RESUMEN
The quality of moxa is an important factor affecting moxibustion therapy, and traditionally, 3-year moxa is considered optimal, although scientific data are lacking. This study focused on 1-year and 3-year moxa from Artemisia stolonifera and A. argyi(leaf-to-moxa ratio of 10â¶1) as research objects. Scanning electron microscopy(SEM), Van Soest method, and simultaneous thermal analysis were used to investigate the differences in the combustion heat quality of 1-year and 3-year moxa and their influencing factors. The results showed that the combustion of A. stolonifera moxa exhibited a balanced heat release pattern. The 3-year moxa released a concentrated heat of 9 998.84 mJ·mg~(-1)(accounting for 54% of the total heat release) in the temperature range of 140-302 â, with a heat production efficiency of 122 mW·mg~(-1). It further released 7 512.51 mJ·mg~(-1)(accounting for 41% of the total heat release) in the temperature range of 302-519 â. The combustion of A. argyi moxa showed a rapid heat release pattern. The 3-year moxa released a heat of 16 695.28 mJ·mg~(-1)(accounting for 70% of the total heat release) in the temperature range of 140-311 â, with an instantaneous power output of 218 mW·mg~(-1). It further released 5 996.95 mJ·mg~(-1)(accounting for 25% of the total heat release) in the temperature range of 311-483 â. Combustion parameters such as-R_p,-R_v, D_i, C, and D_b indicated that the combustion heat quality of 3-year moxa was superior to that of 1-year moxa. It exhibited greater combustion heat, heat production efficiency, flammability, mild and sustained burning, and higher instantaneous combustion efficiency. This study utilized scientific data to demonstrate that A. stolonifera could be used as excellent moxa, and the quality of 3-year moxa surpassed that of 1-year moxa. The research results provide a scientific basis for the in-depth development of A. stolonifera moxa and the improvement of moxa quality standards.
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Artemisia , Moxibustión , Calor , Hojas de la PlantaRESUMEN
The quality of moxa is a key factor affecting the efficacy of moxibustion. Traditional moxa grades are evaluated by the leaf-to-moxa ratio, but there is a lack of support from scientific data. Scanning electron microscopy(SEM), Image Pro Plus, Van Soest method, and stimultaneous thermal analysis(TGA/DSC) were used to characterize the scientific implication of the combustion differences between moxa with different leaf-to-moxa ratios(processed by crusher). The results showed that the median lengths from non-secretory trichomes(NSTs) of natural NSTs and moxa with leaf-to-moxa ratios of 3â¶1, 5â¶1, 10â¶1, and 15â¶1 were 542.46, 303.24, 291.18, 220.69, and 170.61 µm, respectively. The cellulose content of moxa increased significantly(P<0.05) with the increase in leaf-to-moxa ratio and the combustion parameters(T_i, t_i, D_i, C,-R_p,-R_v, S, D_b, and J_(total)) all showed an increasing trend. The correlation results showed that the burning properties of moxa(T_i,-R_v, t_i, and J_2) were significantly and positively correlated with cellulose content. NSTs with a length of 1-200 µm were significantly and positively correlated with J_2. NSTs with a length of 200-600 µm were significantly and positively correlated with J_1, T_(peak2), T_(peak1), and-R_v, and negatively correlated with J_(total), T_b, and t_b. As the leaf-to-moxa ratio increases, the NSTs in the moxa become shorter and the cellulose content increases, which is more conducive to ignition performance, heat release, and a milder, longer-lasting burn. The "NSTs-cellulose-TGA/DSC" quantitative evaluation method scientifically reveals the scientific connotation of the combustion of moxa with different leaf-to-moxa ratios and provides a scientific basis for the establishment of quality evaluation methods for moxa with different leaf-to-moxa ratios.
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Moxibustión , Tricomas , Calor , Hojas de la PlantaRESUMEN
In order to reveal the distribution and population characteristics of endophytic fungi from Zanthoxylum nitidum and the antibacterial potential,this study performed molecular identification and analyzed the genetic diversity and antibacterial activity of endophytic fungi from Z. nitidum in Guangxi. Through culture and molecular identification,35 strains,belonging to 15 genera,12 families,10 orders,4 classes,and 2 phyla,were isolated from various tissues of Z. nitidum,of which Colletotrichum and Fusarium were the dominant genera,respectively accounting for 20% of total strains. The diversity of endophytic fungi was significantly different among roots,stems,and leaves,as manifested by the significantly higher Shannon index( H') in stems( 1. 678) than in roots( 0. 882 1) and leaves( 0. 515 4). The antimicrobial activity analysis showed that 14. 28% of endophytic fungi inhibited at least one indicator pathogen. Among them,Fusarium sp. ZN-34 and Fusarium sp. ZN-26 separately demonstrated the strongest inhibitory effect on Escherichia coli and Staphylococcus aureus. In general,Fusarium sp. ZN-26 and Phialemoniopsis plurioloculosa ZN-35 were advantageous in suppressing the two bacteria owing to the broad spectrum and strong efficacy. In summary,Z. nitidum in Guangxi boasts rich endophytic fungi with the majority showing strong antibacterial activity,which can be used as candidates for the extraction and separation of basic antibacterial substances and the development of natural antibacterial agents.
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Antiinfecciosos , Colletotrichum , Zanthoxylum , Antibacterianos/farmacología , China , Endófitos/genética , Hongos/genética , Variación Genética , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
Using the White as basic medium, the effects of the exogenous IBA and endophytic fungal elicitor on the growth of in vitro roots cultures of Dysosma versipellis and production of podophyllotoxin were investigated in this study. The results showed that the IBA and the endophytic fungus Zasmidium syzygii elicitor could increase the content of podophyllotoxin of in vitro roots of D. versipellis after 3 weeks. The White medium added with 3 mg·L~(-1) IBA induced the highest increase of podophyllotoxin(1 830.86 µg·g~(-1)), which was 2.07 folds greater than the control, and followed by 1.5 mg·L~(-1) IBA, fungal elicitor, 1 mg·L~(-1) IBA, 0.5 mg·L~(-1) IBA and 4.5 mg·L~(-1) IBA, which was 1.82, 1.71, 1.63, 1.43 and 1.1 folds greater than the control, respectively. The results also showed that the growth of roots was certain positively correlated with the change of IBA concentration. Therefore, 3 mg·L~(-1) IBA was the most suitable for the production of podophyllotoxin in the in vitro roots of D. versipellis, and the stimulating effect of Z. syzygii fungal elicitor was between 1.5 mg·L~(-1) and 1 mg·L~(-1) IBA, which was a potential natural elicitor to induce the accumulation of podophyllotoxin in future production.
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Ascomicetos , Berberidaceae/química , Raíces de Plantas/crecimiento & desarrollo , Podofilotoxina/biosíntesis , Técnicas de Cultivo de Tejidos , Endófitos , Raíces de Plantas/efectos de los fármacosRESUMEN
Acetaminophen overdose-induced hepatotoxicity is the most common cause of acute liver failure in many countries. Previously, alpha-mangostin (α-MG) has been confirmed to exert protective effects on a variety of liver injuries, but the protective effect on acetaminophen-induced acute liver injury (ALI) remains largely unknown. This work investigated the regulatory effect and underlying cellular mechanisms of α-MG action to attenuate acetaminophen-induced hepatotoxicity in mice. The increased serum aminotransferase levels and glutathione (GSH) content and reduced malondialdehyde (MDA) demonstrated the protective effect of α-MG against acetaminophen-induced hepatotoxicity. In addition, α-MG pretreatment inhibited increases in tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) caused by exposure of mice to acetaminophen. In liver tissues, α-MG inhibited the protein expression of autophagy-related microtubule-associated protein light chain 3 (LC3) and BCL2/adenovirus E1B protein-interacting protein 3 (BNIP3). Western blotting analysis of liver tissues also proved evidence that α-MG partially inhibited the activation of apoptotic signaling pathways via increasing the expression of Bcl-2 and decreasing Bax and cleaved caspase 3 proteins. In addition, α-MG could in part downregulate the increase in p62 level and upregulate the decrease in p-mTOR, p-AKT and LC3 II /LC3 I ratio in autophagy signaling pathways in the mouse liver. Taken together, our findings proved novel perspectives that detoxification effect of α-MG on acetaminophen-induced ALI might be due to the alterations in Akt/mTOR pathway in the liver.
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Acetaminofén/toxicidad , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Xantonas/farmacología , Animales , Medicamentos Herbarios Chinos/uso terapéutico , Garcinia mangostana , Humanos , Hígado/patología , Masculino , Ratones , Ratones Endogámicos ICR , Proteínas Asociadas a Microtúbulos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Xantonas/uso terapéuticoRESUMEN
Although Radix Paeoniae Alba (RPA) has been ranked as one of the top 6 herbs used frequently to prevent and treat miscarriages clinically, there is no clear evidence regarding its safety in embryonic development. This study aims to evaluate the potential impacts of RPA on embryonic stem cells (ESCs) and pregnant mice. Cytotoxicity assays of the extract were performed in ESCs and 3T3 cells. Pregnant ICR mice were orally treated with RPA extracts at dosages of 0 (G1 group as negative controls), 2, 8 and 32 g/kg/day (G2, G3 and G4 groups) respectively from the gestation day (Gd) 6-15. On Gd 18, there was no significant difference in the IC50 values between ESCs and 3T3 cells (p > 0.05). There was no significant difference in the maternal and fetal evaluations among four groups (p > 0.05). Fetal IL-2, IL-2r, TNF-α, TNF-αr, IL-4, IL-4r, IL-10r, IL-17 and IL-17r of G4 group were significantly lower than G1 group (p < 0.05). In conclusion, RPA at dosage of 32 g/kg/day (16-folds of human daily dosage) did not cause adverse impact in cultured ESCs and pregnant mice. RPA might down-regulate fetal Th1/Th2/Th17 cytokines and receptors maybe beneficial to embryonic survival and development. Copyright © 2017 John Wiley & Sons, Ltd.
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Medicamentos Herbarios Chinos/farmacología , Desarrollo Embrionario/efectos de los fármacos , Células Madre Embrionarias/efectos de los fármacos , Paeonia/química , Células 3T3 , Animales , Citocinas/metabolismo , Femenino , Feto/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , Embarazo , Receptores de Citocinas/metabolismoRESUMEN
Although cisplatin is an anticancer drug that has activity against malignant tumor, it often causes nephrotoxicity. Previous reports have confirmed that the saponins from the leaves of P. quinquefolium (PQS) exerted many pharmacological activities. However, the renoprotective effects of PQS were still unknown. The purpose of the present research was to discuss renoprotective effect of PQS in a mouse model of cisplatin-induced acute kidney injury (AKI). The levels of blood urea nitrogen (BUN) and serum creatinine (CRE) were evidently increased in cisplatin-intoxicated mice, which were reversed by PQS. Renal oxidative stress, evidenced by increased malondialdehyde (MDA) level and decline of glutathione (GSH) and superoxide dismutase (SOD) activities, was significantly alleviated by PQS pretreatment. The suppression of inflammatory response by PQS was realized through the decrease the mRNA expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in kidney tissues, which were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Simultaneously, the overexpression of cytochrome P450 E1 (CYP2E1) and heme oxygenase-1 (HO-1) were attenuated by PQS. Furthermore, the effects of Western blotting demonstrated that PQS administration significantly suppressed the protein expression levels of nicotinamide adenine dinucleotide phosphate oxidase type 4 (Nox4), cleaved Caspase-3, cleaved Caspase-9, Bax, nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), suggesting the inhibition of apoptosis and inflammation response. Overall, PQS may possess protective effects in cisplatin-induced AKI through suppression of oxidative stress, inflammation and apoptosis.
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Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Cisplatino/efectos adversos , Fármacos Neuroprotectores/uso terapéutico , Panax/química , Hojas de la Planta/química , Saponinas/uso terapéutico , Lesión Renal Aguda/patología , Lesión Renal Aguda/fisiopatología , Animales , Apoptosis/efectos de los fármacos , Citocinas/metabolismo , Glutatión/metabolismo , Inflamación/patología , Riñón/efectos de los fármacos , Riñón/enzimología , Riñón/patología , Riñón/fisiopatología , Masculino , Malondialdehído/metabolismo , Ratones Endogámicos ICR , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Saponinas/farmacología , Superóxido Dismutasa/metabolismoRESUMEN
Resveratrol (RV), a dietary antioxidant polyphenolic compound found in grapes and red wine, exerts a wide variety of pharmacological activities. However, lower content in plants compared with polydatin (PD, the glucoside of RV) limits its application in the food and pharmaceutical industries. In this paper, we carried out efficient biotransformation of PD to RV with 100% conversion yield by snailase hydrolysis. Moreover, response surface methodology (RSM) was used to optimize the effects of the reaction temperature, enzyme load, and reaction time on the conversion process. Validation of the RSM model was verified by the good agreement between the experimental and the predicted RV yield values. The optimum preparation conditions were as follows: temperature of 62.0 °C, enzyme load of 6.6%, and reaction time of 96 min. The proposed method may be highly applicable for the enzymatic preparation of RV for medicinal purposes.
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Biotransformación , Glucósidos/química , Estilbenos/química , Antioxidantes/química , Humanos , Hidrólisis , Resveratrol , Propiedades de Superficie , Temperatura , Vitis/químicaRESUMEN
In the present work, we reported the enzymatic preparation of deapio-platycodin D (dPD) and platycodin D (PD) optimized by response surface methodology (RSM) from Radix Platycodi. During investigation of the hydrolysis of crude platycosides by various glycoside hydrolases, snailase showed a strong ability to transform deapio-platycoside E (dPE) and platycoside E (PE) into dPD and PD with 100% conversion. RSM was used to optimize the effects of the reaction temperature (35-45 °C), enzyme load (5-20%), and reaction time (4-24 h) on the conversion process. Validation of the RSM model was verified by the good agreement between the experimental and the predicted values of dPD and PD conversion yield. The optimum preparation conditions were as follows: temperature, 43 °C; enzyme load, 15%; reaction time, 22 h. The biotransformation pathways were dPEâdPD3âdPD and PEâPD3âPD, respectively. The determined method may be highly applicable for the enzymatic preparation of dPD and PD for medicinal purposes and also for commercial use.
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Extractos Vegetales/síntesis química , Platycodon/metabolismo , Saponinas/síntesis química , Triterpenos/síntesis química , Hidrólisis , Medicina Tradicional China , Modelos Estadísticos , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/química , Ácido Oleanólico/metabolismo , Extractos Vegetales/química , Raíces de Plantas/metabolismo , Saponinas/química , Saponinas/metabolismo , Triterpenos/químicaRESUMEN
In this work, pressurized liquid extraction (PLE) of three acetophenones (4-hydroxyacetophenone, baishouwubenzophenone, and 2,4-dihydroxyacetophenone) from Cynanchum bungei (ACB) were investigated. The optimal conditions for extraction of ACB were obtained using a Box-Behnken design, consisting of 17 experimental points, as follows: Ethanol (100%) as the extraction solvent at a temperature of 120 °C and an extraction pressure of 1500 psi, using one extraction cycle with a static extraction time of 17 min. The extracted samples were analyzed by high-performance liquid chromatography using an UV detector. Under this optimal condition, the experimental values agreed with the predicted values by analysis of variance. The ACB extraction yield with optimal PLE was higher than that obtained by soxhlet extraction and heat-reflux extraction methods. The results suggest that the PLE method provides a good alternative for acetophenone extraction.
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Acetofenonas/química , Acetofenonas/aislamiento & purificación , Cynanchum/química , Extracción Líquido-Líquido , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Análisis de Varianza , Extracción Líquido-Líquido/métodos , Estructura MolecularRESUMEN
In this work, a rapid extraction method based on ultrasound-assisted extraction (UAE) of syringin from the bark of Ilex rotunda Thumb using response surface methodology (RSM) is described. The syringin was analyzed and quantified by high performance liquid chromatography coupled with UV detection (HPLC-UV). The extraction solvent, extraction temperature and extraction time, the three main factors for UAE, were optimized with Box-Behnken design (BBD) to obtain the highest extraction efficiency. The optimal conditions were the use of a sonication frequency of 40 kHz, 65% methanol as the solvent, an extraction time of 30 min and an extraction temperature of 40 °C. Using these optimal conditions, the experimental values agreed closely with the predicted values. The analysis of variance (ANOVA) indicated a high goodness of model fit and the success of the RSM method for optimizing syringin extraction from the bark of I. rotunda.
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Glucósidos/aislamiento & purificación , Ondas de Choque de Alta Energía , Ilex/química , Fenilpropionatos/aislamiento & purificación , Corteza de la Planta/química , Glucósidos/química , Fenilpropionatos/químicaRESUMEN
A new method based on accelerated solvent extraction (ASE) combined with response surface methodology (RSM) modeling and optimization has been developed for the extraction of four lignans in Fructus Schisandrae (the fruits of Schisandra chinensis Baill). The RSM method, based on a three level and three variable Box-Behnken design (BBD), was employed to obtain the optimal combination of extraction condition. In brief, the lignans schizandrin, schisandrol B, deoxyschizandrin and schisandrin B were optimally extracted with 87% ethanol as extraction solvent, extraction temperature of 160 ° C, static extraction time of 10 min, extraction pressure of 1,500 psi, flush volume of 60% and one extraction cycle. The 3D response surface plot and the contour plot derived from the mathematical models were applied to determine the optimal conditions. Under the above conditions, the experimental value of four lignans was 14.72 mg/g, which is in close agreement with the value predicted by the model.
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Lignanos/química , Extractos Vegetales/química , Schisandra/química , Solventes , Simulación por Computador , Modelos EstadísticosRESUMEN
Although naturally occurring flavonoids have shown beneficial effects on the side effects caused by cisplatin, there are few reports on the protective effect of dihydrochalcone on the cisplatin-induced toxicity. Trilobatin (TLB), as the major sweetener and active ingredient in Lithocarpus polystachyus Rehd, is a dihydrochalcone-like compound that can be present in concentrations of up to 10% or more in tender leaves. Herein, a cisplatin-induced acute kidney injury (AKI) model was established to investigate the protective effect and mechanism of TLB against the cisplatin-induced nephrotoxicity in mice. The results showed that TLB significantly reversed the inhibition of CRE, BUN, and MDA levels compared with the cisplatin group. Furthermore, TLB treatment (50 and 100 mg/kg) for 10 days significantly alleviated cisplatin-induced renal pathological changes. TUNEL staining showed that TLB administration can effectively improve the occurrence of apoptosis of renal tissue cells caused by cisplatin exposure. Importantly, western blot analysis verified that TLB alleviated cisplatin-induced nephrotoxicity by regulating the AKT/MAPK signaling pathway and apoptosis. In summary, our findings showed clearly that TLB has a significant preventive effect on cisplatin-induced AKI.
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[This retracts the article DOI: 10.1039/D0RA00020E.].
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In this paper, ultrasound-assisted extraction (UAE) was applied to the extraction of anthraquinones (aloe-emodin, rhein, emodin, chrysophanol and physcion) from Rheum palmatum L. The five anthraquinones were quantified and analyzed by high performance liquid chromatography coupled with UV detection (HPLC-UV). The extraction solvent, extraction temperature and extraction time parameters, the three main factors for UAE, were optimized with response surface methodology (RSM) to obtain the highest extraction efficiency. The optimal conditions were the use of 84% methanol as solvent, an extraction time of 33 min and an extraction temperature of 67°C. Under these optimal conditions, the experimental values agreed closely with the predicted values. The analysis of variance indicated a high goodness of model fit and the success of RSM method for optimizing anthraquinones extraction in Rheum palmatum L.
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Antraquinonas/aislamiento & purificación , Emodina/análogos & derivados , Emodina/aislamiento & purificación , Rheum/química , UltrasonidoRESUMEN
In the present study, we developed a liquid chromatography-diode array detector-electrospray ionization/mass spectrometric (LC-DAD-ESI/MS) method for analysis of saikosaponins in Bupleurum falcatum. The LC method employed a ZORBAX SB-Aq analytical column (150 x 4.6 mm i.d., 5 µm) at a flow rate of 0.8 mL/min coupled with a diode array detector at 204 nm. A step gradient of acetonitrile-water (v/v) containing 0.5% formic acid from 30 to 70% was applied, leading to a sample analysis time of 30 min. The ESI-MS was carried out in positive and negative modes from 500 to 1,500 m/z. Saikosaponins c, a, and d gave strong sodium adducts at m/z 949.6, 803.5 and 803.6, respectively, in positive mode. The data indicate that the present LC-DAD-ESI/MS assay is an effective method for the determination of saikosaponins c, a and d from the roots of Bupleurum falcatum.
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Bupleurum/química , Cromatografía Liquida/métodos , Ácido Oleanólico/análogos & derivados , Raíces de Plantas/química , Saponinas/análisis , Espectrometría de Masa por Ionización de Electrospray/métodos , Cromatografía Liquida/instrumentación , Límite de Detección , Medicina Tradicional China , Estructura Molecular , Ácido Oleanólico/análisis , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrometría de Masa por Ionización de Electrospray/instrumentaciónRESUMEN
BACKGROUND: Nuezhenide (NZD), an iridoid glycoside isolated from Ilex pubescens Hook. & Arn. var. kwangsiensis Hand.-Mazz., used as a traditional Chinese medicine for clearing away heat and toxic materials, displays a variety of biological activities such as anti-tumor, antioxidant, and other life-protecting activities. However, a few studies involving anti-inflammatory activity and the mechanism of NZD have also been reported. In the present study, the anti-inflammatory and antioxidative effects of NZD are illustrated. OBJECTIVE: This study aims to test the hypothesis that NZD suppresses LPS-induced inflammation by targeting the NF-κB pathway in RAW264.7 cells. METHODS: LPS-stimulated RAW264.7 cells were employed to detect the effect of NZD on the release of cytokines by ELISA. Protein expression levels of related molecular markers were quantitated by western blot analysis. The levels of ROS, NO, and Ca2+ were detected by flow cytometry. The changes in mitochondrial reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were observed and verified by fluorescence microscopy. Using immunofluorescence assay, the translocation of NF-κB/p65 from the cytoplasm into the nucleus was determined by confocal microscopy. RESULTS: NZD exhibited anti-inflammatory activity and reduced the release of inflammatory cytokines such as nitrite, TNF-α, and IL-6. NZD suppressed the expression of the phosphorylated proteins like IKKα/ß, IκBα, and p65. Besides, the flow cytometry results indicated that NZD inhibited the levels of ROS, NO, and Ca2+ in LPS-stimulated RAW264.7 cells. JC-1 assay data showed that NZD reversed LPS-induced MMP loss. Furthermore, NZD suppressed LPS-induced NF-B/p65 translocation from the cytoplasm into the nucleus. CONCLUSION: NZD exhibits anti-inflammatory effects through the NF-κB pathway on RAW264.7 cells.
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Antiinflamatorios/química , Glucósidos/química , Piranos/química , Factor de Transcripción ReIA/metabolismo , Animales , Antiinflamatorios/farmacología , Supervivencia Celular/efectos de los fármacos , Citocinas/metabolismo , Glucósidos/farmacología , Humanos , Interleucina-6/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Inhibidor NF-kappaB alfa/metabolismo , Óxido Nítrico/metabolismo , Nitritos/metabolismo , Piranos/farmacología , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Previous report has confirmed the beneficial effects of α-mangostin (α-MG), a major and representative xanthone distributed in mangosteen (Garcinia mangostana) on the cisplatin-induced rat model. However, the molecular mechanisms related to its renoprotection have not been elucidated exhaustively. The present study investigated the protective effect of α-MG against cisplatin-induced cytotoxicity in the human embryonic kidney (HEK293) cell model. In this study, α-MG prevented cisplatin-induced cell death, accompanied with the decreased levels of malondialdehyde and increased glutathione content. Particularly, α-MG significantly suppressed the overproduction of reactive oxygen species (ROS), restored the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and downregulated the c-JUN N-terminal kinase (JNK) pathways following cisplatin challenge. Subsequently, the cleavage of caspases and poly-ADP-ribose polymerase (PARP) implicating ROS-mediated apoptosis pathways induced by cisplatin was effectively inhibited by α-MG. In conclusion, our findings provided a rationale for the development of α-MG to attenuate cisplatin-induced nephrotoxicity.
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Procyandin A2 (PCA2) is a polyphenolic compound which is isolated from grape seeds. It has been reported that PCA2 exhibits antioxidative and anti-inflammatory effects, but its molecular mechanism is still poorly understood. This study tests the hypothesis that PCA2 suppresses lipopolysaccharide (LPS)-induced inflammation and oxidative stress through targeting the nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and NF-E2-related factor 2 (Nrf2) pathways in RAW264.7 cells. PCA2 (20, 40, 80 µM) exhibited no significant cytotoxicity in RAW264.7 cells and showed an inhibitory effect on an LPS-induced nitrite level. Pro-inflammatory cytokines like tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), nitric oxide (NO), and reactive oxygen species (ROS) were suppressed by PCA2 with a concentration range of 0-80 µM. The mRNA levels of TNF-α and IL-6 were inhibited by PCA2 (80 µM). The hallmark-protein expression of the NF-κB (p-IKKα/ß, p-IκBα, and p-p65) and MAPK (p-p38, p-JNK, and p-ERK) pathways were decreased by PCA2 in LPS-stimulated RAW264.7 cells. In addition, immunofluorescence results indicated that PCA2 (80 µM) promoted the translocation of NF-κB/p65 from the cytoplasm into the nucleus. PCA2 upregulated the expressions of Nrf2 and HO-1 and downregulated the expression of Keap-1. Simultaneously, PCA2 (80 µM) reversed LPS-induced Nrf2 translocation from the nucleus into the cytoplasm. Collectively, PCA2 protect cells against the damage from inflammation and oxidative injury, which suggest a potential therapeutic strategy for inflammatory and oxidative stress through targeting NF-κB, MAPK, and Nrf2 pathways in RAW264.7 cells.
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Catequina/metabolismo , Catequina/farmacología , Inflamación/tratamiento farmacológico , Proantocianidinas/metabolismo , Proantocianidinas/farmacología , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Citocinas/metabolismo , Dinoprostona/metabolismo , Hemo-Oxigenasa 1/metabolismo , Lipopolisacáridos/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Proteína Quinasa 1 Activada por Mitógenos/efectos de los fármacos , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Factor 2 Relacionado con NF-E2/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Inhibidor NF-kappaB alfa/metabolismo , FN-kappa B/efectos de los fármacos , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Células RAW 264.7 , Transducción de Señal/efectos de los fármacosRESUMEN
Acetaminophen (APAP)-induced acute liver injury (ALI) is a health issue that has gradually attracted attention, and is often regarded as a model of drug-induced hepatotoxicity. The leaves of Lithocarpus polystachyus Rehd. (named as "sweet tea", ST) usually serve as tea drink and folk medicine for healthcare in the southwest part of China. In previous reports, it has been proven to protect various animal models, except for APAP-induced liver injury model. Therefore, this study initially explored the protective effect of ST leaf extract (STL-E) on hepatotoxicity induced by APAP in ICR mice. STL-E of 50 and 100 mg kg-1 were given to each group for 7 days. ALI was intraperitoneally induced by APAP treatment (i.p. 250 mg per kg body weight). Biochemical markers, levels of inflammatory factors, histopathological staining and western blotting were used to analyze the inflammation and apoptosis of liver tissues. Interestingly, the treatment with STL-E significantly attenuated APAP-induced liver injury (p < 0.05). Moreover, STL-E partially mitigated APAP-induced liver injury by effectively activating the PI3K/Akt pathway and inhibiting the NF-κB pathway. In a word, STL-E protected liver against APAP-induced hepatotoxicity by inhibiting the PI3K/Akt-mediated apoptosis signal pathway and inhibiting the NF-κB-mediated signaling pathway.