Protective effect of the mixture of Lactiplantibacillus plantarum KC3 and Leonurus Japonicas Houtt extract on respiratory disorders.

Air pollutants, such as particulate matter (PM) and diesel exhaust particles (DEP), are associated with respiratory diseases. Therefore, preventive and therapeutic strategies against PM-and DEP (PM10D)-induced respiratory diseases are needed. Herein, we evaluate the protective effects of a mixture of Lactiplantibacillus plantarum KC3 and Leonurus Japonicas Houtt (LJH) extract against airway inflammation associated with exposure to PM10D. To determine the anti-inflammatory effects of the LJH extract, reactive oxygen species (ROS) production and the expression of inflammatory pathways were determined in PM10-induced MH-S cells. For the respiratory protective effects, BALB/c mice were exposed to PM10D via intranasal injection, and a mixture of L. plantarum KC3 and LJH extract was administered orally for 12 days. LJH extract inhibited ROS production and the phosphorylation of downstream factors of NF-κB in PM10-stimulated MH-S cells. The mixture of L. plantarum KC3 and LJH repressed the infiltration of neutrophils, reduced the immune cells number, and suppressed the proinflammatory mediators and cyclooxygenase (COX)-2 expressions in PM10D-induced airway inflammation with reduced phosphorylation of downstream factors of NF-κB. In addition, these effects were not observed in an alveolar macrophage depleted PM10D-induced mouse model using clodronate liposomes. The extract mixture also regulated gut microbiota in feces and upregulated the mRNA expression of Foxp3, transforming growth factor (TGF)-ß1, and interleukin (IL)-10 in the colon. The L. plantarum KC3 and LJH extract mixture may inhibit alveolar macrophage- and neutrophil-mediated inflammatory responses and regulate gut microbiota and immune response in PM10D-induced airway inflammation, suggesting it is a potential remedy to prevent and cure airway inflammation and respiratory disorders.

Protective Effects of Glycine soja Leaf and Stem Extract against Chondrocyte Inflammation and Osteoarthritis.

Wild soybean, also known as Glycine soja Sieb. et Zucc. (GS), has long been known for its various health benefits. Although various pharmacological effects of G. soja have been studied, the effects of GS leaf and stem (GSLS) on osteoarthritis (OA) have not been evaluated. Here, we examined the anti-inflammatory effects of GSLS in interleukin-1ß (IL-1ß)-stimulated SW1353 human chondrocytes. GSLS inhibited the expression of inflammatory cytokines and matrix metalloproteinases and ameliorated the degradation of collagen type II in IL-1ß-stimulated chondrocytes. Furthermore, GSLS played a protective role in chondrocytes by inhibiting the activation of NF-κB. In addition, our in vivo study demonstrated that GSLS ameliorated pain and reversed cartilage degeneration in joints by inhibiting inflammatory responses in a monosodium iodoacetate (MIA)-induced OA rat model. GSLS remarkably reduced the MIA-induced OA symptoms, such as joint pain, and decreased the serum levels of proinflammatory mediators, cytokines, and matrix metalloproteinases (MMPs). Our findings show that GSLS exerts anti-osteoarthritic effects and reduces pain and cartilage degeneration by downregulating inflammation, suggesting that it is a useful therapeutic candidate for OA.

Photoprotective Effects of Processed Ginseng Leaf Administration against UVB-Induced Skin Damage in Hairless Mice.

Although ginseng leaves contain a larger amount of ginsenosides than the roots, studies on the protective effect of oral administration of ginseng leaves against photoaging are lacking. Processed ginseng leaves (PGL) prepared by acid reaction to increase effective ginsenoside content showed higher levels of Rg3 (29.35 mg/g) and Rk1 (35.16 mg/g) than ginseng leaves (Rg3 (2.14 mg/g) and Rk1 (ND)), and ginsenosides Rg3 and Rk1 were evaluated as active ingredients that protected human keratinocytes against UVB-induced cell damage by increasing cell proliferation and decreasing matrix metalloproteinase (MMP)-2 and 9 secretion. Herein, the effect of oral PGL administration (50, 100, or 200 mg/kg, daily) against photoaging in HR-1 hairless mice was assessed by measuring wrinkle depth, epidermal thickness, and trans-epidermal water loss for 16 weeks. The PGL treatment group showed reduced skin wrinkles, inhibited MMP-2 and MMP-9 expression, and decreased IL-6 and cyclooxygenase-2 levels. These data suggest that oral PGL administration inhibits photoaging by inhibiting the expression of MMPs, which degrade collagen, and inhibiting cytokines, which induce inflammatory responses. These results reveal that ginseng leaves processed by acid reaction may serve as potential functional materials with anti-photoaging activities.

Hypericum ascyron L. extract reduces particulate matter-induced airway inflammation in mice.

The consequences of increased industrialization increased the risk of asthma and breathing difficulties due to increased particulate matter in the air. We aim to investigate the therapeutic properties of Hypericum ascyron L. extract (HAE) in airway inflammation and unravel its mechanism of action. We conducted nitric oxide and cell viability assay, real-time PCR and western blot analyses along with in vitro studies. in vivo studies include a model of coal fly ash and diesel exhaust particle (CFD)-induced airway inflammation in mice. HAE reduced coal fly ash (CFA)-induced nitric oxide secretion without exhibiting cytotoxicity in MH-S cells. HAE also reduced the mRNA expression of pro-inflammatory cytokines and reduced the expression of proteins in the NFκB and MAPK pathways. In a mice model of CFD-induced airway inflammation, HAE effectively reduced neutrophil infiltration in bronchoalveolar lavage fluid (BALF) and increased the amount of T cells in the BALF, lungs, and blood while reducing all other immune cell subtypes to reduce airway inflammatory response. CXCL-1, IL-17, MIP-2, and TNF-α expression in the BALF were also reduced. HAE effectively reduced MIP-2 and TNF-α mRNA expression in the lung tissue of mice. In a nutshell, HAE is effective in preventing airway inflammation induced by CFA in MH-S cells, as well as inflammation induced by CFD in mice.

Coptidis Rhizoma Extract Reverses 5-Fluorouracil Resistance in HCT116 Human Colorectal Cancer Cells via Modulation of Thymidylate Synthase.

Colorectal cancer (CRC) is a malignancy of the colon or rectum. It is ranked as the third most common cancer in both men and women worldwide. Early resection permitted by early detection is the best treatment, and chemotherapy is another main treatment, particularly for patients with advanced CRC. A well-known thymidylate synthase (TS) inhibitor, 5-fluorouracil (5-FU), is frequently prescribed to CRC patients; however, drug resistance is a critical limitation of its clinical application. Based on the hypothesis that Coptidis Rhizoma extract (CRE) can abolish this 5-FU resistance, we explored the efficacy and underlying mechanisms of CRE in 5-FU-resistant (HCT116/R) and parental HCT116 (HCT116/WT) cells. Compared to treatment with 5-FU alone, combination treatment with CRE and 5-FU drastically reduced the viability of HCT116/R cells. The cell cycle distribution assay showed significant induction of the G0/G1 phase arrest by co-treatment with CRE and 5-FU. In addition, the combination of CRE and 5-FU notably suppressed the activity of TS, which was overexpressed in HCT116/R cells, as compared to HCT116/WT cells. Our findings support the potential of CRE as an adjuvant agent against 5-FU-resistant colorectal cancers and indicate that the underlying mechanisms might involve inhibition of TS expression.

Cryptotympana pustulata Extract and Its Main Active Component, Oleic Acid, Inhibit Ovalbumin-Induced Allergic Airway Inflammation through Inhibition of Th2/GATA-3 and Interleukin-17/RORγt Signaling Pathways in Asthmatic Mice.

Cicadae Periostracum (CP), derived from the slough of Cryptotympana pustulata, has been used as traditional medicine in Korea and China because of its diaphoretic, antipyretic, anti-inflammatory, antioxidant, and antianaphylactic activities. The major bioactive compounds include oleic acid (OA), palmitic acid, and linoleic acid. However, the precise therapeutic mechanisms underlying its action in asthma remain unclear. The objective of this study was to determine the antiasthmatic effects of CP in an ovalbumin (OVA)-induced asthmatic mouse model. CP and OA inhibited the inflammatory cell infiltration, airway hyperresponsiveness (AHR), and production of interleukin (IL)7 and Th2 cytokines (IL-5) in the bronchoalveolar lavage fluid and OVA-specific imunoglobin E (IgE) in the serum. The gene expression of IL-5, IL-13, CCR3, MUC5AC, and COX-2 was attenuated in lung tissues. CP and OA might inhibit the nuclear translocation of GATA-binding protein 3 (GATA-3) and retinoic acid receptor-related orphan receptor γt (RORγt) via the upregulation of forkhead box p3 (Foxp3), thereby preventing the activation of GATA-3 and RORγt. In the in vitro experiment, a similar result was observed for Th2 and GATA-3. These results suggest that CP has the potential for the treatment of asthma via the inhibition of the GATA-3/Th2 and IL-17/RORγt signaling pathways.

Vagal afferent fibers contribute to the anti-inflammatory reactions by vagus nerve stimulation in concanavalin A model of hepatitis in rats.

BACKGROUND: Increasing number of studies provide evidence that the vagus nerve stimulation (VNS) dampens inflammation in peripheral visceral organs. However, the effects of afferent fibers of the vagus nerve (AFVN) on anti-inflammation have not been clearly defined. Here, we investigate whether AFVN are involved in VNS-mediated regulation of hepatic production of proinflammatory cytokines. METHODS: An animal model of hepatitis was generated by intraperitoneal (i.p.) injection of concanavalin A (ConA) into rats, and electrical stimulation was given to the hepatic branch of the vagus nerve. AFVN activity was regulated by administration of capsaicin (CAP) or AP-5/CNQX and the vagotomy at the hepatic branch of the vagus nerve (hVNX). mRNA and protein expression in target tissues was analyzed by RT-PCR, real-time PCR, western blotting and immunofluorescence staining. Hepatic immune cells were analyzed by flow cytometry. RESULTS: TNF-α, IL-1ß, and IL-6 mRNAs and proteins that were induced by ConA in the liver macrophages were significantly reduced by the electrical stimulation of the hepatic branch of the vagus nerve (hVNS). Alanine transaminase (ALT) and aspartate transaminase (AST) levels in serum and the number of hepatic CD4+ and CD8+ T cells were increased by ConA injection and downregulated by hVNS. CAP treatment deteriorated transient receptor potential vanilloid 1 (TRPV1)-positive neurons and increased caspase-3 signals in nodose ganglion (NG) neurons. Concomitantly, CAP suppressed choline acetyltransferase (ChAT) expression that was induced by hVNS in DMV neurons of ConA-injected animals. Furthermore, hVNS-mediated downregulation of TNF-α, IL-1ß, and IL-6 expression was hampered by CAP treatment and similarly regulated by hVNX and AP-5/CNQX inhibition of vagal feedback loop pathway in the brainstem. hVNS elevated the levels of α7 nicotinic acetylcholine receptors (α7 nAChR) and phospho-STAT3 (Tyr705; pY-STAT3) in the liver, and inhibition of AFVN activity by CAP, AP-5/CNQX and hVNX or the pharmacological blockade of hepatic α7 nAChR decreased STAT3 phosphorylation. CONCLUSIONS: Our data indicate that the activity of AFVN contributes to hepatic anti-inflammatory responses mediated by hVNS in ConA model of hepatitis in rats.

Anti-Melanogenic Effects of Korean Red Ginseng Oil in an Ultraviolet B-Induced Hairless Mouse Model.

A 'remedy for all' natural product widely known in the Korean Peninsula is called Panax Ginseng Meyer. Globalization represents a persistent risk to the ozone layer, leading to bountiful amounts of Ultra-Violet B beams (UVB). The variety in human skin hues is ascribed to the characteristic color called Melanin. However, Melanin overproduction due to UVB beams promotes skin staining and tumorigenesis, a process called photo aging, which damages skin quality. To assess the effects of Korean Red Ginseng Oil (KGO) on photo aging, the murine melanoma cell lines B16/F10 were used in vitro and HRM-2 hairless mice exposed to UVB were studied in vivo. Our results revealed that KGO reduced tyrosinase activity and melanin production in B16/F10 cells along with the suppression of upstream factors involved in the melanin production pathway, both transcriptionally and transitionally. In the in vivo studies, KGO suppressed the expression of Matrix Metalloproteinase (MMP) and Interleukins along with a reduction of depth in wrinkle formation and reduced collagen degradation. Moreover, the feed intake and feed efficiency ratio that decreased as a result of UVB exposure was also improved by KGO treatment. In light of our results, we conclude that KGO can have considerable benefits due to its various properties of natural skin enhancement.

The Ethanol Extract of Holotrichia diomphalia Larvae, Containing Fatty acids and Amino acids, Exerts Anti-Asthmatic Effects through Inhibition of the GATA-3/Th2 Signaling Pathway in Asthmatic Mice.

Holotrichia diomphalia larvae (HD), a natural product from an insect resource, possesses many pharmacological properties, including anticoagulant, antitumor, anti-inflammatory, and analgesic activity. The major bioactive ingredients include oleic acid, palmitic acid, palmitoleic acid, linoleic acid, proline, and glutamic acid. Although HD is associated with immunoregulatory activities in allergic diseases, the therapeutic mechanisms of the action of HD in allergic diseases have not been investigated. The aim of this study was to evaluate the anti-asthmatic potential of HD in an ovalbumin (OVA)-induced mouse model of allergic asthma. Moreover, the anti-inflammatory potential of HD was examined to identify a plausible mechanism of action of HD in vitro. HD strongly reduced goblet cell hyperplasia, eosinophil infiltration, and reactive oxygen species (ROS), which reduced airway hyperresponsiveness (AHR), inflammation, and the expression of Th2 cytokines (IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF). The expression of IL-5, IL-4, eotaxin-2, lysyl oxidase-like 2 (loxl2), and GATA-binding protein 3 (GATA-3) was attenuated in the lungs. In an in vitro assay, HD exerted immunomodulatory effects through the suppression of Th2 cytokines (IL-5, IL-13), IL-17, and tumor necrosis factor (TNF)-α production through downregulation of GATA-3 expression in EL-4 T cells. These findings suggest that the anti-asthmatic activity of HD may occur through the suppression of Th2 cytokines and total Immunoglobulin E (IgE) production by inhibition of the GATA-3 transcription pathway. Our results suggest that HD may be a potential alternative therapy, or a novel therapeutic traditional medicine, for the treatment of allergic asthma.

Anti-inflammatory and anti-osteoarthritis effect of Mollugo pentaphylla extract.

CONTEXT: Mollugo pentaphylla L. (Molluginaceae) extract (MPE) has been reported to have anti-inflammatory effect on MSU-induced gouty arthritis in a mouse model. OBJECTIVE: This study examined the anti-inflammatory activities of an MPE in vitro and anti-osteoarthritis effects on monosodium iodoacetate (MIA)-induced osteoarthritis (OA) in vivo. MATERIALS AND METHODS: The dried whole plants of M. pentaphylla were extracted with 70% ethanol under reflux. The anti-inflammatory effect of MPE was evaluated in vitro in lipopolysaccharide (LPS)-treated RAW264.7 cells. The anti-osteoarthritic effect of MPE was investigated in a Sprague-Dawley rat model of MIA-induced OA. Each seven male rats were orally administered MPE (75, 150 or 300 mg/kg) or the positive control drug indomethacin (1 mg/kg) 3 days before MIA injection and once daily for 11 days thereafter. After the treatment with MPE, no evidence of systemic adverse effects was observed in any study group. RESULTS: MPE exhibited anti-inflammatory activity via inhibition of the production of NO (57.8%), PGE2 (97.1%) and IL-6 (93.2%) in LPS-treated RAW264.7 cells at 200 µg/mL. In addition, MPE suppressed IL-1ß (60.9%), TNF-α (37.9%) and IL- 6 (40.9%) production and suppressed the synthesis of MMP-2, MMP-9 and COX-2 in the MIA-induced OA rat model. CONCLUSIONS: These results demonstrate that MPE exerts potent anti-inflammatory activities and protects cartilage in an OA rat model. This might be a potential candidate for therapeutic OA treatment.

Aqueous and ethanolic extracts of welsh onion, Allium fistulosum, attenuate high-fat diet-induced obesity.

BACKGROUND: Allium fistulosum (Welsh onion) is a traditional medicinal plant used for the treatment of colds, influenza, abdominal pain, headache, and heart disease. This study evaluated the effects of A. fistulosum ethanolic extract (AFE) and aqueous extract (AFW) on body weight and other obesity-related parameters. METHODS: Male 8-week-old C57BL/6 J mice were fed either a standard chow diet (normal control) or a high-fat diet (HFD) either alone (HFD-control) or in combination with G. cambogia extract containing hydroxycitric acid (HCA, an herbal weight-loss supplement), conjugated linoleic acid (CLA, a weight-loss supplement), orlistat (a clinically available anti-obesity drug), AFW, or AFE (n = 6 mice per group) for 6 weeks. At the end of 6 weeks, several body weight and obesity-related parameters were examined, including: liver and adipose weight, adipocyte size, serum lipid profiles, liver expression of adenosine monophosphate-activated protein kinase (AMPK), and adipose tissue expression of uncoupling protein 2 (UCP2). RESULTS: High-performance liquid chromatography showed that both AFE and AFW contain ferulic acid and quercetin. Oral administration of AFW and AFE to HFD-fed mice decreased body weight as well as liver and adipose tissue weight and adipocyte size. Serum lipid profiles and adiponectin levels were improved in HFD-fed mice treated with AFE but not AFW. However, both AFW and AFE significantly attenuated HFD-induced changes in serum leptin and insulin-like growth factor 1 levels, liver expression of AMPK, and adipose tissue expression of UCP2. CONCLUSIONS: The findings from this study suggest that A. fistulosum extracts have potential as functional food materials for weight control in obesity.

Effects of Toona sinensis Leaf Extract and Its Chemical Constituents on Xanthine Oxidase Activity and Serum Uric Acid Levels in Potassium Oxonate-Induced Hyperuricemic Rats.

Toona sinensis leaf is used as a seasonal vegetable in Korea. A 70% ethanol extract of these leaves exhibited potent xanthine oxidase (XO) inhibition, with a 50% inhibitory concentration (IC50) of 78.4 µM. To investigate the compounds responsible for this effect, bioassay-guided purification led to the isolation of five constituents, identified as quercetin-3-O-rutinoside, quercetin-3-O-ß-d-glucopyranoside, 1,2,3,4,6-penta-O-galloyl-ß-d-glucopyranose (compound 3), quercetin-3-O-α-l-rhamnopyranoside, and kaempferol-3-O-α-l-rhamnopyranoside. Compound 3 showed the most potent inhibition of XO, with an IC50 of 2.8 µM. This was similar to that of allopurinol (IC50 = 2.3 µM), which is used clinically to treat hyperuricemia. Kinetic analyses found that compound 3 was a reversible noncompetitive XO inhibitor. In vivo, the T. sinensis leaf extract (300 mg/kg), or compound 3 (40 mg/kg), significantly decreased serum uric acid levels in rats with potassium oxonate-induced hyperuricemia. Furthermore, ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry analysis identified a high level of compound 3 in the leaf extract. These findings suggest that T. sinensis leaves could be developed to produce nutraceutical preparations.

Illicium verum Extract and Trans-Anethole Attenuate Ovalbumin-Induced Airway Inflammation via Enhancement of Foxp3+ Regulatory T Cells and Inhibition of Th2 Cytokines in Mice.

Illicium verum is used in traditional medicine to treat inflammation. The study investigates the effects of IVE and its component, trans-anethole (AET), on airway inflammation in ovalbumin- (OVA-) induced asthmatic mice. Asthma was induced in BALB/c mice by systemic sensitization to OVA, followed by intratracheal, intraperitoneal, and aerosol allergen challenges. IVE and AET were orally administered for four weeks. We investigated the effects of treatment on airway hyperresponsiveness, IgE production, pulmonary eosinophilic infiltration, immune cell phenotypes, Th2 cytokine production in bronchoalveolar lavage, Th1/Th2 cytokine production in splenocytes, forkhead box protein 3 (Foxp3) expression, and lung histology. IVE and AET ameliorated OVA-driven airway hyperresponsiveness (p < 0.01), pulmonary eosinophilic infiltration (p < 0.05), mucus hypersecretion (p < 0.01), and IL-4, IL-5, IL-13, and CCR3 production (p < 0.05), as well as IgE levels (p < 0.01). IVE and AET increased Foxp3 expression in lungs (p < 0.05). IVE and AET reduced IL-4 and increased IFN-γ production in the supernatant of splenocyte cultures (p < 0.05). Histological studies showed that IVE and AET inhibited eosinophilia and lymphocyte infiltration in lungs (p < 0.01). These results indicate that IVE and AET exert antiasthmatic effects through upregulation of Foxp3+ regulatory T cells and inhibition of Th2 cytokines, suggesting that IVE may be a potential therapeutic agent for allergic lung inflammation.

Torilin Inhibits Inflammation by Limiting TAK1-Mediated MAP Kinase and NF-κB Activation.

Torilin, a sesquiterpene isolated from the fruits of Torilis japonica, has shown antimicrobial, anticancer, and anti-inflammatory properties. However, data on the mechanism of torilin action against inflammation is limited. This study aimed at determining the anti-inflammatory property of torilin in LPS-induced inflammation using in vitro model of inflammation. We examined torilin's effect on expression levels of inflammatory mediators and cytokines in LPS-stimulated RAW 264.7 macrophages. The involvement of NF-kB and AP-1, MAP kinases, and adaptor proteins were assessed. Torilin strongly inhibited LPS-induced NO release, iNOS, PGE2, COX-2, NF-α, IL-1ß, IL-6, and GM-CSF gene and protein expressions. In addition, MAPKs were also suppressed by torilin pretreatment. Involvement of ERK1/2, P38MAPK, and JNK1/2 was further confirmed by PD98059, SB203580, and SP600125 mediated suppression of iNOS and COX-2 proteins. Furthermore, torilin attenuated NF-kB and AP-1 translocation, DNA binding, and reporter gene transcription. Interestingly, torilin inhibited TAK1 kinase activation with the subsequent suppression of MAPK-mediated JNK, p38, ERK1/2, and AP-1 (ATF-2 and c-jun) activation and IKK-mediated I-κBα degradation, p65/p50 activation, and translocation. Together, the results revealed the suppression of NF-κB and AP-1 regulated inflammatory mediator and cytokine expressions, suggesting the test compound's potential as a candidate anti-inflammatory agent.

Anti-obesity activity, acute toxicity, and chemical constituents of aqueous and ethanol Viola mandshurica extracts.

BACKGROUND: Viola mandshurica has traditionally been used as an expectorant, diuretic, and anti-inflammatory drug. The present study was designed to test the hypothesis that low doses of two different V. mandshurica extracts have anti-obesity effects. METHODS: We evaluated the effects of ethanol extract (VME) and aqueous extract (VMA) from V. mandshurica on high-fat diet (HFD)-induced obese mice as well as the acute oral toxicities and chemical compositions of both extracts. RESULTS: Oral administration of VME or VMA (50, 100, or 200 mg/kg) decreased body weight gain, liver and adipose tissue mass, adipocyte size, and serum lipid levels. Both extracts increased adiponectin serum concentrations and mRNA expression in epididymal adipose tissue. VME and VMA also reversed the HFD-induced mRNA expression of lipogenic genes such as CCAAT/enhancer binding protein (C/EBP)α, C/EBPß, sterol regulatory element-binding protein 1c, and leptin in adipose tissue, whereas they increased mRNA expression of uncoupling protein 2 and adenosine monophosphate-activated protein kinase (AMPK). VME and VMA increased the phosphorylation of AMPK and acetyl-coA carboxylase with a concomitant decrease in fat accumulation in the liver. High performance liquid chromatography analysis revealed that both VME and VMA contained esculetin (0.566% for VME, 0.231% for VMA) and schaftoside (0.147% for VME, 0.126% for VMA). In a 2-week acute toxicity study, administration of a single oral dose of VME or VMA (5000 mg/kg) caused no signs of toxicity or mortality. CONCLUSIONS: These results suggest that both VM extracts exert anti-obesity effects in HFD-induced obese mice by suppressing lipogenesis and activating AMPK in the liver and adipose tissue. Our findings suggest that VM extracts could be a safe and effective treatment for obesity.

Antiplatelet mechanism of an herbal mixture prepared from the extracts of Phyllostachys pubescens leaves and Prunus mume fruits.

BACKGROUND: Bamboo (Phyllostachys pubescens) leaves and Japanese apricot (Mume fructus) fruit are traditionally recognized to be safe herbs broadly used for food and medicinal purposes in Southeast Asia. Our group previously explored their antiplatelet effects. This study was designed to confirm inhibition effects of PM21 (a 2:1 mixture of bamboo leaf extract and Japanese apricot fruit extract) on platelet aggregation and evaluate its potency to use as an herbal remedy to prevent and/or treat the diseases caused by platelet aggregation and thrombus formation. METHODS: Washed platelets were prepared and platelet aggregation was induced by adding 5 µg/mL collagen. Anti-platelet effects of PM21 (75 mg/kg, 150 mg/kg, and 300 mg/kg for ex vivo and in vivo assays, and 50, 100, 200 µg/mL for in vitro assays) were evaluated. In ex vivo assays, PM21 was orally administered to rats daily after overnight fasting for 3 days and blood was collected 1 h after the final treatment. In vivo antithrombotic effect of PM21 was observed from a carrageenan induced mouse tail thrombosis model. RESULTS: In ex vivo assay, PM21 inhibited platelet aggregation significantly. PM21 showed a strong antithrombotic effect by reducing significantly the length of mouse tail thrombus. PM21 increased intracellular cAMP level and reduced the release of ATP, TXA2, and serotonin. PM21 also reduced intracellular concentration of calcium ion, fibrinogen binding to integrin αIIbß3, and phosphorylation of ERK2, p38, PLCγ2, and PI3 K. CONCLUSIONS: PM21 showed remarkable inhibitory effects on platelet aggregation and thrombus formation. Its inhibitory function seems to influence on GPVI binding to its ligand and subsequent initiation of a signaling cascade that involves activation of effector proteins and secretion of effector molecules, such as ATP, TXA2, serotonin, and Ca2+. PM21 also appears to exert its anti-platelet effect by deactivation of ERKs activation pathway as well as inhibition of fibrinogen binding to integrin αIIbß3.

Anti-Photoaging Effect of Jeju Putgyul (Unripe Citrus) Extracts on Human Dermal Fibroblasts and Ultraviolet B-induced Hairless Mouse Skin.

Ultraviolet (UV) radiation stimulates the expression of matrix metalloproteinases (MMPs) and inflammatory cytokines. These signaling pathways participate in the degradation of the extracellular matrix and induce inflammatory responses that lead to photoaging. This study evaluated the antioxidant activity and the effect on MMPs and procollagen of putgyul extract in vitro. The anti-photoaging activity of putgyul extracts was estimated in vivo using hairless mice (HR-1). The putgyul extracts reduced MMP-1 production and increased the content of procollagen type I carboxy-terminal peptide in human dermal fibroblasts. Ultravilot-B (UVB)-induced expression of inflammatory cytokines and MMPs was detected in mice, and putgyul extracts suppressed the expression. These results suggest that putgyul extract inhibits photoaging by inhibiting the expression of MMPs that degrade collagen and inhibiting cytokines that induce inflammatory responses. The mouse model also demonstrated that oral administration of putgyul extracts decreased wrinkle depth, epidermal thickness, collagen degradation, and trans-epidermal water loss, and increased ß-glucosidase activity on UVB exposed skin. Putgyul extract protects against UVB-induced damage of skin and could be valuable in the prevention of photoaging.

Timosaponin AIII inhibits melanoma cell migration by suppressing COX-2 and in vivo tumor metastasis.

Melanoma is the leading cause of death from skin disease, due in large part to its propensity to metastasize. We examined the effects of timosaponin AIII, a compound isolated from Anemarrhena asphodeloides Bunge, on melanoma cancer cell migration and the molecular mechanisms underlying these effects using B16-F10 and WM-115 melanoma cells lines. Overexpression of COX-2, its metabolite prostaglandin E2 (PGE2), and PGE2 receptors (EP2 and EP4) promoted cell migration in vitro. Exposure to timosaponin AIII resulted in concentration-dependent inhibition of cell migration, which was associated with reduced levels of COX-2, PGE2, and PGE2 receptors. Transient transfection of COX-2 siRNA also inhibited cell migration. Exposure to 12-O-tetradecanoylphorbal-13-acetate enhanced cell migration, whereas timosaponin AIII inhibited 12-O-tetradecanoylphorbal-13-acetate-induced cell migration and reduced basal levels of EP2 and EP4. Moreover, timosaponin AIII inhibited activation of nuclear factor-kappa B (NF-κB), an upstream regulator of COX-2 in B16-F10 cells. Consistent with our in vitro findings, in vivo studies showed that timosaponin AIII treatment significantly reduced the total number of metastatic nodules in the mouse lung and improved histological alterations in B16-F10-injected C57BL/6 mice. In addition, C57BL/6 mice treated with timosaponin AIII showed reduced expression of COX-2 and NF-κB in the lung. Together, these results indicate that timosaponin AIII has the capacity to inhibit melanoma cell migration, an essential step in the process of metastasis, by inhibiting expression of COX-2, NF-κB, PGE2, and PGE2 receptors.

The nutritional composition and anti-obesity effects of an herbal mixed extract containing Allium fistulosum and Viola mandshurica in high-fat-diet-induced obese mice.

BACKGROUND: In traditional oriental medicine, A. fistulosum and V. mandshurica are considered to be effective in promoting blood circulation. Therefore, in this study, we investigated whether a solution containing both A. fistulosum and V. mandshurica (AFE + VME) extracts has synergistic effects on the treatment of hyperlipidemia and obesity. METHODS: Anti-obesity effects of an herbal extract containing Allium fistulosum and Viola mandshurica (AFE + VME) were investigated in high-fat diet (HFD)-induced obese mice. AFE + VME was orally administrated to mice with the HFD at a dose of 200 mg/kg/day for 8 weeks. We observed the effects of mixed extract on body weight, fat mass, serum lipid levels, and mRNA expression levels of lipid metabolism-related genes in the adipose tissue of mice. RESULTS: The nutritional analysis revealed that this mixed extract is high in carbohydrate (72.2 g/100 g) and protein (11.5 g/100 g); low in fat (1.7 g/100 g); rich in vitamins E (4.8 mg/100 g), B1 (14.8 mg/100 g), B2 (1.0 mg/100 g), niacin (7.9 mg/100 g), and folic acid (1.57 mg/100 g); and rich in minerals such as calcium (600 mg/100 g), iron (106.1 mg/100 g), and zinc (5.8 mg/100 g). The oral administration of AFE + VME in obese mice reduced body weight, tissue weight, adipocyte size, and lipid accumulation in the liver compared with HFD control mice. AFE + VME also decreased serum triglyceride, total cholesterol, and leptin concentrations. Furthermore, AFE + VME markedly increased the mRNA expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), uncoupling protein-2 (UCP-2), and adiponectin and decreased leptin expression in the epididymal white adipose tissue. Our results suggest that the extract containing A. fistulosum and V. mandshurica improved lipid metabolism via the up-regulation of PPAR-γ, UCP-2, and adiponectin expression and the down-regulation of leptin in HFD-induced obese mice. CONCLUSIONS: Therefore, the extract containing Allium fistulosum and Viola mandshurica may be a potentially effective therapy for obesity and its related metabolic disorders such as hyperlipidemia and insulin resistance.

Korean red ginseng saponin fraction rich in ginsenoside-Rb1, Rc and Rb2 attenuates the severity of mouse collagen-induced arthritis.

Despite a multitude of reports on anti-inflammatory properties of ginseng extracts or individual ginsenosides, data on antiarthritic effect of ginseng saponin preparation with mixed ginsenosides is limited. On the other hand, a combined therapy of safe and inexpensive plant-derived natural products such as ginsenosides can be considered as an alternative to treat arthritis. Our previous in vitro data displayed a strong anti-inflammatory action of red ginseng saponin fraction-A (RGSF-A). We, herein, report a marked antiarthritic property of RGSF-A rich in ginsenoside Rb1, Rc, and Rb2. Collagen-induced arthritic (CIA) mice were treated with RGSF-A or methotrexate (MTX) for 5 weeks. Joint pathology, serum antibody production and leukocye activation, cytokine production in the circulation, lymph nodes, and joints were examined. RGSF-A markedly reduced severity of arthritis, cellular infiltration, and cartilage damage. It suppressed CD3(+)/CD69(+), CD4(+)/CD25(+), CD8(+) T-cell, CD19(+), B220/CD23(+) B-cell, MHCII(+)/CD11c(+), and Gr-1(+)/CD11b(+) cell activations. It further suppressed anti-CII- or anti-RF-IgG/IgM, TNF-α, IL-1ß, IL-17, and IL-6 secretions but stimulated IL-10 levels in the serum, joint, or splenocyte. RGSF-A attenuated arthritis severity, modified leukocyte activations, and restored cytokine imbalances, suggesting that it can be considered as an antiarthritic agent with the capacity to ameliorate the immune and inflammatory responses in CIA mice.