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This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 ℃ for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.
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Ratones , Animales , Antioxidantes/análisis , Extractos Vegetales/farmacología , Medicamentos Herbarios Chinos/química , Rizoma/química , Paeonia/química , Glutatión/análisisRESUMEN
For the first time, this study evaluated the gender differences and mechanisms of the antidepressant effects of raw Rehmanniae Radix(RRR) based on the classic depression model with traditional Chinese medicine syndrome of Yin deficiency and internal heat. The depression model with Yin deficiency and internal heat was established by the widely recognized and applied method of thyroxine induction of the classic depression model with Yin deficiency and internal heat(chronic unpredictable mild stress). Male and female mice were simultaneously treated with RRR. The study analyzed indicators of nourishing Yin and clearing heat, conventional antidepressant efficacy test indicators, and important biomolecules reflecting the pathogenesis and prevention and treatment mechanisms of depression, and conducted a correlation analysis of antidepressant efficacy, Yin-nourishing and heat-clearing efficacy, and biological mechanism in different genders, thereby comprehensively assessing the antidepressant effects of RRR on depression of Yin deficiency and internal heat, as well as its gender differences and mechanisms. RRR exhibited antidepressant effects in both male and female mouse models, and its antidepressant efficacy showed gender differences, with a superior effect observed in females. Moreover, the effects of RRR on enhancing or improving hippocampal neuronal pathology, nucleus-positive areas, postsynaptic dense area protein 95, and synaptophysin protein expression were more significant in females than in males. In addition, RRR significantly reversed the abnormal upregulation of nuclear factor(NF)-κB/cyclooxygenase 2(COX2)/NOD-like receptor thermal protein domain associated protein 3(NLRP3) pathway proteins in the hippocampus of both male and female mouse models. The antidepressant effects of RRR were more pronounced in depression female mice with Yin deficiency and internal heat syndrome, possibly due to the improvement of neuronal damage and enhancement of neuroplasticity. The antidepressant mechanisms of RRR for depression with Yin deficiency and internal heat syndrome may be associated with the downregulation of the NF-κB/COX2/NLRP3 pathway to reduce neuronal damage and enhance neuroplasticity.
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Masculino , Femenino , Ratones , Animales , Deficiencia Yin , Proteína con Dominio Pirina 3 de la Familia NLR , Factores Sexuales , Ciclooxigenasa 2 , FN-kappa B , Antidepresivos/farmacologíaRESUMEN
This study aims to investigate the detoxification effects of different processing methods on the cardiotoxicity induced by radix Tripterygium wilfordii, and preliminarily explore the detoxification mechanism via the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase 1(HO-1) pathway. The raw and processed products [stir-fried product, product stir-fried with Lysimachiae Herba(JQC), product stir-fried with Phaseoli Radiati Semen(LD), product stir-fried with Paeoniae Radix Alba(BS), product stir-fried with Glycyrrhizae Radix et Rhizoma(GC), and product stir-fried with vinegar(CZ)] of radix T. wilfordii were administrated to mice by gavage at a dose of 2 g·kg~(-1)(based on crude drugs) for 28 days. Twenty-four hours after the last administration, we measured the serum biochemical indexes of mice to evaluate the detoxification effect. Furthermore, we determined the expression of key proteins of Nrf2/HO-1 pathway in mouse heart tissue by Western blot and some oxidation/antioxidation-related indexes by corresponding kits to explore the detoxification mechanism. The administration of the raw product elevated the levels of serum creatine kinase, lactate dehydrogenase, and malondialdehyde, a product of cardiac lipid peroxidation(P<0.01), down-regulated the protein levels of Nrf2 and HO-1(P<0.01), and reduced the levels of total superoxide dismutase, glutathione, glutathione peroxidase, and glutathione S-transferase(P<0.01). However, after the administration of the products stir-fried with JQC, LD, BS, GC, and CZ, the abnormalities of the above indexes induced by the raw product were recovered(P<0.05 or P<0.01). In particular, the product stir-fried with JQC showed the best performance. Taken all together, the cardiotoxicity induced by radix T. wilfordii could be attenuated by stir-frying with JQC, LD, BS, GC, and CZ, and the stir-frying with JQC showed the best detoxification effect. The mechanism might be associated with the cardiac antioxidant defense and oxidative damage mitigation mediated by the up-regulated Nrf2.
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Animales , Ratones , Antioxidantes/farmacología , Cardiotoxicidad , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , TripterygiumRESUMEN
On the basis of the previous work of the research group, the orthogonal design method was further used to optimize the processing technology for reducing toxicity of fried Tripterygium wilfordii in Lysimachia christinae Decoction. A total of 9 processed products of T.wilfordii in L.christinae decoction were prepared by four factors and three levels orthogonal design table. The contents of triptolide in T.wilfordii were determined by high performance liquid chromatography(HPLC) before and after processing: 4.27, 3.92, 3.57, 2.75, 2.42, 2.66, 3.51, 1.87, 1.75, 2.03 μg·g~(-1). On this basis, the above processed products were orally given to mice for 28 days. 12 hours after the last administration, food fasting except water was provided, and 24 hours later, the eyeballs were taken for blood and liver tissue. Serum biochemical indexes, liver lipid peroxidation and antioxidant related indexes were detected by kit method. Twenty-eight days after oral administration of raw T.wilfordii, the levels of serum alanine aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP) and liver malondialdehyde(MDA) in mice increased by 91%(P<0.01), 46%(P<0.05), 73%(P<0.01) and 99%(P<0.01), while the liver antioxidant indexes such as superoxide dismutase(SOD), glutathione(GSH), glutathione peroxidase(GPX) and glutathione-S transferase(GST) significantly decreased(P<0.01). After administration of the processed products, the above indexes were significantly reversed(P<0.01 or P<0.05). Especially, the processing conditions of A_3B_2C_1D_3 had the best detoxification effect on T.wilfordii, which decreased the high levels of AST, ALT, ALP and MDA by 49%(P<0.01), 32%(P<0.01), 42%(P<0.01), and 17%(P<0.05). Therefore, the best processing conditions for T.wilfordii in L.christinae decoction were A_3B_2C_1D_3, namely "15% mass fraction of L.christinae, 1 h moistening time, 160 ℃ frying temperature, and 9 min frying time".
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Animales , Ratones , Antioxidantes , Hígado , Primulaceae , Tecnología , TripterygiumRESUMEN
Objective:To investigate the effect of different extracts of Lysimachiae Herba on the main toxicity induced by Tripterygii Radix et Rhizoma. Method:Ninety male SPF Kunming mice were randomly divided into 9 groups according to their body weight,control group, Lysimachiae Herba water extract group, Lysimachiae Herba 30% ethanol extract group, Tripterygii Radix et Rhizoma group, Tripterygii Radix et Rhizoma combined with Lysimachiae Herba water extract group, Tripterygii Radix et Rhizoma combined with Lysimachiae Herba 30% ethanol extract group, Tripterygii Radix et Rhizoma combined with Lysimachiae Herba 60% ethanol extract group, Tripterygii Radix et Rhizoma combined with Lysimachiae Herba 95% ethanol extract group and Tripterygii Radix et Rhizoma combined with Lysimachiae Herba ethyl acetate extract group. The dosage of Tripterygii Radix et Rhizoma and Lysimachiae Herba were 2,1 g·kg<sup>-1</sup> based on crude drugs, respectively. The control group was given an equal volume of solvent, and each group was given by gavage for 14 consecutive days. The blood and liver tissues were taken 24 hours after the last administration. The enzyme linked immunosorbent assay (ELISA) was used to detect serum biochemical indexes and liver lipid peroxidation/antioxidant indexes in mice. Meanwhile, principal component analysis was used to evaluate the attenuating effect and the mechanism of Lysimachiae Herba extract on toxicity of Tripterygii Radix et Rhizoma. Result:Compared with control group, Tripterygii Radix et Rhizoma caused the levels of alanine aminotransferase(ALT),aspartic acid amino transferase(AST),alkaline phosphatase(ALP) in serum of mice, and the levels of malondialdehyde (MDA) in liver, and comprehensive score of toxicity (Z value) produced by the above four indexes increased significantly (<italic>P</italic><0.01). The levels of total superoxide dismutase (T-SOD),glutathione-peroxidase (GPX),glutathione-S transferase (GST) decreased significantly (<italic>P</italic><0.01) in liver. Compared with Tripterygii Radix et Rhizoma group, after intervention with extracts of two solvents (water, 30% ethanol) of Lysimachiae Herba, the levels of serum ALT, AST, ALP and liver MDA were significantly decreased (<italic>P</italic><0.05, <italic>P</italic><0.01), while the levels of liver T-SOD, GPX and GST were significantly increased (<italic>P</italic><0.01). After intervention with extracts of two solvents (60% ethanol, 95% ethanol) of Lysimachiae Herba, the levels of serum ALT, AST, ALP were significantly decreased (<italic>P</italic><0.01), and liver GPX levels were significantly increased (<italic>P</italic><0.01). After the intervention with ethyl acetate extract of Lysimachiae Herba, only the level of serum AST was significantly decreased (<italic>P</italic><0.05) and the level of GPX was significantly increased (<italic>P</italic><0.05). After the intervention with extracts of different solvents (water, 30% ethanol, 60% ethanol, 95% ethanol, ethyl acetate) of Lysimachiae Herba, it can significantly reduce the comprehensive score of toxicity (<italic>P</italic><0.01). The overall decline rates of toxicity were 127.5%, 113.4%, 98.1%, 56.3% and 31.0% respectively. Among them, the toxicity reduction rate of the extracts with water as a solvent was 14.1%, 29.4%, 71.2%, 96.5% higher than those of other solvent extracts with ethanol. Conclusion:The extracts of different solvents (water, 30% ethanol, 60% ethanol, 95% ethanol and ethyl acetate) of Lysimachiae Herba can reverse the toxicity induced by Tripterygii Radix et Rhizoma in varying degrees. Among them, water and 30% ethanol are the best solvents for detoxification, especially water as the extraction solvent, and with the increase of ethanol content or fat solubility of extraction solvent, the detoxification shows a downward trend.
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Objective: To overall evaluate the mutual detoxication mechanism of Tripterygii Radix et Rhizoma(LGT) compatible with Lysimachiae Herba(JQC) in tumor-bearing state.Method: Twelve differentially characteristic components before and after compatibility were used as chemical composition spectrum,six indicators including serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine(Cr) and urea nitrogen(BUN),malondialdehyde(MDA) levels in the liver and kidney tissues were used as attenuation spectrum,and twelve biological indicators including glutathione(GSH),glutathione-S-transferase(GST),glutathione peroxidase(GPx),superoxide dismutase(SOD),catalase(CAT) and interleukin(IL)-10 in the liver and kidney were used as the biological information spectrum.Mutual detoxication mechanisms of LGT compatible with JQC in tumor-bearing state were overall evaluated by principal component analysis(PCA),and the contribution of chemical components and biological indicators to mutual detoxication was further evaluated by gray correlation analysis(GCA) of "chemical composition spectrum-attenuation spectrum-biological information spectrum".Result: Compared with the model group,the attenuation spectrum scores Z values of S180(Z1 value) and H22(Z3 value) increased significantly after LGT being used alone(PZ1 value and Z3 value caused by LGT when the ratio of LGT and JQC was 4:1,2:1,1:1,1:2 and 1:4(PZ values(Z1 value and Z3 value) of LGT-JQC in the mass ratios including 4:1,1:1,1:2 and 1:4 was significantly higher than that in the ratio of 2:1(PZ values of the bioinformatics scores in the S180(Z2 value) and H22(Z4 value) tumor-bearing state,these two values were significantly increased after compatibility with JQC.The chemical components contributing the most to the attenuating effect of S180 and H22 in tumor-bearing state were 3# and 10#,respectively.The most important biological indicators were kidney GPx and renal GSH.Conclusion: LGT combined with JQC in the mass ratio of 4:1-1:4 can attenuate LGT-induced subacute toxicity in S180 and H22 tumor-bearing state,and the best ratio of such effect is 2:1.The attenuating effect reflects the thought of "there is no reason why there is no meteorology".The mechanism of attenuating action involves antioxidative damage and anti-inflammatory reaction of the liver and kidney,especially the renal GPx(S180) and renal GSH(H22) as the greatest contribution to the detoxication mechanism.
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Objective: To strengthen the quality control of musculoskeletal ultrasound (MSKUS) equipment so as to enhance medical service level. Methods: The application status of MSKUS was analyzed, and the management system of MSKUS equipment was established. And hospital strengthened the quality control of equipment and the talent cultivation, and function department combined with function examination department to carry out application research of MSKUS technique for patients with traumatic superficial soft tissue injury. And the accuracy of examination about injury between MSKUS and MRI was compared. Results: Through established quality control system of MSKUS equipment and adopted relative measures, the failure rates of ultrasonic equipment decreased by 98% than before that, and the accuracy rates of examination was nearly 100%, and the errors rates of operation significantly decreased. On the other hand, the difference of examination accuracy between MSKUS and MRI was not significant, while the treatment cost of MSKUS was lower than that of MRI and it enhanced the medical service quality. Conclusion:Through strengthened the management of MSKUS equipment and established the quality control system, hospital can promote the constant improvement of the management of ultrasound equipment, and extend the application range of MSKUS equipment, and effectively enhance the medical services quality.
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Objecttve To compare the difference of relaxation distribution of zonule in different orientations between primary angle closure suspects (PACS) and normal controls,and to explore the role of latent subluxated lens in the pathogenesis of glaucoma.Methods Together 19 eyes of 19 PACS (PACS group) and 19 eyes of 19 age-,gender-and eye-matched normal controls (control group) were enrolled in this study.Pentacam was performed under standardized dark conditions before and 30 min after instillation of compound tropicamide eye drop.Peripheral anterior chamber depth (peri-ACD) of 8 orientations (superior,temporal superior,temporal,temporal inferior,inferior,nasal inferior,nasal,nasal superior position) in the central 4 mm diameter was measured automatically in each eye.The differences of peri-ACD (△ peri-ACD) before and after mydriasis were measured to reflex the relaxation of zonule.The difference of peri-ACD in 8 orientations after mydriasis could confirm the possibility of latent subluxated lens,and its range could verify the degree of lens deviation.Results Significant difference was observed in each groups in terms of △peri-ACD (P<0.001,0.043).The △peri-ACD of the temporal inferior position was (0.40 ± 0.28)mm in PACS group,which was smaller than that in the control group [(0.55 ±0.15)mm] (P =0.041),but no significant difference was observed between PACS patients and normal controls in other orientations (all P > 0.05).And significant difference was detected between the 8 positions of peri-ACD after mydriasis in each groups (P =0.001,0.009),and these parameters between the two groups were also significantly different (all P < 0.01).Moreover,there was no significant difference in the difference of between the minimum and maximum peri-ACD in the PACS group and the control group [(0.35 ± 0.18)mm vs.(0.43 ± 0.28) mm] (P =0.362).Conclusion The uneven relaxation distribution of zonule may exist in both PACS patients and normal controls,and the relaxation of zonule may be significant in temporal inferior position in PACS patients.
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AIM: To explore the differences of anterior segment parameters in the patients with fellow eyes of unilateral acute angle-closure glaucoma ( AACG ) , primary angle-closure suspects ( PACS) and normal group. METHODS: Twenty-six eyes of 26 patients with fellow eyes of AACG, 28 eyes of 28 age- and gender-matched PACS and 34 normal eyes were imaged using optical coherence tomography ( OCT) and pentacam scheimpflug system ( Pentacam ) . Anatomical parameters including central corneal thickness ( CCT ) , corneal volume ( CV ) , pupillary diameter ( PD ) , central anterior chamber depth ( CACD ) , peripheral anterior chamber depth ( PACD ) , anterior chamber volume ( ACV ) and anterior chamber angle ( ACA) were obtained from Pentacam. Iris thickness (IT750,IT2000), cross-sectional area (IS), volume (IV) and angle opening distance 500 (AOD500) were estimated using OCT combined with a computer image processing. Statistic analysis was performed with SPSS. RESULTS: There were no significant differences in corneal parameters (CCT, CV), PD and iris values (IT750, IT2000, IS, IV) among the three groups (P> 0. 05). Compared with the fellow eyes of AACG and PACS, normal eyes had larger ACV, wider AOD500 and ACA, deeper CACD and PACD ( P 0. 05). Using the fellow eyes of AACG as the standard to predict high risk of angle closure, areas under the receiver operating characteristic curve of the above parameters were all less than 0. 7. CONCLUSION:All the anterior segment parameters are no different significantly between the fellow eyes of AACG and PACS. They may be notaccurate criteria for determining high risk group of PACS.
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AIM: To evaluate the diagnostic accuracy of macular ganglion cell - inner plexiform layer ( GCIPL ) measurements using high- definition optical coherence tomography ( Cirrus HD - OCT ) ganglion cell analysis algorithm for detecting early and moderate to severe glaucoma. METHODS:Twenty normal control persons, 26 patients with early glaucoma and 29 patients with moderate to severe glaucoma were enrolled in this study. Macular GCIPL, optic nerve head ( ONH ) parameters and peripapillary retinal nerve fiber layer ( RNFL ) thickness were measured in each subject. Then all measured results of each parameter were calculated using SPSS17. 0. Areas under the receiver operating characteristic curves ( AUC) of each parameter were calculated to compare the diagnostic accuracy for detecting early and moderate to severe glaucoma. RESULTS: For detecting early glaucoma, AUC of average RNFL and seven clock value of RNFL were the biggest ( 0. 871 and 0. 896 respectively ), the AUC of parameters in GCIPL were also significant, among them, the average GCIPL showed bigger AUC(0. 847) than the minimum GCIPL (0. 812). For diagnosing moderate to severe glaucoma, the AUC of rim area was 0. 992, which was bigger than that of average RNFL ( 0. 991 ). The minimum GCIPL showed bigger AUC ( 0. 983 ) than the average GCIPL (0. 967). For early glaucoma diagnosis, the sensitivity of average RNFL was the highest (76. 9%), while the average GCIPL has the highest specificity (93. 5%). CONCLUSION: AS a new diagnostic parameter for detecting glaucoma, GCIPL shows similar diagnostic potential compared with RNFL. For early glaucoma diagnosis, average RNFL is the most important parameter, while screening early glaucoma, average GCIPL should be paid more attention.
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OBJECTIVE: To investigate the antidepressant-like effect of extracts from dried root of Rehmannia glutinosa Libosch. (Dihuang) (RG).
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<p><b>OBJECTIVE</b>To study the effect of matrine on Fas, VEGF, and activities of telomerase of MCF-7 cells.</p><p><b>METHODS</b>In vitro cultured human breast cancer MCF-7 cells were randomly divided into the experimental group and the control group. The matrine solution was added in cells of the experimental group. Equal volume of culture medium was added in cells of the control group or the negative control group. Zedoary Turmeric Oil, the telomerase inhibitor was added in cells of the positive control group. Morphological changes were observed under an inverted microscope. The telomerase activity was detected by TRAP-ELISA. Expressions of Fas and VEGF protein were detected by immunocytochemical assay.</p><p><b>RESULTS</b>Matrine obviously inhibited the growth and induced apoptosis of breast cancer cells. MCF-7 cells were treated by matrine of different concentrations at 24, 48, and 72 h, the telomerase activity gradually decreased along with increased matrine concentration and prolonged action time, showing dose-effect and time-effect positive relations. Matrine could up-regulate Fas protein expression and downregulate VEGF protein expression of MCF-7 cells.</p><p><b>CONCLUSION</b>Matrine showed obvious effect in inhibiting the growth of MCF-7 cells and promoting the apoptosis, which might be achieved by up-regulating the expression of Fas protein, inhibiting telomerase activity induced apoptosis of breast cancer cells, down-regulating the expression of VEGF protein, and inhibiting the tumor vascular formation.</p>
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Femenino , Humanos , Alcaloides , Farmacología , Apoptosis , Células MCF-7 , Quinolizinas , Farmacología , Telomerasa , Metabolismo , Factor A de Crecimiento Endotelial Vascular , Metabolismo , Receptor fas , MetabolismoRESUMEN
OBJECTIVE: To investigate the hepatoprotective effects of Lysimachia christinae Hance against acute liver injury induced by tripterygium glycosides (TG) in vivo and the related mechanism for the first time. METHODS: The mice were administered ethanol extract of L. christinae (JE), water extract of L. christinae (JW), and bifendate by ig for seven consecutive days. 12 h after the last dose, the mice were orally given TG 270 mg · kg-1 except those in the normal group. Serum and liver tissue samples were collected at 18 h after TG treatment. Besides, the amounts of quercetin and kaempferol in JE and JW were analyzed by high-performance liquid chromatography (HPLC). RESULTS: TG-induced elevated serum alanine transferase(ALT) and aspartate transaminase (AST) activities were significantly reduced by JE(100, 200 mg · kg-1) in dose-dependent manners, but not by JW. Further analysis demonstrated that lipid peroxidation(LPO) level significantly decreased, while superoxide dismutase(SOD) and catalase(CAT) activities increased in livers of JE-treated mice. Besides, the amounts of quercetin and kaempferol were 9.8 and 8.9 mg · g-1 in JE, and 2.8 and 1.9 mg · g-1 in JW, respectively. CONCLUSION: This study for the first time demonstrates that L. christinae can protect against TG-induced acute liver injury in dose-dependent manners in vivo, the potential mechanism may be related to inhibiting liver oxidative stress injury, and the hepatoprotective activity may be correlated with the contents of quercetin and kaempferol. Copyright 2013 by the Chinese Pharmaceutical Association.
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Metabolic profile of bile acids was used to evaluate hepatotoxicity of mice caused by ethanol extraction of Dioscorea bulbifera L. (ethanol extraction, ET) and diosbulbin B (DB), separately. Ultra-performance liquid chromatography coupled with quadrupole mass spectrometry (UPLC-MS) was applied to determine the contents of all kinds of endogenous bile acids including free bile acids, taurine conjugates and glycine conjugates. Obvious liver injuries could be observed in mice after administrated with ET and DB. Based on the analysis using principle components analysis (PCA), toxic groups could be distinguished from their control groups, which suggested that the variance of the contents of bile acids could evaluate hepatotoxicity caused by ET and DB. Meanwhile, ET and DB toxic groups were classified in the same trends comparing to control groups in the loading plot, and difference between the two toxic groups could also be observed. DB proved to be one of the toxic components in Dioscorea bulbifera L. Bile acids of tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), taurodeoxycholic acid (TDCA), cholic acid (CA) and others proved to be important corresponds to ET and DB induced liver injury according to analysis of partial least square-discriminant analysis (PLS-DA) and the statistical analysis showed that there were significant differences between the control groups and toxic groups (P < 0.01). Furthermore, good correlation could be revealed between the foregoing bile acids and ALT, AST. It indicated that taurine conjugated bile acids as TUDCA, TCDCA, TCA and TDCA along with CA could be considered as sensitive biomarkers of ET and DB induced liver injury. This work can provide the base for the further research on the evaluation and mechanism of hepatotoxicity caused by Dioscorea bulbifera L.
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Animales , Masculino , Ratones , Ácidos y Sales Biliares , Metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas , Metabolismo , Ácido Cólico , Metabolismo , Cromatografía Líquida de Alta Presión , Métodos , Dioscorea , Toxicidad , Medicamentos Herbarios Chinos , Toxicidad , Compuestos Heterocíclicos de 4 o más Anillos , Toxicidad , Análisis de los Mínimos Cuadrados , Ratones Endogámicos ICR , Plantas Medicinales , Toxicidad , Análisis de Componente Principal , Rizoma , Toxicidad , Espectrometría de Masas en Tándem , Métodos , Ácido Tauroquenodesoxicólico , Metabolismo , Ácido Taurocólico , Metabolismo , Ácido Taurodesoxicólico , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To investigate the effect of carbon disulfide (CS2) on inducible nitric oxide synthase (iNOS) and apoptosis in in the retina of rats.</p><p><b>METHODS</b>Twenty-four male SD rats were randomly divided into 3 groups the control group, the group receiving high-dose CS2 and the group receiving low-dose CS2. After treatment, retina were harvested and made into slice. The thickness of inner retina including outer plexiform layer, inner nuclear layer, ganglion cell layer, optic nerve fiber and inner limiting membrane was measured. Expression of iNOS in retina was measured by NADPH-NDP histochemical assay. Apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL).</p><p><b>RESULTS</b>(1) The thickness of inner retina decreased in groups receiving CS2. There was significant difference between control group and groups receiving CS2 (P < 0.05). There was also significant difference between group receiving high-dose CS2 and group receiving low-dose CS2 (P < 0.05). (2) The expression of iNOS increased in groups receiving CS2. There was significant difference between control group and groups receiving CS2 (P < 0.05 or P < 0.01). There was also significant difference between the group receiving high-dose CS2 and the group receiving low-dose CS2 (P < 0.05). (3) Apoptosis was observed in groups receiving CS2. There were significant differences in apoptosis index between the control group and groups receiving CS2 (P < 0.05 or P < 0.01). There was also significant difference between the group receiving high-dose CS2 and the group receiving low-dose CS2 (P < 0.05).</p><p><b>CONCLUSIONS</b>CS2 can evoke the expression of iNOS, and the nitric oxide thus produced can be one of the causes of retina destruction. And apoptosis is also one of the causes of retina destruction.</p>