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1.
J Ethnopharmacol ; 234: 44-56, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30610932

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Chrysanthemum indicum Linne (C. indicum), a healthy food and folk medicine in China for thousands of years, has been reported to exert heat-clearing and detoxifying effects and extensively applied to treat various symptoms such as inflammation diseases, hepatitis and headache. AIM OF THIS STUDY: The purpose of the present study was to investigate the protective effect of the supercritical carbon dioxide fluid extract from flowers and buds of C. indicum (CISCFE) on D-galactose-induced brain and liver damage during aging process and to illuminate the underlying mechanisms. MATERIALS AND METHODS: Mice were orally administrated with CISCFE (100, 150 and 300 mg/kg) after injection with D-galactose. 24 h after the last administration, the blood samples, whole brain and liver tissues were collected for biochemical analysis, histological examination and western blot analysis. The body weight, spleen and thymus indexes, alanine transaminase (ALT), aspartate transaminase (AST), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) in brain and liver, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and necrosis factor-α (TNF-α) were detected. Besides, the expressions of Bax, Bcl-2 and cleaved caspase-3 were determined by western blot assay. RESULTS: The results indicated that CISCFE effectively increased the suppressed body weight, attenuated the decline of thymus and spleen indexes, and reduced the elevated levels of ALT and AST induced by D-gal. Furthermore, CISCFE might notably alleviate D-gal-induced abnormal alterations in structure and function of brain and liver dose-dependently via renewing normal antioxidant enzymes activities (SOD, CAT, GSH-Px), reducing MDA accumulation, decreasing inflammatory cytokines productions (IL-1ß, IL-6, TNF-α), as well as attenuating the increase of Bax/Bcl-2 ratio and cleaved caspase-3 activation in the liver and brain. CONCLUSIONS: Taken together, our present results suggested that CISCFE treatment could effectively mitigate the D-gal-induced hepatic and cerebral injury, and the underlying mechanism might be tightly related to the decreased oxidative stress, inflammation and apoptosis, indicating CISCFE might be an alternative and promising agent for the treatment of aging and age-associated brain and liver diseases.


Assuntos
Chrysanthemum/química , Inflamação/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Envelhecimento/patologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Dióxido de Carbono/química , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Flores , Galactose/toxicidade , Inflamação/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Extratos Vegetais/administração & dosagem , Superóxido Dismutase/metabolismo
2.
Phytomedicine ; 52: 272-283, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30599908

RESUMO

BACKGROUND: Berberine (BBR) is the most abundant and major active constituent of Rhizoma Coptidis (RC), which has been widely used to treat inflammatory diseases in traditional oriental medicine. Despite BBR has been found to exhibit pronounced anti-inflammatory effect, the anti-inflammatory activities of its natural derivatives were sparsely dissected out. PURPOSE: To comparatively investigate the anti-inflammatory potential of BBR, and its natural oxoderivative (oxyberberine, OBB) and reduced derivative (dihydroberberine, DHBB) in vitro and in vivo, and delineate the possible underlying mechanism. METHODS: LC-MS/MS was used to identify the natural derivatives of BBR in RC. The potential anti-inflammatory properties of BBR and its natural derivatives were comparatively evaluated in vitro by lipopolysaccharide (LPS)-induced RAW264.7 macrophages cells, and in vivo via three typical acute inflammation murine models. Some important inflammation-related molecules were analyzed by ELISA, qRT-PCR and Western blotting. RESULTS: LC-MS/MS led to the identification of BBR, OBB and DHBB in RC ethyl acetate extract. The in vitro assay indicated that BBR, OBB and DHBB (1.25, 2.5 and 5 µM) pretreatment significantly decreased the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), prostaglandinE2 (PGE2) and nitricoxide (NO), and inhibited the mRNA expressions of cyclooxygenase-2 (COX-2) and inducible nitricoxide synthase (iNOS) in a dose-dependent manner, with relative efficiency of OBB > BBR > DHBB. Furthermore, OBB, BBR and DHBB remarkably inhibited the phosphorylation of nuclear factor-κB (NF-κB) p65 and inhibitory kappa Bα (IκBα). In vivo, BBR (20 mg/kg) and OBB (5, 10, and 20 mg/kg) pretreatment significantly ameliorated the xylene-induced ear edema, carrageenan-stimulated paw edema, and acetic acid-elicited vascular permeability in mice in a dose-dependent manner, with OBB exhibiting superior anti-inflammatory effect at the same dose (20 mg/kg). Histopathological analysis indicated that OBB and BBR could markedly attenuate the inflammatory deterioration and decrease the cellular infiltration in paw tissues. Additionally, the carrageenan-induced increases in TNF-α, IL-6, IL-1ß, PGE2 and NO productions, and COX-2 and iNOS mRNA expressions were effectually and concentration-dependently suppressed by OBB and BBR pretreatment. CONCLUSION: The anti-inflammatory activity of BBR and its natural derivatives was in the order of OBB > BBR > DHBB. OBB was for the first time found to be endowed with pronounced anti-inflammatory property, which was probably associated with suppressing the activation of NF-κB signaling pathway, and the subsequent gene expressions and productions of pro-inflammatory mediators. The results might contribute to illuminating the pharmacodynamic underpinnings of RC and provide evidence for developing OBB as a safe and promising natural lead compound in inflammation treatment.


Assuntos
Anti-Inflamatórios/farmacologia , Berberina/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Animais , Berberina/análogos & derivados , Carragenina/efeitos adversos , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Feminino , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Inibidor de NF-kappaB alfa/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
3.
Front Pharmacol ; 9: 615, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29962947

RESUMO

Bleomycin (BLM) is a broad spectrum anti-tumor drug and inducing pulmonary fibrosis. As an anti-tumor drug without immunosuppression, it is urgent to find a drug that reduces the side effects of BLM. Scutellarin (SCU), a flavone extracted from Erigeron breviscapus (Vant.) Hand-Mazz, has anti-inflammatory activity and ability to inhibit tumor cell growth, migration, and invasion. However, the combined role of SCU and BLM treatment in tumor is unclear. This study aimed to investigate the possible effect and related mechanisms of BLM combined with SCU in the treatment of tumor through in vivo and in vitro experiments. In vivo experiments showed that BLM combined with SCU in the treatment of mice bearing H22 ascites tumor prolonged the survival time, alleviated BLM-induced pulmonary fibrosis, reduced the production of TNF-α; IL-6, and the levels of MDA and MPO. BLM combined with SCU increased the apoptotic rate of H22 ascites cells and the levels of cleaved-caspases-3 and -8. Furthermore, BLM combined with SCU increased the protein expression of p53 and gene expression of miR-29b, and decreased the expression of TGF-ß1. In vitro experiment results showed that BLM combined with SCU inhibited the viability of H22 cells and MRC-5 cells, promoted H22 cell apoptosis, up-regulated the protein expression of p53 and down-regulated the protein expression of α-SMA and collagen-I in MRC-5 cells. These experimental results suggested that SCU could enhance the anti-tumor effect of BLM and reduce BLM-induced pulmonary fibrosis, indicating SCU as a potential adjuvant for BLM in the future.

4.
Int Immunopharmacol ; 62: 15-22, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29966943

RESUMO

Pogostone (PO), a major component of Pogostemon cablin, displays potent protective effects against lipopolysaccharide-induced acute lung injury (ALI) in mice. This study aimed to investigate the protective effect of PO on TNF-α-induced cell injury in human alveolar epithelial cells in vitro and its underlying mechanism. The cell viability was measured using the MTS method. The cell apoptosis was determined using flow cytometry. The activities of reactive oxygen species (ROS) were detected using a fluorescence microscope. The pro-inflammatory cytokines and antioxidant genes were assessed using reverse transcription-polymerase chain reaction. The protein expression of Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha (IκBα), and nuclear factor-kappa B (NF-κB) p65 was analyzed using the Western blot analysis. PO alleviated cell apoptosis and inhibited ROS production. It alleviated TNF-α-induced cell injury, suppressed the levels of inflammatory cytokines [interleukin (IL)-6, IL-1ß, and IL-8], and enhanced the expression of antioxidant genes (quinine oxidoreductase 1, glutamate cysteine ligase catalytic subunit, heme oxygenase-1). It increased the expression of Keap1 and promoted the activation of Nrf2. However, the phosphorylation of IκBα and the nuclear expression of NF-κB p65 decreased. The anti-inflammatory and antioxidant effects of PO were abrogated following Nrf2 and NF-κB p65 knockdown. The results indicated a protective effect of PO against TNF-α-induced cell injury in A549 cells by modulating the balance between Nrf2 and NF-κB p65 signaling pathways. They verified PO as a promising anti-inflammatory adjuvant drug for treating ALI.

5.
Artigo em Inglês | MEDLINE | ID: mdl-29250126

RESUMO

Excessive alcohol consumption leads to serious liver injury, associating with oxidative stress and inflammatory response. Previous study has demonstrated that polydatin (PD) exerted antioxidant and anti-inflammatory effects and attenuated ethanol-induced liver damage, but the research remained insufficient. Hence, this experiment aimed to evaluate the hepatoprotective effect and potential mechanisms of PD on ethanol-induced hepatotoxicity. Our results showed that PD pretreatment dramatically decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in the serum, suppressed the malonaldehyde (MDA) and triglyceride (TG) content and the production of reactive oxygen species (ROS), and enhanced the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), andalcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH), paralleled by an improvement of histopathology alterations. The protective effect of PD against oxidative stress was probably associated with downregulation of cytochrome P450 2E1 (CYP2E1) and upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its target gene haem oxygenase-1 (HO-1). Moreover, PD inhibited the release of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) via downregulating toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) p65. To conclude, PD pretreatment protects against ethanol-induced liver injury via suppressing oxidative stress and inflammation.

6.
Int Immunopharmacol ; 50: 270-278, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28711783

RESUMO

ß-Patchoulene (ß-PAE), a tricyclic sesquiterpene isolated from the essential oil of the leaves and stems of Pogostemon cablin (Blanco) Benth., has been reported to have potent anti-inflammatory activity. The aim of this study was to evaluate the potential protective effect of ß-PAE on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and to illuminate the underlying mechanisms. ALI was induced by intracheal instillation of LPS into lung, and dexamethasone (DEX) was used as a positive control. Results indicated that pretreatment with ß-PAE significantly decreased the mortality rate of mice and lung W/D weight ratio, ameliorated lung pathological changes as compared to model group. Meanwhile, ß-PAE pretreatment markedly inhibited the increase of TNF-α, IL-6 and IL-1ß secretions in the bronchoalveolar lavage fluid, and prevented LPS-induced elevations of MPO activity and MDA level in the lung. Additionally, ß-PAE pretreatment significantly elevated miR-146a expression and suppressed the LPS-induced activation of NF-κB and expression of its mediated genes (TNF-α, IL-6 and IL-1ß). ß-PAE was also observed to markedly upregulate the Nrf2 and HO-1 expression and activate the antioxidant genes (NQO-1, GCLC and HO-1). Taken together, ß-PAE possessed protective effect against LPS-induced ALI, which might be associated with its differential regulation of NF-κB and Nrf2 activities and up-regulation of expression of miR-146a. The results rendered ß-PAE a promising anti-inflammatory agent worthy of further development into a pharmaceutical drug for the treatment of ALI.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Pulmão/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Sesquiterpenos/uso terapêutico , Animais , Citocinas/metabolismo , Dexametasona/imunologia , Modelos Animais de Doenças , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/imunologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos , MicroRNAs/genética , Fator 2 Relacionado a NF-E2/genética , NF-kappa B/metabolismo , Peroxidase/metabolismo , Pogostemon/imunologia , Transdução de Sinais
7.
Artigo em Inglês | MEDLINE | ID: mdl-28424738

RESUMO

Li-Fei-Xiao-Yan prescription (LFXY) has been clinically used in China to treat inflammatory and infectious diseases including inflammatory lung diseases. The present study was aimed at evaluating the potential therapeutic effects and potential mechanisms of LFXY in a murine model of lipopolysaccharide- (LPS-) induced acute lung injury (ALI). In this study, the mice were orally pretreated with LFXY or dexamethasone (positive drug) before the intratracheal instillation of LPS. Our data indicated that pretreatment with LFXY enhanced the survival rate of ALI mice, reversed pulmonary edema and permeability, improved LPS-induced lung histopathology impairment, suppressed the excessive inflammatory responses via decreasing the expression of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) and chemokine (MIP-2) and inhibiting inflammatory cells migration, and repressed oxidative stress through the inhibition of MPO and MDA contents and the upregulation of antioxidants (SOD and GSH) activities. Mechanistically, treatment with LFXY significantly prevented LPS-induced TLR4 expression and NF-κB (p65) phosphorylation. Overall, the present study suggests that LFXY protected mice from acute lung injury induced by LPS via inhibition of TLR4/NF-κB p65 activation and upregulation of antioxidative enzymes and it may be a potential preventive and therapeutic agent for ALI in the clinical setting.

8.
Int Immunopharmacol ; 46: 146-155, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28284148

RESUMO

Usnic acid (UA) can be found in certain lichen species. Growing evidence suggests that UA possesses antitumoral, antioxidative and anti-inflammatory activities. Bleomycin (BLM) is widely used in the treatment of malignant ascites, however, it unexpectedly causes pulmonary fibrosis (PF). Researches show that excessive inflammatory response and oxidative stress in lung tissue is conspicuous causes of BLM-induced PF. Here we investigated mechanism underlying the effect-enhancing and toxicity-reducing activity of UA on H22-bearing mice treated with BLM. UA combined with BLM was significantly more effective than BLM alone in inhibiting the tumor growth, arresting the cell cycle at G0/G1 phase, and promoting the cleaved caspase-3 and cleaved caspase-8 activities to induce cancer cellular apoptosis. The mechanism may be associated with the transcriptional regulation of p53/p21/Cyclin pathway. Furthermore, UA effectively moderated the histopathological changes, reduced the content of MDA, HYP, TNF-α, IL-1ß, IL-6 and TGF-ß1, and increased the level of SOD when combined with BLM in lung tissues of H22-bearing mice, which was believed to be related to the inhibition on the protein level of p-Smad2/3 and enhancement of Smad7 expression. These findings suggested that UA might be a potential effect-enhancing and toxicity-reducing candidate for BLM in the treatment of malignant ascites.


Assuntos
Antineoplásicos/uso terapêutico , Ascite/tratamento farmacológico , Benzofuranos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Neoplasias Hepáticas/tratamento farmacológico , Fibrose Pulmonar/prevenção & controle , Adjuvantes Farmacêuticos , Animais , Apoptose/efeitos dos fármacos , Ascite/complicações , Bleomicina/efeitos adversos , Bleomicina/uso terapêutico , Carcinoma Hepatocelular/complicações , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Líquens/imunologia , Neoplasias Hepáticas/complicações , Masculino , Camundongos , Camundongos Endogâmicos , Neoplasias Experimentais , Fibrose Pulmonar/etiologia , Proteínas Smad/metabolismo
9.
Int J Mol Sci ; 18(3)2017 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-28245556

RESUMO

Bleomycin (BLM), a family of anti-tumor drugs, was reported to exhibit severe side effects limiting its usage in clinical treatment. Therefore, finding adjuvants that enhance the anti-tumor effect and reduce the detrimental effect of BLM is a prerequisite. Chrysanthemum indicum, an edible flower, possesses abundant bioactivities; the supercritical-carbon dioxide fluid extract from flowers and buds of C. indicum (CISCFE) have strong anti-inflammatory, anti-oxidant, and lung protective effects. However, the role of CISCFE combined with BLM treatment on tumor-bearing mice remains unclear. The present study aimed to investigate the potential synergistic effect and the underlying mechanism of CISCFE combined with BLM in the treatment of hepatoma 22 (H22) tumor-bearing mice. The results suggested that the oral administration of CISCFE combined with BLM could markedly prolong the life span, attenuate the BLM-induced pulmonary fibrosis, suppress the production of pro-inflammatory cytokines (interleukin-6), tumor necrosis factor-α, activities of myeloperoxidase, and malondiadehyde. Moreover, CISCFE combined with BLM promoted the ascites cell apoptosis, the activities of caspases 3 and 8, and up-regulated the protein expression of p53 and down-regulated the transforming growth factor-ß1 by activating the gene expression of miR-29b. Taken together, these results indicated that CISCFE could enhance the anti-cancer activity of BLM and reduce the BLM-induced pulmonary injury in H22 tumor-bearing mice, rendering it as a potential adjuvant drug with chemotherapy after further investigation in the future.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Bleomicina/farmacologia , Chrysanthemum/química , Extratos Vegetais/farmacologia , Animais , Antibióticos Antineoplásicos/efeitos adversos , Apoptose/efeitos dos fármacos , Bleomicina/efeitos adversos , Dióxido de Carbono , Caspase 3/metabolismo , Caspase 8/metabolismo , Linhagem Celular Tumoral , Citocinas/biossíntese , Modelos Animais de Doenças , Sinergismo Farmacológico , Fibrose , Extração Líquido-Líquido/métodos , Pulmão/metabolismo , Pulmão/patologia , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Neoplasias/patologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Carga Tumoral/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Artigo em Inglês | MEDLINE | ID: mdl-27847530

RESUMO

Clerodendranthus spicatus (Thunb.) C.Y.Wu (CS) is commonly used to treat kidney diseases in traditional Chinese medicine for its prominent anti-inflammatory effect and nourishing function to kidneys. In this study, aqueous extract of CS was assessed for its protective effect on UV-induced skin damage of mice. The chemical compositions of CS aqueous extract were determined by HPLC-ESI-MS/MS, in which 10 components were identified. During the experimental period, CS (0.9, 1.8, and 3.6 g/mL) was externally applied to shaved dorsal skins of mice prior to UV irradiation, daily for ten weeks. The results presented that CS (3.6 g/mL) apparently improved photodamaged skin appearance such as erythema, edema, and coarseness. The abnormal epidermal thickening was significantly reduced, and the dermal structures became more complete. The underlying protective mechanisms were associated with improving antioxidant enzymes activities including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), downregulating inflammatory cytokines (IL-1ß, IL-6, TNF-α, COX-2, and PGE2) expressions, recovering collagen density, and reducing matrix metalloproteinases productions. Sun protection factor of CS (3.6 g/mL) was 16.21 ± 0.03. Our findings for the first time demonstrated that CS had therapeutic effect on the photoaged skin. The results indicated that CS is a potential agent for photoprotective cosmetics.

11.
Int Immunopharmacol ; 32: 55-61, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26800098

RESUMO

Pogostone, a major component of Pogostemon cablin, has been demonstrated to possess antibacterial, anti-fungal, immunosuppressive and anti-inflammatory properties. To investigate the potential therapeutic effect of pogostone on lipopolysaccharide (LPS)-induced acute lung injury (ALI), mice were pretreated with pogostone prior to LPS exposure. After LPS challenge, the lungs were excised and the histological changes, wet to dry weight ratios, MPO activity reflecting neutrophil infiltration, and MDA activity reflecting oxidative stress were examined. The inflammatory cytokines in the BALF were determined by ELISA assay. Moreover, the expressions of p65 and phosphorylated p65 subunit of NF-κB, and Nrf2 in the nucleus in lung tissues were measured by Western blot analysis, and meanwhile the dependent genes of NF-κB and Nrf2 were assessed by RT-qPCR. The results showed that pretreatment with pogostone markedly improved survival rate, attenuated the histological alterations in the lung, reduced the MPO and MDA levels, decreased the wet/dry weight ratio of lungs, down-regulated the level of pro-inflammatory mediators including TNF-a, IL-1ß and IL-6. Furthermore, pretreatment with pogostone enhanced the Nrf2 dependent genes including NQO-1, GCLC and HO-1 but suppressed NF-κB regulated genes including TNF-α, IL-1ß and IL-6. The mechanism behind the protective effect was correlated with its regulation on the balance between Keap1-Nrf2 and NF-κB signaling pathways. Therefore, pogostone may be considered as a potential therapeutic agent for preventing and treating ALI.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/patologia , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/genética , Citocinas/imunologia , Proteínas do Citoesqueleto/imunologia , Proteína 1 Associada a ECH Semelhante a Kelch , Lipopolissacarídeos , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Malondialdeído/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/imunologia , NF-kappa B/imunologia , Peroxidase/metabolismo , Transdução de Sinais/efeitos dos fármacos
12.
Nutrients ; 7(10): 8657-69, 2015 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-26506375

RESUMO

Millettiae speciosae Champ. Leguminosae (MSC), is a well-known Chinese herb traditionally used as food material and medicine for enhancing physical strength. Our preliminary study found that the aqueous extract of this herb (MSE) had an anti-fatigue effect. In this paper, we further separated MSE into total polysaccharides (MSP) and supernatant (MSS) by alcohol precipitation, and explored which fraction was active for its anti-fatigue effect. Mice were orally administered with MSP or MSS at the doses of 200, 400, and 800 mg/kg for 20 days and the anti-fatigue effect was assessed by exhaustive swimming exercise (ESE). The biochemical parameters related to fatigue after ESE and the in vitro antioxidant activity of active fraction were determined. Our results showed that MSP, instead of MSS, significantly extended the swimming time to exhaustion (p < 0.05), indicating that MSP is responsible for the anti-fatigue effect of MSE. In addition, MSP treatment increased the levels of glucose (Glu) and muscle glycogen, whereas it decreased the accumulations of blood urea nitrogen (BUN) and lactic acid (Lac). Moreover, ESE increased the levels of creatine phosphokinase (CK), lactic dehydrogenase (LDH), and malondialdehyde (MDA) but reduced superoxide dismutase (SOD) and glutathione (GSH) in plasma. In contrast, MSP inhibited all the above changes relating to fatigue. Furthermore, an in vitro antioxidant test revealed that MSP dose-dependently scavenged ·OH and DPPH free radicals. Taken together, these findings strongly suggested that MSP was able to alleviate physical fatigue by increasing energy resources and decreasing accumulation of detrimental metabolites. The antioxidant activity may crucially contribute to the observed anti-fatigue effect of MSP.


Assuntos
Antioxidantes/uso terapêutico , Fabaceae/química , Fadiga/tratamento farmacológico , Resistência Física/efeitos dos fármacos , Fitoterapia , Polissacarídeos/uso terapêutico , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Fadiga/metabolismo , Masculino , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Natação
13.
Artigo em Inglês | MEDLINE | ID: mdl-25878714

RESUMO

A standardized traditional Chinese medicine preparation named Yejuhua capsule (YJH) has been clinically used in treatments of various acute respiratory system diseases with high efficacy and low toxicity. In this study, we were aiming to evaluate potential effects and to elucidate underlying mechanisms of YJH against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. Moreover, the chemical analysis and chromatographic fingerprint study were performed for quality evaluation and control of this drug. ALI was induced by intratracheal instillation of LPS (5 mg/kg) into the lung in mice and dexamethasone (5 mg/kg, p.o.) was used as a positive control drug. Results demonstrated that pretreatments with YJH (85, 170, and 340 mg/kg, p.o.) effectively abated LPS-induced histopathologic changes, attenuated the vascular permeability enhancement and edema, inhibited inflammatory cells migrations and protein leakages, suppressed the ability of myeloperoxidase, declined proinflammatory cytokines productions, and downregulated activations of nuclear factor-κB (NF-κB) and expressions of toll-like receptor 4 (TLR4). This study demonstrated that YJH exerted potential protective effects against LPS-induced ALI in mice and supported that YJH was a potential therapeutic drug for ALI in clinic. And its mechanisms were at least partially associated with downregulations of TLR4/NF-κB pathways.

14.
Rejuvenation Res ; 18(5): 437-48, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25849065

RESUMO

It is known that solar ultraviolet (UV) radiation to human skin causes photo-aging, including increases in skin thickness and wrinkle formation and reduction in skin elasticity. UV radiation induces damage to skin mainly by superfluous reactive oxygen species and chronic low-grade inflammation, which eventually up-regulate the expression of matrix metalloproteinases (MMPs). In this study, the super-critical carbon dioxide extract from flowers and buds of Chrysanthemum indicum Linnén (CISCFE), which has been reported to possess free radical scavenging and anti-inflammatory properties, was investigated for its photo-protective effect by topical application on the skin of mice. Moreover, CISCFE effectively suppressed the UV-induced increase in skin thickness and wrinkle grading in a dose-dependent manner, which was correlated with the inhibition of loss of collagen fiber content and epidermal thickening. Furthermore, we observed that CISCFE could obviously decrease UV-induced skin inflammation by inhibiting the production of inflammatory cytokines (interleukin-1ß [IL-1ß, IL-6, IL-10, tumor necrosis factor-α), alleviate the abnormal changes of anti-oxidative indicators (superoxide dismutase, catalase, and glutathione peroxidase), and down-regulate the levels of MMP-1 and MMP-3. The results indicated that CISCFE was a novel photo-protective agent from natural resources against UV irradiation.


Assuntos
Dióxido de Carbono/farmacologia , Chrysanthemum/química , Flores/química , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Envelhecimento da Pele/efeitos da radiação , Raios Ultravioleta , Animais , Colágeno/metabolismo , Citocinas/biossíntese , Elasticidade , Epiderme/efeitos dos fármacos , Epiderme/patologia , Epiderme/efeitos da radiação , Feminino , Mediadores da Inflamação/metabolismo , Malondialdeído/metabolismo , Metaloproteinases da Matriz/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Envelhecimento da Pele/efeitos dos fármacos
15.
Phytother Res ; 29(1): 67-72, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25243578

RESUMO

The aim of this study is to evaluate the antibacterial activity and urease inhibitory effects of patchouli alcohol (PA), the bioactive ingredient isolated from Pogostemonis Herba, which has been widely used for the treatment of gastrointestinal disorders. The activities of PA against selected bacteria and fungi were determined by agar dilution method. It was demonstrated that PA exhibited selective antibacterial activity against Helicobacter pylori, without influencing the major normal gastrointestinal bacteria. Noticeably, the antibacterial activity of PA was superior to that of amoxicillin, with minimal inhibition concentration value of 78 µg/mL. On the other hand, PA inhibited ureases from H.pylori and jack bean in concentration-dependent fashion with IC50 values of 2.67 ± 0.79 mM and 2.99 ± 0.41 mM, respectively. Lineweaver-Burk plots indicated that the type of inhibition was non-competitive against H.pylori urease whereas uncompetitive against jack bean urease. Reactivation of PA-inactivated urease assay showed DL-dithiothreitol, the thiol reagent, synergistically inactivated urease with PA instead of enzymatic activity recovery. In conclusion, the selective H.pylori antibacterial activity along with urease inhibitory potential of PA could make it a possible drug candidate for the treatment of H.pylori infection.


Assuntos
Antibacterianos/farmacologia , Helicobacter pylori/efeitos dos fármacos , Lamiaceae/química , Sesquiterpenos/farmacologia , Urease/antagonistas & inibidores , Amoxicilina/farmacologia , Helicobacter pylori/enzimologia , Testes de Sensibilidade Microbiana
16.
Artigo em Inglês | MEDLINE | ID: mdl-25435895

RESUMO

Background. Shaoyao-Gancao Decoction (SGD), a well-known traditional Chinese medicine prescription, has been widely used to treat adenomyosis, dysmenorrhea, abdominal pain, and inflammation in Asia. However, the mechanism underlying the effectiveness of SGD in the treatment of adenomyosis still remains elusive. The present study aimed to investigate the bioactivity of SGD and its underlying molecular mechanisms using cultured human adenomyosis-derived cells. Methods. Human adenomyosis-derived cells were treated with SGD and its major constituents (paeoniflorin and liquiritin) in vitro. Effects of SGD, paeoniflorin, and liquiritin on cell proliferation and apoptosis were examined by MTT assay and flow cytometry analyses. The effects of SGD, paeoniflorin, and liquiritin on the production of PGE2 and PGF2α were assayed using ELISA. ER-α and OTR mRNA expression levels were also evaluated by real-time qRT-PCR. Results. SGD, paeoniflorin, and liquiritin inhibited proliferation and induced apoptosis of human adenomyosis-derived cells in a dose-dependent manner. SGD and paeoniflorin significantly reduced the PGE2 and PGF2α production. Furthermore, they remarkably decreased the mRNA levels of ER-α and OTR. Conclusions. The results of this study provide possible mechanisms for the bioactivity of SGD for treating adenomyosis and contribute to the ethnopharmacological knowledge about this prescription.

17.
Mediators Inflamm ; 2014: 246407, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25214712

RESUMO

The supercritical-carbon dioxide fluid extract of Chrysanthemum indicum Linné. (CFE) has been demonstrated to be effective in suppressing inflammation. The aim of this study is to investigate the preventive action and underlying mechanisms of CFE on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. ALI was induced by intratracheal instillation of LPS into lung, and dexamethasone was used as a positive control. Results revealed that pretreatment with CFE abated LPS-induced lung histopathologic changes, reduced the wet/dry ratio and proinflammatory cytokines productions (TNF-α, IL-1ß, and IL-6), inhibited inflammatory cells migrations and protein leakages, suppressed the levels of MPO and MDA, and upregulated the abilities of antioxidative enzymes (SOD, CAT, and GPx). Furthermore, the pretreatment with CFE downregulated the activations of NF-κB and the expressions of TLR4/MyD88. These results suggested that CFE exerted potential protective effects against LPS-induced ALI in mice and was a potential therapeutic drug for ALI. Its mechanisms were at least partially associated with the modulations of TLR4 signaling pathways.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Dióxido de Carbono/química , Cromatografia com Fluido Supercrítico/métodos , Chrysanthemum/química , Lipopolissacarídeos/toxicidade , Extratos Vegetais/uso terapêutico , Receptor 4 Toll-Like/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Masculino , Camundongos , Extratos Vegetais/química , Transdução de Sinais/efeitos dos fármacos
18.
J Ethnopharmacol ; 157: 212-21, 2014 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-25256685

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Pogostemon cablin (Blanco) Benth is a well-known medicinal herb commonly used in many Asian countries for inflammatory diseases. Pogostone (PO), a natural product isolated from Pogostemon cablin, is known to exert various pharmacological activities. This study aimed to investigate the anti-inflammatory property of PO, to elucidate its mechanism of action, and to evaluate its potential acute toxicity. MATERIALS AND METHODS: The in vitro anti-inflammatory activity of PO was assessed using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The protein and mRNA levels of proinflammatory mediators were measured with ELISA and RT-PCR, respectively. Proteins of the NF-κB and MAPK family were determined by Western blot to investigate the underlying molecular mechanisms. The in vivo anti-inflammatory activity of PO was tested using LPS-induced endotoxic shock in mice. In addition, the median lethal dose (LD50) of PO in mice was tested in an acute toxicity test. RESULTS: In vitro, PO significantly inhibited the protein and mRNA expression of proinflammatory mediators including TNF-α, IL-6, IL-1ß, NO, and PGE2. The action mechanism of the anti-inflammatory activity of PO was partly dependent on inhibition of the activation of NF-κB and the phosphorylation of JNK and p38 MAPK. In vivo, PO was able to significantly reduce the mortality induced by LPS in mice. Furthermore, PO could markedly suppress the production of the proinflammatory mediators in serum, and attenuate liver and lung injury. The action mechanisms of PO during endotoxic shock may be attributed to down-regulation of the mRNA expression of inflammatory mediators in multiple organs via inhibition of the activation of NF-κB and the phosphorylation of p38 MAPK. Moreover, the LD50 of PO in mice was about 163mg/kg with intravenous administration, which was about 8-fold higher than the dose used in the animal experiment. CONCLUSIONS: Our findings regarding the anti-inflammatory effect of PO and the underlying molecular mechanisms help justify the use of Pogostemon cablin in Chinese medicine for the treatment of inflammatory diseases. More importantly, the results also render PO a promising anti-inflammatory agent worthy of further development into a pharmaceutical drug for the treatment of septic shock.


Assuntos
Anti-Inflamatórios/farmacologia , Lamiaceae/química , Óleos Voláteis/farmacologia , Choque Séptico/prevenção & controle , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/toxicidade , Linhagem Celular , Ensaio de Imunoadsorção Enzimática , Mediadores da Inflamação/metabolismo , Dose Letal Mediana , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Masculino , Medicina Tradicional Chinesa , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/toxicidade , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
Artigo em Inglês | MEDLINE | ID: mdl-24991227

RESUMO

This study attempted to explore the effects of white pepper and its major component piperine on puerarin administered to rats. Pharmacokinetic parameters of puerarin in rats were determined by oral administration (400 mg/kg) or intravenous injection (40 mg/kg) of puerarin, pretreated with or without white pepper and piperine given orally. Compared to the control group given oral puerarin only, the combined use of piperine (10 or 20 mg/kg) increased the C max of puerarin by 1.30-fold or 1.64-fold and the AUC0-∞ by 133% or 157%, respectively. In contrast, coadministration of white pepper (125 or 250 mg/kg) decreased oral absorption of puerarin to 83% or 74%, respectively. On the other hand, pretreatment with piperine orally did not alter the intravenous pharmacokinetics of puerarin, while the AUC of puerarin after intravenous administration was increased by pretreatment with white pepper. The results indicate that pretreatment with piperine or pepper exerts different effects on pharmacokinetics of puerarin administrated via intragastric and intravenous routes. Therefore, it is suggested that the combined application of piperine or white pepper with puerarin should be carefully monitored for potential diet-drug interactions.

20.
J Ethnopharmacol ; 151(3): 1124-1132, 2014 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-24389029

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Nephrotic syndrome (NS) is a clinical syndrome with a variety of causes, mainly characterized by heavy proteinuria. Podocyte injury plays a key role in proteinuria, one of the principal means for the control of NS is to prevent podocyte injury. Qi-Dan Fang consists of two of the most extensively applied herbal remedies among Traditional Chinese Medicine (TCM) (Radix Astragali Mongolici and Radix Salviae Miltiorrhizae, with a weight ratio of 5:1) which are specifically used for the treatment of various kidney diseases. In previous studies, we found that Qi-Dan Fang provides improvement to patients with adriamycin-induced nephrotic syndrome by alleviating proteinuria and serum lipid. The aim of this study is to study the efficiency of Qi-Dan Fang on NS model rat with renal dysfunction and podocyte injury, something which has not been carried out yet. MATERIALS AND METHODS: The rats were divided into Normal, Model, Jin Gui Shen Qi Pill (4.12 g/kg), Qi-Dan Fang (3.09, 6.17 and 12.34 g/kg/d) groups, they were each given a single tail intravenous injection of Adriamycin (6.0 mg/kg) except for the Normal group and were orally administered dosages of Qi-Dian Fang and Jin Gui Shen Qi pills once daily for 7 weeks. Following the treatment, the content of cystation C (CysC), blood urea nitrogen (BUN), serum creatinine (Scr) were measured with an autobiochemical analyser. The pathomorphological changes to the glomeruli, the mRNA expressions of nephrin, podocin, CD2AP genes and p53, bax, bcl-2 proteins expressions were also carried out to probe the effects of Qi-Dan Fang. RESULTS: (1) Qi-Dan Fang treatment raised the level of CysC in blood serum while lowering the content of BUN and Scr in the adriamycin-induced nephrotic syndrome rat model; (2) Long-term administration of Qi-Dan Fang was able to ameliorate pathomorphological change of glomeruli and repair the organization structure of Glomerulus; (3) Qi-Dan Fang could increase the mRNA expression of nephrin, podocin and CD2AP genes, down-regulate the expression of p53, bax proteins, while increased bcl-2 protein to protect the podocyte and restore Glomerular selective filtration function. CONCLUSIONS: Results of our present studies reveal that Qi-Dan Fang is able to enhance renal function, inhibit podocyte injury to provide improvements to the Adriamycin-induced nephrotic syndrome.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Antibióticos Antineoplásicos , Proteínas do Citoesqueleto/genética , Modelos Animais de Doenças , Doxorrubicina , Medicamentos de Ervas Chinesas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Rim/ultraestrutura , Masculino , Proteínas de Membrana/genética , Microscopia Eletrônica de Transmissão , Síndrome Nefrótica/induzido quimicamente , Síndrome Nefrótica/metabolismo , Síndrome Nefrótica/patologia , Fitoterapia , Podócitos/efeitos dos fármacos , Podócitos/metabolismo , Podócitos/patologia , Podócitos/ultraestrutura , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo
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