Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.085
Filtrar
1.
Phytomedicine ; 80: 153382, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33113506

RESUMO

BACKGROUND: Although gastroprotective drugs have been used for peptic ulcer disease prevention and treatment, side effects have been observed. Finding a safe and effective treatment strategy is important. PURPOSE: Edible Trichodesma khasianum (T. khasianum) Clarke leaves are considered to protect against peptic ulcers. However, scientific evidence of this effect of T. khasianum Clarke leaves remains limited. STUDY DESIGN/METHODS: In this study, we aimed to evaluate the effect of T. khasianum Clarke leaves on ethanol-induced gastric injury and gut microbiota using RAW 264.7 cells, RGM-1 cells, and BALB/c mice, respectively. RESULT: The rosmarinic acid was identified as the major component of T. khasianum Clarke leaves extracted by 80% ethanol (80EETC). The results showed that 80EETC suppressed inflammatory mediator protein levels in LPS-induced RAW 264.7 cells. Additionally, heat shock protein expression, antiapoptotic ability, and wound healing migration capability were increased by 80EETC pretreatment in RGM-1 cells with the ethanol-induced injury. Remarkably, pretreatment with 80EETC (150 mg/kg b.w.) promoted gastric mucosal healing by decreasing oxidative stress, inflammatory response, proapoptotic protein expression, and gastric mucosa damage in ethanol-induced gastric injury in mice. Crucially, no liver or kidney toxicities were observed by 80EETC oral gavage. Moreover, 80EETC increased gut microbiota diversity and short-chain fatty acid production. CONCLUSION: Our results illustrated the remarkable gastroprotective effect by 80EETC treatment in vitro and in vivo. These findings are the first to demonstrate the powerful protective effect of T. khasianum Clarke leaves against gastric mucosal injury development.


Assuntos
Boraginaceae/química , Cinamatos/farmacologia , Depsídeos/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/metabolismo , Cinamatos/análise , Depsídeos/análise , Etanol/toxicidade , Ácidos Graxos Voláteis/metabolismo , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Úlcera Péptica/prevenção & controle , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Folhas de Planta/química , Substâncias Protetoras/química , Células RAW 264.7
2.
Chem Biol Interact ; 331: 109233, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32991863

RESUMO

Cisplatin (cis-Dichlorodiammine platinum, CP), as the first-line chemotherapy drug of choice for many cancers such as urogenital system tumors and digestive tract tumors, also causes toxicity and side effects to the kidney. Previous studies have shown that Pulsatilla chinensis has significant anti-inflammatory and antioxidant activities, but the mechanism of cisplatin induced acute kidney injury (AKI) in vivo has not been thoroughly studied. The purpose of this study is to investigate the protective effect of pulchinenoside B4 (PB4), a representative and major component with a content of up to 10% in root of P. chinensis, on AKI induced by CP in mice. Our results indicated the significant protective effect of PB4 by evaluating renal function indicators, inflammatory factor levels and renal histopathological changes. In addition, PB4 may mainly act on NF-κB signaling pathway to reduce the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in the kidney after CP exposure, thus exerting anti-inflammatory activity. Furthermore, PB4 regulated MAPK signaling pathway and its downstream apoptotic factors to inhibit the occurrence of apoptosis, such as Bax, Bcl-2, caspase 3 and caspase 9. Notably, the activations of caspase 3 induced by cisplatin were strikingly reduced in PB4-treated mice. Therefore, the above evidence suggested that PB4 is a potential renal protectant with significant anti-inflammatory and anti-apoptotic effects.


Assuntos
Lesão Renal Aguda/patologia , Apoptose/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/veterinária , Animais , Cisplatino/toxicidade , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fosforilação , Substâncias Protetoras/química , Fator de Necrose Tumoral alfa/metabolismo
3.
PLoS One ; 15(9): e0238163, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881885

RESUMO

OBJECTIVE: We evaluated the effects of grape juice (Vitis labrusca L.) on dyslipidemia, resistance to insulin, and left ventricular hypertrophy (LVH) in mice homozygous for the absence of the LDL receptor gene (LDLr -/-) under a hyperlipidemic diet. METHODOLOGY: We divided 30 male mice (3 months old) into three groups (n = 10); the HL group was fed a high-fat diet, the HLU group received a high-fat diet and 2 g/kg/day of grape juice, and the HLS group was fed a high-fat diet and simvastatin (20 mg/kg/day). We assessed the blood pressure profile of the mice. We also determined the levels of C-reactive protein (CRP) and lipid profile, glycemic and insulinemic profiles, and calculated the HOMA-IR. Cardiomyocyte hypertrophy, interstitial collagen deposit, and the expression of CD40 ligand (CD40L) and metalloproteinases 2 and 9 were assessed immunohistologically. RESULTS: After 60 days, the mice treated with grape juice showed similar results as those of the group treated with simvastatin. The use of grape fruit attenuated dyslipidemia and insulin resistance and significantly increased the levels of high cholesterol density lipoproteins (HDLc). The antioxidant potential of phenolic compounds associated with the increase in HDLc levels in the mice of the HLU group prevented the development of LVH and arterial hypertension since it inhibited the inflammatory response induced by the CD40 pathway and its ligand CD40L. Consequently, there was a lower expression of MMP-2 and MMP-9 and lower serum levels of CRP. CONCLUSION: Grape juice has a hypolipidemic and cardiac protective potential, presenting a similar effect as that of simvastatin through a direct antioxidant action of phenolic compounds, or indirectly, via antioxidant action and anti-inflammatory activity of the HDLc. These results suggest that grape juice is a functional food possessing a high potential to prevent cardiovascular diseases.


Assuntos
Dislipidemias/patologia , Sucos de Frutas e Vegetais , Hipertrofia Ventricular Esquerda/prevenção & controle , Vitis/química , Animais , Pressão Sanguínea/efeitos dos fármacos , Proteína C-Reativa/análise , Ligante de CD40/genética , Ligante de CD40/metabolismo , Colágeno/metabolismo , Dieta Hiperlipídica , Dislipidemias/tratamento farmacológico , Sucos de Frutas e Vegetais/análise , Ventrículos do Coração/patologia , Hipertrofia Ventricular Esquerda/patologia , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Substâncias Protetoras/química , Substâncias Protetoras/uso terapêutico , Receptores de LDL/deficiência , Receptores de LDL/genética , Sinvastatina/uso terapêutico , Vitis/metabolismo
4.
J Cancer Res Clin Oncol ; 146(7): 1801-1811, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32435894

RESUMO

PURPOSE: Oral mucositis is a debilitating inflammatory disorder observed in patients undergoing active cancer treatment, particularly cancer of the head and neck region. A key pathway believed to be involved in the pathogenesis of oral mucositis is the formation of reactive oxygen species (ROS). The identification of compounds that can inhibit this pathway may therefore be of benefit in treating this disorder. The kava plant (Piper methysticum) contains various constituents, including flavokawain A (FKA), flavokawain B (FKB), yangonin, methysticin and kavain. These constituents are known to be biologically active and possess anti-oxidative properties. This study therefore focused on examining these constituents for their effect on ROS formation in an in vitro oral mucositis model. METHODS: Cell proliferation was assessed in normal oral keratinocytes (OKF6) treated with and without kava constituents, namely FKA, FKB, yangonin, methysticin and kavain using an MTS in vitro assay. Oxidative stress was assessed by co-treating and pre-treating OKF6 cells with H2O2. The effects were quantified by analysis of ROS production, using a CM-H2DCFDA assay. RESULTS: Pre-treatment of cells for 24 h with 2.5 µg/ml kavain and 5 µg/ml FKA demonstrated a significant protective anti-oxidative effect. Similarly, FKB at a concentration of 2.5 µg/ml, demonstrated a trend of ROS reduction but was observed to be cytotoxic at concentrations greater than 5 µg/ml. Reduction in ROS production by methysticin and yangonin was compromised by their cell cytotoxicity. CONCLUSION: This was the first study to identify the anti-oxidative effects and safety of FKA and kavain with regard to oral keratinocytes, highlighting their potential use in the development of a preventative treatment for oral mucositis.


Assuntos
Kava/química , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Células Cultivadas , Humanos , Peróxido de Hidrogênio/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Substâncias Protetoras/química , Piranos/farmacologia , Pironas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Estomatite/tratamento farmacológico , Estomatite/etiologia
5.
Food Chem ; 327: 127059, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32447138

RESUMO

The aim of this study was to purify and identify antioxidant peptides from watermelon seed protein hydrolysates (WSPHs-I: Mw < 1 kDa) and further evaluate their cytoprotective effects against H2O2-induced oxidative stress in HepG2 cells. After purification by Sephadex G-15 and semi-preparative reversed-phase high performance liquid chromatography (RP-HPLC), five peptides, RDPEER (P1), KELEEK (P2), DAAGRLQE (P3), LDDDGRL (P4), and GFAGDDAPRA (P5) were sequenced by LC-MS/MS and synthesized with solid-phase synthesis method. These peptides showed desirable 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging capacity (IC50: 0.216 ± 0.01-0.435 ± 0.03), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging capacity (IC50: 0.54 ± 0.02-1.23 ± 0.03), and oxygen radical absorbance capacity (ORAC) (82.36 ± 1.2-130.67 ± 2.2 µM TE/mg). Among them, peptide P1 exhibited the strongest antioxidant capacity. Moreover, the results suggested that peptide P1 may protect HepG2 cells from H2O2-induced oxidative damage by significantly inhibiting reactive oxygen species (ROS), [Ca2+]i, malondialdehyde (MDA) levels and increasing antioxidative enzyme activities.


Assuntos
Citrullus/química , Peróxido de Hidrogênio/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/química , Hidrolisados de Proteína/química , Sequência de Aminoácidos , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão , Citrullus/metabolismo , Células Hep G2 , Humanos , Oxirredução , Peptídeos/isolamento & purificação , Peptídeos/farmacologia , Proteínas de Plantas/metabolismo , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sementes/química , Sementes/metabolismo , Relação Estrutura-Atividade , Espectrometria de Massas em Tandem
6.
Food Chem ; 322: 126742, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32305872

RESUMO

Almond hulls, the main by-product of almond production, are considered a valuable source of bioactive phenolic compounds. This study aimed to characterize the phenolic composition, bioavailability of the phenolic-rich extracts from almond hulls (PEAH), and their protective effect on oxidative stressed Caco-2 cells induced by tert-butylhydroperoxide (t-BOOH). The ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) analysis detected 11 phenolic compounds in the PEAH with high total phenolic content and antioxidant activity. Oxidative Caco-2 cell damage was reduced by PEAH, especially at 5 µg/mL, through scavenging reactive oxygen species (ROS), modulating the cellular endogenous antioxidant system and cell redox at a predictable status. Also, in vitro digestion influenced the phenolic compounds' composition and antioxidant power of PEAH. These results suggested that almond hulls, rich in phenolic compounds, can meliorate the oxidative stressed Caco-2 cells and restore its impaired redox balance, and ultimately improve health benefits.


Assuntos
Estresse Oxidativo/efeitos dos fármacos , Fenóis/química , Extratos Vegetais/química , Substâncias Protetoras/farmacologia , Prunus dulcis/química , Antioxidantes/química , Disponibilidade Biológica , Células CACO-2 , Cromatografia Líquida de Alta Pressão , Análise Discriminante , Meia-Vida , Humanos , Análise dos Mínimos Quadrados , Espectrometria de Massas , Oxirredução , Fenóis/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/farmacocinética , Prunus dulcis/metabolismo , Espécies Reativas de Oxigênio/química , terc-Butil Hidroperóxido/toxicidade
7.
J Food Sci ; 85(5): 1586-1595, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32267971

RESUMO

Radix Tetrastigma (RT) is a medicinal plant and functional food in China, distributed in various places in the south of China. Radix Tetrastigma extract (RTE) from different origins were collected and analyzed for their anti-inflammatory effects. Different RTEs showed different abilities to suppress shape deformation, decrease the nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in RAW 264.7 cells. Subsequently, their bioactive components were compared, and results showed RTEs are rich in flavonoid (85.25-436.70 mg RE/g DW), polysaccharides (100.45-349.26 mg glucose/g DW), phenolic (12.92-225.40 mg GAE/g DW) and protein contents (4.429-7.719 mg/g DW). Principal component analysis (PCA) and correlation studies indicated that anti-inflammatory capacity could be more associated with total flavonoid contents. High-performance liquid chromatography (HPLC) and Ultraperformance liquid chromatography-time-of flight mass spectrometry (UPLC-TOF/MS) analysis were conducted, and results showed that rutin, isoquercitrin, kaempferol-3-O-rutinoside and astragalin were main flavonoid compounds, among them astragalin exhibited a prior protective effect, suggesting it might be responsible for RTE's excellent anti-inflammatory capacity.


Assuntos
Anti-Inflamatórios/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Vitaceae/química , Animais , Anti-Inflamatórios/química , Cromatografia Líquida de Alta Pressão , Lipopolissacarídeos/efeitos adversos , Camundongos , Óxido Nítrico/imunologia , Óxido Nítrico Sintase Tipo II/imunologia , Extratos Vegetais/química , Substâncias Protetoras/química , Células RAW 264.7
8.
Nat Commun ; 11(1): 1608, 2020 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-32231209

RESUMO

The emerging resistance of crop pathogens to fungicides poses a challenge to food security and compels discovery of new antifungal compounds. Here, we show that mono-alkyl lipophilic cations (MALCs) inhibit oxidative phosphorylation by affecting NADH oxidation in the plant pathogens Zymoseptoria tritici, Ustilago maydis and Magnaporthe oryzae. One of these MALCs, consisting of a dimethylsulfonium moiety and a long alkyl chain (C18-SMe2+), also induces production of reactive oxygen species at the level of respiratory complex I, thus triggering fungal apoptosis. In addition, C18-SMe2+ activates innate plant defense. This multiple activity effectively protects cereals against Septoria tritici blotch and rice blast disease. C18-SMe2+ has low toxicity in Daphnia magna, and is not mutagenic or phytotoxic. Thus, MALCs hold potential as effective and non-toxic crop fungicides.


Assuntos
Cátions/farmacologia , Produtos Agrícolas/efeitos dos fármacos , Fungicidas Industriais/farmacologia , Doenças das Plantas/prevenção & controle , Substâncias Protetoras/farmacologia , Animais , Ascomicetos/efeitos dos fármacos , Cátions/química , Daphnia/efeitos dos fármacos , Descoberta de Drogas , Grão Comestível/microbiologia , Fibroblastos/efeitos dos fármacos , Fungicidas Industriais/química , Humanos , Mitocôndrias/efeitos dos fármacos , Oryza/microbiologia , Doenças das Plantas/microbiologia , Substâncias Protetoras/química , Triticum/microbiologia , Ustilago/efeitos dos fármacos
9.
Carbohydr Polym ; 235: 115957, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32122493

RESUMO

The present study aimed to investigate the protective effect of cultured Cordyceps sinensis polysaccharides (CSP) on cyclophosphamide (Cy)-induced intestinal mucosal immunosuppression and microbial dysbiosis in mice. Results showed that CSP stimulated cytokines secretion (IL-12, IFN-γ, IL-4, IL-13, IL-6, IL-17, IL-10, TGF-ß3, TNF-α, IL-2, IL-21) and transcription factors production (T-bet, GATA-3, RORγt, Foxp3). TLRs (TLR-2, TLR-4, TLR-6) and NF-κB pathway key proteins (p-IκB-α, NF-κB p65) were also upregulated after CSP administration. Moreover, CSP recovered SCFAs levels which decreased by Cy treatment. Furthermore, 16S rRNA sequencing of fecal samples was performed. α-diversity and ß-diversity analysis revealed CSP improved microbial community diversity and modulated the overall structure of gut microbiota. Taxonomic composition analysis found that CSP increased the abundance of probiotics (Lactobacillus, Bifidobacterium, Bacteroides) and decreased pathogenic bacteria (Clostridium, Flexispira). These findings suggested the potential of CSP as a prebiotics to reduce side effects of Cy on intestinal mucosal immunity and gut microbiota.


Assuntos
Cordyceps/química , Ciclofosfamida/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade nas Mucosas/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Animais , Feminino , Intestinos/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Polissacarídeos/química , Substâncias Protetoras/química , Propriedades de Superfície
10.
Sci Rep ; 10(1): 2056, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029842

RESUMO

The lack of effective pharmacological treatments for acute kidney injury (AKI) remains a significant public health problem. Given the involvement of apoptosis and regulated necrosis in the initiation and progression of AKI, the inhibition of cell death may contribute to AKI prevention/recovery. Curcuminoids are a family of plant polyphenols that exhibit attractive biological properties that make them potentially suitable for AKI treatment. Now, in cultured tubular cells, we demonstrated that a crosslinked self-assembled star-shaped polyglutamate (PGA) conjugate of bisdemethoxycurcumin (St-PGA-CL-BDMC) inhibits apoptosis and necroptosis induced by Tweak/TNFα/IFNγ alone or concomitant to caspase inhibition. St-PGA-CL-BDMC also reduced NF-κB activation and subsequent gene transcription. In vivo, St-PGA-CL-BDMC prevented renal cell loss and preserved renal function in mice with folic acid-induced AKI. Mechanistically, St-PGA-CL-BDMC inhibited AKI-induced apoptosis and expression of ferroptosis markers and also decreased the kidney expression of genes involved in tubular damage and inflammation, while preserving the kidney expression of the protective factor, Klotho. Thus, due to renal accumulation and attractive pharmacological properties, the application of PGA-based therapeutics may improve nephroprotective properties of current AKI treatments.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Diarileptanoides/farmacologia , Túbulos Renais/efeitos dos fármacos , Ácido Poliglutâmico/farmacologia , Substâncias Protetoras/farmacologia , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/imunologia , Lesão Renal Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Linhagem Celular , Diarileptanoides/química , Diarileptanoides/uso terapêutico , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Ácido Fólico/toxicidade , Glucuronidase/metabolismo , Humanos , Túbulos Renais/patologia , Camundongos , Conformação Molecular , NF-kappa B/metabolismo , Necrose/tratamento farmacológico , Necrose/imunologia , Necrose/patologia , Ácido Poliglutâmico/química , Ácido Poliglutâmico/uso terapêutico , Substâncias Protetoras/química , Substâncias Protetoras/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Relação Estrutura-Atividade , Transcrição Genética/efeitos dos fármacos
11.
Mol Med Rep ; 21(3): 1633-1639, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32016475

RESUMO

The present study aimed to clarify the protective effects of p­methoxyphenyl morpholino­phosphinodithioic acid (GYY4137), a water­soluble hydrogen sulfide­releasing molecule, on a rat model of intestinal ischemia­reperfusion (IIR). A total of 40 healthy male Sprague Dawley (SD) rats were randomly divided into four groups (n=10/group): Group A, a sham­surgery group; Group B, the IIR group; group C, rats with IIR that were administered an abdominal injection of low­dose GYY4137 (40 mg/kg); and group D, rats with IIR that were administered high­dose GYY4137 (80 mg/kg). Intestinal histomorphology was observed using hematoxylin and eosin staining, and the concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured. Apoptotic index (AI) was determined by terminal deoxynucleotidyl­transferase­mediated dUTP nick end labeling. Reverse transcription­quantitative PCR analysis was performed to assess the expression levels of intestinal caspase­3, Bax and Bcl­2. Notably, disordered arrangement of intestinal villi and mucosal necrosis were detected in group B, which was substantially improved by GYY4137 treatment (groups C and D). MDA content (nmol/mg) was 2.83±0.36, 9.23±0.78, 4.97±0.45 and 3.51±1.05 nmol/mg in groups A, B, C and D, respectively. In addition, SOD concentration (U/mg) was 135.37±3.34, 76.45±1.39, 95.13±1.64 and 115.13±2.54 in groups A, B, C and D, respectively. Furthermore, AI in group B (21.73±1.17%) was markedly higher than that in group A (4.53±0.28%) and in the GYY4137 intervention groups (9.53±0.96 and 6.53±0.76% in groups C and D, respectively). Compared with in group A, the mRNA expression levels of Bax and caspase­3 were markedly higher in group B (P<0.05), whereas the expression of Bcl­2 was significantly lower (P<0.05). Furthermore, compared with in group B, Bcl­2 expression was higher, and Bax and caspase­3 expression was lower in groups C and D (P<0.05). In conclusion, GYY4137 may alleviate IIR­induced damage in SD rats.


Assuntos
Sulfeto de Hidrogênio/farmacologia , Intestinos/irrigação sanguínea , Intestinos/efeitos dos fármacos , Morfolinas/farmacologia , Compostos Organotiofosforados/farmacologia , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Biomarcadores , Modelos Animais de Doenças , Expressão Gênica , Sulfeto de Hidrogênio/química , Imuno-Histoquímica , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Intestinos/patologia , Masculino , Malondialdeído/metabolismo , Morfolinas/química , Compostos Organotiofosforados/química , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/química , Ratos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Superóxido Dismutase/metabolismo
12.
Biochim Biophys Acta Gen Subj ; 1864(5): 129543, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32007578

RESUMO

BACKGROUND: PYY (1-36) peptides from phylogenetically ancient fish, such as sea lamprey, have previously been shown to function as specific neuropeptide Y1 receptor (NPYR1) agonists. Although, sea lamprey PYY (1-36) is N-terminally stable, we reveal in this study that the peptide is subject to endopeptidase mediated C-terminal dipeptide degradation. In an attempt to prevent this, (d-Arg35)-sea lamprey PYY (1-36) was developed. METHODS: In vitro bioassays assessed enzymatic stability, insulinostatic activity as well as beta-cell anti-apoptotic actions of (d-Arg35)-sea lamprey PYY (1-36). Follow-up studies examined the impact of twice daily administration of sea lamprey PYY (1-36) or (d-Arg35)-sea lamprey PYY (1-36) in multiple low dose STZ-induced diabetic mice. RESULTS: (d-Arg35)-sea lamprey PYY (1-36) was fully resistant to plasma enzymatic degradation. The peptide possessed similar significant insulinostatic, as well as positive anti-apoptotic biological actions, as the parent peptide. Sea lamprey PYY (1-36) and (d-Arg35)-sea lamprey PYY (1-36) delayed diabetes progression in STZ mice. Both treatment interventions induced a significant decrease in body weight, food and fluid intake as well as glucose and glucagon concentrations. In addition, glucose tolerance, plasma and pancreatic insulin were partially normalised. (d-Arg35)-sea lamprey PYY (1-36) was significantly more effective than sea lamprey PYY (1-36) in terms of enhancing glucose-stimulate insulin release. Both treatments improved pancreatic islet morphology, linked to decreased apoptosis of beta-cells. CONCLUSION: We present (d-Arg35)-sea lamprey PYY (1-36) as the first-in-class N- and C-terminally stable PYY (1-36) peptide analogue. GENERAL SIGNIFICANCE: Enzymatically stable, long-acting PYY (1-36) peptides highlight the therapeutic benefits of sustained activation of NPYR1's in diabetes.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Peptídeos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Receptores de Neuropeptídeo Y/agonistas , Animais , Linhagem Celular , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/prevenção & controle , Proteínas de Peixes/química , Proteínas de Peixes/uso terapêutico , Hipoglicemiantes/química , Insulina/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Masculino , Camundongos , Peptídeos/química , Petromyzon , Substâncias Protetoras/química , Receptores de Neuropeptídeo Y/metabolismo
13.
Molecules ; 25(5)2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32106572

RESUMO

Alcoholic liver disease (ALD) threatens human health, so it is imperative that we find ways to prevent or treat it. In recent years, the study of polysaccharides has shown that they have different kinds of bioactivities. Among them are many biological effects that have been attributed to polysaccharide precursors. D-Isofloridoside (DIF) is one of the polysaccharide precursors from the marine red alga Laurencia undulata. This study evaluated the effect of DIF on alcohol-induced oxidative stress in human hepatoma cells (HepG2). As a result, DIF attenuated alcohol-induced cytotoxicity, reduced the amount of intracellular reactive oxygen species (ROS), and effectively reduced alcohol-induced DNA damage in HepG2 cells. In addition, a western blot showed that, after DIF treatment, the expression levels of glutathione (GSH), superoxide dismutase (SOD), and B-cell lymphoma-2 (bcl-2) increased, while the expression levels of γ-glutamyl transferase (GGT), BCL2-associated X (bax), cleaved caspase-3, and mitogen-activated protein kinase (p38 and c-Jun N-terminal kinase ) signal transduction proteins reduced. This showed that DIF may protect cells by reducing the amount of intracellular ROS and inhibiting intracellular oxidative stress and apoptotic processes. Finally, molecular docking demonstrated that DIF can bind to SOD, GGT, B-cell lymphoma-2, and bax proteins. These results indicated that DIF can protect HepG2 cells from alcohol-induced oxidative stress damage, making it an effective potential ingredient in functional foods.


Assuntos
Galactosídeos/farmacologia , Laurencia/química , Hepatopatias Alcoólicas/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/química , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Etanol/toxicidade , Galactosídeos/química , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa/genética , Células Hep G2 , Humanos , Hepatopatias Alcoólicas/patologia , Simulação de Acoplamento Molecular , Polissacarídeos/química , Polissacarídeos/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/química
14.
Molecules ; 25(5)2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32106575

RESUMO

Anaphylactoid shock is a fatal hypersensitivity response caused by non-IgE mediated mast cell activation. These reactions are mediated by a family of G protein-coupled receptors (GPCRs) known as Mas related GPCRX2 (MRGPRX2). Several US FDA approved drugs which are used in day to day life have been reported to cause anaphylactoid shock. Surprisingly, no therapeutic drugs are available which can directly target MRGPRX2 for treatment of anaphylactoid shock. Genistein is a non-steroidal polyphenol known for its diverse physiological and pharmacological activities. In recent studies, Genistein has been reported for its anti-inflammatory activity on mast cells. However, the effects and mechanistic pathways of Genistein on anaphylactoid reaction remain unknown. In the present study, we designed a battery of in-vitro, in-silico and in-vivo experiments to evaluate the anti-anaphylactoid activity of Genistein in order to understand the possible molecular mechanisms of its action. The in-vitro results demonstrated the inhibitory activity of Genistein on MRGPRX2 activation. Further, a mouse model of anaphylactoid shock was used to evaluate the inhibitory activity of Genistein on blood vessel leakage and hind paw edema. Taken together, our findings have demonstrated a therapeutic potential of Genistein as a lead compound in the treatment of anaphylactoid shock via MRGPRX2.


Assuntos
Anafilaxia/tratamento farmacológico , Genisteína/farmacologia , Proteínas do Tecido Nervoso/antagonistas & inibidores , Substâncias Protetoras/farmacologia , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Receptores de Neuropeptídeos/antagonistas & inibidores , Anafilaxia/induzido quimicamente , Anafilaxia/genética , Anafilaxia/patologia , Animais , Degranulação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/genética , Genisteína/química , Humanos , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Mastócitos/patologia , Camundongos , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Substâncias Protetoras/química , Receptores Acoplados a Proteínas-G/genética , Receptores de Neuropeptídeos/genética , p-Metoxi-N-metilfenetilamina/toxicidade
15.
Chem Pharm Bull (Tokyo) ; 68(1): 46-57, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31902901

RESUMO

Over the past decade, a number of new 1,4-naphthoquinones have been isolated from natural sources and new 1,4-naphthoquinones with diverse structural features have been synthesized. Cardioprotective, anti-ischemic, hepatoprotective, neuroprotective and some other new properties were found for these compounds; their role in protecting against neurodegenerative diseases has been established. Their anti-inflammatory, antimicrobial and antitumor activities have been studied in more detail; new, previously unknown intracellular molecular targets and mechanisms of action have been discovered. Some compounds of this class are already being used as a medicinal drugs and some substances can be used as biochemical tools and probes for non-invasive detection of pathological areas in cells and tissues in myocardial infarction and neurodegenerative diseases using modern molecular imaging techniques.


Assuntos
Anti-Infecciosos/química , Anti-Inflamatórios/química , Naftoquinonas/química , Substâncias Protetoras/química , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Bactérias/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Naftoquinonas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Trypanosoma/efeitos dos fármacos
16.
PLoS One ; 15(1): e0227308, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31910239

RESUMO

Seaweed polyphenols and polysaccharide plays a broad range of biological activity. The objective of the present study was to study and compare the skin protection activity of fucoidan rich polysaccharide extract (SPS) and polyphenol-rich extract (SPP) from the seaweed Sargassum vachellianum. The skin protection activity was analyzed based on their ability to scavenge free radicals such as hydrogen peroxide and hydroxyl radicals, UV absorption potential, tyrosinase inhibition, moisture preservation, and antibacterial activity. From the results, both SPP and SPS protects the skin from UV damage. SPP showed good free radical scavenging ability, antimicrobial activity against E.coli and S. aureus and effectively absorbed the UVB and UVA rays whereas SPS hardly absorbs the UVA and UVB rays and showed weak free radical scavenging ability and no antimicrobial activity. SPS showed considerable inhibition on tyrosinase (51.21%) and had better moisture absorption (52.1%) and retention (63.24%) abilities than SPP. The results specified that both SPS and SPP have balancing potential on skin protection and suitable combinations of both could act as an active ingredient in cosmetics.


Assuntos
Polifenóis/farmacologia , Polissacarídeos/farmacologia , Sargassum/química , Alga Marinha/química , Pele/efeitos dos fármacos , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Escherichia coli/efeitos dos fármacos , Depuradores de Radicais Livres/toxicidade , Radicais Livres/toxicidade , Humanos , Peróxido de Hidrogênio/toxicidade , Radical Hidroxila/toxicidade , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Polifenóis/química , Polissacarídeos/química , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Pele/patologia , Pele/efeitos da radiação , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos
17.
Sci Rep ; 10(1): 195, 2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932603

RESUMO

We recently reported that a butanol soluble fraction from the stem of Cassia occidentalis (CSE-Bu) consisting of osteogenic compounds mitigated methylprednisone (MP)-induced osteopenia in rats, albeit failed to afford complete protection thus leaving a substantial scope for further improvement. To this aim, we prepared an oral formulation that was a lipid-based self-nano emulsifying drug delivery system (CSE-BuF). The globule size of CSE-BuF was in the range of 100-180 nm of diluted emulsion and the zeta potential was -28 mV. CSE-BuF enhanced the circulating levels of five osteogenic compounds compared to CSE-Bu. CSE-BuF (50 mg/kg) promoted bone regeneration at the osteotomy site and completely prevented MP-induced loss of bone mass and strength by concomitant osteogenic and anti-resorptive mechanisms. The MP-induced downregulations of miR29a (the positive regulator of the osteoblast transcription factor, Runx2) and miR17 and miR20a (the negative regulators of the osteoclastogenic cytokine RANKL) in bone was prevented by CSE-BuF. In addition, CSE-BuF protected rats from the MP-induced sarcopenia and/or muscle atrophy by downregulating the skeletal muscle atrogenes, adverse changes in body weight and composition. CSE-BuF did not impact the anti-inflammatory effect of MP. Our preclinical study established CSE-BuF as a prophylactic agent against MP-induced osteopenia and muscle atrophy.


Assuntos
Doenças Ósseas Metabólicas/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Glucocorticoides/toxicidade , Atrofia Muscular/tratamento farmacológico , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Senna (Planta)/química , Animais , Doenças Ósseas Metabólicas/induzido quimicamente , Doenças Ósseas Metabólicas/patologia , Butanóis/química , Emulsões , Masculino , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/patologia , Fitoterapia , Extratos Vegetais/química , Caules de Planta/química , Substâncias Protetoras/química , Ratos , Ratos Sprague-Dawley
18.
Food Chem ; 314: 126166, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31972406

RESUMO

The occurrence of the quercetin oxidation metabolite 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone (BZF), whose antioxidant potency is notably higher than the antioxidant potency of quercetin, was investigated in twenty quercetin-rich plant foods. BZF was identified (HPLC-DAD-ESI-MS/MS) only in the dry outer scales of onions and shallots. Aqueous extracts of onions (OAE) and shallots (SAE) were evaluated for their antioxidant and cytoprotective properties. OAE, whose potency did not differ from SAE, protected ROS-exposed Caco2 cells against oxidative (78%) and cellular (90%) damage at a 3 µg/L concentration (corresponding to 0.03 nM of BZF). After chromatographic resolution of OAE, the BZF peak accounted fully and exclusively for its antioxidant effect. The antioxidant effects of OAE and of a pure BZF were described by two perfectly overlapping curves whose concentration-dependence was within the 3 × 10-4 to 102 nM BZF range. Such unprecedented low concentrations place BZF-containing plants on the frontier of the search for novel sources of antioxidants.


Assuntos
Antioxidantes/farmacologia , Benzofuranos/análise , Benzofuranos/farmacologia , Cebolas/química , Quercetina/metabolismo , Antioxidantes/química , Benzofuranos/metabolismo , Células CACO-2 , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Frutas/química , Humanos , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Espectrometria de Massas em Tandem , Verduras/química
19.
Biomed Chromatogr ; 34(4): e4795, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31967660

RESUMO

In this study, we focused on studying the changes in urine metabolites in hyperlipidemic rats using ultra-performance liquid chromatography coupled with quadrupole time-of-fight mass spectrometry (UPLC-Q-TOF/MS) and metabolomics, as well as the effect of Citri Reticulatae Chachiensis Pericarpium (CRCP) on hyperlipidemia. These urine samples were examined by UPLC-Q-TOF/MS to obtain MS data. The MS data were analyzed by principal component analysis and partial least squares-discriminant analysis to identify the differential metabolites. CRCP reduced the body weight and levels of triglycerides, total cholesterol and low-density lipoprotein cholesterol and abnormally decreased high-density lipoprotein cholesterol in hyperlipidemic rats, which were significantly raised by a high-fat diet. Twenty-seven potential biomarkers were identified within the complex sample matrix of urine. Fourteen biomarkers increased in the hyperlipidemia rats compared with normal rats. Meanwhile, 13 biomarkers decreased. CRCP reversed abnormal changes in biomarkers, including 5-l-glutamyl-taurine, 5-aminopentanoic acid, cis-4-octenedioic acid and 2-octenedioic acid. These biomarkers show that hyperlipidemia is related to the metabolic pathways of taurine and hypotaurine metabolism, fatty acid biosynthesis, and arginine and proline metabolism. CRCP mainly prevents hyperlipidemia by intervening in these metabolic pathways.


Assuntos
Citrus/química , Dieta Hiperlipídica , Metaboloma/efeitos dos fármacos , Preparações de Plantas , Substâncias Protetoras , Animais , Biomarcadores/urina , Frutas/química , Masculino , Metabolômica , Preparações de Plantas/química , Preparações de Plantas/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes
20.
Carbohydr Polym ; 230: 115567, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887913

RESUMO

Sulfated oligosaccharide of Gracilaria lemaneiformis (GLSO) was prepared from sulfated polysaccharides which possessed antiallergic activity by degradation with high temperature and pressure combined with vitamin C treatment. The present study demonstrated that GLSO could attenuate food anaphylaxis, and inhibit the production of immunoglobulin E, histamine, and related cytokines in both prevention and therapy ovalbumin-induced mice model. Additionally, the gut microbiota analysis revealed that GLSO markedly rescued OVA-induced changes in the Firmicutes to Bacteroidetes ratio. Following flow cytometry, GLSO was found to suppress the subpopulation of T helper 2 and B cells, and significantly up-regulate regulatory T cells (Tregs) differentiation. Furthermore, GLSO-mediated immunosuppression could be verified by co-culturing Tregs sorted from GLSO-treated mice and CD4+ T cells or mast cells. In a word, GLSO attenuated food anaphylaxis through the regulation of gut microbiota and induction of immunosuppression. GLSO had the potential to be used as a nutrient component against food allergy.


Assuntos
Antialérgicos/farmacologia , Hipersensibilidade Alimentar/tratamento farmacológico , Gracilaria/química , Oligossacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antialérgicos/química , Citocinas/metabolismo , Modelos Animais de Doenças , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/prevenção & controle , Humanos , Imunossupressão , Mastócitos/efeitos dos fármacos , Camundongos , Oligossacarídeos/química , Oligossacarídeos/imunologia , Substâncias Protetoras/química , Sulfatos/química , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...