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Some pharmacokinetic parameters of salvianolic acid A following single-dose oral administration to rats

第一作者:Sun, JL

期刊: PHARMACEUTICAL BIOLOGY, 2018; 56 (无)

Context: Salvianolic acid A (Sal A) is a hydrophilic bioactive compound isolated from Salvia miltiorrhiza Bunge (Lamiaceae). It exerts beneficial effects after oral administration on diabetic complications. Objective: To systematically study the absorption, distribution and excretion of Sal A after single-dose oral administration. Materials and methods: Animal experiments were conducted in Sprague-Dawley rats. Plasma was sampled at designated times after oral doses of 5, 10 and 20 mg/kg, and an intravenous dose of 50 mu g/kg. Tissues were harvested at 10, 60 and 120 min postdosing. Bile, urine and feces were collected at specified intervals before and after dosing. Absorption and distribution characteristics were analyzed by LC-MS, and excretion characteristics were analyzed by UPLC-MS/MS. The Caco-2 cell model was applied to investigate potential mechanisms. Results: The C-max (5 mg/kg: 31.53 mu g/L; 10 mg/kg: 57.39 mu g/L; 20 mg/kg: 111.91 mu g/L) of Sal A increased linearly with doses (r>0.99). The calculated absolute bioavailability was 0.39-0.52%. Transport experiment showed poor permeability and the ratio of PB-A to PA-B was 3.13-3.97. The highest concentration of Sal A was achieved in stomach followed by small intestine and liver, and it could also be detected in brain homogenate. Approximately 0.775% of its administered dose was excreted via feces, followed by bile (0.00373%) and urine (0.00252%). Discussion and conclusions: These results support the future development of Sal A as an oral drug for the treatment of diabetic complications. Future research should be conducted to investigate the reason for its poor bioavailability and improve this situation.

IF:2.49

In vitro inhibitory effects of Friedelin on human liver cytochrome P450 enzymes

第一作者:Wei, JL

期刊: PHARMACEUTICAL BIOLOGY, 2018; 56 (无)

Context: Friedelin is a triterpenoid with several biological activities. However, the affects of Friedelin on the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Objective: This study investigates the inhibitory effects of Friedelin on the major human liver CYP isoforms (CYP3A4, 1A2, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8). Materials and methods: First, the inhibitory effects of Friedelin (100 mu M) on the eight human liver CYP isoforms were investigated in vitro using human liver microsomes (HLMs), and then enzyme inhibition, kinetic studies, and time-dependent inhibition studies were conducted to investigate the IC50, K-i and K-inact/K-i values of Friedelin. Results: The results indicate that Friedelin inhibited the activity of CYP3A4 and 2E1, with the IC50 values of 10.79 and 22.54 mu M, respectively, but other CYP isoforms were not affected. Enzyme kinetic studies showed that Friedelin is not only a noncompetitive inhibitor of CYP3A4, but also a competitive inhibitor of CYP2E1, with K-i values of 6.16 and 18.02 mu M, respectively. In addition, Friedelin is a time-dependent inhibitor of CYP3A4 with K-inact/K-i value of 4.84 nM/min. Discussion and conclusion: The in vitro studies of Friedelin with CYP isoforms suggested that Friedelin has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4 and 2E1. Further clinical studies are needed to evaluate the significance of this interaction.

IF:2.49

Bioinformatics analysis to identify action targets in NCI-N87 gastric cancer cells exposed to quercetin

第一作者:Zeng, Y

期刊: PHARMACEUTICAL BIOLOGY, 2018; 56 (无)

Context: Quercetin exerts antiproliferative effects on gastric cancer. However, its mechanisms of action on gastric cancer have not been comprehensively revealed. Objective: We investigated the mechanisms of action of quercetin against gastric cancer cells. Materials and methods: Human NCI-N87 gastric cancer cells were treated with 15 mu M quercetin or dimethyl sulfoxide (as a control) for 48 h. DNA isolated from cells was sequenced on a HiSeq 2500, and the data were used to identify differentially expressed genes (DEGs) between groups. Then, enrichment analyses were performed for DEGs and a protein-protein interaction (PPI) network was constructed. Finally, the transcription factors (TFs)-DEGs regulatory network was visualized by Cytoscape software. Results: A total of 121 DEGs were identified in the quercetin group. In the PPI network, Fos proto-onco-gene (FOS, degree = 12), aryl hydrocarbon receptor (AHR, degree = 12), Jun proto-oncogene (JUN, degree = 11), and cytochrome P450 family 1 subfamily A member 1 (CYP1A1, degree =11) with higher degrees highly interconnected with other proteins. Of the 5 TF-DEGs, early growth response 1 (EGR1), FOS like 1 (FOSL1), FOS, and JUN were upregulated, while AHR was downregulated. Moreover, FOSL7, JUN, and Wnt family member 7B (WNT7B) were enriched in the Wnt signaling pathway. Discussion and conclusions: CYP1A1 highly interconnected with AHR in the PPI network. Therefore, FOS, AHR, JUN, CYP1A1, EGR1, FOSL1, and WNT7B might be targets of quercetin in gastric cancer.

IF:2.49

Enhanced production of tanshinone IIA in endophytic fungi Emericella foeniculicola by genome shuffling

第一作者:Zhang, PY

期刊: PHARMACEUTICAL BIOLOGY, 2018; 56 (无)

Context: Tanshinone IIA, commercially produced from Salvia miltiorrhiza Bunge (C.Y.Wu) (Labiatae), has various biological benefits. Currently, this compound is mainly extracted from plants. However, because of the long growth cycle and the unstable quality of plants, the market demands can barely be satisfied. Objective: The genomic shuffling technology is applied to screen the high-yield tanshinone IIA strain, which could be used to replace the plant S. miltiorrhiza for the production of tanshinone IIA. The change in the production of tanshinone IIA is clarified by comparing it with the original strain. Materials and methods: Tanshinone IIA was extracted from Strains cells, which was prepared through 0.5 mL protoplast samples by using hypertonic solution I from two different strains. Then, it was analyzed by high-performance liquid chromatography at 30 degrees C and UV 270nm. Total DNA from the strains was extracted for RAPD amplification and electrophoresis to isolate the product. Results: In this study, a high-yield tanshinone IIA strain F-3.4 was screened and the yield of tanshinone IIA was increased by 387.56 +/- 0.02 mg/g, 11.07 times higher than that of the original strain TR21. Discussion: This study shows that the genetic basis of high-yield strains is achieved through genome shuffling, which proves that genome shuffling can shorten the breeding cycle and improve the mutagenesis efficiency in obtaining the strains with good traits and it is a useful method for the molecular breeding of industrial strains.

IF:2.49

Effects of psoralen on the pharmacokinetics of anastrozole in rats

第一作者:Zhang, YZ

期刊: PHARMACEUTICAL BIOLOGY, 2018; 56 (无)

Context: Psoralen and anastrozole are always used together for breast cancer patients in Chinese clinics. Objective: This study investigates the effects of psoralen on the pharmacokinetics of anastrozole in rats and its potential mechanism. Materials and methods: The pharmacokinetics of orally administered anastrozole (0.5 mg/kg) with (test group) or without (Control group) psoralen pretreatment (20 mg/kg/day for 10days) in male Sprague-Dawley rats (six rats in each group) were investigated. The plasma concentration of anastrozole was determined using a sensitive and reliable LC-MS/MS method. Additionally, the effects of psoralen on the intestine transport and metabolic stability of anastrozole (1 mu M) were investigated using a Caco-2 cell transwell model and rat liver microsome incubation systems. Results: The results indicated that psoralen could significantly increase the C-max (from 56.74 +/- 3.17 ng/mL to 83.26 +/- 6.87 ng/mL), and to(1/2) (from 10.80 +/- 1.05 to 14.29 +/- 1.38h) of anastrozole (p< 0.05). Psoralen could also significantly decrease the efflux ratio of anastrozole from 1.88 to 1.32 (p < 0.05). Additionally, the intrinsic clearance rates of anastrozole decreased significantly (from 62.83 to 43.97 mu L/min/mg protein) (p < 0.05) with psoralen pretreatment in rat liver microsome incubation systems. Discussion and conclusions: This study indicates that when the rats were pretreated with psoralen, the system exposure of anastrozole would be increased significantly. The results showed that the herb-drug interaction between psoralen and anastrozole might occur when they were co-administered, and future studies in humans also need to investigate its herb-drug interaction potential.

IF:2.49

Safranal-promoted differentiation and survival of dopaminergic neurons in an animal model of Parkinson's disease

第一作者:Zhao, Y

期刊: PHARMACEUTICAL BIOLOGY, 2018; 56 (无)

Context: Safranal (SAF) is verified to have potential effects in promoting nerve growth. Objectives: This study verifies the role of SAF in promoting dopaminergic neurons growth in vitro and in vivo. Material and methods: Rat neural stem cells (NSC) were treated with 1, 20, or 100 ng/mL of SAF, and the expression levels of tyrosine hydroxylase (TH) and dopamine transporter (DAT) were assayed by flow cytometry and real-time PCR and the secretion of dopamine (DA) was assayed by ELISA. Then, 2 x 10(6) cells of SAF-treated NSC was administrated into PD rat models induced by 6-OHDA. The differentiation and survival of dopaminergic neurons was identified by fluorescence microscope and TH+ cells by immunostaining and DA secretion by ELISA at week 2 and week 4, respectively. Results: After being treated with SAF at 20 and 100 ng/mL for 1 week, TH and DAT positive rates increased 1.4- and 1.7-fold (p < 0.01, respectively). TH and DAT mRNA also increased 8.05- and 4.41-fold, respectively. And the release of DA statistically increased 1.5-fold (p < 0.01). In vivo, the number of rotations decreased to 4.33 +/- 0.97 rpm (p < 0.01) and the survival rates increased to 77.66 +/- 7.87% (p < 0.05) at week 4 after transplantation of SAF-treated NSC. Moreover, the transplanted cells increased three-fold, TH fluorescence density increased four-fold and DA releases increased 1.4-fold (p < 0.01) at week 4 after transplantation. Conclusions: SAF promoted the production of functional DA cells and alleviated PD, which may contribute to a new therapy for PD patients.

IF:2.49

Green synthesis of selenium nanoparticles with extract of hawthorn fruit induced HepG2 cells apoptosis

第一作者:Cui, DX

期刊: PHARMACEUTICAL BIOLOGY, 2018; 56 (无)

Context: Selenium nanoparticles (SeNPs) have attracted worldwide attention due to their unique properties and potential bioactivities. Considering that hawthorn is both a traditional medicine and a common edible food, hawthorn fruit extract (HE) was chosen as a reductant to prepare SeNPs. Objective: SeNPs were synthesized by using an aqueous HE as a reductant and stabilizer. The antitumor activities and potential mechanisms of SeNPs were explored by using a series of cellular assays. Materials and methods: The HE mediated SeNPs (HE-SeNPs) were examined using various characterisation methods. The cytotoxicity was measured against HepG2 cells after treated with 0, 5, 10 and 20g/mL of HE-SeNPs for 24h. Annexin V-FITC/PI staining analysis was performed to observe the apoptosis of HepG2 cells. Additionally, mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) levels were evaluated. Finally, the protein expression levels of caspase-9 and Bcl-2 were identified by Western blot. Results: The mono-dispersed and stable SeNPs were prepared with an average size of 113nm. HE-SeNPs showed obvious antitumor activities towards HepG2 cells with an IC50 of 19.225.3g/mL. Results from flow cytometry revealed that both early and total apoptosis rates increased after treating with HE-SeNPs. After cells were treated with various concentrations of HE-SeNPs (5, 10 and 20g/mL) for 24h, the total rate increased to 7.3 +/- 0.5, 9.7 +/- 1.7 and 19.2 +/- 1.6%, respectively. Meanwhile, treatment of HE-SeNPs up-regulated intracellular ROS levels and reduced the MMP. In addition, HE-SeNPs induced the up-regulation of caspase-9 and down-regulation of Bcl-2. Discussion and conclusions: HE-SeNPs induced intracellular oxidative stress and mitochondrial dysfunction to initiate HepG2 cell apoptosis through the mitochondrial pathway. Therefore, HE-SeNPs may be a candidate for further evaluation as a chemotherapeutic agent for human liver cancer.

IF:2.49

Phylogenetic analysis of Uncaria species based on internal transcribed spacer (ITS) region and ITS2 secondary structure

第一作者:Zhu, S

期刊: PHARMACEUTICAL BIOLOGY, 2018; 56 (无)

Context: The plant genus Uncaria (Rubiaceae), also known as Gouteng, is the source of an important traditional Chinese medicine. Misidentification and adulteration of Gouteng affect the safety and efficacy of the medication. Phylogenetic relationships among the species of this genus are unknown. Objective: The present study sought to detect the phylogenetic relationships based on internal transcribed spacer (ITS) region of all 12 species of Uncaria recorded in the Flora of China. Materials and methods: Accession of seven species of Uncaria served as reference samples. ITS region was used for polymerase chain reaction (PCR) amplification of the reference samples representing 39 specimens. Distance analysis, species discrimination, and secondary structure of ITS2 were used to assess the ability of ITS sequence in authenticating. The phylogenetic relationships were detected using three methods: Bayesian inference (BI), maximum likelihood (ML), and neighbor joining (NJ). Results: Five species of traditional Chinese medicine Gouteng were well resolved in molecular phylogenetic tree. Besides, Uncaria lancifolia Hutch. was closer to U. rhynchophylloides F.C. How and U. sessilifructus Roxb. was closer to U. laevigata Wall. within the tree. Further, we also found that ITS2 secondary structure can be a candidate tool in distinguishing two closely related species U. yunnanensis K.C.Hsia and U. lanosa Wall. For accurate identification of different species of Uncaria based on species-specific nucleotide sites, a consensus sequences database with all 12 species is established. Discussions and conclusions: The results are able to discriminate Uncaria species and illustrate the phylogenetic relationships, which are essential for the investigation of adulterants and misidentifications of Uncaria.

IF:2.49

Ma Huang Tang ameliorates bronchial asthma symptoms through the TLR9 pathway

第一作者:Jiao, JY

期刊: PHARMACEUTICAL BIOLOGY, 2018; 56 (无)

Context: Ma Huang Tang (MHT) has been used to treat influenza, fever, bronchial asthma, etc. as a traditional Chinese medication. However, the anti-inflammation mechanism of MHT remains unclear. Objective: The study identifies the possible mechanisms of MHT on ovalbumin (OVA)-induced acute bronchial asthma in mice. Materials and methods: First, an asthma-related protein-protein interaction (PPI) network was constructed. And then, the acute bronchial asthma mice models were established by exposing to aerosolized 1% ovalbumin for 30 min/day for 1 week, and the mice were administered 2.0, 4.0, or 8.0 g/kg of MHT daily. To evaluate therapeutic effect, sensitization time, abdominal breathing time, eosinophils in bronchoalveolar lavage fluid, and tissue and trachea pathology were examined. Related genes were measured using RNA sequencing (RNA-seq). The expression levels of TLR9 in lung and trachea tissues were determined by immunohistochemical staining. Results: MHT had a LD50 = 19.2 g/kg against asthma, while MHT at high doses (8 g/kg) effectively extended the sensitization time and abdominal breathing time and alleviated OVA-induced eosinophilic airway inflammation and mitigated pathological changes. The RNA-seq assay showed that the high-dose MHT resulted in a significant decrease in the levels of TLR9, TRAF6, TAB2, etc. in the lung tissue. Immunohistochemical assay confirmed the down-regulated of TLR9. Molecular docking revealed that six MHT compounds potentially mediated the TLR9 signaling pathway. Discussion and conclusions: MHT could mitigate the pathological changes of acute asthma-like syndrome through inhibition of the TLR9 pathway. Results of this study may provide a reference for the development of a novel therapy for patients with allergic asthma.

IF:2.49

Comparing coagulation activity of Selaginella tamariscina before and after stir-frying process and determining the possible active constituents based on compositional variation

第一作者:Zhang, Q

期刊: PHARMACEUTICAL BIOLOGY, 2018; 56 (无)

Context: Selaginella tamariscina (P. Beauv.) Spring (Selaginellaceae) (ST) has been widely used in China as a medicine for improving blood circulation. However, its processed product, S. tamariscina carbonisatus (STC), possesses opposite haemostatic activity. Objective: To comprehensively evaluate the activity of ST and STC on physiological coagulation system of rats, and seek potential active substances accounting for the activity transformation of ST during processing. Materials and methods: The 75% methanol extracts of the whole grass (fine powder) of ST and STC were prepared, respectively. Male Sprague-Dawley rats were randomly divided into five groups: control group, model group, model+ST group, model+STC group and positive control group (model+Yunnanbaiyao). The duration of intragastric administration was 72 h at 12 h intervals. Haemorheology parameters were measured using an LB-2 A cone-plate viscometer and the existed classic methods, respectively. SC40 semi-automatic coagulation analyzer was employed to determine coagulation indices. Meanwhile, HPLC and LC-MS were applied for chemical analyses of ST and STC extracts. Results: STC shortened tail-bleeding time, increased whole blood viscosity (WBV) and plasma viscosity (PV), decreased erythrocyte sedimentation rate blood (ESR), reduced activated partial thromboplastin time (APTT) and increased the fibrinogen (FIB) content in the plasma of bleeding model rats. Although ST could shorten APTT and TT, the FIB content was significantly decreased by ST. Dihydrocaffeic acid with increased content in STC vs. ST showed haemostatic activity for promoting the platelet aggregation induced by collagen and trap-6, and reducing APTT and PT significantly with a concentration of 171.7 mu M in vitro. Amentoflavone with reduced content in STC vs. ST inhibited ADP and AA-induced platelet aggregation significantly with a concentration of 40.7 mu M. Discussion and conclusions: As the processed product of ST, STC showed strong haemostatic activity on bleeding rat through regulating the parameters involved in haemorheology and plasma coagulation system. Two active compounds, dihydrocaffeic acid and amentoflavone, might be partially responsible for the haemostatic and anticoagulant activity of STC and ST, respectively.

IF:2.49

Effects of Danshen tablets on pharmacokinetics of atorvastatin calcium in rats and its potential mechanism

第一作者:Sun, S

期刊: PHARMACEUTICAL BIOLOGY, 2018; 56 (无)

Context: Danshen tablets (DST), an effective traditional Chinese multi-herbal formula, are often combined with atorvastatin calcium (AC) for treating coronary heart disease in the clinic. Objective: This study investigated the effects of DST on the pharmacokinetics of AC and the potential mechanism. Materials and methods: The pharmacokinetics of AC (1mg/kg) with or without pretreatment of DST (100mg/kg) were investigated using LC-MS/MS. The effects of DST (50g/mL) on the metabolic stability of AC were also investigated using rat liver microsome incubation systems. Results: The results indicated that C-max (23.874.27 vs. 38.94 +/- 5.32ng/mL), AUC((0-t)) (41.01 +/- 11.32 vs. 77.28 +/- 12.92ngh/mL), and t(1/2) (1.91 +/- 0.18 vs. 2.74 +/- 0.23h) decreased significantly (p<0.05) when DST and AC were co-administered, which suggested that DST might influence the pharmacokinetic behavior of AC when they are co-administered. The metabolic stability (t(1/2)) of AC was also decreased (25.7 +/- 5.2 vs. 42.5 +/- 6.1) with the pretreatment of DST. Discussion and conclusions: This study indicated that the main components in DST could accelerate the metabolism of AC in rat liver microsomes and change the pharmacokinetic behaviors of AC. So these results showed that the herb-drug interaction between DST and AC might occur when they were co-administered. Therefore, the clinical dose of AC should be adjusted when DST and AC are co-administered.

IF:2.49

Effects of glycyrrhizin on the pharmacokinetics of asiatic acid in rats and its potential mechanism

第一作者:Guo, L

期刊: PHARMACEUTICAL BIOLOGY, 2018; 56 (无)

Context: Asiatic acid has been reported to possess a wide range of pharmacological activities. Objective: This study investigates the effects of glycyrrhizin on the pharmacokinetics of asiatic acid in rats and its potential mechanism. Materials and methods: The pharmacokinetics of orally administered asiatic acid (20 mg/kg) with or without glycyrrhizin pretreatment (100 mg/kg/day for seven days) were investigated using a LC-MS method. Additionally, the Caco-2 cell transwell model and rat liver microsome incubation systems were used to investigate the potential mechanism of glycyrrhizin's effects on the pharmacokinetics of asiatic acid. Results: The results showed that the C-max (221.33 +/- 21.06 vs. 324.67 +/- 28.64 ng/mL), AUC(0-inf) (496.12 +/- 109.31 vs. 749.15 +/- 163.95 mu g.h/L) and the t(1/2) (1.21 +/- 0.27 vs. 2.04 +/- 0.32 h) of asiatic acid decreased significantly (p < 0.05) with the pretreatment of glycyrrhizin. The oral clearance of asiatic acid increased significantly from 27.59 +/- 5.34 to 41.57 +/- 9.19 L/h/kg (p < 0.05). The Caco-2 cell transwell experiments indicated that glycyrrhizin could increase the efflux ratio of asiatic acid from 1.63 to 2.74, and the rat liver microsome incubation experiments showed that glycyrrhizin could increase the intrinsic clearance rate of asiatic acid from 138.32 +/- 11.20 to 221.76 +/- 16.85 mu L/min/mg protein. Discussion and conclusions: In conclusion, these results indicated that glycyrrhizin could decrease the system exposure of asiatic acid, possibly by inducing the activity of P-gp or CYP450 enzyme.

IF:2.49

Effects of triptolide on pharmacokinetics of amlodipine in rats by using LC-MS/MS

第一作者:Zhang, CY

期刊: PHARMACEUTICAL BIOLOGY, 2018; 56 (无)

Context: Triptolide and amlodipine are often simultaneously used for reducing urine protein excretion after renal transplantation in China clinics. Objective: This study investigated the effects of triptolide on the pharmacokinetics of amlodipine in male Sprague-Dawley rats. Materials and methods: The pharmacokinetics of amlodipine (1 mg/kg) with or without triptolide pre-treatment (2 mg/kg/day for sevendays) were investigated using a sensitive and reliable LC-MS/MS method. Additionally, the inhibitory effects of triptolide on the metabolic stability of amlodipine were investigated using rat liver microsome incubation systems. Results: The results indicated that when the rats were pre-treated with triptolide, the C-max of amlodipine increased from 13.78 +/- 3.57 to 19.96 +/- 4.56 ng/mL (p<0.05), the T-max increased from 4.04 +/- 1.15 to 5.89 +/- 1.64h (p<0.05), and the AUC(0-t) increased by approximately 104% (p<0.05), which suggested that the pharmacokinetic behaviour of amlodipine was affected after oral co-administration of triptolide. Additionally, the metabolic half-life was prolonged from 22.5 +/- 4.26 to 36.8 +/- 6.37min (p<0.05) with the pre-treatment of triptolide. Conclusions: In conclusion, these results indicated that triptolide could affect the pharmacokinetics of amlodipine, possibly by inhibiting the metabolism of amlodipine in rat liver when they are co-administered.

IF:2.49

Resveratrol mitigates the oxidative stress mediated by hypoxic-ischemic brain injury in neonatal rats via Nrf2/HO-1 pathway

第一作者:Gao, Y

期刊: PHARMACEUTICAL BIOLOGY, 2018; 56 (无)

Context: Hypoxic-ischemic encephalopathy (HIE) has a high morbidity and mortality rate. Resveratrol possesses numerous biological properties including antioxidant, anti-inflammatory and neuroprotective activities. Objective: The current experiment investigates the neuroprotective efficacy of resveratrol (RESV) against HIE by modulating Nrf2/HO-1 pathway in neonatal rats. Materials and methods: Seven-day-old pups (n=48) were divided into four groups. Group-I rats receiving 2% DMSO saline (sham), group-II rats underwent unilateral carotid artery ligation and hypoxia (92% N-2 and 8% O-2) for 2.5 h (hypoxia-ischemia; HI), group-III and IV rats received 20 (RESV 20 + HI) or 40 mg/kg (RESV 40 + HI; group-IV) of RESV via intraperitoneal injection (ip), respectively, for 7 days prior to HI induction. Results: Pre-treatment with RESV (20 or 40) markedly reduced (p < 0.01) the cerebral oedema (86.23-71.26 or 65.24%), infarct area (33.85-19.81 or 14.30%), lipid peroxidation products, inflammatory markers [IL-1 beta 186-110 or 82; IL-6 255-146 or 103; TNF-alpha 310-204 or 137; NF-kappa B 205-115 or 91) p65 subunit] and significantly restored (p < 0.01) the antioxidative status by enhancing the activities of glutathione peroxidase (GPx) 5.22-6.49 or 7.78; catalase (CAT) 51-55 or 59, superoxide dismutase (SOD) 2.5-3.05 or 3.25; through marked upregulation (p < 0.01) of heme oxygenase 1 (HO-1) 0.65-0.69 or 0.73; and nuclear factor erythroid 2 related factor 2 (Nrf2) 0.73-0.86 or 0.91. Discussion and Conclusions: RESV displays its neurotherapeutic potential via upregulating the protein expression of Nrf2 and HO-1 signalling pathway and thereby attenuates oxidative stress and inflammatory response in HI-induced neonatal rats.

IF:2.49

Mechanism of TangGanJian on nonalcoholic fatty liver disease with type 2 diabetes mellitus

第一作者:Fan, YB

期刊: PHARMACEUTICAL BIOLOGY, 2018; 56 (无)

Context: TangGanJian (TGJ) has a curative effect in the clinical treatment of nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes mellitus (T2DM), while the mechanism involved in the treatment process remains unclear. Objective: This study details the mechanism of TGJ on the treatment of NAFLD with T2DM. Materials and methods: NAFLD was induced in T2DM rat model. Male Wistar rats were assigned into six groups: Group I (control), Group II (model), Group III (pioglitazone, 0.5 mg/kg), Group IV (high dose of TGJ, 24.8 g/kg), Group V (middle dose of TGJ, 12.4 g/kg) and Group VI (low dose of TGJ, 6.2 g/kg). All rats in each group were treated with the corresponding drugs by gavage for 8 weeks. Haematoxylin and eosin analysis was conducted. The indicators of inflammatory and oxidative stress were analysed utilizing one-way ANOVA. Results: The contents of TNF-alpha (15.794 +/- 3.302 pg/mL), IL-6 (76.801 +/- 8.491 pg/mL), IL-1 beta (100.101 +/- 13.150 pg/mL), CRP (1.052 +/- 0.079 pg/mL) and MDA (3.972 +/- 0.159 pg/mL) were obviously elevated in NAFLD with T2DM rats compared to controls. Except for the IL-6, the levels of other markers declined in a dose-dependent manner after treatment with TGJ. The SOD (14.139 +/- 1.479 U/mgprot) and GSH-PX (81.511 +/- 5.276 U/mgprot) levels significantly decreased in NAFLD with T2DM rats, while the levels of these indicators increased after treatment with TGJ. Conclusions: TGJ may be a therapy for the NAFLD with T2DM rats by modulating the inflammatory response and the oxidative stress capacity.

IF:2.49

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