD) is estimated to be 25% and has continued to increase; however, no drugs have yet been approved for NAFLD treatments. The ethyl acetate fraction of Amomum xanthioides (EFAX) was previously reported to have an anti-hepatic fibrosis effect, but its effects on steatosis or steatohepatitis remain unclear. This study investigated the anti-fatty liver of EFAX using a high-fat diet mouse model. High-fat diet intake for 8 weeks induced hepatic steatosis with mild inflammation and oxidative damage and increased the adipose tissue weight along with the development of dyslipidemia. EFAX treatment significantly ameliorated the steatohepatic changes, the increased weight of adipose tissues, and the altered serum lipid profiles. These observed effects were possibly due to the lipolysis-dominant activity of EFAX on multiple hepatic proteins including sterol regulatory element-binding protein (mSREBP)-1c, peroxisome proliferator-activated receptor (PPAR)-α, AMP-activated protein kinase, and diglyceride acyltransferases (DGATs). Taken together, these results show that EFAX might be a potential therapeutic agent for regulating a wide spectrum of NAFLDs from steatosis to fibrosis via multiple actions on lipid metabolism-related proteins. Further studies investigating clear mechanisms and their active compounds are needed.
This study aimed to help to understand the influence of stress on depression, which reflects the social environments of especially solitary life and the increasing prevalence of depressive disorders. To determine the distinguishable features of two-representative animal models of stress-induced depressive disorder, we compared isolation stress (IS) and unpredictable chronic mild stress (UCMS). After 4-week of stress, both models showed significant depressive- and anxiety-like behaviors in an open field test (OFT; p < 0.01 for IS, p < 0.01 for UCMS), forced swimming test (FST; p < 0.01 for IS, p < 0.01 for UCMS), and tail suspension test (TST; p < 0.01 for IS, p < 0.05 for UCMS) along with alterations in serum corticosterone levels, serotonin activity in the dorsal raphe nuclei (DRN) and microglial activity in the dentate gyrus of the hippocampus (p < 0.05 for both parameters). In a comparison of the two stress models, IS strongly induced depressive and anxiety features, as indicated by all parameters: behavior test scores (p < 0.05 for OFT, FST, and TST), serum corticosterone levels (p < 0.05), immunohistological alterations for serotonin activity (p < 0.05) and microglial activity (p = 0.072). Our results indicate the suitability of IS for the development of animal models of depressive disorders and may reveal the medical impact of social isolation environment in modern society.
Microglial hyperactivation and neuroinflammation are known to induce neuronal death, which is one of the main causes of neurodegenerative disorders. We previously found that Aquilariae Lignum extract attenuated both neuronal excitotoxicity and neuroinflammation in vivo and in vitro. For further analysis, we extracted the methylene chloride fraction of Aquilariae Lignum to determine the bioactive compounds. In this study, we investigated the anti-neuroinflammatory effects and underlying mechanisms of the Aquilariae Lignum fraction (ALF) using lipopolysaccharide (LPS)-stimulated BV2 microglial cells. BV2 cells were pretreated with ALF (0.5, 1, and 2.5 μg/mL) before treatment with LPS (1 μg/mL). Pretreatment with ALF significantly attenuated the LPS-induced overproductions of nitric oxide (NO), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and interleukin (IL)-1β. These anti-inflammatory effects were supported by ALF-mediated modulation of the nuclear factor-kappa B (NF-κB) pathway. Furthermore, ALF exerted strong anti-inflammasome effects, as shown by IL-1β-specific inhibitory activity, but not activity against tumor necrosis factor (TNF)-α, along with inhibition of caspase-1 activity and NACHT, LRR, and PYD domain-containing protein 3 (NLRP3)-related molecules. These results indicate the potent anti-neuroinflammatory activity of ALF and that its underlying mechanism may involve the regulation of NLRP3 inflammasome-derived neuroinflammation in microglial cells.
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