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1.
J Ethnopharmacol ; 301: 115829, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36252876

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Plant essential oils (PEOs) extracted from aromatic compounds of the plant contain complex mixtures of volatile and lipophilic bioactive compounds. In ancient Egypt, Arabia, Greece, and China, PEOs were traditional used in aromatherapy for various health disorders, including pain and inflammation. AIM OF THE STUDY: In this review, we provide an overview of the anti-inflammatory effects of PEOs and the underlying mechanisms associated with anti-inflammatory effects using in vitro and in vivo models. Further, clinical trials associated with PEOs were explored. MATERIALS AND METHODS: The literature search was performed using various web-based tools and databases like Google Scholar, Web of Science, PubMed, CNKI and SCOPUS. The keywords used for conducting the literature review were general terms like "essential oils" followed by (AND) the subject of interest like "in vitro and/or in vivo anti-inflammatory models," "inflammatory response," "inflammatory indicators," "pro-inflammatory cytokines," "signaling pathway," "anti-inflammatory mechanism," "toxicology and side effects" and "clinical trials." The articles selected were published between 2017 and 2022. The articles prior to 2017 were only considered if they were associated with molecular mechanisms or signaling pathways involved in the inflammatory responses. RESULTS: In vitro and in vivo inflammation models have been used to study the anti-inflammatory effects of 48 PEOs. Studies have reported that PEOs targets and inhibit multiple dysregulated signaling pathways associated with inflammation, including Toll-like receptors, nuclear transcription factor-κ B, mitogen-activated protein kinases, Nod-like receptor family pyrin domain containing 3, and auxiliary pathways like the nuclear factor erythroid 2-related factor 2/antioxidant response element and Janus kinase/signal transducers and activators of transcription) signaling pathways. CONCLUSION: PEOs extracted from different plant materials had varied qualitative and quantitative compositions of biologically active compounds. Different anti-inflammatory potentials and different molecular signal transduction have been attributed to PEOs-derived bioactive compounds with different chemical structures. The data on therapeutic efficacy and the long-term side effects of PEOs as an anti-inflammatory drug are still unknown due to the lack of clinical trials on PEOs. There is still insufficient evidence to draw conclusions on anti-inflammatory properties of PEOs without promising outcomes from clinical trials.


Assuntos
Óleos Voláteis , Humanos , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Óleos Voláteis/química , Óleos Vegetais/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/química , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia
2.
J Ethnopharmacol ; 301: 115833, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36252879

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Acute lung injury (ALI) is a common manifestation of COVID-19. Xuanfei Baidu Formula(XFBD) is used in China to treat mild or common damp-toxin obstructive pulmonary syndrome in COVID-19 patients. However, the active ingredients of XFBD have not been extensively studied, and its mechanism of action in the treatment of ALI is not well understood. AIM OF THE STUDY: The purpose of this study was to investigate the mechanism of action of XFBD in treating ALI in rats, by evaluating its active components. MATERIALS AND METHODS: Firstly, the chemical composition of XFBD was identified using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry. The potential targets of XFBD for ALI treatment were predicted using network pharmacological analysis. Finally, the molecular mechanism of XFBD was validated using a RAW264.7 cell inflammation model and a mouse ALI model. RESULTS: A total of 113 compounds were identified in XFBD. Network pharmacology revealed 34 hub targets between the 113 compounds and ALI. The results of Kyoto Encyclopedia of Genes and Genomes and gene ontology analyses indicated that the NF-κB signaling pathway was the main pathway for XFBD in the treatment of ALI. We found that XFBD reduced proinflammatory factor levels in LPS-induced cellular models. By examining the lung wet/dry weight ratio and pathological sections in vivo, XFBD was found that XFBD could alleviate ALI. Immunohistochemistry results showed that XFBD inhibited ALI-induced increases in p-IKK, p-NF-κB p65, and iNOS proteins. In vitro experiments demonstrated that XFBD inhibited LPS-induced activation of the NF-κB pathway. CONCLUSION: This study identified the potential practical components of XFBD, combined with network pharmacology and experimental validation to demonstrate that XFBD can alleviate lung injury caused by ALI by inhibiting the NF-κB signaling pathway.


Assuntos
Lesão Pulmonar Aguda , COVID-19 , Camundongos , Ratos , Animais , NF-kappa B/metabolismo , Lipopolissacarídeos/toxicidade , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Transdução de Sinais , Pulmão/patologia , Modelos Animais de Doenças
3.
J Ethnopharmacol ; 300: 115690, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36075274

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xianglian Pill (XLP) is a classical Chinese medicine prescription applied for controlling ulcerative colitis (UC). Whereas, the underlying mechanism remains unclear. AIM OF THE STUDY: The present work was aimed to investigate the mechanism of XLP in dextran sulfate sodium (DSS)-induced UC via the Toll Like Receptor 4 (TLR4)/Myeloid Differentiation factor 88 (MyD88)/Nuclear Factor kappa-B (NF-κB) signaling in mice. MATERIALS AND METHODS: The major components of XLP were detected by high-performance liquid chromatography-diode array detection (HPLC-DAD). The ulcerative colitis model was induced by DSS in mice. 5-Amino Salicylic Acid (5-ASA) group and XLP group were intragastrically treated. Disease activity index (DAI) and colon length were monitored and hematoxylin-eosin (HE) staining was conducted. Gasdermin D (GSDMD)-N and TLR4 expressions in colon tissues were visualized by immunofluorescence. TLR4 mRNA was measured by Real Time Quantitative PCR (RT-qPCR). The expressions of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), active-caspase-1, GSDMD-N, TLR4, MYD88, NF-κB, p-NF-κB, and the ubiquitination of TLR4 in colon tissues were detected by Western blot. Myeloperoxidase (MPO) enzyme activity was examined and serum inflammatory factors Interleukin (IL)-1ß, IL-6, Tumor Necrosis Factor-α (TNF-α), and IL-18 were determined by Enzyme-linked Immunosorbent Assay (ELISA). TLR4-/- mice were applied for verifying the mechanism of XLP attenuated DSS symptoms. RESULTS: The XLP treatment extended colon length, reduced DAI, and attenuated histopathological alteration in DSS-induced mice. XLP administration suppressed MPO activity and reduced the content of IL-1ß, IL-6, TNF-α and IL-18 in serum. XLP also inhibited the expression levels of GSDMD-N, TLR4, NLRP3, active-caspase-1, MyD88, p-NF-κB/NF-κB in colon tissues of DSS-induced mice. TLR4-/- mice proved that TLR4 was involved in XLP-mediated beneficial effect on DSS-induced ulcerative colitis. CONCLUSIONS: XLP might treat ulcerative colitis by regulating the TLR4/MyD88/NF-κB signaling pathway.


Assuntos
Colite Ulcerativa , Fator 88 de Diferenciação Mieloide , Animais , Caspases/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Amarelo de Eosina-(YS)/metabolismo , Amarelo de Eosina-(YS)/farmacologia , Amarelo de Eosina-(YS)/uso terapêutico , Hematoxilina/metabolismo , Hematoxilina/farmacologia , Hematoxilina/uso terapêutico , Interleucina-18/metabolismo , Interleucina-18/farmacologia , Interleucina-18/uso terapêutico , Interleucina-6/metabolismo , Camundongos , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Peroxidase/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
4.
J Ethnopharmacol ; 301: 115846, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36280015

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hedychium flavum, an ornamental, edible, and medicinal plant, is extensively cultivated as a source of aromatic essential oils (EO). Its flower is a traditional Chinese medicine for treating inflammation-related diseases like indigestion, diarrhea, and stomach pain. In particular, H. flavum flower EO has been used in cosmetics and as an aromatic stomachic to treat chronic gastritis in China. AIM OF THE STUDY: This research aimed to analyze H. flavum flower EO's chemical composition and explore its anti-inflammatory activities and related mechanisms in vitro and in vivo. MATERIALS AND METHODS: EO's chemical composition was determined by GC-FID/MS analysis. For in vitro test, the anti-inflammatory activity of EO was demonstrated by measuring the LPS-induced release of NO, PGE2, IL-1ß, TNF-α, and IL-6 in RAW264.7 macrophages, and then its related mechanisms were explored using qRT-PCR, western blot, and immunofluorescent staining analysis. Next, EO's in vivo anti-inflammatory potential was further evaluated using a xylene-induced ear edema model, in which ear swelling and TNF-α, IL-6, and IL-1ß levels in serum and tissue were examined. RESULTS: The main components of EO were ß-pinene (20.2%), α-pinene (9.3%), α-phellandrene (8.3%), 1,8-cineole (7.1%), E-nerolidol (5.4%), limonene (4.4%), borneol (4.1%), and ß-caryophyllene (3.7%). For the anti-inflammatory activities in vitro, EO dramatically reduced the LPS-stimulated NO and PGE2 release by suppressing the mRNA and protein expression of iNOS and COX-2. Meanwhile, it remarkably decreased IL-6, TNF-α, and IL-1ß production by inhibiting their mRNA levels. Related mechanism studies indicated that it not only inhibited IκBα phosphorylation and degradation, leading to blockade of NF-κB nuclear transfer but also suppressed MAPKs (ERK, p38, and JNK) phosphorylation in LPS-stimulated RAW264.7 cells. Further in vivo assay showed that EO ameliorated xylene-induced ear edema in mice and reduced TNF-α, IL-6, and IL-1ß levels in serum and tissue. CONCLUSIONS: H. flavum EO exerted significant anti-inflammatory activity in vivo and in vitro, and its mechanism of action is related to the inhibition of MAPK and NF-κB activation. Thus, H. flavum EO could be considered a novel and promising anti-inflammatory agent and possess high potential for utilization in the pharmaceutical field.


Assuntos
Óleos Voláteis , Zingiberaceae , Animais , Camundongos , Anti-Inflamatórios , Dinoprostona/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Flores/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Células RAW 264.7 , RNA Mensageiro , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Xilenos , Zingiberaceae/metabolismo
5.
Food Chem ; 400: 133904, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36055136

RESUMO

Resveratrol is a dietary polyphenol that interacts with gut microbiota to possess various biological activities. To identify the microbial metabolites of resveratrol, fresh feces from 12 volunteers were cultured in vitro. Their urine samples were collected after taking a commercial capsule containing 600 mg of resveratrol. Metabolites were characterized and quantified by UPLC-Q-Exactive plus orbitrap MS/MS. The results showed that dihydroresveratrol, 3-(4-hydroxyphenyl)-propionic acid, and lunularin were the major microbial metabolites of RSV with interindividual differences. 3-(4-Hydroxyphenyl)-propionic acid significantly attenuated the inflammatory response of LPS-treated RAW264.7 cells and DSS-induced colitis in antibiotics-treated pseudo-germ-free mice by regulating MAPK and NF-κB pathways. In contrast, dihydroresveratrol did not exhibit significant anti-inflammatory effects, and lunularin exhibited pro-inflammatory effects in cells. This study may help to better understand the health effects of resveratrol and its microbial metabolites.


Assuntos
Anti-Inflamatórios , Colite , Resveratrol , Animais , Antibacterianos , Bibenzilas , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/genética , Sulfato de Dextrana , Lipopolissacarídeos , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , Fenóis , Fenilpropionatos , Polifenóis , Propionatos , Resveratrol/farmacologia , Estilbenos , Espectrometria de Massas em Tandem
6.
J Ethnopharmacol ; 300: 115691, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36087844

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The plant Erigeron breviscapus (Vant.) Hand.-Mazz.,a Chinese herbal medicine with multiple pharmacological effects and clinical applications, has been traditionally used in the treatment of paralysis caused by stroke and joint pain from rheumatism by the Yi minority people of Southwest China for generations.However, its mechanism involves many factors and has not been fully clarified. AIM OF THE STUDY: Taking intestinal flora as the target, the protective effect of extract(breviscapine) of E. breviscapus on cerebral ischemia and its possible mechanism were discussed from the perspective of brain inflammatory pathway and intestinal CYP3A4, which depends on intestinal flora. MATERIALS AND METHODS: In this study, we first verified the binding ability between major active ingredient of Erigeron breviscapus and the core target TLR4 protein by molecular docking using Vina software.We established a rat model of cerebral ischemia-reperfusion injury in vivo.The neurological function of rats was scored by Bederson score table, the cerebral infarction volume was detected by TTC staining, and the serum NSE level was detected by ELASA. 16S rRNA sequencing was used to detect the intestinal flora of rats in each group.The expression levels of cerebral TLR4/MyD88/NF-κB and CYP3A4 mRNA and protein in different intestinal segments were detected by qRT-PCR and Western blot. RESULTS: Compared with the model group, the neurological injury score, infarct volume and serum NSE concentration of breviscapine low, medium and high dose groups and nimodipine groups decreased significantly. Meanwhile, breviscapine could significantly reduce the expression level of the TLR4/MyD88/NF-κB in brain tissue and CYP3A4 in different intestinal segments of rats with cerebral ischemia-reperfusion injury. In addition, breviscapine also significantly ameliorated intestinal flora dysbiosis of rats with cerebral ischemia-reperfusion injury. CONCLUSIONS: Breviscapine can protect rats from cerebral ischemia-reperfusion injury by regulating intestinal flora, inhibiting brain TLR4/MyD88/NF-κB inflammatory pathway and intestinal CYP3A4 expression.


Assuntos
Isquemia Encefálica , Medicamentos de Ervas Chinesas , Erigeron , Microbioma Gastrointestinal , Traumatismo por Reperfusão , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Erigeron/genética , Erigeron/metabolismo , Flavonoides , Simulação de Acoplamento Molecular , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Nimodipina/farmacologia , RNA Mensageiro/metabolismo , RNA Ribossômico 16S , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
7.
J Ethnopharmacol ; 300: 115750, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36162547

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Different Physalis plants have been widely employed in traditional medicine for management of diabetes mellitus. Previous studies with respect to the in vivo antidiabetic activity of Physalis plants illustrated that they improved glucose and lipid metabolism in streptozotocin (STZ) -induced diabetic rats yet the mechanism of action of bioactive constituents of the different organs of Physalis plants on diabetes remains obscure. AIM OF STUDY: Our objective is to study the effects of the different organs of ground cherry (P. pruinosa) on diabetes in rat models and elucidate their mechanism of actions through serum pharmacochemistry combined to network pharmacology analyses and in-vivo testing. MATERIALS AND METHODS: Characterization of the constituents in the drug-dosed serum samples relative to the blank serum after treatment with different extracts was performed by UPLC -MS/MS technique. The absorbed metabolites where then subjected to network pharmacology analysis to construct an interaction network linking "compound-target-pathway". In vivo verification was implemented to determine a hypothesized mechanism of action on a STZ and high fat diet induced type II diabetes mellitus (T2DM) model based on functional and enrichment analyses of the Kyoto Encyclopedia of Genes and Genome and Gene Ontology. RESULTS: Identification of a total of 73 compounds (22 prototypes and 51 metabolites) derived from P. pruinosa extracts was achieved through comparison of the serum samples collected from diabetic control group and extracts treated groups. The identified compounds were found to belong to different classes according to their structural type including withanolides, physalins and flavonoids. The absorbed compounds in the analyzed serum samples were considered as the potential bioactive components. The component-target network was found to have 23 nodes with 17 target genes including MAPK8, CYP1A1 and CYP1B1. Quercetin and withaferin A were found to possess the highest combined score in the C-T network. Integrated serum pharmacochemistry and network pharmacology analyses revealed the enrichment of leaves extract with the active constituents, which can be utilized in T2DM treatment. In the top KEGG pathways, lipid and atherosclerosis metabolic pathways in addition to T2DM pathways were found to be highly prioritized. The diabetic rats, which received leaves extract exhibited a substantial increment in GLUT2, INSR, IRS-1, PI3K-p85 and AKT-ser473 proteins by 105%, 142%, 109%, 81% and 73%, respectively relative to the untreated diabetic group. The immunoblotting performed for MAPK and ERK1/2 part of the inflammatory pathway studied in STZ induced diabetic rats revealed that leaves, calyces and stems extracts resulted in a substantial diminish in p38-MAPK, ERK 1/2, NF-κB, and TNF-α. Histopathological examination revealed that the hepatic histoarchitecture was substantially improved in the leaves, stems, and clayces-treated rats in comparison with untreated diabetic rats. Further, pancreatic injuries, which induced by STZ were dramatically altered by the treatment with P. pruinosa leaves, calyces and stems extracts. ß-cells in diabetic rats received leaves extract disclosed moderate insulin immunostaining with a notable increase in the mean insulin area%. CONCLUSIONS: The study in hand offers a comprehensive study to clarify the bioactive metabolites of the different organs of P. pruinosa. The basic pharmacological effects and underlying mechanism of actions in the management of STZ and high fat diet induced T2DM were specifically covered in this paper.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Physalis , Vitanolídeos , Animais , Citocromo P-450 CYP1A1 , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Hipoglicemiantes/análise , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Insulina , NF-kappa B , Farmacologia em Rede , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quercetina/uso terapêutico , Ratos , Estreptozocina , Espectrometria de Massas em Tandem , Fator de Necrose Tumoral alfa
8.
J Ethnopharmacol ; 300: 115751, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36162550

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Myocardial fibrosis leads to cardiac remodeling and dysfunction. Curcumae Rhizoma has been utilized in clinical trials to treat a variety of cardiovascular illnesses, although its role in myocardial fibrosis is unknown. AIM OF THE STUDY: The purpose of current study was to explore the potential mechanism action and anti-myocardial fibrosis effects of treatment with Curcumae Rhizoma. MATERIALS AND METHODS: The chemical components in the aqueous extract from Curcumae Rhizoma were identified using GC-MS analysis. A prediction network describing the relationship between Curcumae Rhizoma and MF was established based on information collected from multiple databases. Functional enrichment analysis was performed to investigate the specific functions and pathways involved in the candidate Curcumae Rhizoma targets acting on MF, which were further validated by vivo experiments. RESULTS: There were 444 targets obtained from the 39 active ingredients in Curcumae Rhizoma, and 5691 disease targets related to MF were identified. Then, 41 key targets were determined with the PPI interaction network, which was structured from 324 overlapping gene targets. GO and KEGG analyses revealed that the p38 MAPK/NF-κB and TGF-ß1/Smad2/3 signaling pathways might play crucial roles in the therapeutic mechanism of MF. According to the results of molecular docking, the binding activity between core components and targets was marvelous (affinity < -6 kcal/mol). Take it a step further, the experimental validation data affirmed that Curcumae Rhizoma substantially decreased myocardial fibrosis and recovered cardiac function in the ISO-induced rats. The associated proteins expression data implied that the p38 MAPK/NF-κB and TGF-ß1/Smad2/3 pathways might be vital in the anti-fibrosis effect of Curcumae Rhizoma. CONCLUSION: The findings suggested that Curcumae Rhizoma diminished myocardial fibrosis by suppressing fibrosis multiplication and collagen deposition through inhibiting p38 MAPK/NF-κB and TGF-ß1/Smad2/3 pathways, which might be a promising therapeutic medicament for alleviating myocardial fibrosis.


Assuntos
Medicamentos de Ervas Chinesas , Fator de Crescimento Transformador beta1 , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Fibrose , Simulação de Acoplamento Molecular , NF-kappa B , Farmacologia em Rede , Ratos , Proteínas Quinases p38 Ativadas por Mitógeno
9.
J Ethnopharmacol ; 300: 115725, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36115602

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cimicifuga foetida L. is a well-established traditional Chinese medicine with heat-clearing and detoxifying effects and has good therapeutic effect on oral mucosal ulcer and pharyngitis. The rhizome of this herb is rich in triterpenoid glycosides, including 23-O-acetylshengmanol-3-o-α-L-arabinoside (DA). AIM OF THE STUDY: Whether and how DA attenuates acute lung injury (ALI) are unclear. Accordingly, we focused on its anti-inflammatory effects and underlying molecular mechanisms in lipopolysaccharide (LPS)-stimulated ALI mice and RAW264.7 cells. MATERIALS AND METHODS: The model of ALI mice was established by exposed intratracheal instillation of LPS. Lung pathological changes were evaluated by hematoxylin and eosin staining. Pulmonary function was assessed by whole-body plethysmography. Total protein content in bronchoalveolar lavage fluid (BALF) was detected by bicinchoninic acid method. Wet/dry lung ratio was used to evaluate the degree of pulmonary edema in mice. The levels of pro-inflammatory mediators were measured using enzyme-linked immunosorbent assay. The relative expression of pro-inflammatory gene mRNA was examined by RT-qPCR. The expression of inflammatory-related proteins was detected by Western blot. RAW264.7 cells were used to test the anti-inflammatory effects of DA in vitro. Cytotoxicity was assessed using a MTT assay. Nitric oxide production was measured by Griess assay. The production and expression of inflammatory mediators and the protein levels of inflammatory signaling molecules in the NF-κB and MAPK pathways were measured. Furthermore, immunofluorescence staining was used to analyze the expression of p-IκBα, p-ERK, and p-p38 in lung macrophages and the nuclear translocation of NF-κB p65 and AP-1 in cells. RESULTS: DA evidently alleviated histopathological changes and ameliorated pulmonary edema. Moreover, DA could reduce excessive inflammatory reaction in lung tissue as manifested by the reduction of proinflammatory mediators (IL-1ß, IL-6, TNF-α, MCP-1, iNOS, and COX-2) in BALF, serum, and lung tissues. Further, DA inhibited the activation of the NLRP3/caspase-1 pathway in the lung. DA reduced the production and expression of the proinflammatory mediators above in RAW264.7 cells. Mechanistically, DA remarkably blocked the nuclear translocation of NF-κB p65, suppressed IκBα phosphorylation, and markedly reduced the nuclear translocation of AP-1 and the phosphorylation of ERK and p38. CONCLUSIONS: The findings demonstrated that DA exerts anti-inflammatory effects in LPS-stimulated ALI mice and macrophages by downregulating the NLRP3/caspase-1 signaling pathway in lung tissue and the IκB/NF-κB and MAPKs/AP-1 pathways in macrophages, suggesting that DA may be promising in ALI treatment.


Assuntos
Lesão Pulmonar Aguda , Edema Pulmonar , Triterpenos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Animais , Anti-Inflamatórios , Caspases/metabolismo , Ciclo-Oxigenase 2/metabolismo , Amarelo de Eosina-(YS) , Glicosídeos/farmacologia , Hematoxilina/farmacologia , Hematoxilina/uso terapêutico , Proteínas I-kappa B/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-6 , Lipopolissacarídeos/toxicidade , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Óxido Nítrico/metabolismo , RNA Mensageiro , Transdução de Sinais , Fator de Transcrição AP-1/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
10.
J Ethnopharmacol ; 300: 115743, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36152783

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The flowers of Trollius chinensis Bunge (Ranunculaceae) is a traditional Chinese medicine used to treat various inflammatory diseases, including upper respiratory infections, chronic tonsillitis, and pharyngitis. Recently, there has been growing research on the antiviral role of the flowers of T. chinensis Bunge. However, little is known about its anti-influenza virus effects and the underlying mechanisms. AIM OF THE STUDY: This study aims to evaluate the therapeutic effects of the crude extract from the flowers of T. chinensis Bunge (CEFTC) on mice infected with influenza virus. We further explored its mechanism by detecting the expression of vital proteins (TLR3, TBK1, TAK1, IKKα, IRF3, and IFN-ß) related to TLR3 signaling pathway. MATERIALS AND METHODS: Mice were infected with influenza A virus (H1N1) through the nasal cavity and were intragastrically administered CEFTC at the dose of 0.2 mg/g once daily. The therapeutic effects of CEFTC were evaluated by blood cell count, lung index, spleen index, alveolar lavage fluid testing, and HE staining. Network pharmacology analysis predicted the potential signaling pathway between the flowers of T. chinensis Bunge and pneumonia. The expression of TLR3, TBK1, TAK1, IKKα, IRF3, and IFN-ß in lung tissues were examined by Western blot assay. In addition, the immunofluorescence assay was applied to assess the effect of CEFTC on the distribution of IRF3 and IFN-ß between nuclei and cytoplasm. RESULTS: Compared with the infected group, the lung index was markedly reduced, and the pathological damage of the lungs was also attenuated in the CEFTC treatment group. The network pharmacology analysis indicated that the NF-κB pathway was a potential signaling pathway in the flowers of T. chinensis Bunge for the treatment of pneumonia, TLR3, IRF3, and TBK1 were crucial targets associated with pneumonia. Western blot assay demonstrated that in the high-dose virus infected group, CEFTC reduced the expression of TLR3, TAK1, TBK1, and IRF3. Furthermore, CEFTC could increase the nuclear distribution of IRF3 in alveolar epithelial cells after virus infection. CONCLUSIONS: These results suggested that different doses of influenza virus could cause varying infection symptoms in mice. Moreover, CEFTC could exert anti-influenza virus effects by regulating the expression of TLR3, IRF3, IFN-ß, TAK1, and TBK1 in the TLR3 signaling pathway.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Ranunculaceae , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Misturas Complexas/farmacologia , Flores , Quinase I-kappa B , Interferon beta , Camundongos , NF-kappa B , Extratos Vegetais , Transdução de Sinais , Receptor 3 Toll-Like
11.
Food Chem ; 401: 134083, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36099816

RESUMO

The impact of Spirulina, Chlorella and Phaeodactylum tricornutum (P. tricornutum) microalgal extracts obtained by pressurized liquid extraction (PLE) on antioxidant and anti-inflammatory activities, microbial growth and in vitro gut microbiota composition was evaluated. PLE, compared to conventional extraction, led to a significant (p < 0.05) increase in proteins, carbohydrates, polyphenols, and antioxidant capacities of the three microalgal extracts. Moreover, Spirulina and P. tricornutum extracts significantly (p < 0.05) reduced the in vitro activation of the inflammatory NF-κB pathway. The microalgal extracts had also an inhibitory effect on the pathogenic bacteria while potential beneficial Lactobacillus and Bifidobacterium strains increased growth. The effects of microalgal extracts on specific bacterial groups were analyzed by quantitative PCR technology, and bacterial gene copy numbers were affected by in vitro digestion process and colonic fermentation time. GC-MS results showed that microalgal biomolecules' digestion promoted the release of short-chain fatty acids (SCFAs) during in vitro colonic microbiota fermentation, particularly acetic, butanoic and propanoic, indicating that the biomolecules in microalgae extracts have potential health benefits for human gut.


Assuntos
Chlorella , Microbioma Gastrointestinal , Microalgas , Spirulina , Humanos , Chlorella/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Spirulina/metabolismo , NF-kappa B/metabolismo , Microalgas/metabolismo , Ácidos Graxos Voláteis/metabolismo , Bactérias/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , Carboidratos
12.
Food Chem ; 402: 134232, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36137374

RESUMO

Noni fruit has certain anti-obesity effect. However, the bioactive ingredients in noni fruit that contribute to anti-obesity activity as well as the relation between its anti-obesity activity and gut microbiota remain unclear. In this study, obese mice induced by high-fat diet (HFD) and were intervened with noni fruit phenolic extract (NFE) for 10 weeks. The results showed NFE supplementation decreased body weight, lipid accumulation in liver andadiposetissues, ameliorated gut microbiota dysbiosis by increasing short-chain fatty acid (SCFA)-producing bacteria and decreasing lipopolysaccharide (LPS)-producing bacteria, and mitigated intestinal inflammation and oxidative stress. Moreover, NFE supplementation improved intestinal barrier dysfunction by elevating the protein expression levels of Claudin-1, Occludin and ZO-1, alleviated the HFD-induced intestinal inflammation by repressing the LPS/TLR4/NF-κB pathway. Collectively, the findings revealed NFE intervention inhibits obesity by improving gut microbiota disorder, barrier function, and inflammation. Hence, NFE may be an effective way to ameliorate HFD-induced damage.


Assuntos
Microbioma Gastrointestinal , Morinda , Camundongos , Animais , Dieta Hiperlipídica/efeitos adversos , Morinda/metabolismo , Lipopolissacarídeos/farmacologia , Frutas/metabolismo , Ocludina/metabolismo , Receptor 4 Toll-Like , NF-kappa B/genética , Claudina-1/farmacologia , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Obesidade/genética , Obesidade/metabolismo , Ácidos Graxos Voláteis/metabolismo , Fenóis/farmacologia , Inflamação/tratamento farmacológico , Inflamação/genética , Extratos Vegetais/farmacologia
13.
Theriogenology ; 195: 138-148, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36332373

RESUMO

Damage to Sertoli cell junction proteins caused by inflammation can lead to male infertility. Nerve growth factor (NGF) plays an important role in reproductive and inflammatory disease; however, whether and how NGF regulates Sertoli cell function remains unclear. Here, we aimed to assess the effect of NGF on the growth of Sertoli cells isolated from the testes of dairy goats and evaluate if NGF has a protective effect on these cells. We confirmed that Sertoli cell viability, proliferation, and ATP content increased following NGF treatment. In addition, qPCR results suggested that Sertoli cell apoptosis was inhibited after NGF treatment. To investigate the protective effect of NGF on Sertoli cells under pathological inflammatory conditions, LPS was used to induce inflammatory response in Sertoli cells. Post-treatment, the entangled filamentous pseudopodia of the cells loosened and no longer spanned adjacent cells. The expression of several junction proteins (ZO-1, occludin, CX-43, ß-catenin, and N-cadherin), which was down-regulated after inflammatory response induction, was restored following NGF treatment. LPS-induced changes in cytotoxicity and transepithelial electrical resistance were reversed and the intercellular connections became tighter after NGF treatment. We further demonstrated that NGF prevented the inflammatory response of Sertoli cells via the PI3K/AKT/NFκB signaling pathway, similar to the effect of the PI3K-inhibitor, LY294002, which is modified by the PI3K activator, 740Y-P. These results provide insights for devising strategies for protecting the male reproductive system and curing or preventing associated pathological conditions.


Assuntos
Fator de Crescimento Neural , Células de Sertoli , Masculino , Animais , Fator de Crescimento Neural/farmacologia , Fosfatidilinositol 3-Quinases , Lipopolissacarídeos/toxicidade , Proteínas Proto-Oncogênicas c-akt , NF-kappa B , Proliferação de Células , Transdução de Sinais
14.
J Steroid Biochem Mol Biol ; 225: 106179, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36150640

RESUMO

Various endocrinometabolic diseases, inclusively polycystic ovarian syndrome (PCOS) has been linked with increased risk of renal dysfunction with attendant cardiovascular disease (CVD) in women of reproductive age. Short chain fatty acids (SCFAs) especially acetate have been suggested as an immunometabolic modulator. However, the impact of SCFAs, particularly acetate on renal disorder in PCOS individuals is unknown. The present study therefore hypothesized that acetate would circumvent renal dysfunction in a rat model of PCOS, probably by suppressing NF-κB-dependent mechanism. Eight-week-old female Wistar rats were randomly distributed into four groups (n = 6), which received vehicle, sodium acetate (200 mg/kg), letrozole (1 mg/kg) and letrozole plus sodium acetate, respectively. The administrations were done by oral gavage once daily for a duration of 21 days. Animals with PCOS showed insulin resistance, lipid dysmetabolism, hyperandrogenism, hyperleptinemia and hypoadiponectinemia. Besides, the result also revealed increased renal malondialdehyde, lactate production, inflammatory mediators (NF-κB and TNF-α), urea and creatinine concentration. Immunohistochemical evaluation of renal tissue also demonstrated severe expression of apoptosis and inflammation with BAX/NLRP3 antibodies. However, supplementation with acetate significantly attenuated these anomalies. Collectively, the present results suggest that acetate abolishes renal dysfunction in experimentally induced PCOS animals by attenuating androgen excess, apoptosis, oxidative stress and NF-κB/NLRP3 immunoreactivity.


Assuntos
Resistência à Insulina , Nefropatias , Síndrome do Ovário Policístico , Animais , Feminino , Ratos , Modelos Animais de Doenças , Letrozol/uso terapêutico , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Síndrome do Ovário Policístico/metabolismo , Ratos Wistar , Acetato de Sódio
15.
Respir Physiol Neurobiol ; 307: 103965, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36150645

RESUMO

BACKGROUND: This study aimed to elucidate the effect and underlying molecular mechanisms of SZ168 (Podoplanin (PDPN) monoclonal antibody) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice and LPS-induced MH-S cells. METHODS: The survival rate was calculated by recording the death of mice in each group. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of interleukin (IL)- 6 and tumor necrosis factor-alpha (TNF-α) in blood and bronchoalveolar lavage fluid (BALF) of mice. Hematoxylin-eosin (H&E) staining were performed to evaluate the pathological changes in pulmonary tissues. Additionally, the phagocytosis of cells was tested by flow cytometry, and the expression levels of caveolin-1 (CAV-1) and Occludin proteins in lung tissue and the expression of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway-related proteins in MH-S cells were determined by western blot. RESULTS: SZ168 significantly improved the survival rate of ALI mice. Briefly speaking, SZ168 protected pulmonary vascular permeability, reduced the level of pro-inflammatory cytokines, improved the pathological changes of lung tissue, reduced the infiltration of inflammatory cells, increased CAV-1 and Occludin protein expression, and then effectively relieved lung injury. In addition, SZ168 could significantly reduce the phagocytic ability of LPS-induced MH-S cells and inhibit the expression of hospho-extracellular regulated protein kinases (p-ERK), Phospho-Jun N-terminal kinase (p-JNK), Phospho-NF-κB p65 (p-p65) and Phospho-IkappaB-alpha (p-IκBα). CONCLUSION: SZ168 can treat ALI by inhibiting the activation of NF-κB and MAPK signaling pathways and restoring tight junction protein expression.


Assuntos
Lesão Pulmonar Aguda , NF-kappa B , Camundongos , Animais , NF-kappa B/metabolismo , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/metabolismo , Ocludina/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Pulmão , Fator de Necrose Tumoral alfa/metabolismo
16.
Cytokine ; 161: 156074, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36323191

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disorder in which the immune system mistakenly attacks joints. The molecular mechanisms underlying RA pathology are still under investigation. In this study, we discovered overexpression of nuclear receptor coactivator 3 (NCOA3) in the joint tissues of type II collagen-induced arthritis (CIA) mice, an important autoimmune model of human RA. Administration of two NCOA3 inhibitors, gossypol (GSP) and SI-2 hydrochloride (SHC), significantly alleviated inflammation and improved the outcomes of CIA mice. In vivo and in vitro experiments revealed that NCOA3 assembled a transcriptional complex with a histone acetyltransferase p300 and two subunits of nuclear factor kappa B (NF-κB). This complex specifically controlled the expression of proinflammatory cytokine genes by binding to their promoters. Knockdown of NCOA3 or in vitro treatments with GSP and SHC impaired the assembly of NCOA3-p300-NF-κB complex and decreased the expression of proinflammatory cytokine genes. Taken together, our results demonstrated that NCOA3 acts as a mediator of proinflammatory cytokine genes in CIA mice and that inhibition of the NCOA3-p300-NF-κB complex may represent a new avenue for improving RA outcomes.


Assuntos
Artrite Experimental , Artrite Reumatoide , Coativador 3 de Receptor Nuclear , Animais , Humanos , Camundongos , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Citocinas/metabolismo , NF-kappa B/metabolismo , Coativador 3 de Receptor Nuclear/genética , Coativador 3 de Receptor Nuclear/metabolismo
17.
Phytomedicine ; 108: 154519, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36332391

RESUMO

BACKGROUND: Hypertension is a common risk factor for heart failure, and excessive angiotensin II (Ang II) leads to hypertensive cardiac alterations such as hypertrophy, cardiac fibrosis, remodeling, and dysfunction. Leonurine is the major active alkaloid compound obtained from the traditional Chinese herbal medicine, Leonurus japonicus Houtt. The effects of leonurine on Ang II-induced hypertensive cardiac injury remain unknown. HYPOTHESIS/PURPOSE: In the present study, we investigated the cardioprotective effects of leonurine in Ang II-infused mice and explored the underlying mechanisms in cardiomyocytes. METHODS: Cardiac injury was induced by Ang II infusion in experimental mice with or without leonurine (at 10 or 20 mg/kg) treatment. H9c2 cells and neonatal rat primary cardiomyocytes were used to investigate the mechanisms through which leonurine exerts its protection effects. RESULTS: The results showed that leonurine significantly alleviated Ang II-induced cardiac hypertrophy, fibrosis, and inflammation in both mice and cultured cardiomyocytes. Echocardiography revealed that leonurine preserved cardiac function in mice. Further investigations revealed that leonurine inhibited the activation of the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways to reduce inflammatory response and injuries in Ang II-challenged cardiomyocytes. Inhibition of MAPKs and NF-κB in cardiomyocytes abolished the anti-inflammatory effects of leonurine. CONCLUSIONS: Our study provides evidence that leonurine exerts protective effects against Ang II-induced hypertensive cardiac remodeling and dysfunction by inhibiting the MAPK and NF-κB pathways. Leonurine may be a promising agent for treating hypertensive heart failure.


Assuntos
Insuficiência Cardíaca , NF-kappa B , Ratos , Camundongos , Animais , NF-kappa B/metabolismo , Angiotensina II/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Miócitos Cardíacos , Fibrose , Insuficiência Cardíaca/metabolismo
18.
Phytomedicine ; 108: 154522, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36332392

RESUMO

BACKGROUND: Toxoplasma gondii is an opportunistic protozoan that can infect host to cause toxoplasmosis. We have previously reported that resveratrol (RSV) has protective effects against liver damage in T. gondii infected mice. However, the effect of RSV on lung injury caused by T. gondii infection and its mechanism of action remain unclear. PURPOSE: In this work, we studied the protective effects of RSV on lung injury caused by T. gondii infection and explored the underlying mechanism. METHODS: Molecular docking and localized surface plasmon resonance assay were used to detect the molecular interactions between RSV and target proteins. In vitro, the anti-T. gondii effects and potential anti-inflammatory mechanisms of RSV were investigated by quantitative competitive-PCR, RT-PCR, ELISA, Western blotting and immunofluorescence using RAW 264.7 cells infected with tachyzoites of T. gondii RH strain. In vivo, the effects of RSV on lung injury caused by T. gondii infection were assessed by observing pathological changes and the expression of inflammatory factors of lung. RESULTS: RSV inhibited T. gondii loads and T. gondii-derived heat shock protein 70 (T.g.HSP70) expression in RAW 264.7 cells and lung tissues. Moreover, RSV interacts with T.g.HSP70 and toll-like receptor 4 (TLR4), respectively, and interferes with the interaction between T.g.HSP70 and TLR4. It also inhibited the overproduction of inducible nitric oxide synthase, TNF-α and high mobility group protein 1 (HMGB1) by down-regulating TLR4/nuclear factor kappa B (NF-κB) signaling pathway, which is consistent with the effect of TLR4 inhibitor CLI-095. In vivo, RSV improved the pathological lung damage produced by T. gondii infection, as well as decreased the number of inflammatory cells in bronchoalveolar lavage fluid and the release of HMGB1 and TNF-α. CONCLUSION: These findings indicate that RSV can inhibit the proliferation of T. gondii and T.g.HSP70 expression both in vitro and in vivo. RSV can inhibit excessive inflammatory response by intervening T.g.HSP70 and HMGB1 mediated TLR4/NF-κB signaling pathway activation, thereby ameliorating lung injury caused by T. gondii infection. The present study provides new data that may be useful for the development of RSV as a new agent for the treatment of lung damage caused by T. gondii infection.


Assuntos
Proteína HMGB1 , Lesão Pulmonar , Toxoplasma , Animais , Camundongos , Toxoplasma/metabolismo , Receptor 4 Toll-Like/metabolismo , Proteína HMGB1/metabolismo , Resveratrol/farmacologia , NF-kappa B/metabolismo , Lesão Pulmonar/tratamento farmacológico , Fator de Necrose Tumoral alfa , Simulação de Acoplamento Molecular , Proteínas de Choque Térmico HSP70
19.
J Nutr Biochem ; 111: 109173, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36228975

RESUMO

The antidiabetic effects of green tea have been demonstrated in clinical trials and epidemiological studies. This study investigated the antidiabetic effects of green tea extract (GTE) and its underlying molecular mechanisms using a leptin receptor-deficient db/db mouse model (Leprdb/db). Treatment with GTE for 2 weeks improved glucose tolerance and insulin sensitivity in Leprdb/db mice. In addition, GTE treatment reduced the body weight and adiposity of Leprdb/db mice. Furthermore, GTE treatment reduced pro-inflammatory gene expression, including nuclear factor kappa B (NF-κB) in white adipose tissue (WAT), and also reduced dipeptidyl peptidase-4 (DPP4) expression levels in WAT as well as in the serum. The promoter region of Dpp4 contains the NF-κB binding site, and DPP4 was found to be a direct target of NF-κB. Consistently, in vitro treatment of cells with GTE or its main constituent epigallocatechin gallate reduced lipopolysaccharide-induced NF-κB/DPP4 expression in 3T3-L1 adipocytes and RAW264.7 cells. Overall, our data demonstrated that GTE exerts an anti-diabetic effect by regulating the expression levels of NF-κB and DPP4 in WAT.


Assuntos
Dipeptidil Peptidase 4 , Hipoglicemiantes , Camundongos , Animais , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/metabolismo , Dipeptidil Peptidase 4/genética , Dipeptidil Peptidase 4/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/uso terapêutico , Tecido Adiposo/metabolismo , Chá/química
20.
J Surg Res ; 281: 264-274, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36219938

RESUMO

INTRODUCTION: Persistent lung inflammation is a characteristic of sepsis-induced lung injury. Matrine, the active ingredient from Sophora flavescens, has exhibited anti-inflammatory activities. This study investigated the effects of prophylactic administration of matrine on macrophage polarization, apoptosis, and tissue injury in a cecal ligation and puncture (CLP)-induced murine lung injury model. METHODS: Mice were randomly allocated into four groups: Sham, CLP, Sham + Matrine, and CLP + Matrine. Lung tissues were collected at 24 h post-CLP. Histopathology and immunofluorescence analysis were performed to evaluate lung injury and macrophage infiltration in the lung, respectively. Caspase-3 activities, TUNEL staining, and anti-apoptotic proteins were examined to assess apoptosis. To determine the mechanism of action of matrine, protein levels of Sirtuin 1 (SIRT1), nuclear factor κB (NF-κB), p53 and the messenger RNA levels of p53-mediated proapoptotic genes were examined to elucidate the associated signaling pathways. RESULTS: Histopathological evaluation showed that matrine prophylaxis attenuated sepsis-induced lung injury. Matrine prophylaxis attenuated sepsis-induced infiltration of the total population of macrophages in the lung. Matrine inhibited M1 macrophage infiltration, but increased M2 macrophage infiltration, thus resulting in a decrease in the proportion of M1 to M2 macrophages in septic lung. Sepsis-induced lung injury was associated with apoptotic cell death as evidenced by increases in caspase-3 activity, TUNEL-positive cells, and decreases in antiapoptotic proteins, all of which were reversed by matrine prophylaxis. Matrine restored sepsis-induced downregulation of SIRT1 and deacetylation of NF-κB p65 subunit and p53, thus inactivating NF-κB pathway and suppressing p53-induced proapoptotic pathway in septic lung. CONCLUSIONS: In summary, this study demonstrated that matrine exhibited pro-M2 macrophage polarization and antiapoptotic effects in sepsis-induced lung injury, which might be, at least partly, due to the modulation of SIRT1/NF-κB and SIRT1/p53 pathways.


Assuntos
Lesão Pulmonar , Sepse , Animais , Camundongos , Apoptose , Caspase 3/metabolismo , Lesão Pulmonar/complicações , Macrófagos/metabolismo , NF-kappa B/metabolismo , Sepse/complicações , Sepse/tratamento farmacológico , Sepse/metabolismo , Sirtuína 1/metabolismo , Proteína Supressora de Tumor p53
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