RESUMEN
Lead (Pb), a heavy metal environmental pollutant, poses a threat to the health of humans and birds. Inflammation is one of the most common pathological phenomena in the case of illness and poisoning. However, the underlying mechanisms of inflammation remain unclear. The cerebellum and the thalamus are important parts of the nervous system. To date, there have been no reports of Pb inducing inflammation in animal cerebellums or thalami. Selenium (Se) can relieve Pb poisoning. Therefore, we aimed to explore the mechanism by which Se alleviates Pb toxicity to the cerebellums and thalami of chickens by establishing a chicken Pb or/and Se treatment model. Our results demonstrated that exposure to Pb caused inflammatory damage in cerebellums and thalami, evidenced by the characteristics of inflammation, the decrease in anti-inflammatory factors (interleukin (IL)-2 and interferon-γ (INF-γ)), and the increase in pro-inflammatory factors (IL-4, IL-6, IL-12ß, IL-17, and nitric oxide (NO)). Moreover, we found that the IL-2/IL-17-NO pathway took part in Pb-caused inflammatory injury. The above findings were reversed by the supplementation of dietary Se, meaning that Se relieved inflammatory damage caused by Pb via the IL-2/IL-17-NO pathway. In addition, an up-regulated oxidative index malondialdehyde (MDA) and two down-regulated antioxidant indices (glutathione (GSH) and total antioxidant capacity (TAC)) were recorded after the chickens received Pb stimulation, indicating that excess Pb caused an oxidant/antioxidant imbalance and oxidative stress, and the oxidative stress mediated inflammatory damage via the GSH-IL-2 axis. Interestingly, exposure to Pb inhibited four glutathione peroxidase (GPx) family members (GPx1, GPx2, GPx3, and GPx4), three deiodinase (Dio) family members (Dio1, Dio2, and Dio3), and fifteen other selenoproteins (selenophosphate synthetase 2 (SPS2), selenoprotein (Sel)H, SelI, SelK, SelM, SelO, SelP1, SelPb, SelS, SelT, SelU, and selenoprotein (Sep)n1, Sepw1, Sepx1, and Sep15), suggesting that Pb reduced antioxidant capacity and resulted in oxidative stress involving the SPS2-GPx1-GSH pathway. Se supplementation, as expected, reversed the changes mentioned above, indicating that Se supplementation improved antioxidant capacity and mitigated oxidative stress in chickens. For the first time, we discovered that the SPS2-GPx1-GSH-IL-2/IL-17-NO pathway is involved in the complex inflammatory damage mechanism caused by Pb in chickens. In conclusion, this study demonstrated that Se relieved Pb-induced oxidative stress and inflammatory damage via the SPS2-GPx1-GSH-IL-2/IL-17-NO pathway in the chicken nervous system. This study offers novel insights into environmental pollutant-caused animal poisoning and provides a novel theoretical basis for the detoxification effect of Se against oxidative stress and inflammation caused by toxic pollutants.
RESUMEN
Allergic disease is caused by exposure to normally innocuous substances that activate mast cells. Mast cell-mediated allergic inflammation is closely related to a number of allergic disorders, such as anaphylaxis, allergic rhinitis, asthma and atopic dermatitis. The discovery of drugs for treating allergic disease is an interesting subject and important to human health. The aim of the present study was to investigate the antiallergic and anti-inflammatory effects of the aqueous extract of Pogostemon cablin (Blanco) Benth (AEPC) (a member of the Labiatae family) using mast cells, and also to determine its possible mechanisms of action. An intraperitoneal injection of compound 48/80 or a serial injection of immunoglobulin E and antigen was used to induce anaphylaxis in mice. We found that AEPC inhibited compound 48/80induced systemic and immunoglobulin E-mediated cutaneous anaphylaxis in a dose-dependent manner. The release of histamine from mast cells was reduced by AEPC, and this suppressive effect was associated with the regulation of calcium influx. In addition, AEPC attenuated the phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated expression of pro-inflammatory cytokines in mast cells. The inhibitory effects of AEPC on pro-inflammatory cytokines were dependent on the activation of nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK). AEPC blocked the PMACI-induced translocation of NF-κB into the nucleus by hindering the degradation of IκBα and the phosphorylation of p38 MAPK. Our results thus indicate that AEPC inhibits mast cellmediated allergic inflammation by suppressing mast cell degranulation and the expression of pro-inflammatory cytokines caused by reduced intracellular calcium levels and the activation of NF-κB and p38 MAPK.
Asunto(s)
Anafilaxia/tratamiento farmacológico , Antialérgicos/uso terapéutico , Antiinflamatorios/uso terapéutico , Lamiaceae , Mastocitos/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Anafilaxia/inducido químicamente , Anafilaxia/inmunología , Animales , Antialérgicos/química , Antialérgicos/farmacología , Antiinflamatorios/química , Antiinflamatorios/farmacología , Calcio/inmunología , Degranulación de la Célula/efectos de los fármacos , Células Cultivadas , Citocinas/inmunología , Lamiaceae/química , Masculino , Ratones Endogámicos ICR , FN-kappa B/inmunología , Anafilaxis Cutánea Pasiva/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Ratas Sprague-Dawley , p-Metoxi-N-metilfenetilamina , Proteínas Quinasas p38 Activadas por Mitógenos/inmunologíaRESUMEN
The present paper discusses ultrasonic extraction method aided extraction of coumarin from a Mongolian drug, Chagan-sorlo (Radix Glehniae), aiming to study out how much coumarin contained in Chagan-sorlo, and to provide the scientific basis and production guidance for extracting coumarin from Chagan-sorlo. Under different conditions the coumarin in Chagan-sorlo was extracted by ultrasonic, measured and analyzed, and then HPLC was used to carry out the measurement. Result showed that with solvent volume fraction of 70%, extraction time of 20 min, ultrasonic power of 175 W, temperature of 25 degrees C, solid-liquid ratio of 1 : 20, and 80-100 mesh extraction, the coumarin extraction reaches the highest yield.
Asunto(s)
Apiaceae/química , Cumarinas/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Raíces de Plantas/química , Cromatografía Líquida de Alta Presión , Solventes , Temperatura , UltrasonidoRESUMEN
Biotransformation of deoxyandrographolide (1) by Alternaria alternata AS 3.4578 gave five derivatives identified by spectral methods including 2D NMR as the known dehydroandrographolide (2) and 9beta-hydroxy-dehydroandrographolide (3) and the new compounds 9beta-hydroxy-deoxyandrographolide (4), 3alpha,17,19-trihydroxy-8,13-ent-labdadien-15,16-olide (5) and 3-oxo-9beta-hydroxy-deoxyandrographolide (6).
Asunto(s)
Alternaria/metabolismo , Diterpenos/metabolismo , Andrographis/química , Biotransformación , Diterpenos/química , Estructura Molecular , Hojas de la Planta/química , Tallos de la Planta/químicaRESUMEN
Resibufogenin is one of the major active components of the Chinese medicine ChanSu. In this paper, microbial transformation of resibufogenin by Absidia coerules AS 3.3382 was investigated and five metabolites were isolated and identified as 5beta-hydroxy-resibufogenin (2), 3-epi-resibufogenin (3), 3alpha-hydroxy-15-oxo-14alphaH-bufa-20, 22-dienolide (4), 3alpha,14alpha,15beta-trihydroxy-bufa-20, 22-dienolide (5) and 3-epi-15beta-hydroxy-bufalin (6). Among them, 4-6 are novel compounds, and compound 3 is a major transformed product. The cytotoxicities of the compounds against Bel-7402 and Hela cells were investigated, and our result suggested that 14,15-OH configuration was directly related to the cytotoxicities of bufadienolides.
Asunto(s)
Absidia/metabolismo , Bufanólidos/metabolismo , Antineoplásicos/análisis , Biotransformación , Medicamentos Herbarios Chinos/metabolismo , Células HeLa/efectos de los fármacos , Humanos , Espectroscopía de Resonancia MagnéticaRESUMEN
OBJECTIVE: To define the effects of Astragalus membranaceus on the atrial dynamics and ANP secretion in the perfused beating rabbit atria. METHOD: The experiments have been done in isolated perfused beating rabbit atria. ANP was measured by radioimmunoassay in the atrial perfusate in real-time base. RESULT: A. membranaceus (2.0, 2.5, 3.0 g L(-1)) could increase atria stroke volume from (694.70 +/- 0.01) microL g(-1) (P<0.05) to (1,003.00 +/- 8.80) microL g(-1) (P<0.001); (1,120.00 +/- 17.71) microL g(-1) and (1,195.00 +/- 8.21) microL g(-1) (P<0.001), respectively, and its could difference increase atrial pulse pressure from (0.82 +/- 0.01) kPa to (0.86 +/- 0.01) kPa (P<0.01); (0.96 +/- 0.01) kPa (P<0.001) and (1.02 +/- 0.01) kPa (P<0.001), respectively; A. membranaceus obviously increased rabbit atrial dynamics with dose-dependent manner. Simultaneously, A. membranaceus inhibited ANP secretion. Nifedipine (1.0 micromol L(-1)), a L-type Ca2+ channel inhibitor, and KB-R 7943 (10.0 micromol L(-1)), an inhibitor of reversed Na+ -Ca2+ exchanger, blocked the effects of A. membranaceus-induced augmentation of atrial dynamics but failed to modulation the inhibition of A. membranaceus on ANP secretion. CONCLUSION: A. membranaceus increases the atrial dynamics via Na+ -Ca2+ exchanger and L-type Ca2+ channel and negatively modulates ANP secretion in beating rabbit atria.
Asunto(s)
Astragalus propinquus/química , Factor Natriurético Atrial/metabolismo , Medicamentos Herbarios Chinos/farmacología , Atrios Cardíacos/efectos de los fármacos , Atrios Cardíacos/metabolismo , Contracción Miocárdica/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/química , Femenino , Masculino , Nifedipino/farmacología , Conejos , Radioinmunoensayo , Tiourea/análogos & derivados , Tiourea/farmacologíaRESUMEN
The positive inotropic effect of the aqueous extract of Convallaria keiskei (ACK) and the possible mechanisms responsible for this effect were investigated in beating rabbit atria. ACK significantly increased atrial stroke volume, pulse pressure, and cAMP efflux in beating rabbit atria. The effects were not altered by pre-treatment with staurosporine and diltiazem, a non-selective protein kinase inhibitor and an L-type Ca2+ channel blocker, respectively. In addition, ACK markedly increased the K+ concentration in the beating atria-derived perfusate. Convallatoxin, a well-known digitalis-like cardiac glycosidic constituent of ACK, also increased atrial stroke volume and pulse pressure but did not alter the cAMP efflux level. The increases in atrial stroke volume and pulse pressure induced by convallatoxin were not also altered by pre-treatment with diltiazem. These results suggest that the ACK-induced positive inotropic effect in beating rabbit atria may, at least in part, be due to the digitalis-like activity of convallatoxin.