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1.
Biomed Pharmacother ; 124: 109883, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32004938

RESUMO

Intestinal mucositis causes great suffering to cancer patients who undergo chemotherapy and radiotherapy. Owing to the uncertain side effects of anticancer drugs to attenuate patients' intestinal mucositis, many studies focused on traditional Chinese medicine (TCM). Patchouli alcohol (PA) is an active compound extracted from Pogostemon cablin, and has potent gastrointestinal protective effect. However, whether PA has an effect on intestinal mucositis is still unknown. Therefore, we established a rat model of intestinal mucositis via intraperitoneal injection of 5-fluorouracil, and intragastrically administrated PA (10, 20, and 40 mg/kg) to evaluate the effect of PA on intestinal mucositis. The routine observation (body weight, food intake, and diarrhea) in rats was used to detect whether PA had an effect on intestinal mucositis. Levels of inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-10, and MPO), mucosal barrier proteins (zonula occludens -1 (ZO-1), claudin-1, occludin, myosin light chain (MLC), and mucin-2) and intestinal microbiota were determined to elucidate the underlying mechanism of PA action on intestinal mucositis in rats. The results showed that PA could effectively improve body weight, food intake, and diarrhea in intestinal mucositis rats, preliminary confirming PA efficacy. Further experiments revealed that PA not only decreased the levels of TNF-α, IL-1ß, IL-6, and MPO but also increased the level of IL-10 significantly. In addition, the expression of mucosal barrier proteins and microbiota community were also improved after PA treatment in diseased rats. Hence, PA may prevent the development and progression of intestinal mucositis by improving inflammation, protecting mucosal barrier, and regulating intestinal microbiota.

2.
Planta Med ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31975362

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Nevertheless, no first-line therapy exists. Hepatic steatosis is the earliest stage of NAFLD, which is characterized by an accumulation of hepatic lipids. Patchouli oil (PO), which is isolated from the well-known Chinese herb named Pogostemon cablin (Blanco) Benth. (Lamiaceae), inhibits hepatic lipid accumulation effectively. However, its potential ability for the treatment of NAFLD had not been reported before. Thus, the objective of this study was to investigate the effectiveness of PO against hepatic steatosis and its underlying mechanisms. We used a high fat diet (HFD)-induced hepatic steatosis model of rats to estimate the effect of PO against NAFLD. Hematoxylin-eosin and oil red O staining were used to analyze the hepatic histopathological changes. ELISA, RT-qPCR, and Western blotting analysis were applied to evaluate the parameters for hepatic steatosis. Our results showed that PO significantly attenuated the lipid profiles and the serum enzymes, evidenced by quantitative and histopathological analyses. It also markedly down-regulated the expression of sterol regulatory element-binding protein 1 (SREPB-1c) with its downstream factors in de novo lipogenesis. And, likewise, in lipid export by very low-density lipoproteins (VLDL), related molecules were dramatically improved. Furthermore, PO observably normalized the aberrant peroxisome proliferator-activated receptor α (PPAR-α) signal in fatty acids oxidation. In conclusion, PO exerted a preventing effect against HFD-induced steatosis and might be due to decrease de novo lipogenesis, promote export of lipids, as well as owing to improve fatty acids oxidation.

3.
J Ethnopharmacol ; 251: 112554, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31923541

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is tightly associated with inflammation response and oxidative stress. As a folk medicine applied in treatment of diarrhea, Bruguiera gymnorrhiza also possesses anti-inflammatory and anti-oxidative activities, which indicated that B. gymnorrhiza may exert anti-colitis effect. AIM OF THE STUDY: To investigate effect and mechanism of B. gymnorrhiza on experimental UC. MATERIALS AND METHODS: Aqueous extract of B. gymnorrhiza leaves (ABL) was used for investigation in the present study. Murine UC was established through access to 3% dextran sulfate sodium (DSS) for 7 days. Meanwhile, mice accepted treatment with ABL (25, 50, 100 mg/kg) or sulfasalazine (200 mg/kg) once daily. On the last day, disease activity index (DAI) including body weight loss, fecal character and degree of bloody diarrhea was evaluated, colon segments were obtained for length measurement and further analysis and feces were collected for intestinal microbiota analysis. RESULTS: ABL ameliorated DAI scores, colon length shortening and histopathological damage in DSS-induced colitis mice obviously. SOD activity, levels of MDA and GSH altered by colitis were restored remarkably after ABL treatment. ABL inhibited increases in levels of colonic COX-2, iNOS, TNF-α, IL-6, IL-1ß, IL-4, IL-10 and IL-11 in colitis mice. Moreover, ABL prominently suppressed NF-κB p65 and IκB phosphorylation and down-regulated mRNA levels of COX-2, iNOS, TNF-α, IL-6 and IL-1ß elevated by colitis. As shown in microbiota analysis, ABL modulated composition of intestinal microbiota of colitis mice. CONCLUSION: ABL exhibited protective effect against DSS-induced ulcerative colitis through suppressing NF-κB activation and modulating intestinal microbiota.

4.
J Ethnopharmacol ; 250: 112519, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-31883475

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Pogostemon cablin, commonly named "Guang-Huo-Xiang" in China, has long been renowned for its ability to dispel dampness and regulate gastrointestinal functions. Patchouli oil (P.oil), the major active fraction of Pogostemon cablin, has been traditionally used as the principal component of Chinese medicinal formulae to treat exterior syndrome and diarrhea. However, the effects of P.oil in treating 5-fluorouracil (5-FU)-induced intestinal mucositis have not yet been reported. AIM OF THE STUDY: To investigate the protective effects of P.oil against 5-FU-induced intestinal mucositis and the mechanisms underlying these effects. MATERIALS AND METHODS: Sprague-Dawley rats were intraperitoneally injected with 5-FU (30 mg/kg) to establish an intestinal mucositis model. Meanwhile, rats with intestinal mucositis were orally administered with P.oil (25, 50, and 100 mg/kg). Histological analysis, ELISA (for detecting inflammatory cytokines and aquaporins), immunohistochemistry analysis (for examining caspases), qRT-PCR analysis (for assessment tight junctions), and western blotting analysis (for the assessment of TLR2/TLR4-MyD88 and VIP-cAMP-PKA signaling pathway-related proteins) were performed to estimate the protective effects of P.oil against intestinal mucositis and the mechanisms underlying these effects. RESULTS: The histopathological assessment preliminarily exhibited that P.oil alleviated the 5-FU-induced damage to the intestinal structure. After P.oil administration, the elevation of the expression of cytokines (TNF-α, IFN-γ, and IL-13) decreased markedly and the activation of NF-κB and MAPK signaling was significantly inhibited. P.oil also increased the mRNA expression of ZO-1 and Occludin, thereby stabilizing intestinal barrier. In addition, P.oil decreased the expressions of caspase-8, caspase-3, and Bax, and increased the expression of Bcl-2, thereby reducing the apoptosis of the intestinal mucosa. These results were closely related to the regulation of the TLR2/TLR4-MyD88 signaling pathway. It has been indicated that P.oil possibly protected the intestinal barrier by reducing inflammation and apoptosis. Furthermore, this study showed that P.oil inhibited the abnormal expression of AQP3, AQP7, and AQP11 by regulating the VIP-cAMP-PKA signaling pathway. Furthermore, it restored the intestinal water absorption, thereby alleviating diarrhea. CONCLUSIONS: P.oil ameliorated 5-FU-induced intestinal mucositis in rats via protecting intestinal barrier and regulating water transport.

5.
Sci Adv ; 5(11): eaax9989, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31763457

RESUMO

Heterostructures having both magnetism and topology are promising materials for the realization of exotic topological quantum states while challenging in synthesis and engineering. Here, we report natural magnetic van der Waals heterostructures of (MnBi2Te4) m (Bi2Te3) n that exhibit controllable magnetic properties while maintaining their topological surface states. The interlayer antiferromagnetic exchange coupling is gradually weakened as the separation of magnetic layers increases, and an anomalous Hall effect that is well coupled with magnetization and shows ferromagnetic hysteresis was observed below 5 K. The obtained homogeneous heterostructure with atomically sharp interface and intrinsic magnetic properties will be an ideal platform for studying the quantum anomalous Hall effect, axion insulator states, and the topological magnetoelectric effect.

6.
Front Pharmacol ; 10: 1134, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632274

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic hepatic disorder worldwide. The earliest stage of NAFLD is simple steatosis, which is characterized by the accumulation of triglycerides in hepatocytes. Inhibition of steatosis is a potential treatment for NAFLD. Patchouli alcohol (PA) is an active component of Pogostemon cablin (Blanco) Benth. (Labiatae), which is a medicinal food in Asia countries and proved to possess hepatoprotective effect. This research aimed to investigate the effectiveness of PA against high fat diet (HFD)-induced hepatic steatosis in rats. In this study, male Sprague Dawley rats were fed a HFD for 4 weeks to induce NAFLD. Oral administration with PA significantly reduced pathological severity of steatosis in HFD-fed rats. It was associated with suppressing endoplasmic reticulum (ER) stress and regulating very low-density lipoprotein (VLDL) metabolism. Our data showed that PA treatment effectively attenuated ER stress by inhibiting the activation of protein kinase-like ER kinase (PERK), inositol-requiring transmembrane kinase/endoribonuclease 1 (IRE1), and activating transcription factor 6 (ATF6). Moreover, PA decreased hepatic VLDL uptake by suppressing very low-density lipoprotein receptor (VLDLR) expression. It also restored VLDL synthesis and export by increasing apolipoprotein B100 (apoB 100) secretion and microsomal triglyceride-transfer protein (MTP) activity. Taken together, PA exerted a protective effect on the treatment of NAFLD in HFD-fed rats and may be potential therapeutic agent acting on hepatic steatosis.

7.
Chem Sci ; 10(22): 5712-5718, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31293756

RESUMO

Ruthenium (Ru) loaded catalysts are of significant interest for ammonia synthesis under mild reaction conditions. The B5 sites have been reported as the active sites for ammonia formation, i.e., Ru with other coordinations were inactive, which has limited the utilization efficiency of Ru metal. The implantation of Ru into intermetallic compounds is considered to be a promising approach to tune the catalytic activity and utilization efficiency of Ru. Here we report an acid-durable electride, LnRuSi (Ln = La, Ce, Pr and Nd), as a B5-site-free Ru catalyst. The active Ru plane with a negative charge is selectively exposed by chemical etching using disodium dihydrogen ethylenediaminetetraacetate (EDTA-2Na) acid, which leads to 2-4-fold enhancement in the ammonia formation rate compared with that of the original catalyst. The turnover frequency (TOF) of LnRuSi is estimated to be approximately 0.06 s-1, which is 600 times higher than that of pure Ru powder. Density functional theory (DFT) calculations revealed that the dissociation of N2 occurs easily on the exposed Ru plane of LaRuSi. This systematic study provides firm evidence that layered Ru with a negative charge in LnRuSi is a new type of active site that differs significantly from B5 sites.

8.
Transl Neurodegener ; 8: 18, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223479

RESUMO

Background: Progressive accumulation of α-synuclein is a key step in the pathological development of Parkinson's disease. Impaired protein degradation and increased levels of α-synuclein may trigger a pathological aggregation in vitro and in vivo. The chaperone-mediated autophagy (CMA) pathway is involved in the intracellular degradation processes of α-synuclein. Dysfunction of the CMA pathway impairs α-synuclein degradation and causes cytotoxicity. Results: In the present study, we investigated the effects on the CMA pathway and α-synuclein aggregation using bioactive ingredients (Dihydromyricetin (DHM) and Salvianolic acid B (Sal B)) extracted from natural medicinal plants. In both cell-free and cellular models of α-synuclein aggregation, after administration of DHM and Sal B, we observed significant inhibition of α-synuclein accumulation and aggregation. Cells were co-transfected with a C-terminal modified α-synuclein (SynT) and synphilin-1, and then treated with DHM (10 µM) and Sal B (50 µM) 16 hours after transfection; levels of α-synuclein aggregation decreased significantly (68% for DHM and 75% for Sal B). Concomitantly, we detected increased levels of LAMP-1 (a marker of lysosomal homeostasis) and LAMP-2A (a key marker of CMA). Immunofluorescence analyses showed increased colocalization between LAMP-1 and LAMP-2A with α-synuclein inclusions after treatment with DHM and Sal B. We also found increased levels of LAMP-1 and LAMP-2A both in vitro and in vivo, along with decreased levels of α-synuclein. Moreover, DHM and Sal B treatments exhibited anti-inflammatory activities, preventing astroglia- and microglia-mediated neuroinflammation in BAC-α-syn-GFP transgenic mice. Conclusions: Our data indicate that DHM and Sal B are effective in modulating α-synuclein accumulation and aggregate formation and augmenting activation of CMA, holding potential for the treatment of Parkinson's disease.

9.
Nat Commun ; 10(1): 2284, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31123253

RESUMO

Mn+1AXn phases are a large family of compounds that have been limited, so far, to carbides and nitrides. Here we report the prediction of a compound, Ti2InB2, a stable boron-based ternary phase in the Ti-In-B system, using a computational structure search strategy. This predicted Ti2InB2 compound is successfully synthesized using a solid-state reaction route and its space group is confirmed as P[Formula: see text]m2 (No. 187), which is in fact a hexagonal subgroup of P63/mmc (No. 194), the symmetry group of conventional Mn+1AXn phases. Moreover, a strategy for the synthesis of MXenes from Mn+1AXn phases is applied, and a layered boride, TiB, is obtained by the removal of the indium layer through dealloying of the parent Ti2InB2 at high temperature under a high vacuum. We theoretically demonstrate that the TiB single layer exhibits superior potential as an anode material for Li/Na ion batteries than conventional carbide MXenes such as Ti3C2.

10.
Inorg Chem ; 58(4): 2848-2855, 2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30729788

RESUMO

We describe the synthesis of the new ternary compound CaRuSi whose chemical and physical properties help draw a clear picture of how electronic structure controls the behavior of an isostructural series of intermetallics. DFT calculations reveal that an electronic pseudogap arises near the Fermi level ( EF), corresponding to 14 valence electrons per RuSi unit. The closed-shell-like character is further investigated by comparisons with the electronic structures of CaCoSi (15 electrons), where the EF lies above the corresponding pseudogap, and its hydride CaCoSiH, where formation of H anions restores the 14-electron count on the metal sublattice, returning the EF to the pseudogap. The chemical origin of the 14-electron pseudogap is interpreted with a reversed approximation Molecular Orbital analysis. Here, the pseudogap is shown to coincide with the filling of Ru 16 electron configurations isolobal to the d8 square planar complexes of coordination chemistry (but where 4 electron pairs are shared covalently between Ru atoms such that only 12 electrons are required), and the occupation of Si lone pairs (2 electrons). Experimentally, the pseudogap is confirmed with heat capacity measurements, which indicate that the 14-electron systems CaRuSi and CaCoSiH each exhibit  a smaller electronic density of states at the EF than the 15-electron system CaCoSi. Importantly, the 14-electron pseudogap also significantly affects the chemical properties of the compounds, as evidenced by the difference in the stabilities of CaCoSiH and CaRuSiH observed in hydrogen desorption measurements. These results may support the design of functional materials for superconductivity, hydrogen storage, and catalysis involving hydrogenation.

11.
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
12.
Angew Chem Int Ed Engl ; 58(3): 825-829, 2019 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-30466170

RESUMO

Electrides loaded with transition-metal (TM) nanoparticles have recently attracted attention as emerging materials for catalytic NH3 synthesis. However, they suffer from disadvantages associated with the growth and aggregation of nanoparticles. TM-containing intermetallic electrides appear to be promising catalysts with the advantages of both electrides and transition metals in a single phase. LaRuSi is reported here to be an intermetallic electride with superior activity for NH3 synthesis, and direct evidence is provided supporting its electride-character-induced catalytic performance. The discussion is made mainly based on the contrasting synthesis rates over the isostructural compounds LaRuSi, CaRuSi, and LaRu2 Si2 , and the N2 isotope-exchange reactions over these compounds. Lattice hydride ions, which can reversibly exchange with anionic electrons, are shown to be indispensable in the promotion of NHx formation. The mechanism derived from the present findings provides new guidelines for NH3 synthesis.

13.
Food Funct ; 9(11): 5891-5902, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30375606

RESUMO

Acetaminophen (APAP) is commonly used to relieve pain and fever in a clinical setting, but its excessive use can lead to serious hepatotoxicity. Our previous study demonstrated that polydatin (PD) can effectively attenuate d-galactose- and alcohol-induced hepatotoxicity, however, its effect on APAP-induced hepatotoxicity is still unknown. In this study, we explore the protective effect and potential mechanism of PD against APAP-induced hepatotoxicity in mice. The results indicate that PD effectively improves the survival of mice with APAP-induced hepatotoxicity, significantly alleviating histopathologic alterations in the liver, and decreasing the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). PD significantly and dose-dependently reduces oxidative stress by lowering the content of oxidized glutathione (GSSG), reactive oxygen species (ROS), nitric oxide (NO) and malonaldehyde (MDA), while enhancing the hepatic activities of glutathione (GSH), glutathione peroxidase (GSH-Px) and the GSH/GSSG ratio. Meanwhile, PD also substantially inhibits the levels and mRNA expressions of inducible nitric oxide synthase (iNOS) and NADPH oxidase 2 (NOX2). Additionally, PD markedly arrests apoptosis by assuaging TUNEL-positive hepatocytes and the apoptotic index, decreasing the levels and expression of cytochrome c (CytC), cleaved-caspase-9, apoptotic protease activating factor 1 (Apaf-1), cleaved-caspase-3, and Bax and increasing the level and expression of Bcl-2. Overall, PD pretreatment shows a potent protective effect against APAP-induced hepatotoxicity by relieving oxidative stress and inhibiting apoptosis.


Assuntos
Acetaminofen/toxicidade , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Glucosídeos/farmacologia , Substâncias Protetoras/farmacologia , Estilbenos/farmacologia , Alanina Transaminase/sangue , Animais , Antioxidantes/metabolismo , Fator Apoptótico 1 Ativador de Proteases/genética , Fator Apoptótico 1 Ativador de Proteases/metabolismo , Aspartato Aminotransferases/sangue , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Glutationa/sangue , Dissulfeto de Glutationa/sangue , Dissulfeto de Glutationa/metabolismo , Glutationa Peroxidase/sangue , Glutationa Peroxidase/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/sangue , Camundongos , Camundongos Endogâmicos ICR , NADPH Oxidase 2/genética , NADPH Oxidase 2/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
14.
Pharmacol Res ; 137: 34-46, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30243842

RESUMO

Inflammatory bowel disease (IBD), majorly include Crohn's disease (CD) and ulcerative colitis (UC), is chronic and relapsing inflammatory disorders of the gastrointestinal tract, which treatment options remain limited. Here we examined the therapeutic effects of an isoquinoline alkaloid, Palmatine (Pal), on mice experimental colitis induced by dextran sulfate sodium (DSS) and explored underlying mechanisms. Colitis was induced in BALB/c mice by administering 3% DSS in drinking water for 7 days. Pal (50 and 100 mg kg-1) and the positive drug Sulfasalazine (SASP, 200 mg kg-1) were orally administered for 7 days. Disease activity index (DAI) was evaluated on day 8, and colonic tissues were collected for biochemistry analysis. The fecal microbiota was characterized by high-throughput Illumina MiSeq sequencing. And plasma metabolic changes were detected by UPLC-MS. Our results showed that Pal treatment significantly reduced DAI scores and ameliorated colonic injury in mice with DSS-induced colitis. Mucosal integrity was improved and cell apoptosis was inhibited. Moreover, gut microbiota analysis showed that mice received Pal-treatment have higher relative abundance of Bacteroidetes and Firmicutes, but reduced amount of Proteobacteria. Moreover, Pal not only suppressed tryptophan catabolism in plasma, but also decreased the protein expression of indoleamine 2,3-dioxygenase 1 (IDO-1, the rate-limiting enzyme of tryptophan catabolism) in colon tissue. This is consolidated by molecular docking, which suggested that Pal is a potent IDO-1 inhibitor. Taken together, our findings demonstrate that Pal ameliorated DSS-induced colitis by mitigating colonic injury, preventing gut microbiota dysbiosis, and regulating tryptophan catabolism, which indicated that Pal has great therapeutic potential for colitis.


Assuntos
Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Alcaloides de Berberina/farmacologia , Alcaloides de Berberina/uso terapêutico , Colite/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Triptofano/metabolismo , Animais , Colite/metabolismo , Colite/microbiologia , Colite/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Citocinas/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos BALB C , Mucinas/genética , Proteínas de Junções Íntimas/genética
15.
Phytomedicine ; 39: 111-118, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29433672

RESUMO

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are most widely used as effective anti-inflammatory agents. However, their clinical application brings about inevasible gastrointestinal side effects. Pogostemon cablin is a traditional herbal medicine used for the treatment of gastrointestinal diseases in China. One of its representative components, the tricyclic triterpenoid ß-patchoulone (ß-PAE) has demonstrated great anti-inflammatory activity and gastroprotective effect against ethanol-induced gastric injury, but its protective effect against gastric ulcer induced by indomethacin is still unknown. PURPOSE: To assess the protective effect of ß-PAE against ulcer produced by indomethacin and reveal the underlying pharmacological mechanism. STUDY DESIGN: We used an indomethacin-induced gastric ulcer model of rats in vivo. METHODS: Gastroprotective activity of ß-PAE (10, 20, 40 mg/kg, i.g.) was estimated via indomethacin-induced gastric ulcer model in rats. Histopathological and histochemical assessment of ulcerated tissues were performed. Protein and mRNA expression were determined by Elisa, Western blotting and qRT-PCR. RESULTS: ß-PAE could inhibit ulcer formation. Histopathological and histochemical assessment macroscopically demonstrated that ß-PAE alleviates indomethacin-induced gastric ulceration in dose-dependent manner. After administration of ß-PAE, elevated tumor necrosis factor -α level was significantly decreased and the phosphorylation of JNK and IκB was markedly inhibited. ß-PAE suppressed the levels of E-selectin, P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule and monocyte chemoattractant protein 1, as well as myeloperoxidase. Meanwhile, ß-PAE increased cyclooxygenase enzyme activities (COX-1 and COX-2) to enhance the production of prostaglandin E2. Proangiogenic protein, vascular endothelial growth factor and its receptor fms-like tyrosine kinase-1 mRNA expression were promoted while anti-angiogenic protein, endostatin-1 and its receptor ETAR mRNA expression were decreased. CONCLUSION: ß-PAE may provide gastroprotection in indomethacin-induced gastric ulcer in rats by reducing inflammatory response and improving angiogenesis.


Assuntos
Indometacina/efeitos adversos , Substâncias Protetoras/farmacologia , Sesquiterpenos/farmacologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Indutores da Angiogênese/farmacologia , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Antiulcerosos/farmacologia , Dinoprostona/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Masculino , Pogostemon/química , Ratos Sprague-Dawley , Sesquiterpenos de Guaiano , Úlcera Gástrica/patologia , Fator de Necrose Tumoral alfa/metabolismo
16.
Chem Biol Interact ; 283: 30-37, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29339218

RESUMO

Patchoulene epoxide (PAO), a tricyclic sesquiterpene isolated from the long-stored patchouli oil, has been demonstrated the anti-inflammatory activity in vivo based on our previous study. However, the gastric protective effect of PAO still remains unknown. Therefore, in the present study, ethanol-induced gastric ulcer model was carried out to evaluate the anti-ulcerogenic activity of PAO and to elucidate the potential mechanisms that involves. According to our results, macroscopic examination revealed that PAO could significantly reduce ethanol-induced gastric ulcer areas as compared with the vehicle group, which was also supported by the histological evaluation result. As for its potential mechanism, the anti-inflammatory activity of PAO contributed to gastric protection through reversing the imbalance between pro- and anti-inflammatory cytokines and modulating the expressions of NF-κB pathway-related proteins including p-IκBα, IκBα, p-p65 and p65. Besides, PAO was able to enhance the expressions of antioxidant enzymes including glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), and down-regulate malonaldehyde (MDA), an indicator of lipid peroxidation. Furthermore, immunohistochemistry analysis exhibited potent anti-apoptosis effect of PAO, as evidence by down-regulating the protein expression of caspase-3, Fas and Fasl. Additionally, we also demonstrated that PAO could replenish PGE2 and NO mucosal defense. In conclusion, these findings suggested that PAO has gastric protective activity against ethanol and this might be related to its influence on inflammatory response, oxidative stress, apoptosis cascade and gastric mucosal defense.


Assuntos
Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Sesquiterpenos/farmacologia , Úlcera Gástrica/prevenção & controle , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Caspase 3/metabolismo , Catalase/metabolismo , Citocinas/análise , Citocinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Etanol/toxicidade , Inflamação/prevenção & controle , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Óleos Vegetais/química , Pogostemon/química , Pogostemon/metabolismo , Ratos , Ratos Sprague-Dawley , Sesquiterpenos/química , Sesquiterpenos/uso terapêutico , Estômago/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Superóxido Dismutase/metabolismo
17.
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.

18.
Adv Mater ; 29(36)2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28758714

RESUMO

Electrides-compounds in which electrons localized in interstitial spaces periodically serve as anions-have attracted broad attention for their exotic properties, such as extraordinary electron-donating ability. In our efforts to expand this small family of phases, LaScSi emerges as a promising candidate. Its electron count is 2e- f.u.-1 in excess of that expected from the Zintl concept, while its structure offers interstitial spaces that can accommodate these extra electrons. Herein, this potential is explored through density functional theory (DFT) calculations and property measurements on LaScSi. DFT calculations (validated by heat capacity and electrical transport measurements) reveal electron density peaks at two symmetry-distinct interstitial sites. Importantly, this electride-like character is combined with chemical stability in air and water, an advantage for catalysis. Ru-loaded LaScSi shows outstanding catalytic activity for ammonia synthesis, with a turnover frequency (0.1 s-1 at 0.1 MPa, 400 °C) an order of magnitude higher than those of oxide-based Ru catalysts, e.g., Ru/MgO. As with other electrides, LaScSi's ability to reversibly store hydrogen prevents the hydrogen poisoning of Ru surfaces. The better performance of LaScSi, however, hints at the importance of the high concentration (>1.6 × 1022 cm-3 ) and tiered nature of its anionic electrons, which offers guidance toward new catalysts.

19.
Mediators Inflamm ; 2017: 1089028, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28811678

RESUMO

According to the GC-MS analysis, compositional variation was observed between samples of patchouli oil, of which an unknown compound identified as patchoulene epoxide (PAO) was found only in the long-stored oil, whose biological activity still remains unknown. Therefore, the present study aimed to evaluate the potential anti-inflammatory activity with three in vivo inflammatory models: xylene-induced ear edema, acetic acid-induced vascular permeability, and carrageenan-induced paw edema. Further investigation into its underlying mechanism on carrageenan-induced paw edema was conducted. Results demonstrated that PAO significantly inhibited the ear edema induced by xylene, lowered vascular permeability induced by acetic acid and decreased the paw edema induced by carrageenan. Moreover, PAO markedly decreased levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), prostaglandin E2 (PGE2), and nitric oxide (NO), but increased levels of interleukin-4 (IL-4) and interleukin-10 (IL-10). PAO was also shown to significantly downregulate the protein and mRNA expressions of cyclooxygenase-2 (COX-2) and inducible nitric-oxide synthase (iNOS). Western blot analysis revealed that PAO remarkably inhibited p50 and p65 translocation from the cytosol to the nucleus by suppressing IKKß and IκBα phosphorylation. In conclusion, PAO exhibited potent anti-inflammatory activity probably by suppressing the activation of iNOS, COX-2 and NF-κB signaling pathways.


Assuntos
Compostos de Epóxi/uso terapêutico , Inflamação/tratamento farmacológico , Óleos Vegetais/química , Pogostemon/química , Animais , Carragenina/toxicidade , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Compostos de Epóxi/química , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Inflamação/induzido quimicamente , Interleucina-10/metabolismo , Interleucina-4/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
20.
Sci Rep ; 7(1): 5591, 2017 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-28717228

RESUMO

Pogostemonis Herba is a functional food approved in Asian countries. Its major constituent, patchouli alcohol (PA), possesses a gastroprotective effect and is reported to transform into ß-patchoulene (ß-PAE) under acidic conditions. To investigate whether ß-PAE, the metabolite of PA, has a protective effect on the gastrointestinal tract, the formation of ß-PAE by gastric juice and the anti-ulcerogenic potential of ß-PAE against ethanol-induced gastric injury were evaluated. The Results indicated that PA was converted to ß-PAE by rat gastric juice. Additionally, ß-PAE was significantly better than PA at reducing the area of gastric ulcer. The overproduction of malondialdehyde, tumour necrosis factor-α, interleukin (IL)-1ß, IL-6, Fas, FasL and caspase-3 was markedly inhibited by ß-PAE while the underproduction of superoxide dismutase, glutathione and catalase was significantly improved. ß-PAE also regulated the NF-κB and ERK1/2 signalling pathways. Our findings suggest that ß-PAE has potential therapeutic efficacy for antiulcer treatment.


Assuntos
Etanol/toxicidade , Suco Gástrico/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Úlcera Gástrica/prevenção & controle , Estômago/efeitos dos fármacos , Animais , Células Cultivadas , Depressores do Sistema Nervoso Central/toxicidade , Citocinas/metabolismo , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Sesquiterpenos/metabolismo , Sesquiterpenos de Guaiano , Estômago/citologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia
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