Agaricus blazei Extract Induces Apoptosis through ROS-Dependent JNK Activation Involving the Mitochondrial Pathway and Suppression of Constitutive NF-κB in THP-1 Cells

Agaricus blazei is widely accepted as a traditional medicinal mushroom, and it has been known to exhibit immunostimulatory and anti-cancer activity. However, the apoptotic mechanism in cancer cells is poorly understood. In this study, we have investigated whether A. blazei extract (ABE) exerts antiproliferative and apoptotic effects in human leukemic THP-1 cells. We observed that ABE-induced apoptosis is associated with the mitochondrial pathway, which is mediated by reactive oxygen species (ROS) generation and prolonged c-Jun N-terminal kinase (JNK) activation. In addition, the ABE treatment resulted in the accumulation of cytochrome c in the cytoplasm, an increase in caspase activity, and an upregulation of Bax and Bad. With those results in mind, we found that ABE decreases constitutive NF-κB activation and NF-κB-regulated gene products such as IAP-1 and -2. We concluded that ABE induces apoptosis with ROS-dependent JNK activation and constitutive activated NF-κB inhibition in THP-1 cells

Zanthoxylum ailanthoides

Zanthoxylum ailanthoides (ZA) has been used as folk medicines in East Asian and recently reported to have several bioactivity; however, the studies of ZA on the regulation of triacylglycerol (TG) biosynthesis have not been elucidated yet. In this study, we examined whether the methanol extract of ZA (ZA-M) could reduce oleic acid- (OA-) induced intracellular lipid accumulation and confirmed its mode of action in HepG2 cells. ZA-M was shown to promote the phosphorylation of AMPK and its upstream LKB1, followed by reduction of lipogenic gene expressions. As a result, treatment of ZA-M blocked de novo TG biosynthesis and subsequently mitigated intracellular neutral lipid accumulation in HepG2 cells. ZA-M also inhibited OA-induced production of reactive oxygen species (ROS) and TNF-α, suggesting that ZA-M possess the anti-inflammatory feature in fatty acid over accumulated condition. Taken together, these results suggest that ZA-M attenuates OA-induced lipid accumulation and inflammation through the activation of LKB1/AMPK signaling pathway in HepG2 cells

Black Ginseng Extract Suppresses Airway Inflammation Induced by Cigarette Smoke and Lipopolysaccharides In Vivo

Cigarette smoke (CS) is a risk factor that can induce airway enlargement, airway obstruction, and airway mucus hypersecretion. Although studies have shown that Korean black ginseng extract (BGE) has potent anti-inflammatory and antioxidant activities, the CS-induced inflammatory responses and molecular mechanisms are yet to be examined. The aim of this study was to examine the effect of BGE on the airway inflammatory response and its molecular mechanisms, using CS/lipopolysaccharides (LPS)-exposed animals and PMA-stimulated human airway epithelial NCI-H292 cells. The results show that BGE inhibited the recruitment of immune cells and the release of inflammatory mediators, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, elastase, and reactive oxygen species (ROS) in the airways of CS/LPS-exposed animals. BGE inhibited mucus secretion and the expression of Mucin 5AC (MUC5AC). Furthermore, BGE exhibited an anti-inflammatory effect by downregulating a signaling pathway mediated by transforming growth factor-β-activated kinase (TAK) 1, an important protein that accelerates inflammation by cigarette smoke (CS). Overall, the findings show that BGE inhibits lung inflammation and mucus secretion by decreasing the activation of TAK1 both in human epithelial cells and in CS/LPS-exposed animals, and could be a potential adjuvant in the treatment and prevention of airway inflammatory diseases caused by airway irritants such as CS

Potent inhibition of human tyrosinase inhibitor by verproside from the whole plant of Pseudolysimachion rotundum var. subintegrum

AbstractAffinity-based ultrafiltration–mass spectrometry coupled with ultraperformance liquid chromatography–quadrupole time-of-flight mass spectrometry was utilised for the structural identification of direct tyrosinase ligands from a crude Pseudolysimachion rotundum var. subintegrum extract. False positives were recognised by introducing time-dependent inhibition in the control for comparison. The P. rotundum extract contained nine main metabolites in the UPLC-QTOF-MS chromatogram. However, four metabolites were reduced after incubation with tyrosinase, indicating that these metabolites were bound to tyrosinase. The IC50 values of verproside (1) were 31.2 µM and 197.3 µM for mTyr and hTyr, respectively. Verproside showed 5.6-fold higher efficacy than that of its positive control (kojic acid in hTyr). The most potent tyrosinase inhibitor, verproside, features a 3,4-dihydroxybenzoic acid moiety on the iridoid glycoside and inhibits tyrosinase in a time-dependent and competitive manner. Among these three compounds, verproside is bound to the active site pocket with a docking energy of −6.9 kcal/mol and four hydrogen bonding interactions with HIS61 and HIS85

Assessment of iridoid profiles in the growth period of aerial parts of Pseudolysimachion rotundum var. subintegrum and their antioxidant and MUC5AC inhibitory potential

Abstract YPL-001 is a drug substance of Pseudolysimachion rotundum var. subintegrum and has been reported to be a potent COPD inhibitor. For the first time, this study demonstrated a correlation among the iridoid constituents, antioxidants, and MUC5AC inhibition activities in P. rotundum during different growth stages (5 to 11 weeks). Single-factor extraction was used to optimize the plant extraction conditions to maximize the major iridoid constituents (70% ethanol, 40 °C, 1 h); isolated metabolites 1–6 were identified using nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). The contents of each metabolite and antioxidant/MUC5AC inhibition effects were markedly changed according to the growth stages, especially for catalposide (2, 5.97 → 10.99 mg/g, 1.8-fold) and isovanillyl catapol (5, 4.42 → 20.00 mg/g, 4.5-fold), which were the predominant substances in August. Our results indicated that YPL-001 could potentially contribute to enhancing the P. rotundum value in accumulated iridoids at the growth stage and the biological effect aspects to develop industrial medicinal crops