Potential Phytotherapy of DSS-Induced Colitis: Ameliorating Reactive Oxygen Species-Mediated Necroptosis and Gut Dysbiosis with a New Crataegus pinnatifida Bunge Variety-Daehong.

Developing new plant varieties plays a crucial role in competitiveness in the agricultural and food industries and enhancing food security. Daehong (DH) is a new variety of Crataegus pinnatifida Bunge (CP); however, its physiological functions and potential as a nutraceutical ingredient remain unknown. Here, the efficacy of DH on inflammatory bowel disease (IBD) was investigated using dextran sulfate sodium (DSS)-induced colitis mice, and its relative pharmacological effects were analyzed against CP. DH improved colitis-induced weight loss, colon shortening, and inflammatory responses and reduced intestinal permeability. The reactive oxygen species (ROS)-mediated necroptotic signal that triggers enterocyte cell death in DSS-induced colitis was effectively controlled by DH, attributed to epicatechin. DSS-induced gut dysbiosis was recovered into a healthy gut microbiome environment by DH, increasing beneficial bacteria, like Akkermansia muciniphila, and changing harmful bacteria, including Bacteroides vulgatus and Peptostreptococcaceae. DH shows potential as a dietary or pharmaceutical ingredient to promote gut health and to prevent and treat IBD.

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.

Siraitia grosvenorii Extract Attenuates Airway Inflammation in a Mouse Model of Respiratory Disease Induced by Particulate Matter 10 Plus Diesel Exhaust Particles.

Exposure to particulate matter (PM) causes considerable breathing-related health risks. Siraitia grosvenorii fruit is a traditional remedial plant used in Korea and China to treat respiratory diseases. Our recently published study showed that S. grosvenorii extract (SGE) ameliorated airway inflammation in lipopolysaccharide- and cigarette-smoke-induced chronic obstructive pulmonary disease in mice. Thus, we aimed to assess the inhibitory effects of SGE on airway inflammation in mice exposed to a fine dust mixture of PM10 (PM diameter < 10 mm) and diesel exhaust particles (DEPs) known as PM10D. The mice (BALB/c) were treated with PM10D via intranasal injection three times over a period of 12 days, and SGE 70% ethanolic extract (50 or 100 mg/kg) was orally administered daily for 12 days. SGE attenuated neutrophil accumulation and the number of immune B and T cells from the lung tissue and bronchoalveolar lavage fluid (BALF) of the PM10D-exposed mice. SGE reduced the secretion of cytokines and chemokines, including interleukin (IL)-1α, tumor necrosis factor (TNF)-α, IL-17, C-X-C motif chemokine ligand (CXCL)1, and macrophage inflammatory protein (MIP)-2 in the BALF. Airway inflammation, infiltration of inflammatory cells, and collagen fibrosis in the lung after PM10D exposure were investigated via histopathological analysis, and SGE treatment ameliorated these symptoms. SGE decreased the mRNA expression of mucin 5AC (MUC5AC), CXCL1, TNF-α, MIP-2, and transient receptor potential ion channels in the lung tissues. Furthermore, SGE ameliorated the activation of mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling by PM10D in the lungs. We conclude that SGE attenuated PM10D-induced neutrophilic airway inflammation by inhibiting MAPK/NF-κB activation. These results show that SGE may be a candidate for the treatment of inflammatory respiratory diseases.

Siraitia grosvenorii Residual Extract Inhibits Inflammation in RAW264.7 Macrophages and Attenuates Osteoarthritis Progression in a Rat Model.

Osteoarthritis (OA) is a degenerative joint disease characterised by cartilage degeneration and chondrocyte inflammation. We investigated the anti-inflammatory effects of the Siraitia grosvenorii residual extract (SGRE) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages in vitro and its anti-osteoarthritic effects in a monosodium iodoacetate (MIA)-induced OA rat model. SGRE dose-dependently decreased nitric oxide (NO) production in LPS-induced RAW264.7 cells. Moreover, SGRE reduced the pro-inflammatory mediator (cyclooxygenase-2 (COX2), inducible NO synthase (iNOS), and prostaglandin E2 (PGE2)) and pro-inflammatory cytokine (interleukin-(IL)-1ß, IL-6, and tumour necrosis factor (TNF-α)) levels. SGRE suppressed nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathway activation in RAW264.7 macrophages, thus reducing inflammation. Rats were orally administered SGRE (150 or 200 mg/kg) or the positive control drug JOINS (20 mg/kg) 3 days before MIA injection, and once daily for 21 days thereafter. SGRE elevated the hind paw weight-bearing distribution, thus relieving pain. It also reduced inflammation by inhibiting inflammatory mediator (iNOS, COX-2, 5-LOX, PGE2, and LTB4) and cytokine (IL-1ß, IL-6, and TNF-α) expression, downregulating cartilage-degrading enzymes, such as MMP-1, -2, -9, and -13. SGRE significantly reduced the SOX9 and extracellular matrix component (ACAN and COL2A1) levels. Therefore, SGRE is a potential therapeutic active agent against inflammation and OA.

Potent Xanthine Oxidase Inhibitory Activity of Constituents of Agastache rugosa (Fisch. and C.A.Mey.) Kuntze.

The aerial parts of Agastache rugosa are used as a food material and traditional medicine in Asia. A 50% ethanol extract exhibited potent xanthine oxidase (XO) inhibitory activity (IC50 = 32.4 µg/mL). To investigate the major components responsible for this effect, seven known compounds were identified from A. rugosa; among these, salvianolic acid B (2) was isolated from this plant for the first time. Moreover, acacetin (7) exhibited the most potent inhibitory activity with an IC50 value of 0.58 µM, lower than that of allopurinol (IC50 = 4.2 µM), which is commonly used as a XO inhibitor. Comparative activity screening revealed that the C6-bonded monosaccharides (3) or sugars substituted with acetyl or malonyl groups (4-6) are critical for XO inhibition when converted to aglycone (7). The most potent inhibitor (7) in the A. rugosa extract (ARE) exhibited mixed-type inhibition kinetics and reversible inhibition toward XO. Furthermore, the hydrolysis of ARE almost converted to an inhibitor (7), which displayed the highest efficacy; UPLC-qTof MS revealed an increased content, up to five times more compared with that before treatment. This study will contribute to the enhancement in the industrial value of ARE hydrolysates as a functional ingredient and natural drug toward the management of hyperuricemia and treatment of gout.

Siraitia grosvenorii Extract Attenuates Airway Inflammation in a Murine Model of Chronic Obstructive Pulmonary Disease Induced by Cigarette Smoke and Lipopolysaccharide.

We studied the activities of Siraitia grosvenorii extracts (SGE) on airway inflammation in a mouse model of chronic obstructive pulmonary disease (COPD) stimulated by cigarette smoke extract (CSE) and lipopolysaccharide (LPS), as well as in LPS-treated human bronchial epithelial cell line (BEAS-2B). SGE improved the viability of LPS-incubated BEAS-2B cells and inhibited the expression and production of inflammatory cytokines. SGE also attenuated the mitogen-activated protein kinase (MAPK)-nuclear factor-kappa B (NF-κB) signaling activated by LPS stimulation in BEAS-2B cells. In mice stimulated by CSE and LPS, we observed the infiltration of immune cells into the airway after COPD induction. SGE reduced the number of activated T cells, B cells, and neutrophils in bronchoalveolar fluid (BALF), lung tissue, mesenteric lymph node, and peripheral blood mononuclear cells, as well as inhibited infiltration into organs and mucus production. The secretion of cytokines in BALF and the expression level of pro-inflammatory cytokines, mucin 5AC, Transient receptor potential vanilloid 1, and Transient receptor potential ankyrin 1 in lung tissue were alleviated by SGE. In addition, to investigate the activity of SGE on expectoration, we evaluated phenol red secretions in the trachea of mice. SGE administration showed the effect of improving expectoration through an increase in phenol red secretion. Consequently, SGE attenuates the airway inflammatory response in CSE/LPS-stimulated COPD. These findings indicate that SGE may be a potential herbal candidate for the therapy of COPD.

Duchesnea indica Extract Ameliorates LPS-Induced Septic Shock in Mice.

Objective: Duchesnea indica has been reported for its anti-inflammatory properties. However, its efficacy in sepsis has yet to be reported. In this study, we studied the ability of Duchesnea indica extract (DIE) to rescue mice from septic shock and sepsis. Methods: In vitro studies included the measurement of secreted nitric oxide, cell viability, gene and protein expression via real-time polymerase chain reaction and western blot, and confocal microscopy in RAW 264.7 cells. In vivo studies include a model of septic shock and sepsis in BALB/c mice induced by a lethal and sub-lethal dose of lipopolysaccharide (LPS). Results: DIE suppressed the expression of proinflammatory cytokines induced by LPS and prevented the translocation of NFκB into the nucleus of RAW 264.7 cells. It also prevented reactive oxygen species damage induced by LPS in murine bone marrow-derived macrophages. Models of sepsis and septic shock were established in BALB/c mice and DIE-rescued mice from septic shock. DIE also reversed the increase in tumor necrosis factor-α and nitrite levels in the serum of mice induced with sepsis. DIE also prevented the translocation of NFκB from the cytosol into the nucleus in murine lungs. Histopathological damage induced by sepsis was reversed in the testis, liver, and lungs of mice. Conclusion: In conclusion, DIE is a suitable candidate for development as a therapeutic agent for sepsis.

A Potential Role of Coumestrol in Soybean Leaf Senescence and Its Interaction With Phytohormones.

Coumestrol is a natural organic compound synthesized in soy leaves and functions as a phytoalexin. The coumestrol levels in plants are reported to increase upon insect attack. This study investigates the correlation between coumestrol, senescence, and the effect of phytohormones on the coumestrol levels in soybean leaves. Our analysis involving high-performance liquid chromatography and 2-D gel electrophoresis indicated a significant difference in the biochemical composition of soybean leaves at various young and mature growth stages. Eight chemical compounds were specifically detected in young leaves (V1) only, whereas three different coumestans isotrifoliol, coumestrol, and phaseol were detected only in mature, yellow leaves of the R6 and R7 growth stage. MALDI-TOF-MS analysis was used to identify two proteins 3,9 -dihydroxypterocarpan 6A-monooxygenase (CYP93A1) and isoflavone reductase homolog 2 (IFR2) only in mature leaves, which are key components of the coumestrol biosynthetic pathway. This indicates that senescence in soybean is linked to the accumulation of coumestrol. Following the external application of coumestrol, the detached V1-stage young leaves turned yellow and showed an interesting development of roots at the base of the midrib. Additionally, the application of phytohormones, including SA, methyl jasmonate (MeJA), and ethephon alone and in various combinations induced yellowing within 5 days of the application with a concomitant significant increase in endogenous coumestrol accumulation. This was also accompanied by a significant increase in the expression of genes CYP81E28 (Gm08G089500), CYP81E22 (Gm16G149300), GmIFS1, and GmIFS2. These results indicate that various coumestans, especially coumestrol, accumulate during leaf maturity, or senescence in soybean.

Novel analysis procedure for red ginseng polysaccharides by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry.

BACKGROUND: Red ginseng polysaccharides (RGPs) have been acknowledged for their outstanding immunomodulation and anti-tumor activities. However, their studies are still limited by the complexity of their structural features, the absence of purification and enrichment methods, and the rarity of the analytical instruments that apply to the analysis of such macromolecules. Thus, this study is an attempt to establish a new mass spectrometry (MS)-based analysis procedure for RGPs. METHODS: Saponin pre-excluded powder of RG (RG-SPEP, 10 mg) was treated with 200 µL of distilled water and centrifuged for 5 h at 1000 rpm and 85 °C. Ethanol-based precipitation and centrifugation were applied to obtain RGPs from the heated extracts. Further, endo-carbohydrase treatments were performed to produce specific saccharide fragments. Solid-phase extraction (SPE) processes were implemented to purify and enrich the enzyme-treated RGPs, while matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) MS was employed for the partial structural analysis of the obtained RGPs. RESULTS: Utilizing cellulase, porous graphitized carbon (PGC), hydrophilic interaction chromatography (HILIC), and MALDI-TOF/TOF MS, the neutral and acidic RGPs were qualitatively analyzed. Hexn and Hexn -18 (cellulose analogs) were determined to be novel neutral RGPs. Additionally, the [Unknown + Hexn] species were also determined as new acidic RGPs. Furthermore, HexAn (H) was determined as another form of the acidic RGPs. CONCLUSION: Compared to the previous methods of analysis, these unprecedented applications of HILIC-SPE and MALDI-TOF/TOF MS to analyze RGPs proved to be fairly effective for fractionating and detecting neutral and acidic components. This new procedure exhibits great potential as a specific tool for searching and determining various polysaccharides in many herbal medicines.

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.

Rapid identification of isoprenylated flavonoids constituents with inhibitory activity on bacterial neuraminidase from root barks of paper mulberry (Broussonetia papyrifera).

This study was to assess the possibility of using competitive and slow binding experiments with affinity-based ultrafiltration UPLC-QTof-MS analysis to identify potent bacterial neuraminidase (bNA) inhibitors from the Broussonetia papyrifera roots extract. To isolate unbound compounds from the enzyme-binding complex, the root bark extracts were either incubated in the absence of bNA, in the presence of bNA, or with the time-dependent bNA before the ultrafiltration was performed. Thirteen flavonoids were separated from the target extract, and their inhibitory activities were tested against bNA. The isolated flavonoids exhibited potent inhibition against NA (IC50 = 0.7-54.0 µM). Our kinetic analysis of representative active flavonoids (1, 2, and 6) showed slow and time-dependent reversible inhibition. Additionally, chalcones exhibited noncompetitive inhibition characteristics, whereas flavonols and flavans showed mixed-type behavior. The computational results supported the experimental behaviors of flavonoids 2, 6, 10, and 12, indicating that bounded to the active site, but flavonoids 6 and 10 binds near but not accurately at the active site. Although this is mixed-type inhibition, their binding can be considered competitive.

Effect of Jakyakgamcho-Tang Extracts on H2O2-Induced C2C12 Myoblasts.

Oxidative stress is a major contributor to muscle aging and loss of muscle tissue. Jakyakgamcho-tang (JGT) has been used in traditional Eastern medicine to treat muscle pain. Here, we compared the total phenolic and flavonoid contents in 30% ethanol and water extracts of JGT and tested the preventive effects against oxidative stress (hydrogen peroxide)-induced cell death in murine C2C12 skeletal muscle cells. The total phenolic content and total flavonoid content in 30% ethanol extracts of JGT were higher than those of water extracts of JGT. Ethanol extracts of JGT (JGT-E) had stronger antioxidant activities of 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 2,2'-diphenyl-1-picrylhydrazyl-scavenging activity (DPPH) than water extracts of JGT (JGT-W). JGT-E contained 19-53% (1.8 to 4.9-fold) more active compounds (i.e., albiflorin, liquiritin, pentagalloylglucose, isoliquiritin apioside, isoliquiritin, liquiritigenin, and glycyrrhizin) than JGT-W. The ethanol extracts of JGT inhibited hydrogen peroxide-induced cell death and intracellular reactive oxygen species generation more effectively than the water extract of JGT in a dose-dependent manner. For the first time, these results suggest that ethanol extract of JGT is relatively more efficacious at protecting against oxidative stress-induced muscle cell death.

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.

Ulmus parvifolia Modulates Platelet Functions and Inhibits Thrombus Formation by Regulating Integrin αIIbß3 and cAMP Signaling.

BACKGROUND: The prevalence of cardiovascular diseases (CVDs) is increasing at a high rate, and the available treatment options, sometimes, have complications which necessitates the need to develop safer and efficacious approaches. Ethnomedicinal applications reportedly reduce CVD risk. Ulmus parvifolia Jacq. (Ulmaceae) commonly known as Chinese Elm or Lacebark Elm, is native to China, Japan, and Korea. It exhibits anti-inflammatory, antiviral, and anticancer properties, but its anti-platelet properties have not yet been elucidated. PURPOSE: To investigate the pharmacological anti-platelet and anti-thrombotic effects of U. parvifolia bark extract. STUDY DESIGN AND METHODS: Human and rat washed platelets were prepared; light transmission aggregometry and scanning electron microscopy was performed to assess platelet aggregation and the change in platelet shape, respectively. Intracellular calcium mobilization, ATP release, and thromboxane-B2 production were also measured. Integrin αIIbß3 activation was analyzed in terms of fibrinogen binding, fibronectin adhesion, and clot retraction. The expression of MAPK, Src, and PI3K/Akt pathway proteins was examined. Cyclic nucleotide signaling pathway was evaluated via cAMP elevation and VASP phosphorylation. Anti-thrombotic activity of the extract was evaluated in vivo using an arteriovenous shunt rat model, whereas its effect on hemostasis in mice was assessed via bleeding time assay. RESULTS: U. parvifolia extract significantly inhibited human and rat platelet aggregation in a dose-dependent manner along with inhibition of calcium mobilization, dense granule secretion, and TxB2 production. Integrin αIIbß3 mediated inside-out and outside-in signaling events, as evidenced by the inhibition of fibrinogen binding, fibronectin adhesion, and clot retraction. The extract significantly reduced phosphorylation of Src, MAPK (ERK, JNK, and p38MAPK), and PI3K/Akt pathway proteins. Cyclic-AMP levels were elevated in U. parvifolia-treated platelets, while PKAαßγ and VASPser157 phosphorylation was enhanced. U. parvifolia reduced thrombus weight in rats and moderately increased bleeding time in mice. CONCLUSION: U. parvifolia modulates platelet responses and inhibit thrombus formation by regulating integrin αIIbß3 mediated inside-out and outside-in signaling events and cAMP signaling pathway.

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.

Ulmus parvifolia Jacq. Exhibits Antiobesity Properties and Potentially Induces Browning of White Adipose Tissue.

The bark of Ulmus parvifolia Jacq. (UP) was traditionally used as a diuretic and to treat intestinal inflammation. With modern evidence of the correlation of diuretics, gut inflammation, and obesity, our study has shown the antiobesity effects of the bark of UP. UP treatment reduced lipid production and adipogenic genes in vitro. In vivo studies revealed that UP 100 mg/kg and UP 300 mg/kg treatment significantly reduced mouse weight without reducing food intake, indicating increased energy expenditure. UP significantly reduced the weight of epididymal and subcutaneous adipose tissue and decreased liver weight. Histological analysis revealed improvement in the progression of nonalcoholic fatty liver disease and epididymal white adipose tissue hypertrophy induced by a HFD. Real-Time PCR of epididymal adipose tissue revealed significant increases of uncoupling protein-1 (UCP-1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression after UP 300 mg/kg treatments. Phosphorylation of AMP-activated protein α (AMPKα) was increased, while phosphorylation of Acetyl-CoA Carboxylase (ACC) was reduced. Our findings reveal the ability of UP to reduce the occurrence of obesity through increased browning of white adipose tissue via increased AMPKα, PPARγ, PGC-1α, and UCP-1 expression.

Corrigendum to "Zanthoxylum ailanthoides Suppresses Oleic Acid-Induced Lipid Accumulation through an Activation of LKB1/AMPK Pathway in HepG2 Cells".

[This corrects the article DOI: 10.1155/2018/3140267.].

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.

Biofunctional soyasaponin Bb in peanut (Arachis hypogaea L.) sprouts enhances bone morphogenetic protein-2-dependent osteogenic differentiation via activation of runt-related transcription factor 2 in C2C12 cells.

Improvement of bone formation is necessary for successful treatment of the bone defects associated with osteoporosis. In this study, we sought to elucidate the osteogenic activity of peanut sprouts and their bioactive components. We found that peanut sprout water extract (PSWE) enhanced bone morphogenetic protein-2-mediated osteoblast differentiation in a dose-dependent manner by stimulating expression of runt-related transcription factor 2 (Runx2) via activation of AKT/MAP kinases. We identified a major component of PSWE, soyasaponin Bb, as the bioactive compound responsible for improvement of anabolic activity. Soyasaponin Bb from PSWE enhanced expression of the osteogenic transcription factor Runx2 and alkaline phosphatase. The soyasaponin Bb content depended on sprouting time of peanut, and the anabolic action of PSWE was dependent on soyasaponin Bb content. Thus, PSWE and soyasaponin Bb have the potential to protect against bone disorders, including osteoporosis.