Search

Minoxidil is the most widely used treatment for hair growth, but has been associated with several side effects. In this study, we investigated the effects of heat-killed Enterococcus faecalis EF-2001 on hair loss prevention and regrowth using human dermal papilla cells and male C57BL/6 mice. To examine the effects of EF-2001, we used minoxidil as the positive control. In the in vitro experiments, EF-2001 treatment (75–500 μg/mL) led to the proliferation of human dermal papilla cells in a concentration-dependent manner. In the in vivo experiment, the topical application of 200 µL EF-2001 on the dorsal surface of C57BL/6 male mice led to hair growth. Changes in hair regrowth were examined by visual comparison and hematoxylin and eosin staining of skin sections. We also determined the expression levels of marker genes (Wnt) and growth factors (fibroblast growth factor, insulin growth factor 1, and vascular endothelial growth factor) in the skin tissues of the back of each mouse using a quantitative polymerase chain reaction. EF-2001 accelerated the progression of hair regrowth in mice and promoted hair-follicle conversion from telogen to anagen, likely by increasing the expression levels of growth factors and marker genes.

Minoxidil is the most widely used treatment for hair growth, but has been associated with several side effects. In this study, we investigated the effects of heat-killed

Increasing consumption of food with high caloric density and a sedentary lifestyle have influenced the increasing obesity prevalence worldwide. The recent pandemic has contributed to this problem. Obesity refers to a state in which lipid accumulates excessively in adipocytes and adipose tissues. Dried heat-killed Enterococcus faecalis (EF-2001) prevents allergic mechanisms, inflammation, and tumor progression. In the present study, we investigated the effects of EF-2001 on high fat diet (HFD)-induced obese rats. The degree of obesity in experimental rats was reduced after 6 weeks of oral administration of 3 mg/kg or 30 mg/kg dosages of EF-2001, indicating regulating effects in rats with HFD-induced obesity. We found that EF-2001 decreased the amounts of total cholesterol, triglyceride, and non-high density lipoprotein (HDL) in HFD-induced obese rats. The effects of EF-2001 on 3T3-L1 adipocytes stained with Oil red O stain are shown in reductions of lipid accumulation, respectively. In addition, we examined the relationships between EF-2001 treatment and mechanisms for the insulin signaling of adipogenesis in 3T3-L1 cells. EF-2001 induced down-regulation in phosphorylation of Erk, JNK, and Akt through the inhibition of insulin receptor phosphorylation. EF-2001 inhibits the expressions of C/EBP-α and PPAR-γ, a lipid metabolism-related transcription factor through confocal microscope observation and Western blot on 3T3-L1 adipocytes and HFD-induced obese rats. Based on our results, intake of EF-2001 significantly prevented HFD-induced obesity in rats through inhibition of C/EBP-α and PPAR-γ in the insulin signaling pathway on lipid accumulation.

Muscle atrophy is a major muscle disease, the symptoms of which include decreased muscle volume leading to insufficient muscular support during exercise. One cause of muscle atrophy is the induction of oxidative stress by reactive oxygen species (ROS). This study aimed to identify the antioxidant mechanism of linoleic acid (LA) in muscle atrophy caused by oxidative stress. H2O2 has been used to induce oxidative stress in myoblasts in vitro. C2C12 myoblasts treated with H2O2 exhibited decreased viability and increased ROS synthesis. However, with LA treatment, the cells tended to recover from oxidative effects similar to those of the control groups. At the molecular level, the expression of superoxide dismutase 1 (SOD1), Bax, heat shock protein 70 (HSP70), and phosphorylated forkhead box protein O1 was increased by oxidative stress, causing apoptosis. LA treatment suppressed these changes. In addition, the expression of MuRF1 and Atrogin-1/MAFbx mRNA increased under oxidative stress but not in the LA-treated group. Sciatic denervation of C57BL/6 mice manifested as atrophy of the skeletal muscle in micro-computed tomography (micro-CT). The protein expression levels of SOD1, HSP70, and MuRF1 did not differ between the atrophied muscle tissues and C2C12 myoblasts under oxidative stress. With LA treatment, muscle atrophy recovered and protein expression was restored to levels similar to those in the control. Therefore, this study suggests that LA may be a candidate substance for preventing muscle atrophy.

Increasing consumption of food with high caloric density and a sedentary lifestyle have influenced the increasing obesity prevalence worldwide. The recent pandemic has contributed to this problem. Obesity refers to a state in which lipid accumulates excessively in adipocytes and adipose tissues. Dried heat-killed

Continuous consumption of high-calorie meals causes lipid accumulation in the liver and liver damage, leading to non-alcoholic fatty liver disease (NAFLD). A case study of the hepatic lipid accumulation model is needed to identify the mechanisms underlying lipid metabolism in the liver. In this study, the prevention mechanism of lipid accumulation in the liver of Enterococcus faecalis 2001 (EF-2001) was extended using FL83B cells (FL83Bs) and high-fat diet (HFD)-induced hepatic steatosis. EF-2001 treatment inhibited the oleic acid (OA) lipid accumulation in FL83B liver cells. Furthermore, we performed lipid reduction analysis to confirm the underlying mechanism of lipolysis. The results showed that EF-2001 downregulated proteins and upregulated AMP-activated protein kinase (AMPK) phosphorylation in the sterol regulatory element-binding protein 1c (SREBP-1c) and AMPK signaling pathways, respectively. The effect of EF-2001 on OA-induced hepatic lipid accumulation in FL83Bs enhanced the phosphorylation of acetyl-CoA carboxylase and reduced the levels of lipid accumulation proteins SREBP-1c and fatty acid synthase. EF-2001 treatment increased the levels of adipose triglyceride lipase and monoacylglycerol during lipase enzyme activation, which, when increased, contributed to increased liver lipolysis. In conclusion, EF-2001 inhibits OA-induced FL83B hepatic lipid accumulation and HFD-induced hepatic steatosis in rats through the AMPK signaling pathway.

Acne is a common inflammatory disorder of the human skin and a multifactorial disease caused by the sebaceous gland and

The effects of the Cichorium intybus root extract (Cii) on alcohol-induced liver disease were investigated using Chang liver cells and male Sprague Dawley rats. Silymarin, a liver-protective agent, was used as a positive control. In cell experiments, after 24 h of treatment with the extract, no cytotoxicity was noted, and death by alcohol was avoided. Migration of Chang liver cells increased after exposure to the extract at a concentration of 400 μg/mL. In animal experiments, alcohol was injected into 6-week-old rats for 1, 3, and 50 days. Oral administration of the drug was performed 30 min before alcohol administration. The control was treated with distilled water, and the drug groups were administered EtOH (40% EtOH + 2.5 mL/kg), EtOH + Cii L (low concentration, 2 mg/kg), EtOH + Cii H (high concentration, 10 mg/kg), or EtOH + silymarin (100 mg/kg). Increased liver weight was observed in the alcohol group, as were increased blood-alcohol concentration and liver damage indicators (glutamic oxalacetic transaminase (GOT), glutamic pyruvate transaminase (GPT), and triglycerides (TG)), decreased alcoholysis enzymes (ADH and ALDH), and increased CYP2E1. In the Cii treatment group, liver weight, blood-alcohol concentration, liver damage indicators (GOT, GPT, and TG), and CYP2E1 were decreased, while alcoholysis enzymes (ADH and ALDH) were increased. The degree of histopathological liver damage was compared visually and by staining with hematoxylin and eosin and oil red O. These results indicated that ingestion of Cii inhibited alcohol-induced liver damage, indicating Cii as a useful treatment for alcohol-induced liver injury.

The effects of the Cichorium intybus root extract (Cii) on alcohol-induced liver disease were investigated using Chang liver cells and male Sprague Dawley rats. Silymarin, a liver-protective agent, was used as a positive control. In cell experiments, after 24 h of treatment with the extract, no cytotoxicity was noted, and death by alcohol was avoided. Migration of Chang liver cells increased after exposure to the extract at a concentration of 400 μg/mL. In animal experiments, alcohol was injected into 6-week-old rats for 1, 3, and 50 days. Oral administration of the drug was performed 30 min before alcohol administration. The control was treated with distilled water, and the drug groups were administered EtOH (40% EtOH + 2.5 mL/kg), EtOH + Cii L (low concentration, 2 mg/kg), EtOH + Cii H (high concentration, 10 mg/kg), or EtOH + silymarin (100 mg/kg). Increased liver weight was observed in the alcohol group, as were increased blood-alcohol concentration and liver damage indicators (glutamic oxalacetic transaminase (GOT), glutamic pyruvate transaminase (GPT), and triglycerides (TG)), decreased alcoholysis enzymes (ADH and ALDH), and increased CYP2E1. In the Cii treatment group, liver weight, blood-alcohol concentration, liver damage indicators (GOT, GPT, and TG), and CYP2E1 were decreased, while alcoholysis enzymes (ADH and ALDH) were increased. The degree of histopathological liver damage was compared visually and by staining with hematoxylin and eosin and oil red O. These results indicated that ingestion of Cii inhibited alcohol-induced liver damage, indicating Cii as a useful treatment for alcohol-induced liver injury.

Acne is a common inflammatory disorder of the human skin and a multifactorial disease caused by the sebaceous gland and Propionibacterium acnes (P. acnes). This study aimed to evaluate the anti-inflammatory effect of micro-current stimulation (MC) on peptidoglycan (PGN)-treated raw 264.7 macrophages and P. acnes-induced skin inflammation. To specify the intensity with anti-inflammatory effects, nitric oxide (NO) production was compared according to various levels of MC. As the lowest NO production was shown at an intensity of 50 μA, subsequent experiments used this intensity. The changes of expression of the proteins related to TLR2/NF-κB signaling were examined by immunoblotting. Also, immunofluorescence analysis was performed for observing NF-κB p65 localization. All of the expression levels of proteins regarding TLR2/NF−κB signaling were decreased by the application of MC. Moreover, the application of MC to PGN−treated raw 264.7 cells showed a significant decrease in the amount of nuclear p65−protein. In the case of animal models with P. acnes−induced skin inflammation, various pro−inflammatory cytokines and mediators significantly decreased in MC−applied mice. In particular, the concentration of IL−1β in serum decreased, and the area of acne lesions, decreased from the histological analysis. We suggest for the first time that MC can be a novel treatment for acne.

Angiogenesis, the formation of new blood vessels, plays an important role in tumor growth and metastasis; therefore, it has become an important target in cancer therapy. Novel anticancer pharmaceutical products that have relatively few side effects or are non-cytotoxic must be developed, and such products may be obtained from traditional herbal medicines. Coptis chinensis Franch. is an herb used in traditional medicine for the treatment of inflammatory diseases and diabetes. However, potential antiangiogenic effects of C. chinensis water extract (CCFWE) have not yet been studied. The purpose of this study was to determine the antiangiogenic effect of CCFWE in order to evaluate its potential for an anticancer drug. We found that the treatment with CCFWE inhibited the major steps of the angiogenesis process, such as the endothelial cell proliferation, migration, invasion, and capillary-like tube formation in response to vascular endothelial growth factor (VEGF), and also resulted in the growth inhibition of new blood vessels in an ex vivo rat aortic ring assay. We also observed that CCFWE treatment arrested the cell cycle at the G0/G1 phase, preventing the G0/G1 to S phase cell cycle progression in response to VEGF. In addition, the treatment reduced the VEGF-induced activation of matrix metalloproteinases 2 and 9. Taken together, these findings indicate that CCFWE should be considered a potential anticancer therapy against pathological conditions where angiogenesis is stimulated during tumor development.

Recently, a variety of safe and effective non-pharmacological methods have been introduced as new treatments of alopecia. Micro-current electrical stimulation (MCS) is one of them. It is generally known to facilitate cell proliferation and differentiation and promote cell migration and ATP synthesis. This study aimed to investigate the hair growth-promoting effect of MCS on human hair follicle-derived papilla cells (HFDPC) and a telogenic mice model. We examined changes in cell proliferation, migration, and cell cycle progression with MCS-applied HFDPC. The changes of expression of the cell cycle regulatory proteins, molecules related to the PI3K/AKT/mTOR/Fox01 pathway and Wnt/β-catenin pathway were also examined by immunoblotting. Subsequently, we evaluated the various growth factors in developing hair follicles by RT-PCR in MCS-applied (MCS) mice model. From the results, the MCS-applied groups with specific levels showed effects on HFDPC proliferation and migration and promoted cell cycle progression and the expression of cell cycle-related proteins. Moreover, these levels significantly activated the Wnt/β-catenin pathway and PI3K/AKT/mTOR/Fox01 pathway. Various growth factors in developing hair follicles, including Wnts, FGFs, IGF-1, and VEGF-B except for VEGF-A, significantly increased in MCS-applied mice. Our results may confirm that MCS has hair growth-promoting effect on HFDPC as well as telogenic mice model, suggesting a potential treatment strategy for alopecia.

Cymbidiumhas known antibacterial and antiedema activity and has been used as an ingredient in cosmetics and fragrances. The effects ofCymbidiumethanol extract (CYM) on allergic response and the underlying mechanisms of action have not been reported. Therefore, the purpose of this study was to determine the effect of CYM on allergic responses. Topical application of CYM was effective against immunoglobulin E (IgE)/dinitrophenyl-conjugated bovine serum albumin- (DNP-BSA-) induced degranulation of RBL-2H3 cells and anaphylaxis in ICR mice. An allergic dermatitis-like mouse model was used to evaluate the therapeutic potential of CYMin vivo.Continuous application of 2,4-dinitrochlorobenzene (DNCB) not only induced dermatitis in ICR mice but also aggravated the skin lesioning. However, the application of CYM decreased skin lesion severity, scratching behavior, and IgE levels. In addition, CYM downregulated the expression of the proinflammatory cytokines interleukin- (IL-) 4, IL-13, and tumor necrosis factor- (TNF-)α. Studies of signal transduction pathways showed that CYM suppressed the phosphorylation of spleen tyrosine kinase (Syk), an upstream molecule. It also inhibited the phosphorylation of Akt, phospholipase C- (PLC-)γ, and mitogen-activated protein kinase kinase kinase (MEKK). These results indicate that CYM may be effective in preventing and reducing allergic response and may have therapeutic potential as an antiallergic agent in disorders such as atopic dermatitis.

Blocking new blood-vessel formation (angiogenesis) is now recognized as a useful approach to the therapeutic treatment of many solid tumors. The best validated approach to date is to target the vascular endothelial growth-factor (VEGF) pathway, a key regulator of angiogenesis. Many natural products and extracts that contain a variety of chemopreventive compounds have been shown to suppress the development of malignancies through their anti-angiogenic properties. Phellodendron amurense, which is widely used in Korean traditional medicine, has been shown to possess antitumor, antimicrobial, and anti-inflammatory properties, among others. The present study investigated the effects of P. amurense hot-water extract (PAHWE) on angiogenesis, a key process in tumor growth, invasion, and metastasis. To investigate PAHWE’s anti-angiogenic properties, this study’s authors performed an analysis of angiogenesis and endothelial-cell proliferation, migration, invasion, and tube formation, as well as zymogram assays and the rat aortic ring-sprouting assay. PAHWE inhibited cell growth, mobility, and vessel formation in response to VEGF in vitro and ex vivo. Furthermore, it reduced VEGF-induced intracellular signaling events, such as the activation of matrix metalloproteinases (MMPs) -2 and -9. These results indicate that PAHWE’s anti-angiogenic properties might lead to the development of potential drugs for treating angiogenesis-associated diseases such as cancer.

Streptochlorin, a small compound derived from marine actinomycete, has been shown to have anti-angiogenic, anti-tumor, and anti-allergic activities. However, the anti-inflammatory effects and underlying mechanisms have not yet been reported. In the present study, we investigated the effect of streptochlorin on lipopolysaccharide (LPS)-induced inflammatory responses in vitro and in vivo. Streptochlorin attenuated the production of proinflammatory mediators such as nitric oxide, cyclooxygenase-2, pro-interleukin (IL)-1β, and IL-6 in LPS-stimulated RAW264.7 cells through inhibition of the Toll/interleukin-1 receptor (TIR)-domain-containing adapter-inducing interferon-β (TRIF)-dependent signaling pathway. Furthermore, streptochlorin suppressed the infiltration of immune cells such as neutrophils into the lung and proinflammatory cytokine production such as IL-6 and TNF-α in broncho-alveolar lavage fluid (BALF) in the LPS-induced acute lung injury (ALI) mouse model. Streptochlorin has potent anti-inflammatory effects through regulating TRIF-dependent signaling pathways, suggesting that streptochlorin may provide a valuable therapeutic strategy in treating various inflammatory diseases.

Vascular endothelial growth factor (VEGF) is a key factor involved in the induction of angiogenesis and has become an attractive target for anti-angiogenesis therapies. The purpose of this study was to elucidate the anti-angiogenic activity of Rubus coreanus Miquel water extract (RCME). Rubus coreanus Miquel has long been employed as a traditional medicine, and recent studies have demonstrated that it has measureable biological activities. Thus, we investigated for the first time the effect of RCME on angiogenesis and its underlying signaling pathways. The effects of RCME were tested on in vitro models of angiogenesis, namely, proliferation, migration, invasion and tube formation of human umbilical vein endothelial cells as well as an ex vivo model of vessel sprouting from the rat aorta in response to VEGF. We observed that VEGF-induced angiogenesis was strongly suppressed by RCME treatment compared to that of the control group. Moreover, we found that RCME inhibited VEGF-induced activation of matrix metalloproteinases and phosphorylation of extracellular signal-regulated kinase and p38, and also effectively inhibited phosphorylation of VEGF receptor 2. These results indicated that RCME inhibits angiogenesis by suppressing phosphorylation of the VEGF receptor and may be useful for the treatment of angiogenesis-dependent diseases such as cancer and diabetic retinopathy.

Wan Joong Kim 1 , Han-Sung Kim 2 , Joerg Opitz 3 , Kazuya Kabayama 4 and Tack-Joong Kim 1 * Division of Biological Science and Technology, Yonsei-Fraunhofer Medical Device Lab, College of Science and Technology, Yonsei University, Wonju 220-710, Korea Department of Biomedical Engineering, Yonsei-Fraunhofer Medical Device Lab, College of Health Science, Yonsei University, Wonju 220-710, Korea Fraunhofer Institute for Ceramic Technologies and Systems-Material Diagnostics, Dresden, Germany Department of Chemistry, Graduate School of Science, Osaka University, Osaka, Japan

A new class of amido sulfonamido methane linked bis heterocycles- bis-oxazoles, thiazoles and imidazoles were prepared and screened for antimicrobial and anticancer activities. The chloro substituted amido sulfonamido bisimidazole exhibited excellent antimicrobial activity and also it was the most potent compound on lung, colon and prostate cancer cell lines.

In this study, rice wine cakes (Jubak) was produced using with Astragali memvranaceus with excellent antioxidant and antidiabetic effects and produced . This Jubak was applied to improve the cookies of modern taste and well-being products. The cookies according to the different ratio (added 0-1.0%) of Astragali memvranaceus and investigated the physicochemical characteristics, sensory evaluation, DPPH free radical scavenging activities, polyphenol and flavonoid contents. There were little changes in pH and density. The hardness of all treated cookies increased with Astragali memvranaceus Jubak(AJ) containing of different moisture contents. In color, L and a values of most cases increased in most of the treatments, but b value was reduced. In the sensory evaluation, the flavor and total scores showed the highest in 0.5% AJ cookies. But the higher proportion of AJ cookies that had unique flavors and tastes, so the total acceptance score decreased. The polyphenol and flavonoid contents increased in the higher proportion of AJ. In DPPH free radical scavenging activities, the control (no Jubak added) was 44%, and containing of 1% AJ cookies showed 82%. In conclusion, our study suggests that 0.5% in addition of AJ increased positive attributes and functional to cookies.Key words : Astragali memvranaceus, Rice wine cakes, cookies, antioxidant activity, quality characteristic1)

Triglyceride (TG) induces macrophage cell death which contributes to the development of atherosclerosis. We confirmed that exogenous TG accumulates in human THP-1 macrophages and causes cell death. TG treated THP-1 macrophages exhibited no change in tumor necrosis factor (TNF)-α, interleukin (IL)-18, macrophage inflammatory protein (MIP)-1α, and IL-1R1 receptor mRNA expression. However, there was a marked decrease in IL-1β mRNA expression but an increase in IL-1β protein secretion. Decreased expression of IL-1β mRNA and increased secretion of IL-1β protein was not the direct cause of cell death. Until now, TG was assumed to induce necrotic cell death in macrophages. Since caspase-1 is known to be involved in activation and secretion of IL-1β protein and pyroptotic cell death, next we determined whether caspase-1 is associated with TG-induced macrophage cell death. We found an increase in caspase-1 activity in TG-treated THP-1 macrophages and inhibition of caspase-1 activity using a specific inhibitor partially rescued cell death. These results suggest activation of the pyroptotic pathway by TG. This is the first report implicating the activation of caspase-1 and the triggering of the pyroptosis pathway in TG-induced macrophage cell death.

Atopic dermatitis (AD) is a chronic, allergic, and inflammatory skin disease associated with eczema and dermatitis symptoms. Our previous studies have reported that eriodictyol extract inhibits immunoglobulin E (IgE)/Ag-induced type I hypersensitivity by suppressing the activation of proinflammatory cytokines, such as interleukin-4 (IL-4), and the expression of ceramide kinase. In this study, we investigated the inhibitory effect of eriodictyol on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in ICR mice. Treatment with 2 mg/mL eriodictyol for DNCB-induced AD-like skin lesions in ICR mice improved scratching behavior and skin severity score. Histological analysis demonstrated that thickening of the skin lesions were significantly reduced in the eriodictyol-treated group. Also, eriodictyol suppressed the DNCB-mediated elevation of IgE serum levels. These results suggest that eriodictyol may be a potential therapeutic resource for AD and an adjunctive agent to control itchiness in AD.

Pterocarpus indicus Willd has been widely used as a traditional medicine to treat edema, cancer, and hyperlipidemia, but its antiallergic properties and underlying mechanisms have not yet been studied. The purpose of this study was to evaluate the antiallergic activity of Pterocarpus indicus Willd water extract (PIW) using activated mast cells and an atopic dermatitis (AD)-like mouse model. PIW decreased IgE/Ag-induced mast cell degranulation and the phosphorylation of Syk and downstream signaling molecules such as PLC-γ, Akt, Erk 1/2, JNK compared to stimulated mast cells. In DNCB-induced AD-like mice, PIW reduced IgE level in serum, as well as AD-associated scratching behavior and skin severity score. These results indicate that PIW inhibits the allergic response by reducing mast cell activation and may have clinical potential as an antiallergic agent for disorders such as AD.

Angiogenesis, neovascularization from pre-existing vessels, is a key step in tumor growth and metastasis, and anti-angiogenic agents that can interfere with these essential steps of cancer development are a promising strategy for human cancer treatment. In this study, we characterized the anti-angiogenic effects of Coptis japonica Makino extract (CJME) and its mechanism of action. CJME significantly inhibited the proliferation, migration, and invasion of vascular endothelial growth factor (VEGF)-stimulated HUVECs. Furthermore, CJME suppressed VEGF-induced tube formation in vitro and VEGF-induced microvessel sprouting ex vivo. According to our study, CJME blocked VEGF-induced cell cycle transition in G1. CJME decreased expression of cell cycle-regulated proteins, including Cyclin D, Cyclin E, Cdk2, and Cdk4 in response to VEGF. Taken together, the results of our study indicate that CJME suppresses VEGF-induced angiogenic events such as proliferation, migration, and tube formation via cell cycle arrest in G1.

Obovatol has various biological activities, including anti-proliferative, neurotrophic, anti-fibrillogenic, anti-platelet, anti-fungal and anti-inflammatory activities. In this study, we investigated the effects of JJK694, a synthesized obovatol derivative, on rabbit platelet activation and its molecular mechanisms. JJK694 significantly inhibited washed rabbit platelet aggregation and serotonin secretion induced by collagen and arachidonic acid, but had little effect on thrombin- or U46619-induced aggregation. These results suggest that JJK694 selectively inhibits collagen- and arachidonic acid-mediated signaling. JJK694 also showed a concentration-dependent decrease in cytosolic Ca(2+) mobilization, but it had no effect on arachidonic acid liberation. On the other hand, it significantly inhibited the formation of arachidonic acid metabolites, including thromboxane A(2) (TXA(2)), prostaglandin D(2), and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), by suppression of cyclooxygenase (COX)-1 and lipoxygenase (LOX) activities. These results indicate that JJK694 hasanti-platelet activities through inhibition of arachidonic acid metabolite production by suppression of COX-1 and LOX activities.

Atopic dermatitis is characterized by chronically pruritic and inflammatory dermatitis. In this study, we investigated the effect of Platycodon grandiflorum including platycodin D (PG-Platycodin D) in an atopic dermatitis-like mouse model. An atopic dermatitis-like skin lesion was induced by repeated treatment of 2,4-dinitrochlorobenzene (DNCB) on the dorsal skin of ICR mice. The efficacy of PG-Platycodin D was tested by observing scratching behavior, the skin severity score, and histopathologic analysis. PG-Platycodin D reduced the DNCB-induced increase in scratching behavior and the skin severity score. In addition, histopathologic analysis revealed a reduction in the thickening of the epidermis in the PG-Platycodin D group. These results may contribute to the development of a therapeutic drug for the treatment of atopic dermatitis.

Inflammation is a host defense mechanism that is activated in response to harmful substances or pathogens. However, an excessive inflammatory response is a problem in itself. Macrophages secrete inflammatory mediators such as nitric oxide (NO) or cytokines through various pathways such as the nuclear factor kappa B (NF-κB)-activated pathway after recognizing pathogen-like lipopolysaccharides (LPSs). In this study, anti-inflammatory effects of Eupatorium chinensis var. simplicifolium (EUC) extracts were investigated using LPS-stimulated RAW 264.7 macrophages. The EUC root extract significantly reduced NO production, inducible nitric oxide synthase (iNOS) expression, and cyclooxygenase-2 expression in a concentration-dependent manner. In addition, the EUC root extract reduced phosphorylation of mitogen-activated protein kinases and protein kinase B, which is upstream of NF-κB. The EUC root extract also reduced the degradation of inhibitory kappa B. These results indicate that EUC root extract exerts anti-inflammatory effects, which are mediated by inhibition of iNOS expression and the NF-κB pathway.

Mast cells are the principal effector cells involved in the allergic response, through the release of histamine. We investigated the effect of eriodictyol, derived from the painted maple and yerba santa, on mast cell degranulation and on an allergic response in an animal model. We also investigated its effect on the expression of the ceramide kinase (CERK) involved in calcium-dependent degranulation, and on ceramide activation by multiple cytokines. Eriodictyol suppressed the release of beta-hexosaminidase, a marker of degranulation, and the expression of interleukin (IL)-4 mRNA. It inhibited the expression of CERK mRNA, reduced the ceramide concentration in antigen-stimulated mast cells, and suppressed the passive cutaneous anaphylaxis (PCA) reaction in mice in a dose-dependent manner. These results suggest that eriodictyol can inhibit mast cell degranulation through inhibition of ceramide kinase, and that it might potentially serve as an anti-allergic agent.

Allergic response is associated with mast cells, through the release of arachidonic acid, proinflammatory cytokines, and histamine. We investigated the effect of Platycodon grandiflorum including platycodin D (PG-Platycodin D) on allergic responses in an animal model and on mast cell degranulation. PG-Platycodin D suppressed the release of β-hexosaminidase, a type of marker associated with degranulation. PG-Platycodin D efficiently inhibited the passive cutaneous anaphylaxis (PCA) reaction in ICR mice. In addition, molecular analysis demonstrated that PG-Platycodin D inhibited mRNA expression of both IL-3. These results suggest that PG-Platycodin D can inhibit mast cell degranulation through the inhibition of IL-3 mRNA expression, and that PG-Platycodin D may potentially serve as an anti-allergic agent.

Inflammation is a system used by a host to defend against the presence of bacteria, viruses, or yeasts. Toll-like receptors (TLRs) in the plasma membranes of macrophages are activated when they recognize the molecular structure of a virus or bacterium. Lipopolysaccharide (LPS), an outer cell-wall component of Gram-negative bacteria, initiates an inflammatory process via TLR4. We investigated the effect of the extract of Anethum graveloens flowers (AGFs) on LPS-mediated inflammation in RAW 264.7 cells. The extract markedly suppressed nitric oxide generation in a concentration-dependent manner in LPS-stimulated RAW 264.7 cells. It inhibited inducible nitric oxide synthase (iNOS) and the mRNA expression of cytokines such as interleukin-1 beta and interleukin-6 in LPS-stimulated RAW 264.7 cells. It also inhibited iNOS protein levels in LPS-stimulated RAW 264.7 cells. In addition, AGF decreased the LPS-induced phosphorylation of mitogen-activated protein kinases in LPS-stimulated RAW 264.7 cells. AGF inhibited the phosphorylation of Akt, an upstream molecule of the nuclear factor kappa B (NF-κB) pathway, and thus inhibited NF-κB activity in LPS-stimulated RAW 264.7 cells. These results suggest that AGF exerts an anti-inflammatory effect in LPS-stimulated RAW 264.7 cells by inhibiting iNOS expression and blocking the NF-κB pathway.

Mast cells are major effector cells associated with allergic responses. They are activated through the release of histamine, arachidonic acid, and proinflammatory cytokines. We investigated the effect of nodakenin, derived from the roots of Angelica gigas Nakai, on mast cell degranulation and on an allergic response in an animal model. We also investigated the effect of nodakenin on expression of multiple cytokines. Nodakenin suppressed the release of β-hexosaminidase, a marker of degranulation, as well as the expression of interleukin IL-4 and TNF-α mRNA. Nodakenin inhibited the passive cutaneous anaphylaxis (PCA) reaction in ICR mice in a dose-dependent manner. These results suggest that nodakenin can inhibit mast cell degranulation through the inhibition of IL-4 and TNF-α mRNA expression, and that nodakenin may potentially serve as an anti-allergic agent.

Mast cells, the central effector cells involved in the allergic response, release histamine, arachidonic acid, and proinflammatory cytokines. We investigated the effect of the ethyl acetate fraction (EA), derived from Korean rice wine lees, on RBL-2H3 cell degranulation and passive cutaneous anaphylaxis in an animal model. The EA fraction suppressed the release of beta-hexosaminidase, a marker of degranulation, and the mRNA expression of interleukin-3 (IL-3) and IL-13. EA also successfully suppressed the passive cutaneous anaphylaxis (PCA) reaction in mice in a dose-dependent manner. These results suggest that EA can inhibit mast cell degranulation through the inhibition of IL-3 and IL-13 mRNA expression, and that EA may potentially serve as an anti-allergic agent.

One of the principal regulators of mitogenesis in vascular smooth muscle cells (VSMCs) is platelet-derived growth factor-BB (PDGF-BB). An increase of PDGF-BB expression has been observed in atherosclerotic lesions. The aim of this study was to elucidate the effects and molecular mechanism of (2E)-3-(4-hydroxy-3-methoxyphenyl) phenylpro-2-en-1-one (KTJ2242), a newly synthesized benzylideneacetophenone derivative, on PDGF-BB-stimulated rat aortic VSMCs. KTJ2242 induced accumulation of cells in the G1 phase of the cell cycle of VSMCs. We observed that KTJ2242 inhibited PDGF-BB-stimulated [3H]-thymidine incorporation into the DNA of VSMCs, and the cell number was significantly reduced in a concentration-dependent manner. Also, we observed that KTJ2242 decreased PDGF-BB-stimulated extracellular-regulated kinase 1 and 2 (ERK1/2) and Akt phosphorylation. These results suggest the possibility that KTJ2242 may be a potential agent with which to control vascular disorders and its antiproliferative mechanism may be mediated through partial Akt and ERK1/2-dependent signaling pathways.

Muscle disorders, such as muscular dystrophy, are associated with an increase in oxidative stress. Proposed treatments for muscular dystrophy, some in clinical trials, include gene therapy and muscle cell transplantation. In this study, we investigated the effects of idesolide, isolated from the fruits of Idesia polycarpa, on changes that occur in muscle disuse atrophy. We noted protective effects on oxidative stress response and HSP70 regulation. Pre-treatment with idesolide for 24 h maintained cell viability and decreased apoptosis in H(2)O(2)-treated C(2)C(12) muscle cells. The idesolide pretreatment also increased intracellular HSP70 protein. Our results suggest that idesolide inhibits cell death through induction of HSP70 in C(2)C(12) muscle cells. This work is the first to report that idesolide can regulate the decrease in HSP70 that occurs during skeletal muscle atrophy.

The proliferation of vascular smooth muscle cells (VSMCs) induced by injury to the intima of arteries is an important etiologic factor in vascular proliferative disorders such as atherosclerosis and restenosis. Uncaria rhynchophylla is traditional Chinese herb that has been applied to the treatment of convulsive disorders, such as epilepsy, in China. In the present study, we examined whether corynoxeine exerts inhibitory effects on platelet-derived growth factor (PDGF)-BB-induced rat aortic VSMC proliferation and the possible mechanism of such effects. Pre-treatment of VSMCs with corynoxeine (5-50 microM) for 24 h resulted in significant decreases in cell number without any cytotoxicity; the inhibition percentages were 25.0+/-12.5, 63.0+/-27.5 and 88.0+/-12.5% at 5, 20 and 50 microM, respectively. Also, corynoxeine significantly inhibited the 50 ng/ml PDGF-BB-induced DNA synthesis of VSMCs in a concentration-dependent manner without any cytotoxicity; the inhibitions were 32.8+/-11.0, 51.8+/-8.0 and 76.9+/-7.4% at concentrations of 5, 20 and 50 microM, respectively. Pre-incubation of VSMCs with corynoxeine significantly inhibited PDGF-BB-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation, whereas corynoxeine had no effects on mitogen-activated protein kinase (MAPK/ERK)-activating kinase 1 and 2 (MEK1/2), Akt, or phospholipase C (PLC)gamma1 activation or on PDGF receptor beta (PDGF-Rbeta) phosphorylation. These results suggest that corynoxeine is a potent ERK1/2 inhibitor of key PDGF-BB-induced VSMC proliferation and may be useful in the prevention and treatment of vascular diseases and restenosis after angioplasty.

We have previously reported that green tea catechins displayed a potent antithrombotic effect by inhibition of platelet aggregation. In the present study, the antiplatelet and antithrombotic activities of epigallocatechin gallate (EGCG), the major catechin derived from green tea, were extensively investigated. EGCG inhibited arterial thrombus formation and U46619-, collagen-, and arachidonic acid (AA)-induced washed rabbit platelet aggregation in a concentration-dependent manner, with IC50 values of 61 +/- 3, 85 +/- 4, and 99 +/- 4 microM, respectively. In line with the inhibition of collagen-induced platelet aggregation, EGCG revealed blocking of the collagen-mediated phospholipase (PL) Cgamma2 and protein tyrosine phosphorylation, and it caused concentration-dependent decreases of cytosolic calcium mobilization, AA liberation, and serotonin secretion. In addition, the platelet aggregation, intracellular Ca2+ mobilization, and protein tyrosine phosphorylation induced by thapsigargin, a Ca2(+)-ATPase pump inhibitor, were completely blocked by EGCG. Contrary to the inhibition of AA-induced platelet aggregation, EGCG failed to inhibit cyclooxygenase and thromboxane (TX) A2 synthase activities, but it concentration-dependently elevated AA-mediated PGD2 formation. In contrast, epigallocatechin (EGC), a structural analogue of EGCG lacking a galloyl group in the 3' position, slightly inhibited collagen-stimulated cytosolic calcium mobilization, but failed to affect other signal transductions as did EGCG in activated platelets and arterial thrombus formation. These results suggest that antiplatelet activity of EGCG may be attributable to its modulation of multiple cellular targets, such as inhibitions of PLCgamma2, protein tyrosine phosphorylation and AA liberation, and elevation of cellular PGD2 levels, as well as maintaining Ca2(+)-ATPase activity, which may underlie its beneficial effect on the atherothrombotic diseases.

Molecular mechanisms underlying epothilone-induced apoptotic cell death were investigated in SW620 human colon cancer cells. Treatment with epothilone B and D at different concentrations (1–100 nmol/L) dose-dependently inhibited cell growth and caused cell cycle arrest at G2-M, which was followed by apoptosis. Consistent with this induction of apoptotic cell death, epothilone B and D enhanced the constitutional activation of nuclear factor-κB (NF-κB) via IκB degradation through IκB kinase (IKKα and IKKβ) activation, and this resulted in p50 and p65 translocation to the nucleus. Moreover, cells treated with sodium salicylic acid, an IKK inhibitor, or transiently transfected with mutant IKKα and β did not show epothilone-induced cell growth inhibition or p50 translocation, although p65 was still translocated to the nucleus. Treatment with epothilone B and D also enhanced β-tubulin polymerization and the formation of p50/β-tubulin complex. However, β-tubulin polymerization was not inhibited in the cells treated by sodium salicylic acid or transiently transfected with mutant IKKα and β. Moreover, epothilone B and D increased the expressions of NF-κB–dependent apoptotic cell death regulatory genes, i.e., Bax, p53, and the active form of caspase-3, but reduced Bcl-2 expression, and these actions were partially reversed by salicylic acid. In addition, caspase-3 inhibitor reduced epothilone B–induced cell death and NF-κB activation. These findings suggest that the activation of NF-κB/IKK signals plays an important role in the epothilone-induced apoptotic cell death of SW620 colon cancer cells in a tubulin polymerization–independent manner. [Mol Cancer Ther 2007;6(10):2786–97]

Angiogenesis, the process of new blood vessel formation, has been a major target for cancer therapy. Antiangiogenic herbal medicines are useful in the treatment of cancer. In this study, we found that a water extract of Cinnamomum cassia (CCWE) was a potent inhibitor of angiogenesis. In cultured human umbilical vein endothelial cells, CCWE suppressed vascular endothelial growth factor (VEGF)-induced proliferation, migration, invasion, tube formation, and intracellular signaling events such as phosphorylation of ERK, p38 and VEGFR2, and activation of matrix metalloproteinase. Furthermore, CCWE inhibited VEGF-induced vessel sprouting of rat aorta ex vivo. These findings might be of particular interest for drug development because VEGF signaling is a potential target for treatment of angiogenesis-associated diseases.

Muscle atrophy, a reduction of muscle mass, strength, and volume, results from reduced muscle use and plays a key role in various muscular diseases. In the microgravity environment of space especially, muscle atrophy is induced by muscle inactivity. Exposure to microgravity induces muscle atrophy through several biological effects, including associations with reactive oxygen species (ROS). This study used 3D-clinostat to investigate muscle atrophy caused by oxidative stressin vitro, and sciatic denervation was used to investigate muscle atrophyin vivo. We assessed the effect ofOenothera odorataroot extract (EVP) on muscle atrophy. EVP helped recover cell viability in C2C12 myoblasts exposed to microgravity for 24 h and delayed muscle atrophy in sciatic denervated mice. However, the expressions of HSP70, SOD1, and ceramide in microgravity-exposed C2C12 myoblasts and in sciatic denervated mice were either decreased or completely inhibited. These results suggested that EVP can be expected to have a positive effect on muscle atrophy by disuse and microgravity. In addition, EVP helped characterize the antioxidant function in muscle atrophy.

We investigated the effects of a Eupatorium chinense var. simplicifolium (EUC) root extract on muscle disorders and explored the underlying mechanism for oxidative stress-induced C(2)C(12) myoblast damage. An EUC pre-treatment reduced the decreased cell viability after an H2O2 treatment. The heat shock protein (HSP) 70 level increased, and the phosphorylation of Jun amino-terminal kinases (JNKs) decreased in the EUC-pre-treated C(2)C(12) myoblasts. The results of the present study demonstrate the potential benefit of a herbal medicine in treating oxidative stress-related muscle disorders.

Cell injury associated with reactive oxygen species (ROS) has been reported in various muscular disorders. We found that a Cichorium intybus (Cii) extract reduced H2O2-induced viability loss in C2C12 myoblasts, inhibited oxidative stress-induced apoptosis and increased intracellular heat shock protein 70 (Hsp 70) expression. Cii also inhibited the level of intracellular ceramide. These results indicate that Cii may prevent skeletal muscle atrophy by inducing the expression of Hsp 70 and inhibiting the level of ceramide.