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Berberine reverses LPS-induced repression of CYP7A1 through an anti-inflammatory effect 被引量:3
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作者 Bei Cao run-bin sun +3 位作者 Geng Yan Guang-yu Yang Ji-ye Aa Juan Li 《Chinese Herbal Medicines》 CAS 2019年第3期292-298,共7页
Objective: To evaluate the anti-inflammatory effect of berberine(BBR) on the lipopolysaccharide(LPS)-induced acute phase response and its modulation of the altered bile acid metabolism induced by LPS treatment.Methods... Objective: To evaluate the anti-inflammatory effect of berberine(BBR) on the lipopolysaccharide(LPS)-induced acute phase response and its modulation of the altered bile acid metabolism induced by LPS treatment.Methods: An acute phase response was induced by intraperitoneal injection of LPS(5 mg/kg, ip) in C57 BL/6 J mice, and the BBR treatment group was orally administered with BBR(200 mg/ky, ig). The levels of TNFα, IL-1β and IL-6 in the serum were measured using an ELISA kit, and their expression levels in the liver were measured using q RT-PCR. The bile acid pool was measured using a commercial bile acid kit, and the expression levels of enzymes involved in bile acid metabolism were measured by q RTPCR. The expression levels of CYP7 A1, p65 NF-κ B and the MAPK signaling pathway was measured using Western blotting.Results: LPS treatment suppressed the expression of CYP7 A1 and CYP8 B1, and the total bile acid pool was also reduced. Pretreatment with BBR inhibited the pro-inflammatory biomarkers TNFα and IL-1β in the serum, as well as the expression of TNFα, IL-1β and i NOS mRNA in the liver. BBR treatment did not affect the reduction in the bile acid pool size induced by LPS, but significantly increased the concentration of bile acids in the liver, which was consistent with the upregulated expression of CYP7 A1 and CYP8 B1. The MAPK signaling pathway was activated by BBR treatment, while the p65 NF-κ B signaling pathway was inhibited.Conclusion: BBR can offer an anti-inflammatory effect and reverse the inhibition of CYP7 A1 and CYP8 B1 expression caused by LPS treatment, as well as induce the production of bile acids in liver, probably via MAPK signaling;However, treatment with BBR had no effect on the size of total bile acid pool. 展开更多
关键词 BERBERINE BILE ACIDS CYP7A1 inflammation LPS
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Sensitive Analysis and Pharmacokinetic Study of Berberrubine Using LC-MS/MS 被引量:2
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作者 Yu-qing Zhao Na Yang +7 位作者 Fei Fei run-bin sun Si-qi Feng Jun He Jing-qiu Huang Yue Xie Ji-ye Aa Guang-ji Wang 《Chinese Herbal Medicines》 CAS 2017年第3期236-249,共14页
Objective To develop a sensitive and reproducible liquid chromatography-tandem mass spectrometry(LC-MS/MS) method to evaluate the pharmacokinetic behavior of berberrubine(BRB) and its glucuronide(BRBG) in rats. ... Objective To develop a sensitive and reproducible liquid chromatography-tandem mass spectrometry(LC-MS/MS) method to evaluate the pharmacokinetic behavior of berberrubine(BRB) and its glucuronide(BRBG) in rats. Methods BRB, BRBG and tetrahydroberberine(THB, internal standard) were isolated by liquid-liquid extraction in rat biological samples. Chromatographic separation was achieved on an Agilent Zorbax Eclipse Plus C_(18)(2.1 mm × 50 mm, 3.5-Micron) with a gradient mobile phases primarily containing acetonitrile, water with 0.1% formic acid and 5 mm ammonium acetate. The analytes were monitored by MS/MS in positive electrospray ionization mode. Herein, the feasibility of new developed method was validated with respect to specificity, linearity, precision, accuracy, stability, extraction efficiency and matrix effect. The appropriate method was used for the pharmacokinetic study in rats.Results The new developed method could be applied to the pharmacokinetic study of BRB in rats. BRB and BRBG showed good linearity over the ranges of 2-1000 ng/mL and 5-2000 ng/mL, respectively, and precision was no more than 15%. The accuracy, specificity and stability could be acceptable. Conclusion The new method is sensitive and reproducible. In pharmacokinetic study, BRB showed nonlinear elimination property. Meanwhile, BRB was rapidly absorbed and widely distributed in various tissues with the highest exposure of BRB in kidney and liver. The absolute bioavailability of BRB was determined to be 8.2% and at the dose of 40 mg/kg, a total of 44% BRB was excreted in urine and feces. 展开更多
关键词 berberrubine berberrubine glucuronide LC-MS/MS pharmacokinetic study ratbiological samples
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Protective Effect of Salvianolic Acid A on Brain Endothelial Cells after Treatment with Deprivation and Reperfusion of Oxygen-glucose 被引量:1
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作者 Si-qi Feng Jian-liang Geng +5 位作者 run-bin sun Jing-qiu Huang Zhao-yi Tan Cai-xia Yan Ji-ye AA Guang-ji Wang 《Chinese Herbal Medicines》 CAS 2017年第4期335-343,共9页
Objective Salvianolic acid A(SAA) has a significant protective effect on ischemia/reperfusion injury of brain. However, it is not clear for SAA to exert its cerebral protection by targeting at the microvascular endo... Objective Salvianolic acid A(SAA) has a significant protective effect on ischemia/reperfusion injury of brain. However, it is not clear for SAA to exert its cerebral protection by targeting at the microvascular endothelial cells of blood brain barrier(BBB). Our previous study demonstrated that SAA could hardly pass through the BBB. This present study was therefore designed to investigate the protective effect of SAA on brain microvascular endothelial cells(BMECs) induced by deprivation and reperfusion with oxygen-glucose. Methods Rat BMECs were treated with oxygen glucose deprivation(OGD), followed by reperfusion(OGD/R). Cell viability was assessed by MTT and the content of reactive oxygen species(ROS) in cells after OGD/R in the absence or presence of SAA. GC-MS based metabolomic platform was applied to evaluate the regulation of SAA on the cellular metabolic perturbation induced by OGD/R. Results OGD/R significantly increased the production of intracellular reactive oxygen species(ROS), and decreased the activity of cells. SAA significantly reduced ROS and improve the cell viability. Metabolomic study revealed distinct perturbation of metabolic pathways of energy metabolism in the BMEC induced by OGD/R, while SAA significantly regulated the perturbed metabolism involved in energy metabolism pathways, especially for intermediates in TCA cycle. Conclusion SAA shows protective effects on BMECs involved in central nervous system. 展开更多
关键词 metabolomics oxygen glucose deprivation reperfusion salvianolic acid A
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Salidroside shows a particular pharmacokinetic property in model rats of myocardial ischemia
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作者 Hui-lin Gu run-bin sun +8 位作者 Fei Fei Li-xiang A Hao-xue Cao Ming-xue Tao Si-qi Feng Na Yang Yue Zhang Ji-ye Aa Guang-ji Wang 《Chinese Herbal Medicines》 CAS 2018年第2期169-176,共8页
Objective:Salidroside showed potential pharmacological effect on plateau hypoxia and cardiovascular disease like myocardial ischemia.However,pharmacokinetic differences have not been assessed between the pathological... Objective:Salidroside showed potential pharmacological effect on plateau hypoxia and cardiovascular disease like myocardial ischemia.However,pharmacokinetic differences have not been assessed between the pathological model and the normal animals.This study focused on evaluating the pharmacokinetic properties of salidroside in animals with myocardial ischemia.Methods:A reproducible and sensitive method was established and optimized based on liquid chromatography tandem mass spectrometry(LC–MS/MS)to determine salidroside in rats plasma.The data showed thesalidroside proportionally increased along with dose elevation after singly intragastric administration of salidroside at a dose of 20,50,and 100 mg/kg.Results:Compared to the single dose,the Cmax,andsalidroside markedly decreased while CL/F and V/F increased after multiple dosing.However,theischemic model rats were 0.35 and 0.39 fold lower than those in normal rats after a single dose at 50 mg/kg,with an increased CL/F and V/F.Surprisingly,after a consecutive administration of salidroside for 7 d,the mean Cmax,2.89 and 2.61 fold higher than a single dose in model rats,and even 2.28 and4.03 fold higher than the normal controls after multiple doses.All the above fold values were statistically different(P〈0.01).Conclusion:The particular PK properties of salidroside in ischemic model rats were presented in our study for the first time,suggesting that myocardial ischemia greatly affected pharmacokinetics exposure of the orally administrated salidroside after a single or multiple doses. 展开更多
关键词 LC-MS/MS method validation PHARMACOKINETICS SALIDROSIDE
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