Yellowish oily matter
Ligusticum sinense cv. chuanxiong,Angelica sinensis,Cryptotaenia japonica
seneciphyllin/1(3H)-Isobenzofuranone, 3-butylidene-4,5,6,7-tetrahydro-6,7-dihydroxy-, (3Z,6S,7S)-/SenkyunolideI/(3Z,6S,7S)-3-Butylidene-6,7-dihydroxy-4,5,6,7-tetrahydro-2-benzofuran-1(3H)-one
Senkyunolide I, isolated from Ligusticum chuanxiong Hort, is an anti-migraine compound. Senkyunolide I protects rat brain against focal cerebral ischemia-reperfusion injury by up-regulating p-Erk1/2, Nrf2/HO-1 and inhibiting caspase 3.
Methanol; Ethyl Acetate
444.8±45.0 °C at 760 mmHg
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The aim of this study was to elucidate the effects of warfarin on senkyunolide I in a rat model of biliary drainage after oral administration Chuanxiong extract based on pharmacokinetics. Thirty-two rats were randomly divided into four groups: CN, healthy rats after a single administration of Chuanxiong; CO, rats with biliary drainage after a single administration of Chuanxiong; WCN, healthy rats after the administration of Chuanxiong and warfarin; WCO, rats with biliary drainage after the administration of Chuanxiong and warfarin. A series of blood samples were collected at different time points before and after oral administration. An ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method for quantification of the main components of Chuanxiong and methyclothiazide (internal standard) have been established. The validated method was successfully applied to a comparative pharmacokinetics study. After calculated by the DAS 2.1.1 software, the pharmacokinetics parameters of senkyunolide I showed a significant difference between the CN and CO groups, the AUC0−t, and Cmax of CO group increased by 5.45, 4.02 folds, respectively. There was a significant difference between the WCO and WCN groups, the Tmax of WCO group prolonged 67%; compared to the CN group, the AUC0−t, and Cmax of WCN group raised 4.84, 3.49 folds, respectively; the Tmax and Cmax between the CO and WCO groups also showed a significant difference. The drug warfarin significantly affected the senkyunolide I disposition, which partly due to its enterohepatic circulation process in rat plasma after oral administration of Chuanxiong. The present study highlights an urgent evidence for drug-herb interactions.
senkyunolide I, Chuanxiong, warfarin, pharmacokinetics, UPLC-MS/MS, biliary drainage
The Effects of Warfarin on the Pharmacokinetics of Senkyunolide I in a Rat Model of Biliary Drainage After Administration of Chuanxiong
Haigang Li,1,2 Yu Jiang,3 Yang Wang,2,* Huiying Lv,4 Haitang Xie,5 Guoping Yang,6 Chengxian Guo,6 Jing Tang,1 and Tao Tang2,*
2018 Dec 12.
Senkyunolide I is one of the major bioactive components in the herbal medicine Ligusticum chuanxiong. The aim of this study was to develop and validate a fast, simple and sensitive LC-MS/MS method for the determination of senkyunolide I in dog plasma. The plasma samples were processed with acetonitrile and separated on a Waters Acquity UPLC BEH C18 column (50 × 2.1 mm, 1.7 μm). The mobile phase consisted of 0.1% formic acid aqueous and acetonitrile was delivered at a flow rate of 0.3 mL min-1 . The detection was achieved in the positive selected reaction monitoring mode with precursor-to-product transitions at m/z 225.1 → 161.1 for senkyunolide I and at m/z 349.1 → 305.1 for an internal standard. The assay was linear over the tested concentration range, from 0.5 ng mL-1 to 1000 ng mL-1 , with a correlation coefficient >0.9992. The mean extraction recovery from dog plasma was within the range of 85.78-93.25%, while the matrix effect of the analyte was within the range of 98.23-108.89%. The intra- and inter-day precisions (RSD) were <12.12% and the accuracy (RR) ranged from 98.89% to 104.24%. The validated assay was successfully applied to pharmacokinetic and bioavailability studies of senkyunolide I in dogs. The results demonstrated that (a) senkyunolide I showed short elimination half-life (<1 h) in dog, (b) its oral bioavailability was >40% and (c) senkyunolide I showed dose-independent pharmacokinetic profiles in dog plasma over the dose range of 1-50 mg kg-1 .
Copyright © 2018 John Wiley & Sons, Ltd.
LC-MS/MS; bioavailability; dog; pharmacokinetics; senkyunolide I
A validated LC-MS/MS method for the determination of senkyunolide I in dog plasma and its application to a pharmacokinetic and bioavailability studies.
Li JQ1,2,3, Wang JF2, Li J2, Zhang SH2, He D2, Tong RS1,2,3, She SY1.
Over-activated microglia during stroke has been documented to aggravate brain damage. Our previous studies showed that senkyunolide I (SEI) exerted anti-inflammatory effects against endotoxin insult in vitro and ameliorative effects on cerebral ischemia/reperfusion (I/R) injury in vivo. Using oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic stroke, we here investigated the anti-inflammatory effect of SEI on microglial cells and explored the underlying mechanisms. OGD for 3h followed by reoxygenation for 12h significantly enhanced the release of pro-inflammatory cytokines and expressions of inflammation-related enzymes in BV-2 cells, which was inhibited by pretreatment with SEI. To elucidate the mechanisms, we studied its effect on upstream signaling pathways. It was found that SEI suppressed the activation of NF-κB pathway induced by OGD/R and the MAPK pathway was shown not to be involved. Furthermore, SEI significantly down-regulated TLR4/MyD88 pathway with specifically improving inducible Hsp70 level through increasing HSF-1/DNA binding activity, and these regulations responsive to SEI were attenuated by transfecting Hsp70 siRNA and HSF-1 decoy ODNs. Additionally, SEI exerted similar influence on Hsp70/TLR4/NF-κB pathway in rat primary microglial cells. The results suggested that SEI had a potent effect against stroke-induced neuroinflammation through suppressing the TLR4/NF-κB pathway by up-regulating Hsp70 dependent on HSF-1.
Copyright © 2016 Elsevier B.V. All rights reserved.
HSF-1/Hsp70; Microglial cells; Oxygen-glucose deprivation/reoxygenation; Senkyunolide I; TLR4/NF-κB pathway
Senkyunolide I attenuates oxygen-glucose deprivation/reoxygenation-induced inflammation in microglial cells.
Hu YY1, Wang Y2, Liang S2, Yu XL3, Zhang L3, Feng LY4, Feng Y5.
2016 Oct 15