ABSTRACT
Gypenoside XIII is isolated from Gynostemma pentaphyllum (Thunb.) Makino. In mice, G. pentaphyllum extract and gypenoside LXXV have been shown to improve non-alcoholic steatohepatitis (NASH). This study investigated whether gypenoside XIII can regulate lipid accumulation in fatty liver cells or attenuate NASH in mice. We used HepG2 hepatocytes to establish a fatty liver cell model using 0.5 mM oleic acid. Fatty liver cells were treated with different concentrations of gypenoside XIII to evaluate the molecular mechanisms of lipid metabolism. In addition, a methionine/choline-deficient diet induced NASH in C57BL/6 mice, which were given 10 mg/kg gypenoside XIII by intraperitoneal injection. In fatty liver cells, gypenoside XIII effectively suppressed lipid accumulation and lipid peroxidation. Furthermore, gypenoside XIII significantly increased SIRT1 and AMPK phosphorylation to decrease acetyl-CoA carboxylase phosphorylation, reducing fatty acid synthesis activity. Gypenoside XIII also decreased lipogenesis by suppressing sterol regulatory element-binding protein 1c and fatty acid synthase production. Gypenoside XIII also increased lipolysis and fatty acid ß-oxidation by promoting adipose triglyceride lipase and carnitine palmitoyltransferase 1, respectively. In an animal model of NASH, gypenoside XIII effectively decreased the lipid vacuole size and number and reduced liver fibrosis and inflammation. These findings suggest that gypenoside XIII can regulate lipid metabolism in fatty liver cells and improve liver fibrosis in NASH mice. Therefore, gypenoside XIII has potential as a novel agent for the treatment of NASH.
Subject(s)
Non-alcoholic Fatty Liver Disease , Mice , Animals , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Lipid Metabolism , Gynostemma/chemistry , Gynostemma/metabolism , Mice, Inbred C57BL , Hepatocytes/metabolism , Fatty Acids/metabolism , Fatty Acids/pharmacology , Lipids/pharmacology , Liver Cirrhosis/metabolism , Liver/metabolism , Plant ExtractsABSTRACT
Our previous study found that oral administration of Gynostemma pentaphyllum extract can attenuate airway hyperresponsiveness (AHR) and reduce eosinophil infiltration in the lungs of asthmatic mice. Gypenoside A is isolated from G. pentaphyllum. In this study, we investigated whether gypenoside A can effectively reduce asthma in mice. Asthma was induced in BALB/c mice by ovalbumin injection. Asthmatic mice were treated with gypenoside A via intraperitoneal injection to assess airway inflammation, AHR, and immunomodulatory effects. In vitro, gypenoside A reduced inflammatory and oxidative responses in inflammatory tracheal epithelial cells. Experimental results showed that gypenoside A treatment can suppress eosinophil infiltration in the lungs, reduce tracheal goblet cell hyperplasia, and attenuate AHR. Gypenoside A significantly reduced Th2 cytokine expression and also inhibited the expression of inflammatory genes and proteins in the lung and bronchoalveolar lavage fluid. In addition, gypenoside A also significantly inhibited the secretion of inflammatory cytokines and chemokines and reduced oxidative expression in inflammatory tracheal epithelial cells. The experimental results suggested that gypenoside A is a natural compound that can effectively reduce airway inflammation and AHR in asthma, mainly by reducing Th2 cell activation.
Subject(s)
Asthma , Th2 Cells , Animals , Asthma/drug therapy , Asthma/metabolism , Bronchoalveolar Lavage Fluid , Cytokines/metabolism , Eosinophils/metabolism , Gynostemma , Inflammation/drug therapy , Inflammation/metabolism , Lung/metabolism , Mice , Mice, Inbred BALB C , Ovalbumin/metabolism , Plant Extracts/metabolism , Plant Extracts/pharmacology , Th2 Cells/metabolismABSTRACT
Airway respiratory distress syndrome (ARDS) is usually caused by a severe pulmonary infection. However, there is currently no effective treatment for ARDS. Traditional Chinese medicine (TCM) has been shown to effectively treat inflammatory lung diseases, but a clear mechanism of action of TCM is not available. Perilla fruit water extract (PFWE) has been used to treat cough, excessive mucus production, and some pulmonary diseases. Thus, we propose that PFWE may be able to reduce lung inflammation and neutrophil infiltration in a lipopolysaccharide (LPS)-stimulated murine model. C57BL/6 mice were stimulated with LPS (10 µg/mouse) by intratracheal (IT) injection and treated with three doses of PFWE (2, 5, and 8 g/kg) by intraperitoneal (IP) injections. To investigate possible mechanisms, A549 cells were treated with PFWE and stimulated with LPS. Our results showed that PFWE decreased airway resistance, neutrophil infiltration, vessel permeability, and interleukin (IL)-6 and chemokine (C-C motif) ligand 2 (CCL2/MCP-1) expressions in vivo. In addition, the PFWE inhibited the expression of IL-6, CCL2/MCP-1, chemokine (CXC motif) ligand 1 (CXCL1/GROα), and IL-8 in vitro. Moreover, PFWE also inhibited the MAPK/JNK-AP-1/c-Fos signaling pathway in A549 cells. In conclusion, we demonstrated that PFWE attenuated pro-inflammatory cytokine and chemokine levels and downregulated neutrophil recruitment through the MAPK/JNK-AP-1/c-Fos pathway. Thus, PFWE can be a potential drug to assist the treatment of ARDS.
ABSTRACT
Helminthostachys zeylanica is a traditional folk herb used to improve inflammation and fever in Taiwan. Previous studies showed that H. zeylanica extract could ameliorate lipopolysaccharide-induced acute lung injury in mice. The aim of this study was to investigate whether H. zeylanica water (HZW) and ethyl acetate (HZE) extracts suppressed eosinophil infiltration and airway hyperresponsiveness (AHR) in asthmatic mice, and decreased the inflammatory response and oxidative stress in tracheal epithelial cells. Human tracheal epithelial cells (BEAS-2B cells) were pretreated with various doses of HZW or HZE (1 µg/ml-10 µg/ml), and cell inflammatory responses were induced with IL-4/TNF-α. In addition, female BALB/c mice sensitized with ovalbumin (OVA), to induce asthma, were orally administered with HZW or HZE. The result demonstrated that HZW significantly inhibited the levels of proinflammatory cytokines, chemokines, and reactive oxygen species in activated BEAS-2B cells. HZW also decreased ICAM-1 expression and blocked monocytic cells from adhering to inflammatory BEAS-2B cells in vitro. Surprisingly, HZW was more effective than HZE in suppressing the inflammatory response in BEAS-2B cells. Our results demonstrated that HZW significantly decreased AHR and eosinophil infiltration, and reduced goblet cell hyperplasia in the lungs of asthmatic mice. HZW also inhibited oxidative stress and reduced the levels of Th2 cytokines in bronchoalveolar lavage fluid. Our findings suggest that HZW attenuated the pathological changes and inflammatory response of asthma by suppressing Th2 cytokine production in OVA-sensitized asthmatic mice.
Subject(s)
Asthma/drug therapy , Cytokines/biosynthesis , Eosinophils/drug effects , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Respiratory Hypersensitivity/drug therapy , Th2 Cells/immunology , Tracheophyta , Animals , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Eosinophils/physiology , Female , Mice , Mice, Inbred BALB C , Plant Extracts/therapeutic use , Reactive Oxygen Species/metabolismABSTRACT
Licochalcone A was isolated from Glycyrrhiza uralensis and previously reported to have antitumor and anti-inflammatory effects. Licochalcone A has also been found to inhibit the levels of Th2-associated cytokines in the bronchoalveolar lavage fluid (BALF) of asthmatic mice. However, the molecular mechanism underlying airway inflammation and how licochalcone A regulates oxidative stress in asthmatic mice are elusive. In this study, we investigated whether licochalcone A could attenuate inflammatory and oxidative responses in tracheal epithelial cells, and whether it could ameliorate oxidative stress and airway inflammation in asthmatic mice. Inflammatory human tracheal epithelial (BEAS-2B) cells were treated with licochalcone A to evaluate oxidative responses and inflammatory cytokine levels. In addition, BALB/c mice were sensitized with ovalbumin (OVA) and injected intraperitoneally with licochalcone A (5 or 10 mg/kg). Licochalcone A significantly inhibited reactive oxygen species, eotaxin, and proinflammatory cytokines in BEAS-2B cells. Licochalcone A also decreased intercellular adhesion molecule 1 levels in inflammatory BEAS-2B cells, blocking monocyte cell adherence. We also found that licochalcone A significantly decreased oxidative responses, reduced malondialdehyde levels, and increased glutathione levels in the lungs of OVA-sensitized mice. Furthermore, licochalcone A decreased airway hyper-responsiveness, eosinophil infiltration, and Th2 cytokine production in the BALF. These findings suggest that licochalcone A alleviates oxidative stress, inflammation, and pathological changes by inhibiting Th2-associated cytokines in asthmatic mice and human tracheal epithelial cells. Thus, licochalcone A demonstrated therapeutic potential for improving asthma.
Subject(s)
Asthma/complications , Asthma/drug therapy , Chalcones/therapeutic use , Oxidative Stress , Protective Agents/therapeutic use , Respiratory Hypersensitivity/complications , Respiratory Hypersensitivity/drug therapy , Animals , Antibody Specificity , Asthma/pathology , Bronchoalveolar Lavage Fluid/cytology , Cell Adhesion/drug effects , Chalcones/pharmacology , Chemokines/metabolism , Collagen/metabolism , Cyclooxygenase 2/metabolism , DNA Damage , Disease Models, Animal , Eosinophils/drug effects , Eosinophils/pathology , Female , Glutathione/metabolism , Goblet Cells/drug effects , Goblet Cells/pathology , Humans , Hyperplasia , Inflammation Mediators/metabolism , Lung/metabolism , Lung/pathology , Malondialdehyde/metabolism , Mice, Inbred BALB C , Ovalbumin , Oxidative Stress/drug effects , Protective Agents/pharmacology , Reactive Oxygen Species/metabolism , THP-1 CellsABSTRACT
BACKGROUND: A compound isolated from Sophora flavescens-sophoraflavanone G (SG)-showed anti-tumor and anti-inflammatory properties. We previously demonstrated that SG promoted apoptosis in human leukemia HL-60 cells. In the present study, we investigated the effects of SG on apoptosis in human breast cancer MDA-MB-231 cells, and explored the underlying molecular mechanisms. METHODS: MDA-MB-231 cells were treated with various SG concentrations, and cell viability was evaluated by MTT assay. Apoptotic signal proteins were detected by western blotting, and cell apoptosis was assessed using flow cytometry. RESULTS: Our results demonstrated that SG induced nuclear condensation, DNA fragmentation, reactive oxygen species production, and increased cell apoptosis in MDA-MB-231 cells. SG also suppressed migration and invasion, likely via blockage of the MAPK pathway. In the apoptotic signaling pathway, SG increased cleaved caspase-8, caspase-3, and caspase-9. SG treatment also decreased Bcl-2 and Bcl-xL expression, increased Bax expression, and prompted release of more cytochrome c from mitochondria to the cytoplasm in MDA-MB-231 cells. CONCLUSION: Overall, our findings suggest that SG might increase apoptosis, and decrease migration and invasion, in MDA-MB-231 cells through suppression of a MAPK-related pathway.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Flavanones/pharmacology , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology , Apoptosis/physiology , Autophagy/drug effects , Caspases/metabolism , Cell Line, Tumor , Cell Movement/drug effects , Cell Survival/drug effects , Cytochromes c/metabolism , Female , Humans , MAP Kinase Signaling System/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Reactive Oxygen Species/metabolism , Sophora/chemistry , Triple Negative Breast Neoplasms/metabolismABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Previous studies showed that Helminthostachys zeylanica (L.) Hook. could reduce inflammatory responses in macrophage and brain astrocytes. AIM OF THE STUDY: In the present study, we evaluated whether an ethyl acetate extract (HZE) or a water extract (HZW) of H. zeylanica could reduce inflammatory responses in lung epithelial cells and ameliorate lipopolysaccharide (LPS)-induced acute lung injury in mice. METHODS: Human lung epithelial A549 cells were pre-treated with HZE or HZW (1-10µg/mL), then stimulated with LPS. BALB/c mice received oral HZW for 7 consecutive days, then an intratracheal instillation of LPS to induce lung injury. RESULTS: HZW reduced chemokine and proinflammatory cytokine production in LPS-activated A549 cells. HZW also suppressed ICAM-1 expression and reduced the adherence of acute monocytic leukemia cells to inflammatory A549 cells. HZE had less efficacy than HZW in suppressing inflammatory responses in A549 cells. In vivo, HZW significantly suppressed neutrophil infiltration and reduced the TNF-α and IL-6 levels in bronchoalveolar lavage fluid and serum from LPS-treated mice. HZW also modulated superoxide dismutase activity, glutathione, and myeloperoxidase activity in lung tissues from LPS-treated mice. HZW decreased the phosphorylation of mitogen-activated protein kinase and nuclear factor kappa B, and promoted heme oxygenase-1 expression in inflamed lung tissue from LPS-treated mice. CONCLUSION: Our findings suggested that HZW reduced lung injury in mice by reducing oxidative stress and inflammatory responses. HZW also reduced inflammatory responses in human lung epithelial cells.
Subject(s)
Acute Lung Injury/drug therapy , Acute Lung Injury/metabolism , Drugs, Chinese Herbal/therapeutic use , Lipopolysaccharides/toxicity , MAP Kinase Signaling System/physiology , NF-kappa B/metabolism , A549 Cells , Acute Lung Injury/chemically induced , Animals , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/pharmacology , Female , Humans , MAP Kinase Signaling System/drug effects , Mice , Mice, Inbred BALB C , NF-kappa B/antagonists & inhibitors , Plant Roots , Random Allocation , WaterABSTRACT
[This corrects the article DOI: 10.1155/2015/298635.].
ABSTRACT
Sophoraflavanone G (SG) was isolated from Sophora flavescens. Previously, we have found that SG is able to suppress the inflammatory response in lipopolysaccharide-stimulated RAW 264.7 macrophages. This study aimed to evaluate the effects of SG on apoptosis, and explore its molecular mechanism in human leukemia HL-60 cells. HL-60 cells were treated with various concentrations of SG (3-30 [Formula: see text]M). The viability of the HL-60 cells was assessed using the MTT method, and the nuclear condensation indicative of apoptosis was observed by DAPI fluorescence staining. In addition, apoptotic signal proteins were examined using Western blotting. The results showed that apoptosis, including DNA fragmentation and nuclear condensation, increased significantly in SG-treated HL-60 cells. SG activated caspase-3 and caspase-9, and downregulated Bcl-2 and Bcl-xL. SG also upregulated Bax and released cytochrome c from the mitochondria into the cytoplasm, enabling apoptosis via the mitochondrially-mediated "intrinsic" pathway. Additionally, SG was able to cleave poly (ADP-ribose) polymerase 1 and activate mitogen-activated protein kinase (MAPK) pathways. These results suggest that SG might increase the effect of apoptosis on HL-60 cells through caspase-3 activation, mitochondrial-mediated pathways, and the MAPK pathway.
Subject(s)
Apoptosis/drug effects , Apoptosis/genetics , Flavanones/pharmacology , Leukemia, Promyelocytic, Acute/enzymology , Leukemia, Promyelocytic, Acute/pathology , Mitogen-Activated Protein Kinases/metabolism , Signal Transduction/drug effects , Signal Transduction/genetics , Anti-Inflammatory Agents , Caspase 3/metabolism , Caspase 9/metabolism , Cytochromes c/metabolism , DNA Fragmentation/drug effects , Dose-Response Relationship, Drug , Down-Regulation/drug effects , Flavanones/isolation & purification , HL-60 Cells , Humans , Mitochondria/enzymology , Poly (ADP-Ribose) Polymerase-1/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Sophora/chemistry , Up-Regulation/drug effects , bcl-2-Associated X Protein/metabolism , bcl-X Protein/metabolismABSTRACT
Ginkgolide C, isolated from Ginkgo biloba leaves, is a diterpene lactone derivative [corrected] reported to have multiple biological functions, from decreased platelet aggregation to ameliorating Alzheimer disease. The study aim was to evaluate the antiadipogenic effect of ginkgolide C in 3T3-L1 adipocytes. Ginkgolide C was used to treat differentiated 3T3-L1 cells. Cell supernatant was collected to assay glycerol release, and cells were lysed to measure protein and gene expression related to adipogenesis and lipolysis by western blot and real-time PCR, respectively. Ginkgolide C significantly suppressed lipid accumulation in differentiated adipocytes. It also decreased adipogenesis-related transcription factor expression, including peroxisome proliferator-activated receptor and CCAAT/enhancer-binding protein. Furthermore, ginkgolide C enhanced adipose triglyceride lipase and hormone-sensitive lipase production for lipolysis and increased phosphorylation of AMP-activated protein kinase (AMPK), resulting in decreased activity of acetyl-CoA carboxylase for fatty acid synthesis. In coculture with an AMPK inhibitor (compound C), ginkgolide C also improved activation of sirtuin 1 and phosphorylation of AMPK in differentiated 3T3-L1 cells. The results suggest that ginkgolide C is an effective flavone for increasing lipolysis and inhibiting adipogenesis in adipocytes through the activated AMPK pathway.
ABSTRACT
Danggui Buxue Tang (DBT) is a herbal decoction that has been used in Chinese medicine to enhance qi and blood circulation. Previously, we found that DBT can suppress allergy-related asthma in mice, leading us to hypothesize that DBT might ameliorate allergy disease. In this study, we evaluated whether DBT can attenuate atopic dermatitis (AD) symptoms and have an anti-inflammatory effect on AD-like mice. The dorsal skin of female mice was shaved and sensitized cutaneously (skin smear) with 1-chloro-2,4-dinitrobenzene. Mice were then given various doses of DBT from days 14 to 29 cutaneously. DBT treatment suppressed ear swelling and skin inflammation and decreased mast cell and eosinophil infiltration into skin and ear tissue. DBT also inhibited levels of IgE and Th2-associated cytokine levels in serum. These results demonstrate that cutaneous administration of DBT reduced the development of AD-like skin lesions in mice.
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: The fruits of Vitex rotundifolia L. are widely used to treat inflammation of the airway in Traditional Chinese medicine. Previous studies found that casticin, isolated from Vitex rotundifolia, could induce apoptosis of tumor cells. In this study, we evaluated the anti-inflammatory effects of casticin and its underlying molecular mechanism in lipopolysaccharide (LPS)-stimulated macrophages. MATERIALS AND METHODS: RAW264.7 cells were pretreated with various concentrations of casticin (0.3-10µM), and then treated with LPS to induce inflammation. We assayed the levels of proinflammatory cytokines and prostaglandin E2 (PGE2) using ELISA, and examined the protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and heme oxygenase (HO)-1 by Western blot. We also investigated the anti-inflammatory molecular mechanism by analyzing inflammatory-associated signaling pathways, including the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. RESULTS: We found casticin inhibited the levels of nitric oxide and PGE2, and decreased the production of proinflammatory cytokines such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor α (TNF-α). In addition, iNOS and COX-2 expression levels were suppressed and casticin increased HO-1 and Nrf2 production in a concentration-dependent manner. Furthermore, casticin significantly inhibited NF-κB subunit p65 proteins in the nucleus and decreased Akt and MAPK activation. CONCLUSION: These results suggest that the anti-inflammatory effect of casticin is due to inhibition of proinflammatory cytokines and mediators by blocking the NF-κB, Akt, and MAPK signaling pathways.
Subject(s)
Cyclooxygenase 2/metabolism , Flavonoids/pharmacology , Lipopolysaccharides/pharmacology , MAP Kinase Signaling System/drug effects , Macrophages/drug effects , NF-kappa B/antagonists & inhibitors , Nitric Oxide Synthase Type II/antagonists & inhibitors , Animals , Cell Line , Macrophages/enzymology , Macrophages/metabolism , Mice , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/metabolism , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Matrine has been isolated from Sophora flavescens, and found to show anti-inflammatory effects in macrophages and anti-cachectic effects in hepatomas. The present study investigated whether matrine suppressed eosinophil infiltration and airway hyperresponsiveness (AHR) in mice, and decreased the inflammatory response of tracheal epithelial cells. MATERIALS AND METHODS: BALB/c mice were sensitized and challenged with ovalbumin to induce allergic asthma in mice. These asthmatic mice were given various doses of matrine by intraperitoneal injection. Additionally, activated human tracheal epithelial cells (BEAS-2B cells) were treated with matrine, and evaluated for levels of proinflammatory cytokines and chemokines. RESULTS: We found that matrine significantly decreased AHR, and suppressed goblet cell hyperplasia, eosinophil infiltration, and inflammatory response in the lung tissue of asthmatic mice. Matrine also reduced the levels of Th2 cytokines and chemokines in bronchoalveolar lavage fluid, and suppressed OVA-IgE production in serum. Furthermore, matrine treatment of activated BEAS-2B cells decreased production of proinflammatory cytokines and eotaxins, as well as suppressed ICAM-1 expression and thus adhesion of eosinophils to inflammatory BEAS-2B cells in vitro. CONCLUSIONS: Our findings suggest that matrine can improve allergic asthma in mice, and therefore has potential therapeutic potential in humans.
Subject(s)
Alkaloids/pharmacology , Asthma/drug therapy , Cytokines/metabolism , Eosinophils/drug effects , Quinolizines/pharmacology , Animals , Asthma/immunology , Cell Adhesion , Cell Line , Cytokines/genetics , Eosinophils/physiology , Gene Expression Regulation , Goblet Cells/drug effects , Humans , Hypersensitivity , Lung/cytology , Lung/drug effects , Lung/pathology , Mice , Mice, Inbred BALB C , Ovalbumin , MatrinesABSTRACT
BACKGROUND: Th2 cells are overexpressed in the skin and serum of atopic dermatitis (AD) patients. Previously, we found that dehydroepiandrosterone (DHEA) decreased eosinophil infiltration in asthmatic mice through the suppression of Th2-associated cytokines. Therefore, we hypothesized that DHEA might improve the symptoms of AD syndrome. OBJECTIVE: In this study, we evaluated the symptom improvement and anti-inflammatory response that result from the modulation of immunity by DHEA modulated in AD-like mice. METHODS: Female BALB/c mice were sensitized and challenged with 1-chloro-2,4-dinitrobenzene. On days 14-29 after sensitization, mice were treated with cutaneous (skin smear) or oral administration of DHEA. In addition, human keratinocyte (HaCat) cells were used to evaluate the effect of DHEA on the in vitro production of proinflammatory cytokines and chemokines. RESULTS: Both cutaneous and oral DHEA were able to decrease ear swelling and skin inflammation in AD-like mice. DHEA also attenuated eosinophil and mast cell infiltration into ear and skin tissue. Additionally, Th2-associated cytokines were inhibited in splenocyte culture, and suppressed the levels of IgE and interleukin 4 in serum. Oral and cutaneous administration of DHEA reduced the inflammatory response, as evidenced by AD-like skin lesions, in a similar manner. DHEA significantly reduced inflammatory cytokines and chemokines through the nuclear factor-κB and mitogen-activated protein kinases pathways in tumor necrosis factor-α activated HaCat cells. CONCLUSION: DHEA ameliorates AD-like mouse skin inflammation and reduces eosinophil and mast cell infiltration by reducing the production of Th2-associated cytokines and chemokines.
Subject(s)
Adjuvants, Immunologic/pharmacology , Dehydroepiandrosterone/pharmacology , Dermatitis, Atopic/drug therapy , Dinitrochlorobenzene/pharmacology , Skin/drug effects , Animals , Anti-Inflammatory Agents/pharmacology , Chemokines/metabolism , Cytokines/metabolism , Eosinophils/metabolism , Female , Humans , Inflammation , Keratinocytes/drug effects , Mast Cells/metabolism , Mice , Mice, Inbred BALB C , Phosphorylation , Spleen/cytology , Th2 Cells/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
A previous study found that eosinophil infiltration and Th2 cell recruitment are important causes of chronic lung inflammation in asthma. The plant flavonoid acacetin is known to have an anti-inflammatory effect in vitro. This study aims to investigate the anti-inflammatory effect of orally administered acacetin in ovalbumin- (OVA-) sensitized asthmatic mice and its underlying molecular mechanism. BALB/c mice were sensitized by intraperitoneal OVA injection. OVA-sensitized mice were fed acacetin from days 21 to 27. Acacetin treatment attenuated airway hyperresponsiveness and reduced eosinophil infiltration and goblet cell hyperplasia in lung tissue. Additionally, eotaxin-1- and Th2-associated cytokines were inhibited in bronchoalveolar lavage fluid and suppressed the level of OVA-IgE in serum. Human bronchial epithelial (BEAS-2B) cells were used to examine the effect of acacetin on proinflammatory cytokines, chemokines, and cell adhesion molecule production in vitro. At the molecular level, acacetin significantly reduced IL-6, IL-8, intercellular adhesion molecule-1, and eotaxin-1 in activated BEAS-2B cells. Acacetin also significantly suppressed the ability of eosinophils to adhere to inflammatory BEAS-2B cells. These results suggest that dietary acacetin may improve asthma symptoms in OVA-sensitized mice.
ABSTRACT
BACKGROUND: Danggui Buxue Tang (DBT), an herbal formula containing Angelica sinensis (AS) and Astragalus membranaceus (AM) (AS:AM = 1:5, designated as DBT1 here), has been used in Chinese medicine to enhance qi and blood circulation. In addition, DBT has served as a treatment for atopic dermatitis in dogs in Taiwan. It also may improve fibrosis in a rat model of pulmonary fibrosis. OBJECTIVE: In this study, we evaluated the effect of oral administration of DBT1 in asthma in ovalbumin (OVA)-sensitized mice. METHODS: Female BALB/c mice were sensitized and challenged with OVA and fed with DBT1 or modified formulas of DBT1, designated as DBT2 (AS:AM = 1:1) and DBT3 (AS:AM = 5:1), from days 21 to 27. RESULTS: DBT1 suppressed airway hyperresponsiveness and eosinophil infiltration in bronchoalveolar lavage fluid (BALF) and lung, and Th2-associated cytokines and chemokines were inhibited in BALF. In addition, levels of OVA-immunoglobulin E (IgE) also were suppressed in serum. However, treatment with DBT2 or DBT3 showed no improved effects relative to DBT1 in treating asthmatic symptoms. CONCLUSIONS: These results suggest that orally administered DBT (DBT1) can reduce allergic reactions in OVA-sensitized mice.
Subject(s)
Asthma/drug therapy , Asthma/immunology , Bronchial Hyperreactivity/drug therapy , Bronchial Hyperreactivity/immunology , Drugs, Chinese Herbal/pharmacology , Animals , Asthma/blood , Bronchial Hyperreactivity/blood , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Cytokines/blood , Disease Models, Animal , Female , Immunoglobulin E/blood , Immunohistochemistry , Mice , Mice, Inbred BALB C , Ovalbumin/immunology , Random AllocationABSTRACT
AIM OF THE STUDY: Viscum coloratum Nakai is used in traditional Chinese medicine to treat various diseases, including hemorrhage, hypertension, and inflammatory diseases. A previous study demonstrated a partially purified extract (PPE-SVC) and viscolin from Viscum coloratum Nakai inhibited phosphodiesterase activity. In this study, we evaluated the anti-asthmatic effects of PPE-SVC and viscolin, from Viscum coloratum Nakai, in OVA-sensitized mice. MATERIALS AND METHODS: Female BALB/c mice were sensitized and challenged with ovalbumin (OVA). The mice were randomized into groups and treated with PPE-SVC, viscolin, or rolipram by intraperitoneal injection on 1h before each inhalation of OVA and airway hyperresponsiveness (AHR). RESULTS: PPE-SVC and viscolin suppressed AHR and reduced eosinophil infiltration of the lungs in OVA-sensitized mice. Moreover, PPE-SVC and viscolin inhibited chemokines, including CCL11 and CCL24, and Th2-associated cytokines in bronchoalveolar lavage fluid. However, PPE-SVC and viscolin could not decrease IL-4, IL-5, and IL-13 levels in cultures of OVA-activated spleen cells. CONCLUSION: PPE-SVC and viscolin attenuate airway inflammation and eosinophil infiltration in OVA-sensitized mice.
Subject(s)
Anti-Asthmatic Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Biphenyl Compounds/therapeutic use , Bronchial Hyperreactivity/prevention & control , Eosinophils/metabolism , Plant Extracts/therapeutic use , Propane/analogs & derivatives , Viscum/chemistry , Animals , Anti-Asthmatic Agents/isolation & purification , Anti-Asthmatic Agents/pharmacology , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Biphenyl Compounds/isolation & purification , Biphenyl Compounds/pharmacology , Bronchial Hyperreactivity/immunology , Bronchial Hyperreactivity/metabolism , Bronchoalveolar Lavage Fluid/chemistry , Chemokines/metabolism , Cytokines/metabolism , Female , Inflammation/immunology , Inflammation/metabolism , Inflammation/prevention & control , Lung/drug effects , Lung/immunology , Medicine, Chinese Traditional , Mice , Mice, Inbred BALB C , Ovalbumin , Phytotherapy , Plant Extracts/chemistry , Plant Extracts/pharmacology , Propane/isolation & purification , Propane/pharmacology , Propane/therapeutic use , Random Allocation , Rolipram , Spleen/cytology , Spleen/drug effectsABSTRACT
Our previous report demonstrated that the oral administration of short-term high dose Gynostemma pentaphyllum extract (5 g/kg per day for 7days) decreased allergic reactions in ovalbumin (OVA)-sensitized mice. The aim of this study was to determine whether long-term oral administration of G. pentaphyllum attenuated airway inflammation in OVA-sensitized mice. Mice were sensitized and challenged with normal saline or OVA. OVA-sensitized mice were fed with 1.75 g/kg (low dose, GPL) or 5 g/kg (high dose, GPH) G. pentaphyllum extract, five days a week for 4 weeks. The airway hyperresponsiveness (AHR) and eosinophilia in bronchoalveolar lavage fluid (BALF) were examined. The cytokine levels or antibodies in BALF, serum and spleen cell culture supernatants were also determined. Both high and low dose extracts reduced AHR, serum OVA-IgE, and Th2-associated cytokine levels in spleen cell supernatants and BALF in OVA-sensitized mice. These results show that long-term orally administered G. pentaphyllum extract reduced allergic reactions in OVA-sensitized mice.
Subject(s)
Anti-Inflammatory Agents , Gynostemma/chemistry , Respiratory Hypersensitivity/drug therapy , Th2 Cells/drug effects , Animals , Asthma/drug therapy , Asthma/pathology , Bronchial Hyperreactivity/drug therapy , Bronchial Hyperreactivity/physiopathology , Bronchoalveolar Lavage Fluid/cytology , Cytokines/analysis , Cytokines/biosynthesis , Eosinophils/drug effects , Eosinophils/pathology , Female , Immunoglobulin E/analysis , Immunoglobulin E/metabolism , Immunoglobulin G/analysis , Immunoglobulin G/metabolism , Lung/pathology , Mice , Mice, Inbred BALB C , Ovalbumin/immunology , Plant Extracts/pharmacology , Respiratory Hypersensitivity/pathology , Spleen/cytologyABSTRACT
The increasing incidence of asthma in developing countries emphasizes the importance of identifying more effective treatments that have low cost. Gynostemma pentaphyllum (Thunb.) Makino (Cucurbitaceae), a common herbal tea in China, has been used to treat lung inflammation. Since the Th2 cytokines are the major mediators in the pathogenesis of asthma, Th1-biased immune responses caused by G. pentaphyllum might have the potential to relieve asthmatic symptoms. We hypothesized that oral administration of G. pentaphyllum extracts might suppress Th2 cytokine-induced airway inflammation responses in ovalbumin (OVA)-sensitive mice. BALB/c mice were sensitized with intraperitoneal injection and challenged 3 times with OVA inhalation (IH) (the IH3 model). G. pentaphyllum was orally administered for 7 consecutive days before the end of the OVA challenge. In the IH5 model, 2 more OVA challenges were administered to mimic the encounter with an allergen after drug treatment. G. pentaphyllum extracts significantly attenuated airway hyperresponsiveness (AHR) and inhibited eosinophil infiltration in mice in both models. Serum OVA-specific antibodies were also reduced with the treatment. Decreased Th2-type cytokines and increased IFN-gamma were detected in the cultures of OVA-activated splenocytes from treated mice. Our results suggest that G. pentaphyllum extracts might be beneficial for asthma airway inflammation through the suppression of Th2 activity.
Subject(s)
Asthma/drug therapy , Drugs, Chinese Herbal/therapeutic use , Gynostemma , Phytotherapy , Animals , Antibodies/blood , Asthma/chemically induced , Asthma/metabolism , Bronchoalveolar Lavage Fluid/cytology , Cytokines/metabolism , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Female , Interleukin-5/metabolism , Mice , Mice, Inbred BALB C , Ovalbumin/adverse effects , Ovalbumin/immunology , Spleen/metabolism , Th2 Cells/metabolismABSTRACT
Gynostemma pentaphyllum is a popular herbal tea in China and some Asian countries. The modulatory function of G. pentaphyllum total plant extracts on immune cells was evaluated in this study. The extract was intraperitoneally injected into mice for 5 consecutive days. The production of antibodies from B cells or cytokines from T cells was determined mainly with ELISA. After the treatment, serum IgM and IgG2a were significantly enhanced and showed dose-dependent effect. Moreover, serum IgA and IgG1 were also increased when received the extract at the doses of 0.05 or 0.50 g/kg/day. In addition to the serum levels, the injection of the extract enhanced the production of all antibodies from LPS-activated spleen cells. Furthermore, more cytokines were secreted from Con A-stimulated splenocytes of G. pentaphyllum-treated mice. Our results suggest that the extract of G. pentaphyllum might promote immune responses through the activation of T and B cells.