Pharmacological Properties of Jaeumgeonbi-Tang on Redox System and Stress-Related Hormones in Chronic Subjective Dizziness: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial.

Jaeumgeonbi-Tang (JGT), a traditional herbal medicine, has been used to treat dizziness and vertigo in Korea and China for hundreds of years. The purpose of this study was to evaluate the pharmacological properties of JGT in chronic subjective dizziness (CSD) patients. A randomized, double-blind, parallel-group and placebo-controlled trial was performed with a total of 50 CSD patients. The patients were randomly assigned to one of two groups: JGT or placebo (n = 25 for each). All participants received the treatment (placebo or JGT, 24 g/day) for 4 weeks. We analyzed the serum levels of oxidative stressors, antioxidants, and stress hormones. Serum levels of lipid peroxidation, but not nitric oxide, were significantly decreased in the JGT group. JGT not only prevented the decline of serum total glutathione contents and total antioxidant capacity, but it also increased superoxide dismutase and catalase activities. Serum levels of stress hormones including cortisol, adrenaline, and serotonin were notably normalized by JGT treatment, but noradrenaline levels were not affected. Regarding the safety and tolerability of JGT, we found no allergic, adverse, or side effects in any of the participants. JGT showed beneficial effects on CSD patients by improving redox status and balancing psycho-emotional stress hormones.

Ethyl Acetate Fraction of Amomum villosum var. xanthioides Attenuates Hepatic Endoplasmic Reticulum Stress-Induced Non-Alcoholic Steatohepatitis via Improvement of Antioxidant Capacities.

Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH), affects 25% of the global population. Despite the prevalence of NAFLD worldwide, effective therapeutics are currently lacking. Amomum villosum var. xanthioides (Wall. ex Baker) T.L.Wu & S.J.Chen (AX) is a medicinal herb traditionally used for treating digestive tract disorders in countries across Asia. We aimed to examine the pharmacological effects of the ethyl acetate fraction of AX (AXEF) against tunicamycin (TM)-induced ER stress in a NASH mouse model using C57/BL6J male mice. Following TM injections (2 mg/kg), the mice were orally administrated AXEF (12.5, 25, or 50 mg/kg), silymarin (50 mg/kg), or distilled water daily for 5 days, and the outcomes for fatty liver, inflammation, and oxidative stress were measured in serum or liver tissue levels. AXEF drastically attenuated hepatic ER stress-induced NASH as indicated by decreases in lipid droplet accumulations, serum liver enzymes, hepatic inflammations, and cell death signals in the hepatic tissue and/or serum levels. Interestingly, AXEF showed potent antioxidant effects by quenching reactive oxidative stress and its final product lipid peroxide in the hepatic tissue, specifically an increase in metallothionein (MT). To confirm the underlying actions of AXEF, we observed that AXEF increases MT1 gene promoter activities in the physiological levels. Collectively, AXEF showed antioxidant properties on TM-induced ER stress in a NASH mice model through the improvement of MTs.

Traditional Korean herbal formulae, Yuk-Mi-Ji-Hwang-Tang, ameliorates impairment of hippocampal memory ability by chronic restraint stress of mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: Yuk-Mi-Jihwang-Tang (YJT) has been popularly prescribed to treat aging related disorders over than hundreds of years in East Asia countries. AIM OF THE STUDY: To investigate possible modulatory actions of YJT on chronic restraint stress (CRS)-induced neurodegeneration on hippocampus neuronal injuries. MATERIALS AND METHODS: Mice were orally administered with YJT (100, 200, or 400 mg/kg) or ascorbic acid (100 mg/kg) before 4 h of stress for 28 days. Morris water maze task was completed from day 24th to 28th, and stress hormones and biochemical analyzes were measured. RESULTS: Four weeks of the CRS abnormally affected memory impairments by measurement of escape latency and time spent in the target quadrant. Additionally, neurotransmitters were also drastically altered in serum or hippocampus protein levels by CRS. Gene expressions for 5-hydroxytryptamine (5-HT) receptor, 5-HT-transport, and tryptophan hydroxylase were also altered, whereas YJT led to normalize the above alterations. Additionally, YJT also beneficially worked on endogenous redox system as well as inflammatory reactions in the hippocampal neurons. We observed that hippocampal excitotoxicity was induced by CRS which were evidenced by depletion of phosphor-cAMP response element-binding protein, brain-derived neurotrophic factor, nuclear factor erythroid-2-related factor 2, heme oxygenase-1 and abnormally increases of acetylcholine esterase activities in hippocampus protein levels; however, YJT considerably improved the above pathological conditions. CONCLUSIONS: Our findings supported YJT enhance memory function via regulation of hippocampal excitotoxicity-derived memory impairment, stress hormone, and endogenous redox, respectively.

An Herbal Formula CGplus Ameliorates Stress-Induced Hepatic Injury in a BALB/c Mouse Model.

INTRODUCTION: Stress is a well-known factor for inflammation in diverse organs/tissues. Stress also leads to liver injury, which was supported by clinical observations and animal studies. We herein investigated the hepatoprotective property of an herbal formula (called as CGplus) consisting of Artemisia gmelinii Weber ex Stechm. (syn, Artemisia iwayomogi Kitamura), Wurfbainia villosa var. xanthioides (Wall. ex Baker) Skornick. & A.D.Poulsen (syn, Amomum xanthioides Wallich), and Salvia miltiorrhiza Bunge against stress-induced hepatic damage. METHODS: Male BALB/c mice were orally administered water extract of CGplus (0, 50, 100, or 200 mg/kg) daily for 5 days, and then subjected to immobilization stress for 6 h on the 5th day. RESULTS: Acute immobilization stress elevated remarkably serum concentrations of stress hormones (corticosterone and adrenaline) and two hepatic injury parameters (ALT and AST), while these alterations were significantly attenuated by the administration of CGplus. The increases of oxidative parameters (ROS, NO, lipid peroxidation, and protein carbonyl) and deviation of IL-1ß and IL-10 in opposite directions in hepatic tissues were significantly normalized by CGplus. Pre-treatment with CGplus also notably ameliorated the abnormal activation of toll-like receptor 4 (TLR4), CD14, and lipopolysaccharide-binding protein (LPB) as well as infiltration of neutrophils in hepatic tissues. CONCLUSION: These results suggest that an herbal formula (CGplus) derived from traditional pharmaceutical theory has a potent protective effect against stress-induced hepatic injury via regulation of pro- (IL-1ß) and anti-inflammatory (IL-10) cytokines.

Anti-hepatofibrotic effects of CGX, a standardized herbal formula: A multicenter randomized clinical trial.

BACKGROUND: Chunggan extract (CGX) is an herbal formula used for the treatment of chronic liver disease in traditional Korean medicine. Many preclinical studies have suggested its therapeutic or preventive effects on liver fibrosis. To evaluate the efficacy and safety of CGX, we conducted a randomized controlled clinical trial of CGX in patients with liver fibrosis diagnosed by Fibroscan. METHODS: We enrolled 67 subjects at two hospitals with chronic liver disorders with a 5.5 ≤ liver stiffness measurement (LSM) score ≤ 16 kPa. Subjects were randomly assigned at a 1:1:1 ratio with stratification (with/without concomitant use of antivirals) and orally administered CGX (1 g or 2 g) or placebo twice daily for 24 weeks. The end point was the change in instantaneous elasticity of the liver assessed by Fibroscan before and after treatment. RESULTS: LSM scores were significantly decreased in both the CGX1 g (2.5 ± 1.7 kPa, p < 0.01) and CGX2 g (1.9 ± 2.0 kPa, p < 0.05) groups compared to the placebo (0.6 ± 1.6 kPa) group. The change was also significant in 35 subjects without concomitant use of antiviral agents in the CGX1 g group (placebo 0.1 ± 1.4 kPa vs. 2.7 ± 1.6 kPa, p < 0.01) but not in those with concomitant antiviral use (p > 0.05). No notable adverse events were present. CONCLUSION: CGX appeared to have a pharmacological effect against liver fibrosis. Further studies to confirm the results are needed in the future using a larger sample size.

Synergistic hepatoprotective effects of CGplus on CCl4-induced acute injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese/Korean medicine suggests "blood stasis ()", "stagnation of vital energy ()" and "dampness and Phlegm ()" as the main etiologies of liver disorders, and multiherbal formulas are generally believed to exert synergistic action. AIM OF THE STUDY: The present study aimed to investigate the synergistic hepatoprotective effects of CGplus (a mixture of Salviae miltiorrhiza, Artemisia iwayomogi and Ammomum xanthioides) compared to those of the individual herbs. METHODS AND MATERIALS: A total of fifty-six male Balb/C mice were randomly divided into eight groups and were administered water (normal and CCl4 groups), 100 mg/kg S. miltiorrhiza, A. iwayomogi, or A. xanthioides, 50 or 100 mg/kg CGPlus or dimethyl dimethoxybiphenyl dicarboxylate (DDB) as a positive control for 4 consecutive days. After a single CCl4 injection (i.p., 10 mL/kg of 0.2% CCl4 in olive oil), blood and liver tissues were collected after 18 h of fasting for serum biochemistry, histopathological examination and molecular analyses. RESULTS: CCl4 injection induced drastic hepatic injury characterized by a more than 30-fold increase in the release of AST and ALT into the serum. These alterations were significantly attenuated by pretreatment with each of the three herbs, while the effects of the individual herbs were synergistically augmented by CGPlus pretreatment. The synergistic hepatoprotective actions of CGPlus were demonstrated consistently by analyses of oxidative stress (oxidative stressors, oxidation products and antioxidant enzymes), pro-/anti-inflammatory cytokines (TNF-ɑ, IL-1ß, IL-6, IL-10), and apoptosis (caspase-3, p53 and BAX) and histopathology. CONCLUSIONS: These data suggest that CGPlus exerts its hepatoprotective effects in a synergistic manner, and further studies are required for clinical application using other chronic models.

CGplus, a standardized herbal composition ameliorates non-alcoholic steatohepatitis in a tunicamycin-induced mouse model.

BACKGROUND: The prevalence of Non-alcoholic fatty liver disease (NAFLD) including non-alcoholic steatohepatitis (NASH) has increased by 15-39% worldwide, but no pharmaceutical therapeutics exists. HYPOTHESIS/PURPOSE: This study investigated anti-hepatosteatotic effect of CGplus (a standardized herbal composition of Artemisia iwayomogi, Amomum xanthioides, and Salvia miltiorrhiza) and its underlying mechanisms in a tunicamycin-induced NASH model. METHODS: C57/BL6J male mice were orally administrated CGplus (50, 100, or 200 mg/kg), dimethyl dimethoxy biphenyl dicarboxylate (DDB, 50 mg/kg) or distilled water daily for 5 days. 18 h after a single injection of tunicamycin (ip, 2 mg/kg), the parameters for hepatic steatosis and inflammation were measured. RESULTS: Pretreatment with CGplus significantly attenuated the accumulation of triglycerides and total cholesterol as well as lipid peroxidation, evidenced by quantitative and histopathological analyses in liver tissues. The elevations of serum aspartate transaminase, alanine transaminase and lactate dehydrogenase were significantly ameliorated by CGplus. Also, it normalized the altered activities of pro- (TNF-α, IL-1ß and IL-6), anti-inflammatory (IL-10) cytokines and lipid metabolism-related molecules in protein and gene expression analyses. CONCLUSION: Our data present experimental evidence for the potential of CGplus as an herbal therapeutic against NAFLD and NASH. Its underlying mechanisms may involve the modulations of pro- and anti-inflammatory cytokines, but further study is required especially for the actions of CGplus on lipid metabolisms.

Yuk-Mi-Jihwang-Tang, a Traditional Korean Multiple Herbal Formulae, Improves Hippocampal Memory on Scopolamine Injection-Induced Amnesia Model of C57BL/6 Mice.

We evaluated neuropharmacological properties of Yuk-Mi-Jihwang-Tang (YJT) against scopolamine injection-induced memory impairment mice model. Mice were orally administered with YJT (50, 100, or 200 mg/kg) or tacrine (TAC, 12.5 mg/kg) for 10 days. At the first day of Morris water maze task, scopolamine (2 mg/kg) was intraperitoneally injected before 30 min of it. The hippocampal memory function was determined by the Morris water maze task for 5 days consecutively. Scopolamine drastically increased escape latency and decreased time spent in target quadrant. Pretreatment YJT properly improved them. Regarding the redox status, YJT significantly reduced the oxidative stress and it also exerted much effort to improve both superoxide dismutase and catalase activities in hippocampal gene expression and protein levels. These effects were well coincided with immunohistochemical analysis of 4-hydroxyneal-positive signals in hippocampal areas. Additionally, acetylcholine esterase activities and brain-derived neurotrophic factor abnormalities in the hippocampal protein levels were significantly normalized by YJT, and their related molecules were also improved. The neuronal proliferation in hippocampal regions was markedly inhibited by scopolamine, whereas YJT notably recovered them. Collectively, YJT exerts much effort to enhance memorial functions through improving redox status homeostasis and partially regulates acetylcholine esterase activities as well as neuronal cell proliferation.

Artemisia iwayomogi plus Curcuma longa Synergistically Ameliorates Nonalcoholic Steatohepatitis in HepG2 Cells.

The combination of Artemisia iwayomogi and Curcuma longa radix is frequently prescribed for liver diseases in TKM. However, the synergic effects of the two herbs on nonalcoholic steatohepatitis (NASH) have not yet been studied. Therefore, we investigated the anti-NASH effects of the water extract of A. iwayomogi (AI), C. longa radix (CL), and combination of the two herbs (ACE). Hepatic steatosis and NASH were induced in HepG2 cells by treatment with palmitic acid (PA, for 6 h) with/without pretreatment of ACE (25 or 50 µg/mL), AI (50 or 100 µg/mL), CL (50 or 100 µg/mL), curcumin (5 µg/mL), or scopoletin (5 µg/mL). The PA treatment (200 µM) drastically altered intracellular triglyceride levels, total cholesterol, and expression levels of genes related to lipid metabolism (CD36, SREBP1c, PPAR-γ, and PPAR-α), whereas pretreatment with ACE significantly attenuated these alterations. ACE also protected HepG2 cells from PA- (300 µM-) induced endoplasmic reticulum (ER) stress and apoptosis and attenuated the related key molecules including GRP78, eIF2, and CHOP, respectively. In conclusion, we found synergic effects of A. iwayomogi and C. longa on NASH, supporting the clinical potential for fatty liver disorders. In addition, modulation of ER stress-relative molecules would be involved in its underlying mechanism.

The ethanol extract of Aquilariae Lignum ameliorates hippocampal oxidative stress in a repeated restraint stress mouse model.

BACKGROUND: Chronic stress contributes to the development of brain disorders, such as neurodegenerative and psychiatric diseases. Oxidative damage is well known as a causative factor for pathogenic process in brain tissues. The aim of this study is to evaluate the neuroprotective effect of a 30% ethanol extract of Aquilariae Lignum (ALE) in repeated stress-induced hippocampal oxidative injury. METHODS: Fifty BALB/c male mice (12 weeks old) were randomly divided into five groups (n = 10). For 11 consecutive days, each group was orally administered with distilled water, ALE (20 or 80 mg/kg) or N-acetylcysteine (NAC; 100 mg/kg), and then all mice (except unstressed group) were subjected to restraint stress for 6 h. On the final day, brain tissues and sera were isolated, and stress hormones and hippocampal oxidative alterations were examined. We also treated lipopolysaccharide (LPS, 1 µg/mL)-stimulated BV2 microglial cells with ALE (1 and 5 µg/mL) or NAC (10 µM) to investigate the pharmacological mechanism. RESULTS: Restraint stress considerably increased the serum levels of corticosterone and adrenaline and the hippocampal levels of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA). ALE administration significantly attenuated the above abnormalities. ALE also significantly normalized the stress-induced activation of astrocytes and microglial cells in the hippocampus as well as the elevation of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß). The in vitro assay outcome supplemented ALE could dramatically block NF-κB activation in microglia. The anti-oxidative stress effects of ALE were supported by the results of antioxidant components, 4-hydroxynonenal (4-HNE), NADPH oxidase 2 (NOX2), inducible nitric oxide synthase (iNOS) and NFE2L2 (Nrf2) in the hippocampal tissues. CONCLUSIONS: We firstly demonstrated the neuroprotective potentials of A. Lignum against hippocampal oxidative injury in repeated restraint stress. The corresponding mechanisms might involve modulations in the release of ROS, pro-inflammatory cytokines and stress hormones.

Pine needle extract prevents hippocampal memory impairment in acute restraint stress mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: The Pinus densiflora leaf has been traditionally used to treat mental health disorders as a traditional Chinese medicine. Here we examined the ethnopharmacological relevance of pine needle on memory impairment caused by stress. AIM OF THE STUDY: To elucidate the possible modulatory actions of 30% ethanolic pine needle extract (PNE) on stress-induced hippocampal excitotoxicity, we adopted an acute restraint stress mouse model. MATERIALS AND METHODS: Mice were orally administered with PNE (25, 50, or 100mg/kg) or ascorbic acid (100mg/kg) for 9 days, and were then subjected to restraint stress (6h/day) for 3 days (from experimental day 7-9). To evaluate spatial cognitive and memory function, the Morris water maze was performed during experimental days 5-9. RESULTS: Restraint stress induced the memory impairment (the prolonged escape latency and cumulative path-length, and reduced time spent in the target quadrant), and these effects were significantly prevented by PNE treatment. The levels of corticosterone and its receptor in the sera/hippocampus were increased by restraint stress, which was normalized by PNE treatment. Restraint stress elicited the hippocampal excitotoxicity, the inflammatory response and oxidative injury as demonstrated by the increased glutamate levels, altered levels of tumor necrosis factor (TNF)-α and imbalanced oxidant-antioxidant balance biomarkers. Two immunohistochemistry activities against glial fibrillary acidic protein (GFAP)-positive astrocytes and neuronal nuclei (NeuN)-positive neurons supported the finding of excitotoxicity especially in the cornu ammonis (CA)3 region of the hippocampus. Those alterations were notably attenuated by administration of PNE. CONCLUSIONS: The above findings showed that PNE has pharmacological properties that modulate the hippocampal excitotoxicity-derived memory impairment under severe stress conditions.

Antiemetic and Myeloprotective Effects of Rhus verniciflua Stoke in a Cisplatin-Induced Rat Model.

Rhus verniciflua Stoke has been commonly used in traditional medicine to treat gastrointestinal (GI) dysfunction diseases. In order to investigate pharmacological properties of Rhus verniciflua Stoke water extract (RVX) on cisplatin-induced amnesia, RVX (0, 25, 50, or 100 mg/kg) was orally administrated for five consecutive days after a single intraperitoneal injection of cisplatin (6 mg/kg) to SD rat. Cisplatin injection significantly increased the kaolin intake (emesis) but reduced the normal diet intake (anorexia) whereas the RVX treatment significantly improved these abnormal diet behaviors at both the acute and delayed phase. The serotonin concentration and the related gene expressions (5-HT3 receptors and SERT) in small intestine tissue were abnormally altered by cisplatin injection, which were significantly attenuated by the RVX treatment. Histological findings of gastrointestinal tracts, as well as the proteins level of proinflammatory cytokines (TNF-α, IL-6, and IL-1ß), revealed the beneficial effect of RVX on cisplatin-induced gastrointestinal inflammation. In addition, RVX significantly improved cisplatin-induced myelosuppression, as evidenced by the observation of leukopenia and by histological examinations in bone marrow. Our findings collectively indicated Rhus verniciflua Stoke improved the resistance of rats to chemotherapy-related adverse effects in the gastrointestinal track and bone marrow.

Ethyl Acetate Fraction of Amomum xanthioides Exerts Antihepatofibrotic Actions via the Regulation of Fibrogenic Cytokines in a Dimethylnitrosamine-Induced Rat Model.

Amomum xanthioides has been traditionally used to treat diverse digestive system disorders in the Asian countries. We investigated antihepatofibrotic effects of ethyl acetate fraction of Amomum xanthioides (EFAX). Liver fibrosis is induced by dimethylnitrosamine (DMN) injection (intraperitoneally, 10 mg/kg of DMN for 4 weeks to Sprague-Dawley rats). EFAX (25 or 50 mg/kg), silymarin (50 mg/kg), or distilled water was orally administered every day. The DMN injection drastically altered body and organ mass, serum biochemistry, and platelet count, while EFAX treatment significantly attenuated this alteration. Severe liver fibrosis is determined by trichrome staining and measurement of hydroxyproline contents. EFAX treatment significantly attenuated these symptoms as well as the increase in oxidative by-products of lipid and protein metabolism in liver tissues. DMN induced a dramatic activation of hepatic stellate cells and increases in the levels of protein and gene expression of transforming growth factor-beta (TGF-ß), platelet derived growth factor-beta (PDGF-ß), and connective tissue growth factor (CTGF). Immunohistochemical analyses revealed increases in the levels of protein and gene expression of α-smooth muscle actin. These alterations were significantly normalized by EFAX treatment. Our findings demonstrate the potent antihepatofibrotic properties of EFAX via modulation of fibrogenic cytokines, especially TGF-ß in the liver fibrosis rat model.

Gongjin-Dan Enhances Hippocampal Memory in a Mouse Model of Scopolamine-Induced Amnesia.

We evaluated the neuropharmacological effects of Gongjin-Dan (GJD) on the memory impairment caused by scopolamine injection. BALB/c mice were orally treated with GJD (100, 200, or 400 mg/kg, daily) or tacrine (THA, 10 mg/kg) for 10 days, and scopolamine (2 mg/kg) was injected intraperitoneally. The radial arm maze and passive avoidance tests were performed to evaluate the animal's learning and memory. Scopolamine increased the task completing time, the number of total errors (reference and working memory error) in the radial arm maze task, and the latency time in the passive avoidance test, which were significantly ameliorated by treatment with GJD. The GJD treatment also attenuated the scopolamine-induced hyperactivation of acetylcholinesterase activity, and suppression of the expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and their receptors in the hippocampus. These effects of GJD were supported by both the doublecortin (DCX)-positive staining and Nissl staining, which were used to measure hippocampal neurogenesis and atrophy, respectively. These findings strongly suggest that GJD exerts a potent anti-amnesic effect, and its underlying mechanism might involve the modulation of cholinergic activity.

A Herbal Formula, CGXII, Exerts Antihepatofibrotic Effect in Dimethylnitrosamine-Induced SD Rat Model.

We aimed to evaluate the antihepatofibrotic effects of CGXII, an aqueous extract which is composed of A. iwayomogi, A. xanthioides, and S. miltiorrhiza, against dimethylnitrosamine- (DMN-) induced hepatofibrosis. Male Sprague Dawley rats were intraperitoneally injected with 10 mg/kg of DMN for 4 weeks (three consecutive days weekly). Rats were orally given distilled water, CGXII (50 or 100 mg/kg), or dimethyl dimethoxy biphenyl dicarboxylate (50 mg/kg) daily. DMN injection caused substantial alteration of total body weight and liver and spleen mass, whereas they were notably normalized by CGXII. CGXII treatment also markedly attenuated the elevation of serum aspartate aminotransferase and alanine aminotransferase levels, hepatic lipid peroxidation, and protein carbonyl contents. Collagen accumulation in hepatic tissue evidenced by histopathological analysis and quantitative assessment of hepatic hydroxyproline was ameliorated by CGXII. Immunohistochemistry analysis revealed decreased α-smooth muscle actin supporting the antihepatofibrotic effect of CGXII. The profibrogenic cytokines transforming growth factor-ß, platelet-derived growth factor-ß, and connective tissue growth factor were increased by DMN injection. Administration of CGXII normalized the protein and gene expression levels of these cytokines. Our findings suggest that CGXII lowers the levels of profibrogenic cytokines and thereby exerts antifibrotic effects.

Terminalia Chebula provides protection against dual modes of necroptotic and apoptotic cell death upon death receptor ligation.

Death receptor (DR) ligation elicits two different modes of cell death (necroptosis and apoptosis) depending on the cellular context. By screening a plant extract library from cells undergoing necroptosis or apoptosis, we identified a water extract of Terminalia chebula (WETC) as a novel and potent dual inhibitor of DR-mediated cell death. Investigation of the underlying mechanisms of its anti-necroptotic and anti-apoptotic action revealed that WETC or its constituents (e.g., gallic acid) protected against tumor necrosis factor-induced necroptosis via the suppression of TNF-induced ROS without affecting the upstream signaling events. Surprisingly, WETC also provided protection against DR-mediated apoptosis by inhibition of the caspase cascade. Furthermore, it activated the autophagy pathway via suppression of mTOR. Of the WETC constituents, punicalagin and geraniin appeared to possess the most potent anti-apoptotic and autophagy activation effect. Importantly, blockage of autophagy with pharmacological inhibitors or genetic silencing of Atg5 selectively abolished the anti-apoptotic function of WETC. These results suggest that WETC protects against dual modes of cell death upon DR ligation. Therefore, WETC might serve as a potential treatment for diseases characterized by aberrantly sensitized apoptotic or non-apoptotic signaling cascades.

A manual acupuncture treatment attenuates common cold and its symptoms: a case series report from South Korea.

OBJECTIVE: To investigate beneficial effects of manual acupuncture on common cold periods and its symptoms depended on the difference onset time of common cold, within 36 h or over than that. To prove effects of manual acupuncture on common cold, a retrospective chart review was conducted. METHODS: Chart data for patients with common cold who were treated with only manual acupuncture with fulfilling Jackson scales and satisfaction at the end of each treatment were collected via multi-centers of Oriental hospitals, Oriental medicine clinics and covalent hospital in South Korea. Totally 187 patients were divided into two groups, Group Ⅰ (115 patients, within 36 h) and Group Ⅱ (72 patients, onset time of cold over than 36 h). Finally 120 patients were observed until entire resolution of cold symptoms. RESULTS: Group Ⅰ showed significant decreases themediandurationsofcompletelyrecovery (3 days; 95% CI 3.0-4.0) as compared with Group Ⅱ (6 days; 95% CI 4.0-7.0, P < 0.001). The manual acupuncture beneficially worked for reduction rate of common cold symptoms by 50% after initial treatment, decreased cold symptoms, and reduced cold duration. CONCLUSION: Manual acupuncture beneficially affected common cold and its symptoms. Moreover it is more susceptibility on the early time of onset cold.

A Herbal Formula, Atofreellage, Ameliorates Atopic Dermatitis-Like Skin Lesions in an NC/Nga Mouse Model.

We evaluated the anti-atopic dermatitis (AD) effect of Atofreellage (AF), a herbal formula composed of 10 medicinal plants. AD was induced on the dorsal skin areas of NC/Nga mice (male, seven weeks old) by daily application of 2,4-dinitrochlorobenzene (DNCB) for five weeks. After three weeks of DNCB application, 200 µL of AF (0, 25, 50 or 100 mg/mL) was applied to the skin lesions. Histological findings, blood cell populations, serum levels of immunoglobulin E (IgE), histamine, pro-inflammatory cytokines, and inflammatory signaling in the skin tissue, and T-helper cell type 2 (Th2)-related cytokines in splenocytes were analyzed. Histopathological findings showed AF treatment notably attenuated the thickness of dorsal skin, and eosinophil infiltration. AF treatment (especially 100 mg/mL) also demonstrably ameliorated the blood cell population abnormalities, as the notable elevation of serum concentrations of IgE, histamine, TNF-α, IL-6 and IL-1ß were remarkably normalized by AF treatment. Western blot analysis evidenced the apparent normalization of inflammatory signals (ERK, p38 MAP kinase, JNK, and NF-κB) in the skin tissue. Additionally, AF treatment notably attenuated the activation of Th2-dominant cytokines (IL-13, IL-4, and IL-5) in Con A-treated splenocytes in an ex vivo assay. In conclusion, this study provides experimental evidence for the clinical relevance of Atofreellage.

Serum Levels of Stress Hormones and Oxidative Stress Biomarkers Differ according to Sasang Constitutional Type.

Objectives. This study investigated whether Sasang constitutional type is associated with differences in the serum levels of stress hormones and oxidative stress. Methods. A total of 236 participants (77 males and 159 females) were enrolled. The serum levels of cortisol, adrenaline, reactive oxygen species (ROS), and malondialdehyde (MDA) were analyzed. Results. The distribution of Sasang constitutional types was as follows: Taeumin, 35.6%; Soumin, 33.0%; and Soyangin, 31.4%. The serum cortisol levels of Taeumin were significantly lower than Soumin (p < 0.1 in both sexes) and Soyangin (p < 0.05 in males and p < 0.1 in females). The adrenaline levels were also significantly lower in Taeumin than in Soumin (p < 0.05 in males and p < 0.1 in females) and Soyangin (p < 0.1 in males). Serum ROS levels were significantly higher in Soyangin than in Taeumin and Soumin (p < 0.05 in males), whereas MDA levels were significantly lower in Taeumin compared with Soumin and Soyangin (p < 0.05 in males and p < 0.1 in females). Conclusion. Taeumin type may tolerate psychological or oxidative stress better than other types, which suggests a biological mechanism to explain the different pathophysiological features of Sasang constitutional types.

Ethyl acetate fraction of Amomum xanthioides improves bile duct ligation-induced liver fibrosis of rat model via modulation of pro-fibrogenic cytokines.

We investigated anti-hepatofibrotic effects of ethyl acetate fraction of Ammomum xanthoides (EFAX) using bile duct ligation (BDL)-induced hepatic fibrosis in a rat model. Male SD rats (6 weeks old) underwent BDL followed by 15 days of orall administration of EFAX (12.5, 25 or 50 mg/kg) or ursodeoxycholic acid (25 mg/kg). BDL caused animal death, ascites formation, alterations in serum biochemistries, and severe hepatic injury with excessive collagen deposition, whereas EFAX treatment significantly attenuated these effects. BDL markedly increased the pro-fibrogenic cytokines (TGF-ß, PDGF-ß, and CTGF) and the extracellular matrix indicators α-SMA, TIMP-1 and collagen type 1 in hepatic proteins and gene expression levels, which were notably normalized by EFAX treatment. EFAX also markedly normalized pro-fibrogenic signaling molecules including Smad2/3, Smad7, Akt, p44/42, and p38. We further explored EFAX mechanisms of actions using LX-2 cells (human derived hepatic stellate cell line). Pre-treatment with EFAX drastically attenuated the activation of α-SMA and Smad2/3, which are downstream molecules of TGF-ß. These findings suggest that EFAX may be a potent anti-hepatofibrotic agent, and its corresponding mechanisms primarily involve the modulation of pro-fibrogenic cytokines.