RESUMO
Difenoconazole (DFZ) is a fungicidal pesticide extensively employed for the management of fungal diseases in fruits, vegetables, and cereal crops. However, its potential environmental impact cannot be ignored, as DFZ accumulation is able to lead to aquatic environment pollution and harm to non-target organisms. Quercetin (QUE), a flavonoid abundant in fruits and vegetables, possesses antioxidant and anti-inflammatory properties. In this article, carp were exposed to 400 mg/kg QUE and/or 0.3906 mg/L DFZ for 30 d to investigate the effect of QUE on DFZ-induced respiratory toxicity in carp. Research shows that DFZ exposure increases reactive oxygen species (ROS) production in the carp's respiratory system, leading to oxidative stress, inflammation, and damage to gill tissue and tight junction proteins. Further research demonstrates that DFZ induces mitochondrial dynamic imbalance and gill cell apoptosis. Notably, QUE treatment significantly reduces ROS levels, alleviates oxidative stress and inflammation, and mitigates mitochondrial dynamics imbalance and mitochondrial apoptosis. This study emphasizes the profound mechanism of DFZ toxicity to the respiratory system of common carp and the beneficial role of QUE in mitigating DFZ toxicity. These findings contribute to a better understanding of pesticide risk assessment in aquatic systems and provide new insights into strategies to reduce their toxicity.
Assuntos
Carpas , Dioxolanos , Praguicidas , Triazóis , Animais , Quercetina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Dinâmica Mitocondrial , Carpas/metabolismo , Antioxidantes/farmacologia , Estresse Oxidativo , Inflamação , Sistema Respiratório , ApoptoseRESUMO
Avermectin is one of the widely used anthelmintics in aquaculture and exhibits substantial toxicity to aquatic organisms. Silybin is extensively used for its anti-inflammatory, antioxidant and anti-apoptotic biological properties. Heart is essential for the survival of fish and plays a vital role in pumping blood oxygen and nutrients. Residual avermectin in water poses harm to carp. However, there is still insufficient research on whether silybin can mitigate the toxicity of avermectin to carp heart tissues. In this research, we established a model involving carp subjected to acute avermectin exposure and administered diets containing silybin to explore the potential protective effects of silybin against avermectin-induced cardiotoxicity. The results revealed that avermectin induced oxidative stress, inflammation, endoplasmic reticulum (ER) stress, mitochondrial pathway apoptosis and autophagy in the cardiac tissues of carp. Compared with the avermectin group, silybin significantly reduced ROS accumulation in cardiac tissues, restored antioxidant enzyme activity, inhibited mRNA transcript levels of pro-inflammatory-related factors, and attenuated ER stress, mitochondrial pathway apoptosis and autophagy. Protein-protein interaction (PPI) analysis demonstrated that silybin mitigated avermectin-induced cardiac oxidative stress, inflammation, ER stress, mitochondrial pathway apoptosis and autophagy. Silybin exerted anti-inflammatory effects through the Nuclear Factor kappa B (NF-κB) pathway, antioxidant effects through the Nuclear factor erythroid 2-related factor 2 (Nrf2) - Kelch-like ECH-associated protein 1 (Keap1) pathway, alleviated cardiac ER stress through the Glucose-regulated protein 78 (GRP78)/Activating Transcription Factor 6 (ATF6)/C/EBP homologous protein (CHOP) axis, suppressed apoptosis through the mitochondrial pathway, and inhibited excessive autophagy initiation through the PTEN-induced putative kinase 1 (PINK1)/Parkin RBR E3 ubiquitin protein ligase (PARKIN) signaling pathway. This study provided evidence supporting the protective effect of silybin against avermectin-induced cardiotoxicity in carp, highlighting its potential as a dietary additive to protect fish from adverse effects caused by avermectin exposure.
Assuntos
Anti-Helmínticos , Carpas , Ivermectina , Substâncias Protetoras , Silibina , Silibina/farmacologia , Silibina/uso terapêutico , Estresse do Retículo Endoplasmático , Cardiotoxicidade/tratamento farmacológico , Carpas/fisiologia , Animais , Ivermectina/toxicidade , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Apoptose/efeitos dos fármacos , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Fator 6 Ativador da Transcrição/metabolismo , Fator de Transcrição CHOP/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Inflamação/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Biomarcadores/sangue , Coração/efeitos dos fármacos , Coração/fisiologia , Miocárdio/patologiaRESUMO
As an important antibiotic, avermectin (AVM) has been widely used in China, but its unreasonable application has caused serious harm to the water environment. In view of the various pharmacological effects of quercetin (QUE), such as anti-inflammatory and antioxidant, the scientific hypothesis that "QUE may cause carp poisoning by inhibiting AVM" was proposed in this study. However, its protective effect in AVM -induced heart damage has not been reported. QUE reduced the symptoms of AVM toxicity and decreased the levels of creatine kinase, lactate dehydrogenase, and creatine kinase in the serum of carp. By histological observation, QUE was found to significantly reduce cardiac fiber swelling in carp. A DHE fluorescence probe study showed that QUE was able to inhibit AVM -induced accumulation of reactive oxygen species (ROS) in carp myocardium. We found that QUE significantly increased the intracellular antioxidant enzymes CAT, T-AOC and GSH enzyme activity and reduced intracellular MDA content. In addition, QUE significantly increased il-10 and tgf-ß1 expression, and significantly down-regulated tnf-α, il-6, il-1ß and inos expression. Tunel assay showed that QUE attenuated AVM -induced apoptosis, significantly decreased the transcript levels of pro-apoptosis-related genes, and increased the expression of anti-apoptosis-related genes. We also detected the protein expression of LC3 in the AVM group and QUE + AVM group, and found that the expression of LC3 was significantly increased in both groups compared with the Control group, but after adding QUE, the expression of LC3 was significantly decreased compared with the AVM group. In addition, the transcript levels of p62 and atg5 were also detected by qPCR. QUE significantly increased the expression of p62 and decreased the expression of atg5, suggesting that QUE could attenuate AVM -induced cardiac autophagy in carp. This study will provide preliminary evidence of the principle of QUE attenuating AVM -induced myocardial injury in carp from four aspects, including oxidative stress, inflammatory response, apoptosis and autophagy, and provide a theoretical basis for its prevention and treatment.
Assuntos
Carpas , Traumatismos Cardíacos , Animais , Quercetina/farmacologia , Antioxidantes/metabolismo , Carpas/metabolismo , Estresse Oxidativo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/veterinária , Apoptose , Autofagia , Creatina Quinase/metabolismo , Creatina Quinase/farmacologia , Creatina Quinase/uso terapêuticoRESUMO
INTRODUCTION: During breast cancer chemotherapy, the chemoresistance that frequently accompanies the treatment has become a big challenge. Long noncoding RNAs (LncRNAs) have been related to the development of chemoresistance in multiple cancer types. LncRNA DDX11-AS1 has shown a carcinogenic role in lung and colorectal cancer and was reported to enhance oxaliplatin resistance in gastric cancer and Taxol insensitivity in esophageal cancer. But its role in breast cancer chemotherapy drug resistance remains unknown. This study aimed to investigate the function and mechanism of lncRNA DDX11-AS1 in breast cancer chemoresistance. METHODS: The relationship between DDX11-AS1 and adriamycin (ADR) resistance was confirmed by qPCR, cell viability tests, and survival analysis. Then, RNA immunoprecipitation was conducted to evaluate the interaction between DDX11-AS1 and RNA-binding protein LIN28A. The regulation effect of LIN28A on autophagy-related genes ATG7 or ATG12 was detected by RNA stability assay and Western blot. Their correlation analysis was evaluated in GEO datasets and further validated by immunohistochemical results. The clinical significance of DDX11-AS1, ATG7, or ATG12 was evaluated by Kaplan-Meier Plotter analysis. RESULTS: Here, we reported DDX11-AS1 was significantly upregulated in chemoresistant breast cancer cells and overexpression of DDX11-AS1 promoted ADR resistance in breast cancer. LIN28A could interact with DDX11-AS1 and was involved in DDX11-AS1-mediated ADR resistance. Interfering with LIN28A reversed DDX11-AS1-induced ADR resistance. LIN28A could increase the protein level of ATG7 and ATG12 by increasing their mRNA stability. Survival analysis showed that ATG12 expression level was negatively correlated with the prognosis of breast cancer patients. CONCLUSION: This study clarifies the role of DDX11-AS1 in breast cancer chemoresistance and revealed a new mechanism, that is, interacting with LIN28A to stabilize ATG7 and ATG12 and jointly promote chemorefractory. These findings warrant further in vivo investigations to study DDX11-AS1 as a potential target to overcome chemoresistance.
Assuntos
Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , RNA Mensageiro , Proliferação de Células/genética , Linhagem Celular Tumoral , MicroRNAs/genética , Proteína 12 Relacionada à Autofagia/genética , Proteína 12 Relacionada à Autofagia/metabolismo , DNA Helicases/genética , DNA Helicases/metabolismo , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismoRESUMO
Sepsis, one of the most destructive diseases in the world, is a syndrome of systemic inflammatory response caused by the invasion of pathogenic microorganisms such as bacteria into the body. Malvidin is one of the most widespread anthocyanins, and its significant antioxidant and anti-inflammatory activities have been widely reported. However, the effect of Malvidin on sepsis and related complications is still unclear. The present study aimed to determine the mechanisms of Malvidin's potential protection from lipopolysaccharide (LPS)-induced spleen injury model of sepsis. In the LPS-induced mouse spleen injury model of sepsis, pretreatment with Malvidin was performed to assess morphological damage in spleen tissue and to detect the expression of mRNA levels of serum necrosis factor α, interleukin 1ß and interleukin 6, and IL-10. Apoptosis was detected using the TUNEL technique, and the levels of oxidative stress-related oxidase and antioxidant enzymes were measured by kit to assess the effect of Malvidin on inflammation and oxidative stress associated with septic spleen injury. The results of this study indicated that Malvidin was be a potentially effective drug for the treatment of sepsis.
Assuntos
Antocianinas , Sepse , Camundongos , Animais , Antocianinas/farmacologia , Lipopolissacarídeos/farmacologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Baço , Sepse/induzido quimicamente , Sepse/tratamento farmacológico , Sepse/complicações , ApoptoseRESUMO
Avermectin is widely used as an important insecticide in agricultural production, but it also shows strong toxicity to non-target organisms. Quercetin is a natural flavonoid that is widely used due to its good anti-inflammatory and antioxidant effects. We believe that quercetin may have a potential therapeutic effect on avermectin poisoning. This experiment was proposed to observe the effect of quercetin on the toxic response to avermectin by observing the toxic response caused by avermectin in the brain of carp. In this project, 60 carp were studied as control group (Control), quercetin administration group (QUE), avermectin exposure group (AVM) and quercetin treatment avermectin exposure group (QUE + AVM) with different interventions to study the effect of quercetin on avermectin. The carp brain tissues were stained and simultaneously analyzed for blood-brain barrier (BBB), oxidative stress indicators, inflammatory factors, and apoptosis using qPCR technique. The results of the study indicate that avermectin exhibits a neurotoxic mechanism of action in fish by decreasing the transcript levels of tight junction protein-related genes, which in turn leads to the rupture of the BBB in the carp brain tissue. Avermectin induced apoptosis in carp brain tissue by increasing oxidative stress response and promoting inflammatory cell infiltration. Quercetin could reduce the accumulation of reactive oxygen species (ROS) in the brain tissue of carp caused by avermectin exposure toxicity, maintain redox homeostasis, reduce inflammatory response, and protect brain tissue cells from apoptosis. The present study confirmed the therapeutic and protective effects of quercetin on neurotoxicity in carp caused by avermectin exposure.
Assuntos
Carpas , Quercetina , Animais , Quercetina/farmacologia , Antioxidantes/farmacologia , Estresse Oxidativo , Encéfalo , ApoptoseRESUMO
Context: The dried fruits of Arctium lappa L. have been used in two forms in traditional Chinese medicine; crude and stir-heating Fructus Arctii. However, its processed product possesses better activity. Objective: In this study, the chemical constituents of both crude and processed Fructus Arctii and their antiproliferative activities were evaluated. Materials and methods: The seven main active components in crude and various processed Fructus Arctii were quantitatively determined using high-performance liquid chromatography (HPLC). According to the actual amount in crude and five processed samples, seven single components were combined as multi-component combinations with six different proportions. The antiproliferative activities of these compatibility component groups were examined using the CCK-8 assay. Results: During the heating process, the proportion of the seven main components changed dynamically. The contents of 3-caffeoylquinic acid (3-CQA), 3,5-dicaffeoylquinic acid (3,5-diCQA), and arctiin (ARC) declined, while the contents of 4-caffeoylquinic acid (4-CQA), 3,4-dicaffeoylquinic acid (3,4-diCQA), 4,5-dicaffeoylquinic acid (4,5-diCQA), and arctigenin (ARG) increased very significantly. Discussion and conclusions: The results also indicated that seven components in the processed samples had higher cytotoxic profiles against HL-60 cells than those in the crude sample. Therefore, the heating process may enhance the antitumor activity of Fructus Arctii by changing the proportion of active components.
Assuntos
Arctium/química , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Ácido Clorogênico/análogos & derivados , Cromatografia Líquida de Alta Pressão , Frutas/química , Furanos , Glucosídeos , Células HL-60 , Humanos , Lignanas , Medicina Tradicional Chinesa , Ácido Quínico/análogos & derivadosRESUMO
In this paper, human umbilical vein endothelial cells (HUVEC) hypoxic injury models were established by sodium dithionite (Na2S2O4). With the protective effects of total salvianolic acids components (TSAC) against oxidative damage of HUVEC as a starting point, cellviability was measured by MTT colorimetric methodï¼ intracellular superoxide dismutase (SOD) activity, malondialdehyde (MDA), lactatedehydrogenase (LDH) level, nitric oxide (NO) level, interleukin6 (IL-6), and human tumor necrosis factor α (TNF-α) expression were measured by kits, to investigate the effect of seven kinds of phenolic acids of TSAC on Na2S2O4-induced HUVEC hypoxic injury. Based on the "component structure" theory, the contribution of the main components in TSAC for the protective effect on hypoxic injury of HUVEC was studied. The results showed that salvianolic acid B, posrnarinic acid A, salvianolic acid A, lactic acid, and lithospermic acid in TSAC play a larger role in protective effect of hypoxic injury of HUVEC. These five components were administered in combinations respectively, and it was concluded that the four components including salvianolic acid B, posrnarinic acid A, salvianolic acid A, lactic acid could be used as the representative components of TSAC.
Assuntos
Alcenos/farmacologia , Hipóxia Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Polifenóis/farmacologia , Substâncias Protetoras/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismoRESUMO
To observe the effect of Epimedii Herba alcohol extract (HE) on tumor growth of lung cancer by establishing the model of Lewis tumor-bearing mice, ELISA method was used to detect the levels of TNF-α, IL-10, IL-17, IL-2 in serum. Ki67 and P53 protein expression was detected in lung cancer tissues by using Western blot assay method and immunohistochemical assay method. The experimental results showed that HE has certain inhibitory effect on Lewis lung cancer tumor growth, and it can reduce the levels of TNF-α, IL-10 and IL-17 in serum, improve the level of IL-2,significantly decrease the expression of Ki67, and significantly increase P53 expression. HE has obvious inhibitory effect against lung cancer, and has the ability to improve immune regulating effect. This study reveals the anti-lung cancer effect of HE may be related to its ability of improving immunity, thus provides the basis for further research on anti-lung cancer effect of HE.
Assuntos
Carcinoma Pulmonar de Lewis/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Epimedium/química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Animais , Carcinoma Pulmonar de Lewis/genética , Carcinoma Pulmonar de Lewis/imunologia , Carcinoma Pulmonar de Lewis/fisiopatologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Feminino , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Neoplasias Pulmonares/genética , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
BACKGROUND: Corydalis bungeana Turcz. (CB; family: Corydalis DC.) is an anti-inflammatory medicinal herb used widely in traditional Chinese medicine (TCM) for upper respiratory tract infection, etc., but its anti-inflammatory active molecules are unknown. This study was designed to screen for the anti-inflammatory components from CB based on macrophage binding combined with HPLC. METHODS: Xylene-induced ear edema in mouse and carrageenan-induced hind-paw edema in rats were used to evaluate the anti-inflammatory activity of CB. The macrophage binding with high-performance liquid chromatography (HPLC) analysis and HPLC-MS were established to screen the potential active compounds. ELISA kits were performed to measure the levels of IL-6, IL-10, TNF-α and NO in RAW 264.7 macrophages culture media. RESULTS: The alkaloid extract of CB could inhibit significantly xylene-induced ear edema in mouse and carrageenan-induced hind-paw edema in rats. Two components binded to RAW 264.7 cell were identified as 12-hydroxycorynoline and corynoline. Bioassays demonstrated that these two compounds significantly inhibited LPS-induced IL-6, IL-10, TNF-α and NO levels. CONCLUSIONS: The results suggest that corynoline and 12-hydroxycorynoline contribute to the anti-inflammatory effects of the alkaloid extract of CB. Our findings suggest that these two compounds can be used as candidate for anti-inflammatory drugs.
Assuntos
Anti-Inflamatórios/análise , Alcaloides de Berberina/análise , Cromatografia Líquida de Alta Pressão/métodos , Corydalis/química , Edema/tratamento farmacológico , Macrófagos/imunologia , Animais , Anti-Inflamatórios/farmacologia , Alcaloides de Berberina/farmacologia , Carragenina/efeitos adversos , Interleucina-10 , Interleucina-6 , Macrófagos/efeitos dos fármacos , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos ICR , Óxido Nítrico , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfaRESUMO
OBJECTIVE: To establish an HPLC method for the content determination of baicalin, wogonin, chlorogenic acid, caffeic acid, cichoric acid, corynoline and adenosine in Pudilan Xiaoyan oral liquid. METHOD: The analysis was performed on a Phenomenex Luna C18 column (4.6 mm x 250 mm, 5 µm) with a gradient mobile phase of methanol-0.1% trifluoroacetic acid solution system at flow rate of 1.0 mL · min(-1). The detective wavelength was at 280 nm. The column temperature was 30 °C. RESULT: The standard curves of seven studied components show good linearity in their concentration ranges with r ≥ 0.999 6. The average recovery was 98.73%-102.1% with RSD less than 2.6%. CONCLUSION: The method is rapid, simple and accurate, and can be applied for the quality control of Pudilan Xiaoyan oral liquid.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/análise , Ácidos Cafeicos/análise , Ácido Clorogênico/análise , Flavanonas/análise , Flavonoides/análise , Succinatos/análiseRESUMO
BACKGROUND: To investigate the effect of Gypenoside XLIX (Gyp-XLIX) on acute splenic injury (ASI) induced by cecal ligation and puncture (CLP) in septic mice, a study was conducted. METHODS: Sixty healthy mice were randomly divided into six groups: the NC group, the Sham group, the Sham + Gyp-XLIX group, the CLP group, the CLP + Gyp-XLIX group, and the CLP + Dexamethasone (DEX) group. The NC group did not undergo any operation, while the rest of the groups underwent CLP to establish the sepsis model. The Sham group only underwent open-abdominal suture surgery without cecum puncture. After the operation, the groups were immediately administered the drug for a total of 5 days. Various methods such as hematoxylin and eosin (HE) staining, biochemical kits, qRT-PCR, and reactive oxygen species (ROS) were used for analysis. RESULTS: The results demonstrated that Gyp-XLIX effectively mitigated the splenic histopathological damage, while reducing the malondialdehyde (MDA) lipid peroxidation index and enhancing the antioxidant activities of catalase (CAT), glutathione (GSH) and total antioxidant capacity (T-AOC). The utilization of Dihydroethidium (DHE) fluorescent probe revealed that Gyp-XLIX inhibited the acute splenic accumulation of ROS induced by CLP in septic mice. Further investigations revealed that Gyp-XLIX exhibited a down-regulatory effect on the protein levels of inflammatory mediators iNOS and COX-2, consequently leading to the suppression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1ß. Additionally, it up-regulated the expression of anti-inflammatory factor IL-10. CONCLUSION: In conclusion, Gyp-XLIX was significantly effective in attenuating CLP-induced acute splenic inflammation and oxidative stress in septic mice.
Assuntos
Antioxidantes , Saponinas , Sepse , Camundongos , Animais , Antioxidantes/uso terapêutico , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio , Inflamação/tratamento farmacológico , Estresse Oxidativo , Fator de Necrose Tumoral alfa/farmacologia , Glutationa , Sepse/tratamento farmacológicoRESUMO
Liver is one of the vital organs in the human body and liver injury will have a very serious impact on human damage. Gypenoside XLIX is a PPAR-α activator that inhibits the activation of the NF-κB signaling pathway. The components of XLIX have pharmacological effects such as cardiovascular protection, antihypoxia, anti-tumor and anti-aging. In this study, we used cecum ligation and puncture (CLP) was used to induce in vivo mice hepatic injury, and lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells, evaluated whether Gypenoside XLIX could have a palliative effect on sepsis-induced acute liver injury via NF-κB/PPAR-α/NLRP3. In order to gain insight into these mechanisms, six groups were created in vivo: the Contol group, the Sham group, the CLP group, the CLP + XLIX group (40 mg/kg) and the Sham + XLIX (40 mg/kg) group, and the CLP + DEX (2 mg/kg) group. Three groups were created in vitro: Control, LPS, LPS + XLIX (40 µM). The analytical methods used included H&E staining, qPCR, reactive oxygen species (ROS), oil red O staining, and Western Blot. The results showed that XLIX attenuated hepatic inflammatory injury in mice with toxic liver disease through inhibition of the TLR4-mediated NF-κB pathway, attenuated lipid accumulation through activation of PPAR-α, and attenuated hepatic pyroptosis by inhibiting NLRP3 production. Regarding the imbalance between oxidative and antioxidant defenses due to septic liver injury, XLIX reduced liver oxidative stress-related biomarkers (ALT, AST), reduced ROS accumulation, decreased the amount of malondialdehyde (MDA) produced by lipid peroxidation, and increased the levels of antioxidant enzymes such as glutathione (GSH) and catalase (CAT). Our results demonstrate that XLIX can indeed attenuate septic liver injury. This is extremely important for future studies on XLIX and sepsis, and provides a potential pathway for the treatment of acute liver injury.
Assuntos
NF-kappa B , Saponinas , Sepse , Humanos , Camundongos , Animais , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Antioxidantes , PPAR alfa/metabolismo , Lipopolissacarídeos/farmacologia , Espécies Reativas de Oxigênio , Fígado/patologia , Glutationa , Sepse/patologiaRESUMO
Baicalin, a flavonoid extracted from traditional Chinese medicine, Scutellaria baicalensis has significant anti-inflammatory effects. Microsponges are drug delivery systems that improve drug stability and slow the release rate. The combination of baicalin and the microsponges produced a new and stable system for its delivery, resulting in a novel formulation of baicalin. Baicalin microsponges (BM) were prepared using the quasi-emulsion solvent diffusion method. Effects of the mass ratio of the polymer (ethylcellulose) to baicalin, the concentration of the emulsifier polyvinyl alcohol (PVA), the stirring speed on the encapsulation efficiency (EE), and yield of the microsponges were investigated by combining the one-factor test and Box-Behnken design (BBD). The preparation process was standardised using 2.61:1 mass ratio of ethyl cellulose to baicalin, 2.17% concentration of PVA, with stirring at 794 rpm. Optimised BM formulations were evaluated for the parameters of EE (54.06 ± 3.02)% and yield of (70.37 ± 2.41)%, transmission electron microscopy (TEM), and in vitro cell evaluation. Results of the in vitro anti-inflammatory assay showed that baicalin microsponges-pretreated-lipopolysaccharide (LPS)-induced RAW264.7, mouse macrophages showed reduced inflammatory response, similar to that seen in baicalin-treated macrophages.
RESUMO
Sepsis is a systemic inflammatory disease that is caused by a dysregulated host response to infection and is a life-threatening organ dysfunction that affects many organs, which includes the colon. Mounting evidence suggests that sepsis-induced colonic damage is a major contributor to organ failure and cellular dysfunction. Monotropein (MON) is the major natural compound in the iris glycoside that is extracted from Morendae officinalis radix, which possesses the potent pharmacological activities of anti-inflammatory and antioxidant properties. This research evaluated whether MON is able to alleviate septic colonic injury in mice by cecal ligation and puncture. Colonic tissues were analyzed using histopathology, immunofluorescence, quantitative real-time polymerase chain reaction, and Western blot methods. It was initially discovered that MON reduced colonic damage in infected mice, in addition to inflammation, apoptosis, and oxidative stress in colonic tissues, while it activated autophagy, with the NRF2/keap1 and PINK1/Parkin pathways also being activated. Through the stimulation of NCM460 cells with lipopolysaccharides, an in vitro model of sepsis was created as a means of further elucidating the potential mechanisms of MON. In the in vitro model, it was found that MON could still activate the NRF2/keap1, PINK1/Parkin, and autophagy pathways. However, when MON was paired with the NRF2 inhibitor ML385, it counteracted MON-induced activation of PINK1/Parkin and autophagy, while also promoting inflammatory response and apoptosis in NCM460 cells. Therefore, the data implies that MON could play a therapeutic role through the activation of the NFR2/PINK pathway as a means of inducing autophagy to alleviate the oxidative stress in colonic tissues that is induced by sepsis, which will improve inflammation and apoptosis in colonic tissues.
Assuntos
Iridoides , Fator 2 Relacionado a NF-E2 , Sepse , Camundongos , Animais , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Inflamação/tratamento farmacológico , Autofagia , Sepse/complicações , Sepse/tratamento farmacológico , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Quinases/metabolismoRESUMO
Avermectin, a widely used deworming drug, poses a significant threat to fisheries. Silybin is recognized for its antioxidant and anti-inflammatory properties. The kidney, being crucial for fish survival, plays a vital role in maintaining ion balance, nitrogen metabolism, and hormone regulation. While residual avermectin in water could pose a risk to carp (Cyprinus carpio), it remains unclear whether silybin can alleviate the renal tissue toxicity induced by avermectin in this species. In current study, we developed a model of long-term exposure of carp to avermectin to investigate the potential protective effect of silybin against avermectin-induced nephrotoxicity. The results indicated that avermectin induced renal inflammation, oxidative stress, ferroptosis, and autophagy in carp. Silybin suppressed the mRNA transcript levels of pro-inflammatory factors, increased catalase (CAT) activity, reduced glutathione (GSH) activity, diminished reactive oxygen species (ROS) accumulation in renal tissues, and promoted the activation of the Nrf2-Keap1 signaling pathway. Furthermore, the transcript levels of ferroptosis-associated proteins, including gpx4 and slc7a11, were significantly reduced, while those of cox2, ftl, and ncoa4 were elevated. The transcript levels of autophagy-related genes, including p62 and atg5, were also regulated. Network pharmacological analysis revealed that silybin inhibited ROS accumulation and mitigated avermectin-induced renal inflammation, oxidative stress, ferroptosis, and autophagy in carp through the involvement of PPAR-γ. Silybin exerted its anti-inflammatory effect through the NF-κB pathway and antioxidant effect through the Nrf2-Keap1 pathway, induced renal cell iron efflux through the SLC7A11/GSH/GPX4, and suppressed autophagy initiation via the PI3K/AKT pathway. This study provides evidence of the protective effect of silybin against avermectin-induced nephrotoxicity in carp, highlighting its potential as a therapeutic agent to alleviate the adverse effects of avermectin exposure in fish.
Assuntos
Autofagia , Carpas , Ferroptose , Ivermectina , Rim , Estresse Oxidativo , PPAR gama , Silibina , Animais , Autofagia/efeitos dos fármacos , Ivermectina/análogos & derivados , Ivermectina/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Silibina/farmacologia , PPAR gama/metabolismo , PPAR gama/genética , Rim/efeitos dos fármacos , Rim/patologia , Poluentes Químicos da Água/toxicidade , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Doenças dos Peixes/induzido quimicamente , Espécies Reativas de Oxigênio/metabolismoRESUMO
Designing heterojunction photocatalysts with strong interfacial interactions is an effective way to reduce the recombination of photogenerated charge carriers. Here, silver phosphate (Ag3PO4) nanoparticles are coupled with hollow flower-like indium selenide (In2Se3) microspheres by a facile Ostwald ripening and in-situ growth method, resulting in the construction of In2Se3/Ag3PO4 hollow microsphere step-scheme (S-scheme) heterojunction with a large contact interface. The flower-like In2Se3 with hollow and porous structure provides a large specific surface area and numerous active sites for photocatalytic reactions to take place. The photocatalytic activity was tested by measuring the hydrogen evolution from antibiotic wastewater, and the H2 evolution rate of In2Se3/Ag3PO4 reached 4206.4 µmol g-1h-1 under visible light, which is approximately 2.8 times greater than that of In2Se3. In addition, the amount of tetracycline (TC) degradation when it was used as a sacrificial agent is about 54.4% after 1 h. On the one hand, Se-P chemical bonds act as electron transfer channels in the S-scheme heterojunctions, which can facilitate the migration and separation of photogenerated charge carriers. On the other hand, the S-scheme heterojunctions can retain the useful holes and electrons with higher redox capacities, which is very favorable for the generation of more â¢OH radicals and the photocatalytic activity is greatly enhanced. This work provides an alternative design approach for photocatalysts toward hydrogen evolution in antibiotic wastewater.
RESUMO
Harvesting solar energy directly to boost the sluggish kinetics of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) on an air cathode is a promising approach. Herein, we synthesize a step-scheme (S-scheme) titanium dioxide-indium selenide (TiO2-In2Se3) heterojunction catalyst. The onset potential in ORR under light illumination reaches 1.28 V and the onset potential decreases to 0.48 V in OER. When an S-scheme TiO2-In2Se3 heterojunction is exposed to light, photogenerated electrons at the conduction band (CB) of TiO2 migrate to the valence band (VB) of In2Se3 due to the built-in electric field. The photogenerated electrons with strong reduction capability on the CB of In2Se3 and the holes with strong oxidation capability on the VB of TiO2 boost the cathode reaction kinetics (ORR/OER). The excellent outcome reveals tremendous commercial potential of photo-enhanced Zn-air batteries.
RESUMO
Avermectin (AVM) is one of the most often used insecticides which is toxic to aquatic organisms, and cause oxidative-induced damages to the fish respiratory organ, the "gills". To better understand the mechanism by which an antioxidant reduces AVM-induced gill damage, we investigated the effects of Quercetin (Que) on AVM induction of oxidative stress to inhibit damages to the gills using common carp as a model organism. The Que is a fruit and vegetable rich flavonoid with antioxidant activity. In this study, four groups were created: the Control group, the Que group (400 mg/kg), the AVM group (2.404 µg/L), and the Que plus AVM group. The analytical methods were pathological structure examination, qPCR, Reactive Oxygen Species (ROS) and Western blot. The results showed that Que alleviated AVM-induced oxidative stress, inflammatory damage and apoptosis in the carp gills by activating the Nrf2 pathway. The mechanism was that Que alleviated the accumulation of ROS, reduced the balance between oxidation and antioxidant disrupted by AVM exposure, lowered the content of lipid peroxidation produced malondialdehyde (MDA), and increased the content of antioxidant enzymes including glutathione (GSH) and catalase (CAT). Nrf2 pathway was activated. Meanwhile, Que inhibited gill apoptosis in carp by decreasing the levels of Bax, Cytochrome C, Caspase9, Cleaved-Caspase3 and reduced Bcl2. This has important implications for future studies on Que and AVM. New suggestions are provided to reduce the threat of aquatic environmental pollution.