The present study investigated the antifatigue effects of Panax ginseng C.A. Meyer in 90 subjects (21 men and 69 women) with idiopathic chronic fatigue (ICF) in a randomised, double-blind, placebo-controlled and parallel designed trial. A bespoke 20% ethanol extract of P. ginseng (1 g or 2 g day–1) or a placebo was administered to each group for 4 weeks, and then fatigue severity was monitored using a self-rating numeric scale (NRS) and a visual analogue scale (VAS) as a primary endpoint. Serum levels of reactive oxygen species (ROS), malondialdehyde (MDA), total glutathione (GSH) contents and glutathione reductase (GSH-Rd) activity were determined. After 4-week, P. ginseng administration decreased the total NRS score, but they were not statistically significant compared with placebo (P>0.05). Mental NRS score was significantly improved by P. ginseng administrations as 20.4±5.0 to 15.1±6.5 [95% CI 2.3∼8.2] for 1 g and 20.7±6.3 to 13.8±6.2 [95% CI −0.1∼4.2] for 2 g compared with placebo 20.9±4.5 to 18.8±2.9 [95% CI 4.1∼9.9, P<0.01]. Only 2 g P. ginseng significantly reduced the VAS score from 7.3±1.3 to 4.4±1.8 [95% CI 0.7∼1.8] compared with the placebo 7.1±1.0 to 5.8±1.3 [95% CI 2.2 ∼3.7, P<0.01]. ROS and MDA levels were lowered by P. ginseng compared to placebo. P. ginseng 1 g increased GSH concentration and GSH-Rd activity. Our results provide the first evidence of the antifatigue effects of P. ginseng in patients with ICF, and we submit that these changes in antioxidant properties contribute in part to its mechanism.Trial RegistrationClinical Research Information Service (CRIS) KCT0000048

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We evaluated the neuropharmacological effects of 30% ethanolic pine needle extract (PNE) on memory impairment caused by scopolamine injection in mice hippocampus. Mice were orally pretreated with PNE (25, 50, and 100 mg/kg) or tacrine (10 mg/kg) for 7 days, and scopolamine (2 mg/kg) was injected intraperitoneally, 30 min before the Morris water maze task on first day. To evaluate memory function, the Morris water maze task was performed for 5 days consecutively. Scopolamine increased the escape latency and cumulative path-length but decreases the time spent in target quadrant, which were ameliorated by pretreatment with PNE. Oxidant-antioxidant balance, acetylcholinesterase activity, neurogenesis and their connecting pathway were abnormally altered by scopolamine in hippocampus and/or sera, while those alterations were recovered by pretreatment with PNE. As lipid peroxidation, 4HNE-positive stained cells were ameliorated in hippocampus pretreated with PNE. Pretreatment with PNE increased the proliferating cells and immature neurons against hippocampal neurogenesis suppressed by scopolamine, which was confirmed by ki67- and DCX-positive stained cells. The expression of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB) in both protein and gene were facilitated by PNE pretreatment. These findings suggest that PNE could be a potent neuropharmacological drug against amnesia, and its possible mechanism might be modulating cholinergic activity via CREB-BDNF pathway.

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Val156 of apolipoprotein A-I (apoA-I) was found to be a key amino acid in the structure and function of high density lipoprotein (HDL) ( J. Biol. Chem. , 275: 26821-26827, 2000). To determine more precisely the functions of the individual amino acids proximal to Val156, serial point mutants of proapoA-I, including V156K, D157K, and A158E, were overexpressed and purified to at least 95% purity. In the lipid-free state, A158E exhibited the most profound self-associative patterns and the least pronounced dimyristoyl phosphatidylcholine (DMPC) clearance activities. In the lipid-bound state, A158E formed a larger reconstituted HDL (rHDL) with palmitoyloleoyl phosphatidylcholine (POPC), ‫ف‬ 120 Å, whereas other mutants and the wild type (WT) formed 97 Å of POPC-rHDL. Cross-linking analysis revealed that A158E-rHDL harbored at least four protein molecules in the particle, while other rHDL conformations contained only two protein molecules. All of the POPC-rHDL produced smaller HDL, around 78 Å, after 24 h of incubation in the presence of low density lipoprotein at 37 ؇ C. V156K and A158E exhibited decreased lecithin:cholesterol acyltransferase activation activity in the POPC-rHDL state, showing Ͻ 2% of WT reactivity (apparent V max / K m ). A158E also displayed markedly different properties in secondary structure, and its accessibility to proteolytic enzymes is different. These results suggest that the two amino acids in helix 6, Val156 and Ala158, are critical to both the structure and function of rHDL. Numerous reports have demonstrated that many of the functions of HDL are highly dependent on the conformation of apoA-I, most notably, the rearrangement of HDL in reverse cholesterol transport (3, 4) and its interaction with the HDL receptor, scavenger receptor class B type I, on the cell surfaces (5, 6). Therefore, a great deal of effort has been focused on the delineation of the structural and functional regions of apoA-I. The central region of apoA-I, spanning residues 143-165, has been implicated in the activation of LCAT and the regulation of high density lipoprotein (HDL) structural rearrangement.Recombinant human proapoA-I has previously been reported to exhibit the same general properties and functions as plasma apoA-I, in both lipid-free and lipid-bound states (7). Previously, Cho and Jonas (8) reported that Valine156 was a key amino acid with regard to the structure and functions of apoA-I, because the recombinant V156E mutant behaved differently from the wild type (WT) in both the lipid-free and lipid-bound states. In the lipid-free state, the V156E mutant exhibited greater protein stability and was quite resistant to self-association, as compared with WT apoA-I. Furthermore, in the palmitoyloleoyl phosphatidylcholine reconstituted HDL (POPCrHDL) state, the V156E did not rearrange its particles to produce smaller particles in the presence of low density lipoprotein (LDL), and exhibited minimal reactivity to LCAT activation. These results indicated that a few of the Abbreviations: ApoA-I, apolipoprot...

Oxidative stress, which is commonly defined as an imbalance between oxidants and antioxidants at the cellular level, has shown a deep interest constantly as the cause of cardiovascular events and a variety of vascular diseases. 1) One of the crucial steps in oxidative stress augmentation is the overproduction of reactive oxygen species (ROS).2) ROS encompass a variety of diverse chemical species including hydroxyl radical, nitric oxide (NO), and superoxide anion. In particular, the interaction between the superoxide anion and NO is important because it leads to the formation of the peroxynitrite. The peroxynitrite activates a variety of signaling pathways 3,4) and works deleteriously through its pro-atherosclerotic properties. 1)In general, NO and ROS are responsible for the regulation of the transcriptional pathways of nuclear factor-kB (NF-kB) that regulates expression of various inflammatory cytokines, chemokines, and adhesion molecules. 5) After activation by inflammatory cytokines and cellular stresses including tumor necrosis factor (TNF)-a and lipopolysaccharide (LPS), NF-kB proteins to translocate to the nucleus and bind their cognate DNA binding sites to regulate the transcription of a large number of genes including antimicrobial peptides, cytokines, chemokines, stress-response proteins, and antiapoptotic proteins.6) In addition to NF-kB, mitogen-activated protein kinases (MAPKs) have also been implicated in cytokine production in macrophages.7) Three MAPK families (extracellular signal-regulated kinase (ERK)1/2, p38 and c-Jun N-terminal kinase (JNK)) are signaling molecules that react to extracellular stimuli (mitogens) and regulate immune responses including proinflammatory cytokine production, mitosis, differentiation, and cell survival/apoptosis. 7,8)Sophora flavescens has long been traditionally used in asthma, bronchitis, bacterial, fungal infections, and skin disorders, and as an antipyretic, analgesic, anthelmintic, and remedy for stomach ailments.9) Lavandulylated (C 10 ) or prenylated (C 5 ) flavanones, lavandulyl chalcones, pterocarpanes, and quinolizidine alkaloids were isolated from S. flavescens. [10][11][12][13][14] They possess various biological activities such as anticancer, antioxidant, antibacterial, antifungal, antiviral, and anti-inflammatory activities. [15][16][17] Although the anti-inflammatory activities of flavonoids from S. flavesens have been reported, the mechanism of kurarinone (1), lavandulyl flavanone and kuraridin (2), lavandulyl chalcone on anti-inflammatory activity remains unclear in macrophages.In this study, we examined the effects of compounds 1 and 2 on LPS-mediated NO production, ROS generation, and expression of inflammatory cytokines, NF-kB activity, and phosphorylation of MAP kinases in murine RAW264.7 macrophages. MATERIALS AND METHODS General Experimental Materials and Cell CultureDulbecco's modified Eagle's medium (DMEM), fetal bovine serum (FBS), penicillin, and streptomycin were obtained from Cambrex (Verviers, Belgium). LPS was obtained from Sigma-Aldr...

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