Effect of Korean Red Ginseng through comparative analysis of cardiac gene expression in db/db mice.

Korean Red Ginseng (KRG) is an herbal oriental medicine known to alleviate cardiovascular dysfunction. To analysis the expression of diabetic cardiac complication-associated genes in db/db mice, we studied the cardiac gene expression following KRG treatment. In result, a total of 585 genes were found to be changed in db/db mice. Among the changed expression, 245 genes were found to 2-fold upregulated, and 340 genes were 2-fold downregulated. In addition, the changed gene expressions were ameliorated by KRG. In conclusion, KRG may be possible to normalize cardiac gene expressions in db/db mice.

Ginsenoside Rb1 inhibits monoiodoacetate-induced osteoarthritis in postmenopausal rats through prevention of cartilage degradation.

BACKGROUND: Ginsenoside Rb1 (G-Rb1), one of the major active compounds in Panax ginseng, has already been shown to reduce inflammation in various diseases. Osteoarthritis (OA) has traditionally been considered a degenerative disease with degradation of joint articular cartilage. However, recent studies have shown the association of inflammation with OA. In the present study, we investigated whether Rb1 had an antiinflammatory effect on monoiodoacetate (MIA)-induced OA in ovariectomized rats as a model of postmenopausal arthritis. METHODS: G-Rb1 at a dosage of 3 and 10 µg/kg body weight was administered every 3 days intraarticularly for a period of 4 weeks to observe antiarthritic effects. Diclofenac (10 mg/kg) served as a positive control. RESULTS: The administration of Rb1 significantly ameliorated OA inflammatory symptoms and reduced serum levels of inflammatory cytokines. Furthermore, G-Rb1 administration considerably enhanced the expression of bone morphogenetic protein-2 and collagen 2A and reduced the levels of matrix metalloproteinase-13 genes, indicating a chondroprotective effect of G-Rb1. G-Rb1 also significantly reduced the expression of several inflammatory cytokines/chemokines (interferon gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP-1)/CCL-2, interleukin [IL]-1ß, and IL-6). Histological analysis demonstrated that G-Rb1 significantly attenuated the pathological changes in MIA-induced OA in ovariectomized rats. Safranin O and toluidine blue staining further demonstrated that G-Rb1 effectively prevented the degradation of cartilage and glycosaminoglycans, respectively. CONCLUSION: Overall, our results suggest that G-Rb1 exerts cartilage protective effect on MIA-induced ovariectomized OA rats, by inhibiting inflammatory mediators such as IL-6, IL-1ß, MCP-1/CCL-2, cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). These results shed a light on possible therapeutic application of G-Rb1 in OA.

Korean Red Ginseng enhances cardiac hemodynamics on doxorubicin-induced toxicity in rats.

BACKGROUND: Korean Red Ginseng (KRG) has been known to possess many ginsenosides. These ginsenosides are used for curing cardiovascular problems. The present study show the protective potential of KRG against doxorubicin (DOX)-induced myocardial dysfunction, by assessing electrocardiographic, hemodynamic, and biochemical parameters and histopathological findings. METHODS: Animals were fed a standard chow and adjusted to their environment for 3 days before the experiments. Next, the rats were equally divided into five groups (n = 9, each group). The animals were administered with KRG (250 and 500 mg/kg) for 10 days and injected with DOX (20 mg/kg, subcutaneously, twice at a 24-h interval) on the 8th and 9th day. Electrocardiography and echocardiography were performed to study hemodynamics. Plasma levels of superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde were measured. In addition, the dose of troponin I and activity of myeloperoxidase in serum and cardiac tissue were analyzed, and the histopathological findings were evaluated using light microscopy. RESULTS: Administration of KRG at a dose of 250 and 500 mg/kg recovered electrocardiographic changes, ejection fraction, fractional shortening, left ventricular systolic pressure, the maximal rate of change in left ventricle contraction (+dP/dtmax), and left ventricle relaxation (-dP/dtmax). In addition, KRG treatment significantly normalized the oxidative stress markers in plasma, dose dependently. In addition, the values of troponin I and myeloperoxidase were ameliorated by KRG treatment, dose dependently. And, KRG treatment showed better histopathological findings when compared with the DOX control group. CONCLUSION: These mean that KRG mitigates myocardial damage by modulating the hemodynamics, histopathological abnormality, and oxidative stress related to DOX-induced cardiomyopathy in rats. The results of the present study show protective effects of KRG on cardiac toxicity.

Antiphotoaging and Antimelanogenic Effects of Penthorum chinense Pursh Ethanol Extract due to Antioxidant- and Autophagy-Inducing Properties.

Ethnopharmacological Relevance. Penthorum chinense Pursh (Penthoraceae) is a traditional herbal plant that has been used in China for the treatment of jaundice, cholecystitis, edema, and infectious hepatitis. In addition, the Korea Medicinal Plant Dictionary states that Penthorum chinense Pursh can be used to treat contusions and skin bruises by improving blood flow. Recent studies have shown that Penthorum chinense Pursh ethanol extract (Pc-EE) exhibits strong antioxidant effects. In this study, we examined the effects of Pc-EE on UVB-induced or H2O2-induced oxidative stress, as well as its antimelanogenic properties. Cell viability, matrix metalloproteinase (MMP) expression, cyclooxygenease-2 (COX-2), and interleukin-6 (IL-6) expression and moisturizing factors were investigated in keratinocytes. Collagen synthesis induction was measured in HEK293T cells. For melanogenesis, the effects of Pc-EE on melanin content and tyrosinase activity were measured. Additionally, the antimelanogenic- and autophagy-inducing activities of Pc-EE were examined using immunoblotting and confocal microscopy. Pc-EE protected HaCaT cells against death from UVB irradiation- or H2O2-induced oxidative stress. Pc-EE increased the promoter activity of the type 1 procollagen gene Col1A1 and decreased the expression of MMPs, COX-2, IL-6, and hyaluronidase induced by UVB irradiation- or H2O2-induced oxidative stress. Pc-EE showed a strong antioxidant effect in the DPPH assay. In α-melanocyte-stimulating hormone- (α-MSH-) stimulated B16F10 cells, Pc-EE reduced melanin production, decreased tyrosinase expression and microphthalmia-associated transcription factor (MITF) protein levels, and decreased the phosphorylation levels of p38 and JNK. In HEK293T cells, Pc-EE promoted the expression of GFP-LC3B. In B16F10 cells, the LC3B and melanin contents were reduced by Pc-EE and were restored by the autophagy inhibitor 3-methyladenine (3-MA). These results suggest that Pc-EE can be used as a skin protection agent due to its antiapoptotic, antiaging, anti-inflammatory, and antimelanogenic properties.

Collagen-based sponge hastens wound healing via decrease of inflammatory cytokines.

The objective of this study was to compare and evaluate the efficacy of collagen-based sponge compared to commercial collagen sponge as a potent open wound-dressing material. In this study, 10 mm diameter skin incision was made on lateral side of rats. The wound was monitored regularly until day 12. Histopathology results revealed the faster re-epithelialization and lesser inflammatory cells, and also masson's trichrome staining showed that collagen fibrils were horizontal and interwoven in collagen-based sponge group. The expression of growth factors such as VEGF and TGF-ß1 was found to be upregulated in transcriptional and translational levels, suggesting the importance of collagen-based sponge as a potent wound-healing material. Furthermore, IL-6 and TNF-α in the wound tissue were significantly down-regulated in 2 and 6 days in collagen-based sponge group and anti-inflammatory cytokine IL-10 level was found to be upregulated throughout 12 days. These results cumulatively revealed that collagen-based sponge may serve as novel material for wound healing in the animal model.

GBCK25, fermented ginseng, attenuates cardiac dysfunction in high fat diet-induced obese mice.

The fermentation of medicinal herbs facilitated by microbes is assumed to exert promising therapeutic efficacy on the absorption, bioavailability, and pharmacological effects by speeding up the making or conversion of active constituents into their metabolites. We examined the cardioprotective potential of fermented ginseng, GBCK25, against high-fat diet (HFD)-induced metabolic and functional illnesses as following the essential analysis such as electrocardiographic parameters, alterations of body and organ weights, and echocardiographic studies. The results exhibited that body weights were significantly reduced and the gain of different organ weights were partly eased by GBCK25 treatment. Echocardiography results proposed the amelioration of heart function through normalized levels of left ventricle systolic pressure, ejection fraction, and fractional shortening. These outcomes deliver straight confirmation that GBCK25 could be a potential nutraceutical source for the relief of HFD-induced obesity mediated cardiac dysfunctions.

Tabetri™ (Tabebuia avellanedae Ethanol Extract) Ameliorates Atopic Dermatitis Symptoms in Mice.

Tabebuia avellanedae has been traditionally used as an herbal remedy to alleviate various diseases. However, the plant's pharmacological activity in allergic and inflammatory diseases and its underlying mechanism are not fully understood. Therefore, we investigated the pharmacological activity of Tabetri (T. avellanedae ethanol extract (Ta-EE)) in the pathogenesis of AD. Its underlying mechanism was explored using an AD mouse model and splenocytes isolated from this model. Ta-EE ameliorated the AD symptoms without any toxicity and protected the skin of 2,4-dinitrochlorobenzene- (DNCB-) induced AD mice from damage and epidermal thickness. Ta-EE reduced the secreted levels of allergic and proinflammatory cytokines, including histamine, immunoglobulin E (IgE), interleukin- (IL-) 4, and interferon-gamma (IFN-γ) in the DNCB-induced AD mice. Ta-EE suppressed the mRNA expression of T helper 2-specific cytokines, IL-4 and IL-5, and the proinflammatory cytokine IFN-γ in the atopic dermatitis skin lesions of AD mice. Moreover, Ta-EE suppressed the mRNA expression of IL-4, IL-5, IFN-γ, and another proinflammatory cytokine, IL-12, in the Con A-stimulated splenocytes. It also suppressed IL-12 and IFN-γ in the LPS-stimulated splenocytes. Taken together, these results suggest that Ta-EE protects against the development of AD through the inhibition of mRNA expression of T helper 2-specific cytokines and other proinflammatory cytokines.

TANK-binding kinase 1 and Janus kinase 2 play important roles in the regulation of mitogen-activated protein kinase phosphatase-1 expression after toll-like receptor 4 activation.

Inflammation is a response that protects the body from pathogens. Through several inflammatory signaling pathways mediated by various families of transcription factors, such as nuclear factor-κB (NF-κB), activator protein-1 (AP-1), interferon regulatory factors (IRFs), and signal transducers and activators of transcription (STATs), various inflammatory cytokines and chemokines are induced and inflammatory responses are boosted. Simultaneously, inhibitory systems are activated and provide negative feedback. A typical mechanism by which this process occurs is that inflammatory signaling molecules upregulate mitogen-activated protein kinase phosphatase-1 (MKP1) expression. Here, we investigated how kinases regulate MKP1 expression in lipopolysaccharide-triggered cascades. We found that p38 and c-Jun N-terminal kinase (JNK) inhibitors decreased MKP1 expression. Using specific inhibitors, gene knockouts, and gene knockdowns, we also found that tumor necrosis factor receptor-associated factor family member-associated nuclear factor κB activator (TANK)-binding kinase 1 (TBK1) and Janus kinase 2 (JAK2) are involved in the induction of MKP1 expression. By analyzing JAK2-induced activation of STATs, STAT3-specific inhibitors, promoter binding sites, and STAT3-/- cells, we found that STAT3 is directly linked to TBK1-mediated and JAK2-mediated induction of MKP1 expression. Our data suggest that MKP1 expression can be differentially regulated by p38, JNK, and the TBK1-JAK2-STAT3 pathway after activation of toll-like receptor 4 (TLR4). These data also imply crosstalk between the AP-1 pathway and the IRF3 and STAT3 pathways.

Src is the primary target of aripiprazole, an atypical antipsychotic drug, in its anti-tumor action.

Aripiprazole (ARP) is an atypical anti-psychotic drug widely used to treat schizophrenia and bipolar disorder. The pharmacological effects of ARP on cancer cells are still poorly understood. In this study, anti-cancer effects of ARP on various malignant tumor cells and its molecular mechanism were further carefully examined by using cell proliferation assay, xenograft mouse model, immunoblotting analysis, migration assay, luciferase reporter gene assay, kinase assay, and overexpression strategy. Treatment with ARP induced cytotoxicity in U251 glioma cells, MKN-1 gastric adenosquamous carcinoma cells, and CT26 colon carcinoma cells. ARP suppressed cell proliferation of LN428, MDA-MB-231, and HEK293 cells. Pro-apoptotic factors active caspase-3, -8, and -9, as well as p53, were upregulated, whereas the protein and mRNA levels of anti-apoptotic factor B-cell lymphoma 2 (Bcl-2) decreased. In agreement with the in vitro results, ARP compound also significantly suppressed the growth of tumor masses formed by injecting CT26 colon cancer cells into mice. ARP treatment also effectively decreased the migratory ability of U251 glioma cells by downregulating metalloproteinase-9. Levels of phosphorylated Src, phosphorylated phosphatidylinositide 3-kinase (PI3K), and phosphorylated signal transducer and activator of transcription 3 (STAT3) were significantly decreased following ARP treatment. ARP compound reduced the kinase activity of Src. Our studies suggest that Src may be an important target molecule linked to the antitumor effects of ARP.

Anti-inflammatory effect of torilidis fructus ethanol extract through inhibition of Src.

CONTEXT: Torilidis fructus, fruits of Torilis japonica Decadolle (Umbelliferae), is a medicinal herb traditionally used as a pesticide, an astrictive, or a medicine for various inflammatory diseases. OBJECTIVES: Due to the lack of pharmacological studies on this herbal medicine, we explored the inhibitory activity of torilidis fructus on the macrophage-mediated inflammatory response using its ethanol extract (Tf-EE). MATERIAL AND METHODS: The Griess assay and prostaglandin (PGE2) ELISA assay were conducted with Tf-EE (0-75 µg/mL) and LPS (1 µg/mL) treated RAW264.7 cells in cultured media. Tf-EE pretreated RAW264.7 cells were incubated with LPS for 6 h and semi-quantitative PCR was performed. Reporter gene assays, overexpression of target enzymes and immunoblotting were performed on macrophages to determine the molecular targets of Tf-EE. RESULTS: Tf-EE markedly suppressed the inflammatory response of macrophages, such as lipopolysaccharide (LPS)-induced nitric oxide (NO) and PGE2 production with IC50 values of 35.66 and 62.47 µg/mL, respectively. It was also found that Tf-EE reduced the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 by 80%. Nuclear translocation and activation of nuclear factor (NF)-κB (p65 and p50) were declined by 60% and 30% respectively, and their regulatory events including the phosphorylation of AKT, IκBα, Src, and the formation of complexes between Src and p-p85 were also recognized to be diminished. CONCLUSIONS: The signalling events managed by Src and p85 complex seemed to be critically involved in Tf-EE-mediated anti-inflammatory response. This might suggest that Tf-EE exhibited anti-inflammatory effects through Src-targeted inhibition of NF-κB.

Anticancer Efficacy of Cordyceps militaris Ethanol Extract in a Xenografted Leukemia Model.

Cordyceps militaris is used widely as a traditional medicine in East Asia. Although a few studies have attempted to elucidate the anticancer activities of C. militaris, the precise mechanism of C. militaris therapeutic effects is not fully understood. We examined the anticancer activities of C. militaris ethanolic extract (Cm-EE) and its cellular and molecular mechanisms. For this purpose, a xenograft mouse model bearing murine T cell lymphoma (RMA) cell-derived cancers was established to investigate in vivo anticancer mechanisms. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, immunoblotting analysis, and flow cytometric assay were employed to check in vitro cytotoxicity, molecular targets, and proapoptotic action of Cm-EE. Interestingly, cancer sizes and mass were reduced in a C. militaris-administered group. Levels of the phosphorylated forms of p85 and AKT were clearly decreased in the group administered with Cm-EE. This result indicated that levels of phosphoglycogen synthase kinase 3ß (p-GSK3ß) and cleaved caspase-3 were increased with orally administered Cm-EE. In addition, Cm-EE directly inhibited the viability of cultured RMA cells and C6 glioma cells. The number of proapoptotic cells was significantly increased in a Cm-EE treated group compared with a control group. Our results suggested that C. militaris might be able to inhibit cancer growth through regulation of p85/AKT-dependent or GSK3ß-related caspase-3-dependent apoptosis.

Anti-Inflammatory Effect of Piper attenuatum Methanol Extract in LPS-Stimulated Inflammatory Responses.

Piper attenuatum is used as a traditional medicinal plant in India. One of the substances in P. attenuatum has been suggested to have anti-inflammatory effects. However, there is insufficient research about the anti-inflammatory mechanisms of action of P. attenuatum. The effects of P. attenuatum methanol extract (Pa-ME) on the production of inflammatory mediators nitric oxide (NO) and prostaglandin E2 (PGE2), the expression of proinflammatory genes, the translocation level of transcription factors, and intracellular signaling activities were investigated using macrophages. Pa-ME suppressed the production of NO and PGE2 in lipopolysaccharide- (LPS-), pam3CSK4-, and poly(I:C)-stimulated RAW264.7 cells without displaying cytotoxicity. The mRNA expression levels of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2) were decreased by Pa-ME. P-ME reduced the translocation of p50/NF-κB and AP-1 (c-Jun and c-Fos), as well as the activity of their upstream enzymes Src, Syk, and TAK1. Immunoprecipitation analysis showed failure of binding between their substrates, phospho- (p-) p85 and p-MKK3/6. p-p85 and p-MKK3/6, which were induced by overexpression of Src, Syk, and TAK1, were also reduced by Pa-ME. Therefore, these results suggest that Pa-ME exerts its anti-inflammatory effects by targeting Src and Syk in the NF-κB signaling pathway and TAK1 in the AP-1 signaling pathway.

Comparison of anticancer activities of Korean Red Ginseng-derived fractions.

BACKGROUND: Korean Red Ginseng (KRG) is an ethnopharmacological plant that is traditionally used to improve the body's immune functions and ameliorate the symptoms of various diseases. However, the antitumorigenic effects of KRG and its underlying molecular and cellular mechanisms are not fully understood in terms of its individual components. In this study, in vitro and in vivo antitumorigenic activities of KRG were explored in water extract (WE), saponin fraction (SF), and nonsaponin fraction (NSF). METHODS: In vitro antitumorigenic activities of WE, SF, and NSF of KRG were investigated in the C6 glioma cell line using cytotoxicity, migration, and proliferation assays. The underlying molecular mechanisms of KRG fractions were determined by examining the signaling cascades of apoptotic cell death by semiquantitative reverse transcriptase polymerase chain reaction and Western blot analysis. The in vivo antitumorigenic activities of WE, SF, and NSF were investigated in a xenograft mouse model. RESULTS: SF induced apoptotic death of C6 glioma cells and suppressed migration and proliferation of C6 glioma cells, whereas WE and NSF neither induced apoptosis nor suppressed migration of C6 glioma cells. SF downregulated the expression of the anti-apoptotic gene B-cell lymphoma-2 (Bcl-2) and upregulated the expression of the pro-apoptotic gene Bcl-2-associated X protein (BAX) in C6 glioma cells but had no effect on the expression of the p53 tumor-suppressor gene. Moreover, SF treatment resulted in activation of caspase-3 as evidenced by increased levels of cleaved caspase-3. Finally, WE, SF, and NSF exhibited in vivo antitumorigenic activities in the xenograft mouse model by suppressing the growth of grafted CT-26 carcinoma cells without decreasing the animal body weight. CONCLUSION: These results suggest that WE, SF, and NSF of KRG are able to suppress tumor growth via different molecular and cellular mechanisms, including induction of apoptosis and activation of immune cells.

Src and Syk contribute to the anti-inflammatory activities of Achyranthes aspera ethanolic extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Nuclear factor-kappa B (NF-κB) plays pivotal roles in inflammation. Src and Syk are two tyrosine kinases that act upstream of NF-κB signaling. Although Achyranthes aspera L. (A. aspera) has been used as a traditional medicine to treat fevers and inflammatory ailments and heal wounds, the molecular mechanisms of its anti-inflammatory actions are not yet fully understood. MATERIALS AND METHODS: In this study, we evaluated the anti-inflammatory effect of A. aspera ethanol extract (Aa-EE). To determine the mechanism by which Aa-EE dampens the inflammatory response, nitric oxide (NO) production and the mRNA expression levels of tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) were examined by Griess assay and RT-PCR. Luciferase assays and immunoblotting were also conducted to examine how Aa-EE regulates the NF-κB pathway. RESULTS: Aa-EE reduced NO production up to 60% without any cytotoxicity. This extract was found to downregulate the mRNA expression levels of inflammatory genes. Aa-EE blocked NF-κB promoter activity induced by both TNF-α and adaptor molecule MyD88 (about 70% and 40%, respectively). Moreover, nuclear translocation of p65 and IκBα phosphorylation were also inhibited. Furthermore, Aa-EE inactivated two upstream signaling molecules, the Src and Syk kinases. In accordance with these data, the kinase activities of Src and Syk were decreased by 50% and 80%, respectively. The anti-inflammatory action of Aa-EE was also confirmed in a gastritis model. CONCLUSION: Our data suggest that Aa-EE targets NF-κB to exert its anti-inflammatory properties by suppressing Src and Syk. Therefore, our study raises the possibility that this extract can be developed as a novel natural anti-inflammatory remedy.

Thymoquinone: An IRAK1 inhibitor with in vivo and in vitro anti-inflammatory activities.

Thymoquinone (TQ) is a bioactive component of black seed (Nigella sativa) volatile oil and has been shown to have anti-oxidative, anti-inflammatory, and anti-cancer properties. In the present study, we explored the molecular mechanisms that underlie the anti-inflammatory effect of TQ and its target proteins using lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 and human monocyte-like U937 cells, together with LPS/D-galactosamine (GalN)-induced acute hepatitis and HCl/EtOH-induced gastritis mouse models. TQ strongly inhibited the production of nitric oxide (NO) and repressed NO synthase (iNOS), tumor necrosis factor (TNF)-α, cyclooxygenase (COX)-2, interleukin (IL)-6, and IL-1ß expression in LPS-activated RAW264.7 cells. Treatment of LPS/D-GalN-induced hepatitis and EtOH/HCl-induced gastritis mouse models with TQ significantly ameliorated disease symptoms. Using luciferase reporter gene assays, we also showed that the nuclear levels of transcription factors and phosphorylation patterns of signaling proteins, activator protein (AP)-1, and nuclear factor (NF)-κB pathways were all affected by TQ treatment. Finally, we used additional kinase and luciferase validation assays with interleukin-1 receptor-associated kinase 1 (IRAK1) to show that IRAK1 is directly suppressed by TQ treatment. Together, these findings strongly suggest that the anti-inflammatory actions of TQ are caused by suppression of IRAK-linked AP-1/NF-κB pathways.

Tabetri™ (Tabebuia avellanedae Ethanol Extract) Ameliorates Osteoarthritis Symptoms Induced by Monoiodoacetate through Its Anti-Inflammatory and Chondroprotective Activities.

Although osteoarthritis (OA), a degenerative joint disease characterized by the degradation of joint articular cartilage and subchondral bones, is generally regarded as a degenerative rather than inflammatory disease, recent studies have indicated the involvement of inflammation in OA pathogenesis. Tabebuia avellanedae has long been used to treat various diseases; however, its role in inflammatory response and the underlying molecular mechanisms remain poorly understood. In this study, the pharmacological effects of Tabetri (Tabebuia avellanedae ethanol extract (Ta-EE)) on OA pathogenesis induced by monoiodoacetate (MIA) and the underlying mechanisms were investigated using experiments with a rat model and in vitro cellular models. In the animal model, Ta-EE significantly ameliorated OA symptoms and reduced the serum levels of inflammatory mediators and proinflammatory cytokines without any toxicity. The anti-inflammatory activity of Ta-EE was further confirmed in a macrophage-like cell line (RAW264.7). Ta-EE dramatically suppressed the production and mRNA expressions of inflammatory mediators and proinflammatory cytokines in lipopolysaccharide-stimulated RAW264.7 cells without any cytotoxicity. Finally, the chondroprotective effect of Ta-EE was examined in a chondrosarcoma cell line (SW1353). Ta-EE markedly suppressed the mRNA expression of matrix metalloproteinase genes. The anti-inflammatory and chondroprotective activities of Ta-EE were attributed to the targeting of the nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) signaling pathways in macrophages and chondrocytes.

Korean Red Ginseng water extract arrests growth of xenografted lymphoma cells.

BACKGROUND: Although numerous studies of the anticancer activities of Korean Red Ginseng (KRG) have been performed, the therapeutic effect of KRG on leukemia has not been fully elucidated. In this study, we investigated the antileukemia activities of KRG and its cellular and molecular mechanisms. METHODS: An established leukemia tumor model induced by xenografted T cell lymphoma (RMA cells) was used to test the therapeutic activity of KRG water extract (KRG-WE). Direct cytotoxic activity of KRG-WE was confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The immunomodulatory activities of KRG-WE were verified by immunohistochemistry, nitric oxide production assay. The inhibitory effect of KRG-WE on cell survival signaling was also examined. RESULTS: Orally administered KRG-WE reduced the sizes of tumor masses. Levels of apoptosis regulatory enzymes and cleaved forms of caspases-3 and -8 were increased by this extract. In addition, expression of matrix metalloproteinase-9, a metastasis regulatory enzyme, was decreased by KRG-WE treatment. The proportion of CD11c+ cells was remarkably increased in the KRG-treated group compared to the control group. However, KRG-WE did not show significant direct cytotoxicity against RMA cells. CONCLUSION: Our results strongly suggest that the KRG might have antileukemia activity through CD11c+ cell-mediated antitumor immunity.

In vitro and in vivo anti-inflammatory activities of Korean Red Ginseng-derived components.

BACKGROUND: Although Korean Red Ginseng (KRG) has been traditionally used for a long time, its anti-inflammatory role and underlying molecular and cellular mechanisms have been poorly understood. In this study, the anti-inflammatory roles of KRG-derived components, namely, water extract (KRG-WE), saponin fraction (KRG-SF), and nonsaponin fraction (KRG-NSF), were investigated. METHODS: To check saponin levels in the test fractions, KRG-WE, KRG-NSF, and KRG-SF were analyzed using high-performance liquid chromatography. The anti-inflammatory roles and underlying cellular and molecular mechanisms of these components were investigated using a macrophage-like cell line (RAW264.7 cells) and an acute gastritis model in mice. RESULTS: Of the tested fractions, KGR-SF (but not KRG-NSF and KRG-WE) markedly inhibited the viability of RAW264.7 cells, and splenocytes at more than 500 µg/mL significantly suppressed NO production at 100 µg/mL, diminished mRNA expression of inflammatory genes such as inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, and interferon-ß at 200 µg/mL, and completely blocked phagocytic uptake by RAW264.7 cells. All three fractions suppressed luciferase activity triggered by interferon regulatory factor 3 (IRF3), but not that triggered by activator protein-1 and nuclear factor-kappa B. Phospho-IRF3 and phospho-TBK1 were simultaneously decreased in KRG-SF. Interestingly, all these fractions, when orally administered, clearly ameliorated the symptoms of gastric ulcer in HCl/ethanol-induced gastritis mice. CONCLUSION: These results suggest that KRG-WE, KRG-NSF, and KRG-SF might have anti-inflammatory properties, mostly because of the suppression of the IRF3 pathway.

Supplementation of a Fermented Soybean Extract Reduces Body Mass and Prevents Obesity in High Fat Diet-Induced C57BL/6J Obese Mice.

Obesity is a growing health problem that many countries face, mostly due to the consumption of a Westernized diet. In this present study we observed the effects of a soybean extract fermented by Bacillus subtilis MORI (BTD-1) containing 1-deoxynojirimycin against high fat diet-induced obesity. The results obtained from this study indicated that BTD-1 reduced body weight, regulated hepatic lipid content and adipose tissue, and also affected liver antioxidant enzymes and glucose metabolism. These results suggest that administration of BTD-1 affects obesity by inhibiting hyperglycemia and free radical-mediated stress; it also reduces lipid accumulation. Therefore, BTD-1 may be potentially useful for the prevention of obesity and its related secondary complications.

Anticancer effect of joboksansam, Korean wild ginseng germinated from bird feces.

BACKGROUND: Joboksansam, Korean bird wild ginseng, is an artificially cultivated wild ginseng germinated from bird feces. Although numerous pharmacologic activities of wild ginsengs have been reported, the beneficial effect of joboksansam in cancer has not been elucidated. In this study, we investigated the in vivo and in vitro anticancer activities of joboksansam powder. METHODS: To evaluate the in vivo anticancer activity of joboksansam, we established a xenograft mouse model bearing RMA cell-derived cancer. Direct cytotoxicity induced by joboksansam powder was also investigated in vitro using (3-4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide (MTT) assay. The inhibitory activity of this powder on the activation of cell survival signaling involving Akt and Src was examined with immunoblot analysis. RESULTS: Joboksansam powder displayed strong inhibitory activity against the increased tumor size, increased weight of total body and cancer tissues, and mortality of tumor-bearing mice. Joboksansam powder also suppressed the activation of survival regulatory enzymes Akt and Src, as assessed by phosphorylation levels in the immunoblot analysis of tumor tissues. Interestingly, the viability of RMA cells in vitro was directly decreased by joboksansam treatment. CONCLUSION: Overall, our results strongly suggest that joboksansam powder has the potential to protect against cancer generation by direct cytotoxic effects on cancer cells resulting from suppression of cell survival signaling.