Securinega suffruticosa extract alleviates atopy-like lesions in NC/Nga mice via inhibition of the JAK1-STAT1/3 pathway.

Securinega suffruticosa (SS) has well-known antioxidant, anti-vascular inflammation, and anti-bone resorption effects; however, the effects of SS in atopic dermatitis (AD) remain unknown. We examined the effects of SS on AD via application of Dermatophagoides farinae extract (DfE) to the ears and skin of NC/Nga mice. As a result of SS administration, DfE-induced AD mice had reduced ear thickness, epidermal thickness, scratching behavior, and transepidermal water loss. The serum levels of immunoglobulin E and thymic interstitial lymphopoietin (TSLP) were reduced by SS application. SS decreased mast cell and eosinophil recruitment to skin lesions. Phosphorylation of signal transducer and activation of transcription (STAT)1, STAT3, and Janus kinase 1 were reduced in the skin tissue of SS-administered mice, and downregulated filaggrin was restored. SS reduced the levels of interleukin-6, regulated on activation, normal T cell expressed and secreted chemokine, and TSLP in interferon-γ/tumor necrosis factor-α-induced keratinocytes. The main components of SS were rutin and geraniin. These study results indicated that SS extract attenuated AD and has potential as a therapeutic natural product candidate for AD.

Synergistic Impacts of Alpinia oxyphylla Seed Extract and Allopurinol against Experimental Hyperuricemia.

In traditional medicine, Alpinia oxyphylla Miquel seed has been used to treat gout and hyperuricemia-related symptoms by enhancing kidney functions. Allopurinol is the most commonly used drug to treat hyperuricemia; however, the drug has many adverse effects. Combining allopurinol with another compound could reduce the need for high doses and result in improved safety. We investigated the possible synergistic effects of Alpinia oxyphylla seed extract (AE) and allopurinol in decreasing urate concentrations in rats with potassium oxonate-induced hyperuricemia. This study evaluated the effects of allopurinol combined with AE on levels of serum urate, blood urea nitrogen (BUN), and creatinine in a hyperuricemic rat model. The effects of allopurinol plus AE on xanthine oxidase (XOD) activity and urate uptake were measured. The concomitant administration of allopurinol and AE normalized serum urate and reduced BUN and creatinine. The attenuation of hyperuricemia-induced impaired kidney function was related to downregulation of renal urate transporter 1 and upregulation of renal organic anion transporter 1, with inhibition of serum and hepatic XOD activities. The antihyperuricemic effects of allopurinol were enhanced when combined with AE. These results suggested that the combined use of allopurinol and AE may have clinical efficacy in treating hyperuricemia.

Saengmaeksan, a traditional herbal formulation consisting of Panax ginseng, ameliorates hyperuricemia by inhibiting xanthine oxidase activity and enhancing urate excretion in rats.

BACKGROUND: Saengmaeksan (SMS) is a traditional Korean medicine composed of three herbs, Panax ginseng, Schisandra chinensis, and Liriope platyphylla. SMS is used to treat respiratory and cardiovascular disorders. However, whether SMS exerts antihyperuricemic effects is unknown. METHODS: Effects of the SMS extract in water (SMS-W) and 30% ethanol (SMS-E) were studied in a rat model of potassium oxonate-induced hyperuricemia. Uric acid concentrations and xanthine oxidase (XO) activities were evaluated in the serum, urine, and hepatic tissue. Using renal histopathology to assess kidney function and uric acid excretion, we investigated serum creatinine and blood urea nitrogen concentrations, as well as protein levels of renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), and organic anion transporter 1 (OAT1). The effects of SMS on in vitro XO activity and uric acid uptake were also evaluated. The components of SMS were identified using Ultra Performance Liquid Chromatography (UPLC). RESULTS: SMS-E reduced serum uric acid and creatinine concentrations, and elevated urine uric acid excretion. SMS-E lowered XO activities in both the serum and liver, and downregulated the expression of renal URAT1 and GLUT9 proteins. SMS-E reduced renal inflammation and IL-1ß levels in both the serum and kidneys. SMS-E inhibited both in vitro XO activity and urate uptake in URAT1-expressing oocytes. Using UPLC, 25 ginsenosides were identified, all of which were present in higher levels in SMS-E than in SMS-W. CONCLUSION: SMS-E exhibited antihyperuricemic effects by regulating XO activity and renal urate transporters, providing the first evidence of its applicability in the treatment of hyperuricemia and gout.

Eggshell Membrane Ameliorates Hyperuricemia by Increasing Urate Excretion in Potassium Oxonate-Injected Rats.

Hyperuricemia is the primary cause of gouty arthritis and other metabolic disorders. Eggshell membrane (EM) is an effective and safe supplement for curing pain and stiffness connected with osteoarthritis. However, the effect of EM on hyperuricemia is unclear. This study determines the effects of EM on potassium oxonate-injected hyperuricemia. Uric acid, creatinine, blood urea nitrogen concentrations in the serum, and xanthine oxidase activity in the liver are measured. Protein levels of renal urate transporter 1 (URAT1), organic anion transporters 1 (OAT1), glucose transporter 9 (GLUT9), and ATP-binding cassette transporter G2 (ABCG2) in the kidney are determined with renal histopathology. The results demonstrate that EM reduces serum uric acid levels and increases urine uric acid levels in hyperuricemic rats. Moreover, EM downregulates renal URAT1 protein expression, upregulates OAT1 and ABCG2, but does not change GLUT9 expression. Additionally, EM does not change xanthine oxidase activity in the liver or the serum. EM also decreases uric acid uptake into oocytes expressing hURAT1. Finally, EM markedly reduces renal inflammation and serum interleukin-1ß levels. These findings suggest that EM exhibits antihyperuricemic effects by promoting renal urate excretion and regulating renal urate transporters. Therefore, EM may be useful in the prevention and treatment of gout and hyperuricemia.

Siraitia grosvenorii Residual Extract Attenuates Atopic Dermatitis by Regulating Immune Dysfunction and Skin Barrier Abnormality.

Atopic dermatitis is a persistent inflammatory skin disorder. Siraitia grosvenorii fruits (monk fruit or nahangwa in Korean, NHG) are used as a natural sweetener and as a traditional medicine for the treatment of asthma and bronchitis. We evaluated the activity of S. grosvenorii residual extract (NHGR) on allergic inflammation of atopic dermatitis in a Dermatophagoides farinae mite antigen extract (DfE)-treated NC/Nga murine model and in vitro. Oral administration of NHGR significantly reduced epidermal hyperplasia and inflammatory cell infiltration in the skin lesions of DfE-induced atopic dermatitis, as well as the dermatitis severity score. NHGR reduced serum immunoglobulin E levels. Splenic concentrations of IFN-γ, interleukin (IL)-4, IL-5, and IL-13 were reduced by NHGR administration. Immunohistofluorescence staining showed that NHGR administration increased the protein levels of claudin-1, SIRT1, and filaggrin in atopic dermatitis skin lesions. In addition, NHGR inhibited the phosphorylation of mitogen-activated protein kinases and decreased filaggrin and chemokine protein expression in TNF-α/IFN-γ-induced human keratinocytes. Moreover, NHGR also inhibited histamine in mast cells. The quantitative analysis of NHGR revealed the presence of grosvenorine, kaempferitrin, and mogrosides. These results demonstrate that NHGR may be an efficient therapeutic agent for the treatment of atopic dermatitis.

Herbal Combination of Phyllostachys pubescens and Scutellaria baicalensis Inhibits Adipogenesis and Promotes Browning via AMPK Activation in 3T3-L1 Adipocytes.

To investigate the anti-obesity effects and underlying mechanism of BS21, a combination of Phyllostachys pubescens leaves and Scutellaria baicalensis roots was used to investigate the effects of BS21 on adipogenesis, lipogenesis, and browning in 3T3-L1 adipocytes. The expression of adipocyte-specific genes was observed via Western blot, and the BS21 chemical profile was analyzed using ultra-performance liquid chromatography (UPLC). BS21 treatment inhibited adipocyte differentiation and reduced the expression of the adipogenic proteins peroxisome proliferator-activated receptor γ (PPAR-γ), CCAAT/enhancer-binding protein (C/EBP-α), and adipocyte protein 2 (aP2), as well as the lipogenic proteins sterol regulatory element-binding protein 1c (SREBP-1c) and fatty-acid synthase (FAS). BS21 enhanced protein levels of the beta-oxidation genes carnitine palmitoyltransferase (CPT1) and phospho-acetyl-coA carboxylase (p-ACC). BS21 also induced protein expressions of the browning marker genes PR domain containing 16 (PRDM16), peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC1α), and uncoupling protein (UCP) 1, and it induced the expression of the thermogenic gene UCP2. Furthermore, BS21 increased adenosine monophosphate-activated protein kinase (AMPK) activation. UPLC analysis showed that BS21 contains active constituents such as chlorogenic acid, orientin, isoorientin, baicalin, wogonoside, baicalein, tricin, wogonin, and chrysin. Our findings demonstrate that BS21 plays a modulatory role in adipocytes by reducing adipogenesis and lipogenesis, increasing fat oxidation, and inducing browning.

Phloroglucinol Derivatives from Dryopteris crassirhizoma as Potent Xanthine Oxidase Inhibitors.

Dryopteris crassirhizoma rhizomes are used as a traditional medicine in Asia. The EtOAc extract of these roots has shown potent xanthine oxidase (XO) inhibitory activity. However, the main phloroglucinols in D. crassirhizoma rhizomes have not been analyzed. Thus, we investigated the major constituents responsible for this effect. Bioassay-guided purification isolated four compounds: flavaspidic acid AP (1), flavaspidic acid AB (2), flavaspidic acid PB (3), and flavaspidic acid BB (4). Among these, 1 showed the most potent inhibitory activity with a half-maximal inhibitory concentration (IC50) value of 6.3 µM, similar to that of allopurinol (IC50 = 5.7 µM) and better than that of oxypurinol (IC50 = 43.1 µM), which are XO inhibitors. A comparative activity screen indicated that the acetyl group at C3 and C3' is crucial for XO inhibition. For example, 1 showed nearly 4-fold higher efficacy than 4 (IC50 = 20.9 µM). Representative inhibitors (1-4) in the rhizomes of D. crassirhizoma showed reversible and noncompetitive inhibition toward XO. Furthermore, the potent inhibitors were shown to be present in high quantities in the rhizomes by a UPLC-QTOF-MS analysis. Therefore, the rhizomes of D. crassirhizoma could be used to develop nutraceuticals and medicines for the treatment of gout.

Anti-hyperuricemic effect of Alpinia oxyphylla seed extract by enhancing uric acid excretion in the kidney.

BACKGROUND: Alpinia oxyphylla is a well-known traditional medicine used in China and Korea to treat intestinal disorders, urosis, diuresis, and chronic glomerulonephritis. PURPOSE: We investigated the anti-hyperuricemic effects of Alpinia oxyphylla seed extract (AE), and the underlying mechanisms of action through in vitro and in vivo studies. METHODS: We evaluated levels of uric acid in the serum and urine, the expression of renal urate transport proteins, and levels of inflammatory cytokines in potassium oxonate (PO)-induced hyperuricemic rats. Xanthine oxidase activity was analyzed in vitro, while cellular uric acid uptake was assessed in oocytes expressing the human urate transporter 1 (hURAT1). Moreover, the main components of AE were analyzed using UPLC. RESULTS: In PO-induced hyperuricemic rats, 200 and 400 mg/kg of AE significantly decreased levels of uric acid in serum, while 400 mg/kg of AE increased uric acid levels in urine. AE did not inhibit xanthine oxidase in vitro; however, 1, 10, and 100 µg/ml of AE significantly decreased uric acid uptake into oocytes expressing hURAT1. Furthermore, 400 mg/kg of AE increased levels of organic anion transporter (OAT) 1 protein, while 200 and 400 mg/kg of AE decreased the protein content of urate transporter, URAT1 and inflammatory cytokines in the kidneys. Nootkatone was identified as one the main chemical components in AE from UPLC analysis. CONCLUSIONS: These findings suggest that AE exerts anti-hyperuricemic and uricosuric effects, which are related to the promotion of uric acid excretion via enhanced secretion and inhibition of uric acid reabsorption in the kidneys. Thus, AE may be a potential treatment for hyperuricemia and gout.

Siraitia grosvenorii residual extract attenuates ovalbumin-induced lung inflammation by down-regulating IL-4, IL-5, IL-13, IL-17, and MUC5AC expression in mice.

BACKGROUND: Siraitia grosvenorii fruits are used in traditional medicine to treat cough, sore throat, bronchitis, and asthma. PURPOSE: This study aimed to investigate the anti-inflammatory and anti-asthmatic effects of S. grosvenorii residual extract (SGRE) on ovalbumin (OVA)-induced asthma in mice. METHODS: Asthma was induced in BALB/c mice by systemic sensitization to OVA, followed by intratracheal, intraperitoneal, and aerosol allergen challenges. SGRE was orally administered for four weeks. We investigated the effects of SGRE on airway hyper-responsiveness, OVA-specific IgE production, histological analysis of lung and trachea, immune cell phenotyping, Th1/Th2 cytokine production in bronchoalveolar lavage fluid (BAL) fluid and splenocytes, and gene expression in the lung. RESULTS: SGRE ameliorated OVA-driven airway hyper-responsiveness, serum IgE production, and histopathological changes in the lung and trachea. SGRE reduced the total number of cells in the lung and BAL, the total number of lymphocytes, neutrophils, monocytes, and eosinophils in the lung and BAL, the absolute number of CD4+/CD69+ T cells in the lung, and the absolute number of CD4+/CD8+ T cells and CD11b+/Gr-1+ granulocytes in the lung and BAL. SGRE also reduced Th2 cytokines (IL-4, IL-5, and IL-13) and increased the Th1 cytokine IFN-γ in the BAL fluid and supernatant of splenocyte cultures. SGRE decreased the OVA-induced increase of IL-13, TARC, MUC5AC, TNF-α, and IL-17 expression in the lung. CONCLUSION: SGRE exerts anti-asthmatic effects via the inhibition of Th2 and Th17 cytokines and the increase of Th1 cytokines, suggesting that SGRE may be a potential therapeutic agent for allergic lung inflammation, such as asthma.

Akebia quinata Decaisne aqueous extract acts as a novel anti-fatigue agent in mice exposed to chronic restraint stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Akebia quinata Decaisne extract (AQE; Lardizabalaceae) is used in traditional herbal medicine for stress- and fatigue-related depression, improvement of fatigue, and mental relaxation. AIM OF THE STUDY: To clarify the effects of AQE on stress-induced fatigue, we investigated the neuroprotective pharmacological effects of A. quinata Decaisne in mice exposed to chronic restraint stress. MATERIALS AND METHODS: Seven-week old C57BL/6 mice chronically stressed by immobilization for 3 h daily for 15 d and non-stressed control mice underwent daily oral administration of AQE or distilled water. The open field, sucrose preference, and forced swimming behavioral tests were carried out once weekly, and immunohistochemical analyses of NeuN, brain-derived neurotrophic factor (BDNF), phosphorylated cAMP response element-binding (CREB) protein, and BDNF receptor tropomyosin receptor kinase B (TrkB) in striatum and hippocampus were performed at the end of the experimental period. Brain levels of serotonin, adrenaline, and noradrenaline as well as serum levels of corticosterone were measured. RESULTS: Behavioral tests showed that treatment with AQE improved all lethargic behaviors examined. AQE significantly attenuated the elevated levels of adrenaline, noradrenaline, and serotonin in the brain and corticosterone, alanine transaminase, and aspartate transaminase levels in the serum. Histopathological analysis showed that AQE reduced liver injury and lateral ventricle size in restraint-stress mice via inhibition of neuronal cell death. Immunohistochemical analysis showed increased phosphorylation of CREB and expression of BDNF and its receptor TrkB in striatum and hippocampus. Chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C were identified as the primary components of AQE. All three agents increased expression of BDNF in SH-SY5Y cells and PC12 cells with H2O2-induced neuronal cell damage. CONCLUSIONS: AQE may have a neuroprotective effect and ameliorate the effects of stress and fatigue-associated brain damage through mechanisms involving regulation of BDNF-TrkB signaling.

Polygonum aviculare L. extract reduces fatigue by inhibiting neuroinflammation in restraint-stressed mice.

BACKGROUND: Chronic fatigue patients experience various neuropsychological symptoms, including fatigue behaviors, chronic pain, and depression. They also display immune system dysregulation. Polygonum aviculare L. extract (PAE) is a traditional herbal medicine used to treat inflammatory diseases by reportedly decreasing pro-inflammatory cytokine production. HYPOTHESIS/PURPOSE: We hypothesized that the anti-inflammatory properties of PAE would attenuate fatigue symptoms in a mouse model of restraint stress. STUDY DESIGN: We evaluated the effects of PAE on fatigue using three experimental groups: unstressed, vehicle-treated stressed, and PAE-treated stressed mice. This restraint stress paradigm, comprised of restraint for 3 h daily for 15 days, was used to model chronic fatigue. METHODS: We compared lethargy-like behavior between our experimental groups using forced-swim, sucrose preference, and open-field tests once per week on days 7 and 14 of restraint stress. We also used histology and western blotting to evaluate pro-inflammatory cytokine expression in the brain and serum, and microglial activation in the brain. Finally, we used liquid chromatography/mass spectroscopy (LC/MS) to identify individual components of PAE, and applied cell culture techniques to test the effects of these components on neuronal cells in vitro. RESULTS: In restraint-stressed mice, PAE treatment decreased lethargy-like behavior relative to vehicle-treated animals. PAE treatment also reduced expression of fatigue-related factors such as corticosterone, serotonin, and catecholamines (adrenaline and noradrenaline) in the brain and serum, and decreased expression of CD68, Ibal-1, and the inflammatory cytokines TNF-α, IL-6, and IL-1ß in the brain. Together, these data indicate that PAE reduced fatigue and is anti-inflammatory. Furthermore, histopathological analyses indicated that PAE treatment recovered atrophic volumes and hepatic injuries. Finally, LC/MS analysis of PAE identified four individual chemicals: myricitrin, isoquercitrin, avicularin, and quercitrin. In neuronal cell cultures, treatment with these PAE components inhibited TNF-α production, confirming that PAE treatment reduces neuroinflammation. CONCLUSIONS: PAE treatment may reduce fatigue by suppressing neuroinflammation and the expression of fatigue-related hormones.

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.

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.

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.

Effects of Viola mandshurica on Atherosclerosis and Hepatic Steatosis in ApoE[Formula: see text] via the AMPK Pathway.

Atherosclerosis was previously thought to be a disease that primarily involves lipid accumulation in the arterial wall. In this report, we investigated the effect of Viola mandshurica W. Becker (V. mandshurica) water extract on atherosclerosis in apolipoprotein E deficient (ApoE[Formula: see text]) mice. The administration of V. mandshurica to high-fat diet-fed mice reduced body weight, liver weight, and serum levels of lipids (total cholesterol, low-density lipoprotein-cholesterol, triglycerides), glucose, alanine transaminase, and aspartate transaminase. Histopathologic analyses of the aorta and liver revealed that V. mandshurica attenuated atherosclerotic lesions and reduced lipid accumulation, inflammatory responses and fatty acid synthesis. V. mandshurica also increased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), thereby reducing acetyl-CoA carboxylase (ACC) in liver tissue and inhibiting sterol regulatory element-binding protein 1c (SREBP-1c). V. mandshurica reduced protein expression levels of adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin) as well as ACC, fatty acid synthase, and SREBP-1c. In addition, quantitative analysis of V. mandshurica by high-performance liquid chromatography revealed the presence of esculetin and scopoletin. Esculetin and scopoletin reduced adhesion molecules in human aortic smooth muscle cells. Our results indicate that the anti-atherosclerotic effects of V. mandshurica may be associated with activation of the AMPK pathway. Therefore, AMPK-dependent phosphorylation of SREBP-1c by V. mandshurica may be an effective therapeutic strategy for combatting atherosclerosis and hepatic steatosis.

Schisandra chinensis and Morus alba Synergistically Inhibit In Vivo Thrombus Formation and Platelet Aggregation by Impairing the Glycoprotein VI Pathway.

Morus alba L. (MAL) extract has been used in traditional medicine for its cardioprotective and antiplatelet effects, while another herbal remedy, Schisandra chinensis (SCC), has been reported to have anti-inflammatory and antioxidant properties. We evaluated underlying cellular changes exerted by extracts of these plants on platelet function and effects of SCC + MAL on in vivo thrombus formation using AV shunt and tail thrombosis-length models in rats. In vitro platelet aggregation, granule secretion, and [Ca2+] i release assays were carried out. The activation of integrin αIIbß3 and phosphorylation of downstream signaling molecules, including MAPK and Akt, were investigated using cytometry and immunoblotting, respectively. Scanning electron microscopy (SEM) was used to evaluate changes in platelet shape and HPLC analysis was carried out to identify the marker compounds in SCC + MAL mixture. In vivo thrombus weight and average length of tail thrombosis were significantly decreased by SCC + MAL. In vitro platelet aggregation, granule secretion, [Ca2+] i release, and integrin αIIbß3 activation were notably inhibited. SCC + MAL markedly reduced the phosphorylation of MAPK pathway factors along with Akt. HPLC analysis identified four marker compounds: isoquercitrin, astragalin, schizandrol A, and gomisin A. The extracts exerted remarkable synergistic effects as natural antithrombotic and antiplatelet agent and a potent drug candidate for treating cardiovascular diseases.

Forsythia suspensa Suppresses House Dust Mite Extract-Induced Atopic Dermatitis in NC/Nga Mice.

Forsythia suspensa (F. suspensa) is a traditional medicine for treatment of inflammation. In this study, we evaluated the therapeutic effects of an ethanol extract from F. suspensa fruits on atopic dermatitis both in vivo and in vitro. We investigated the inhibitory effects of F. suspensa extract on the development of atopic dermatitis-like skin lesions in an NC/Nga mouse model exposed to Dermatophagoides farinae crude extract. Topical application of F. suspensa extract to the mice attenuated the atopic dermatitis symptoms, including increased dermatitis severity score, ear thickness, infiltration of inflammatory cells in the skin lesions, serum levels of IgE, TNF-α, and histamine, and expression of chemokines, cytokines, and adhesion molecules in ear tissue. In addition, F. suspensa extract inhibited the production of chemokines in TNF-α/IFN-γ-activated human keratinocytes. High-performance liquid chromatography analysis of FSE revealed the presence of four chemical constituents (forsythiaside, phillyrin, pinoresinol, and phylligenin). These compounds inhibited the production of chemokines in TNF-α/IFN-γ-activated human keratinocytes. These results suggest that the F. suspensa might be a useful candidate for treating allergic skin inflammatory disorders.

The Korean herbal medicine, Do In Seung Gi-Tang, attenuates atherosclerosis via AMPK in high-fat diet-induced ApoE(-/-) mice.

BACKGROUND: Do In Seung Gi-Tang (DISGT) is an herbal mixture of traditional Korean medicine that is composed of Rheum undulatum Linne, Prunus Persica (L.) Batsch, Conyza canadensis L., Cinnamomum Cassia Presl, and Glycytthiza uralensis Fischer (8: 6: 4: 4: 4 ratio). We investigated the effect of DISGT on vascular inflammation and lipid accumulation in apolipoprotein E-deficient (ApoE(-/-)) mice. METHODS: ApoE(-/-) mice that were fed a high-fat diet (HFD) were treated with DISGT (300 mg/kg/day) or statin (10 mg/kg/day) for 16 weeks. Serum lipid levels were analyzed. Oil Red O staining was used to evaluate atherosclerotic lesions and lipid accumulation in the aorta and liver, respectively. The expression of adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and E-selectin), fatty acid synthase (FAS), adenosine monophosphate-activated protein kinase (AMPK), and acetyl-coA carboxylase (ACC) in the aorta or liver tissues was measured by western blot analysis. Lipid synthesis and inflammatory responses were assessed by immunohistochemistry and hematoxylin & eosin staining, respectively. RESULTS: Treatment of HFD-fed mice with DISGT significantly lowered body weight, liver weight, and the levels of lipids, including total cholesterol, low-density lipoprotein-cholesterol, and triglycerides. Glucose levels were also lowered. In the aorta, DISGT attenuated atherosclerotic lesions and reduced the expression of ICAM-1, VCAM-1, and E-selectin. Moreover, DISGT decreased lipid accumulation, inflammatory responses, and FAS levels, and it activated AMPK and reduced ACC expression in liver tissues. CONCLUSIONS: The beneficial, anti-lipolytic, and anti-inflammatory effects of DISGT were mediated by the AMPK pathway. As a result, the expression of inflammatory factors was reduced. Our data provide evidence that DISGT may have strong therapeutic potential in treating vascular diseases, such as atherosclerosis.

Forsythia suspensa fruit extracts and the constituent matairesinol confer anti-allergic effects in an allergic dermatitis mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: Forsythia suspensa is used in traditional medicine to treat inflammation. To clarify the anti-inflammatory and anti-allergic effects of F. suspensa fruits, we determined the therapeutic effects of crude extract, fractions, and a constituent from F. suspensa fruits on a murine atopic dermatitis (AD) model. MATERIALS AND METHODS: We investigated the inhibitory effects of F. suspensa extract (FSE), extract fractions, and the constituent matairesinol on histamine release from MC/9 mast cells activated by compound 48/80 and the development of AD-like skin lesions and symptoms in NC/Nga mice exposed to Dermatophagoides farinae (mite) extract. High performance liquid chromatography (HPLC) analysis of FSE and its fractions were evaluated using matairesinol standard. RESULTS: FSE, FSE methylene chloride fraction (FSE-MC), and FSE water fraction (FSE-water) inhibited compound 48/80-induced histamine release from MC/9 mast cells. Topical application of FSE or FSE-MC to NC/Nga mice exposed to Dermatophagoides farinae suppressed the development of AD-like skin lesions. Quantitative HPLC analysis of FSE and FSE-MC identified the presence of matairesinol. Topical application of matairesinol to NC/Nga mice effectively reduced AD symptoms, inhibited inflammatory cell infiltration, and lowered immunoglobulin E levels in serum. Further study demonstrated that DfE-induced changes in IL-4 and IFN-γ mRNA expression in the ears of NC/Nga mice were reversed by matairesinol application. CONCLUSIONS: These results indicate that the F. suspensa and its constituent matairesinol might be a therapeutic candidate for treating allergic inflammatory disorders such as AD.

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.