Pharmacokinetics and Metabolism of the Flavonoid Scutellarin in Humans After a Single Oral Administration

Chen, Xiaoyan; Cui, Liang; Duan, Xiaotao; Ma, Bin; Zhong, Dafang

doi:10.1124/dmd.106.009779

Cited by 99 publications

(57 citation statements)

References 36 publications

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“…β-Glucuronidase, which is highly expressed in the liver, is the main enzyme that is responsible for hydrolyzing a glucuronide conjugate [41] . Breviscapine could be hydrolyzed by β-glucuronidase into aglycone [42,43] , which would result in a fast decrease in the Bre-solution in the liver. Conversely, breviscapine was encapsulated in the NLC at a sustained rate.…”

Section: Discussionmentioning

confidence: 99%

Development of ionic-complex-based nanostructured lipid carriers to improve the pharmacokinetic profiles of breviscapine

Zheng

Shan

et al. 2013

Acta Pharmacol Sin

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Aim: Breviscapine isolated from the Chinese herb Erigeron breviscapus (Vant) Hand-Mazz is widely used to treat cardiovascular and cerebrovascular diseases. The aim of this study was to improve the pharmacokinetic profiles of breviscapine using nanostructured lipid carrier based on an ionic complex formation. Methods: Breviscapine nanostructured lipid carrier (Bre-NLC) was prepared using the thin film homogenization method. The morphology of Bre-NLCs was determined using transmission electron microscopy. The mean particle size, polydispersity index, zeta-potential analysis and entrapment efficiency were analized. In vitro release was studied using the dialysis method. In vitro stability was studied in fresh plasma and liver slurry of rats. In vivo pharmacokinetics was analyzed in rats after intravenous injection of a dose equivalent to breviscapine (10 mg/kg). Results: The Bre-NLCs were spherical with a mean particle size of ~170 nm, a zeta potential of ~20 mV and a high entrapment efficiency of ~89%. Compared with a commercially available solution, a substantial decrease in the cumulative release of breviscapine was found for the Bre-NLCs. The NLC has a significantly protective effect against the liver enzyme degradation of breviscapine. After intravenous administration in rats, the Bre-NLCs exhibited a 32 times increase in the AUC 0-t and a 12 times increase in T 1/2 as compared to the commercially available breviscapine solution. Conclusion:The results demonstrate that the NLC has great potential to use as a novel sustained release system for breviscapine.

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Section: Discussionmentioning

confidence: 99%

Development of ionic-complex-based nanostructured lipid carriers to improve the pharmacokinetic profiles of breviscapine

Zheng

Shan

et al. 2013

Acta Pharmacol Sin

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“…These results indicate that scutellarin is transformed in the inferior part of the intestines and the colon by bacterial enzymes into the corresponding aglycone, which is absorbed. The aglycone is then followed by a regioselective glucuronidation to transform scutellarin to enter the bloodstream [13] .…”

Section: Discussionmentioning

confidence: 99%

“…Pharmacological profiles of the parent drug and its metabolites in plasma [12,13] , tissues [14] , www.nature.com/aps Xing JF et al Acta Pharmacologica Sinica npg urine [15] , and bile [16] in humans and rats have been evaluated using high-performance liquid chromatography (HPLC) with ultraviolet detector or HPLC with mass spectrometer. After oral administration of scutellarin, only a minute amount of the compound was detected in human blood [13] , and its bioavailability was estimated to be only 10.67% [17] . However, substantial amounts of scutellarein were present in blood and urine in humans [18] .…”

Section: Introductionmentioning

confidence: 99%

Metabolic and pharmacokinetic studies of scutellarin in rat plasma, urine, and feces

et al. 2011

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Aim: To study the metabolic and pharmacokinetic profile of scutellarin, an active component from the medical plant Erigeron breviscapus (Vant) Hand-Mazz, and to investigate the mechanisms underlying the low bioavailability of scutellarin though oral or intravenous administration in rats. Methods: HPLC method was developed for simultaneous detection of scutellarin and scutellarein (the aglycone of scutellarin) in rat plasma, urine and feces. The in vitro metabolic stability study was carried out in rat liver microsomes from different genders. Results: After a single oral dose of scutellarin (400 mg/kg), the plasma concentrations of scutellarin and scutellarein in female rats were significantly higher than in male ones. Between the female and male rats, significant differences in AUC, t max2 and C max2 for scutellarin were found. The pharmacokinetic parameters of scutellarin in the urine also showed significant gender differences. After a single oral dose of scutellarin (400 mg/kg), the total percentage excretion of scutellarein in male and female rats was 16.5% and 8.61%, respectively. The total percentage excretion of scutellarin and scutellarein in the feces was higher with oral administration than with intravenous administration. The in vitro t 1/2 and CL int value for scutellarin in male rats was significantly higher than that in female rats. Conclusion:The results suggest that a large amount of ingested scutellarin was metabolized into scutellarein in the gastrointestinal tract and then excreted with the feces, leading to the extremely low oral bioavailability of scutellarin. The gender differences of pharmacokinetic parameters of scutellarin and scutellarein are due to the higher CL int and lower absorption in male rats.

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“…They have correlated the activity to 4 0 -hydroscutellarein, 4 0 -hydrobaicalein-7-b-D-plamyagin, 4 0 -hydroscutellarein-7-b-D-glycuron methyl ester, pyromeconic acid, and several kinds of flavones and flavonoids. Chen et al [21] reported that after a single oral administration of scutellarin 60 mg to 20 healthy subjects, plasma concentrations of scutellarin and its major metabolite (isoscutellarin) were found to reach a mean C max of <5.0 and 87 ng/mL, respectively. They have also indicated that after hydrolysis in the gastrointestinal system by bacterial enzymes, the aglycone of scutellarin (scutellarein) was detected in serum as glucuronic acid conjugates, which showed regioselectivity and species difference.…”

mentioning

confidence: 99%

Closed Gateways — Can Neuroprotectants Shield the Retina in Glaucoma?

Velpandian

2010

Drugs R D

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Neuroprotection for glaucoma is a therapeutic approach that aims to prevent optic nerve damage or cell death. An appropriate drug that reaches an adequate concentration across the blood retinal barrier is expected to shield the retina in glaucoma. Several in vitro and in vivo attempts in experimental models indicate the possibility of successful neuroprotection. However, clinical trials might not show the same level of neuroprotection as a result of subtherapeutic concentrations of the drug in the eye. The study by Zhong et al. in this issue of Drugs in R&D could not attribute the observed improvement in visual field indices to any one of the individual active constituents of Erigeron breviscapus (vant.) Hand. Mazz. (EBHM). One of the major constituents of EBHM is scutellarin, which is known to have poor oral bioavailability and an unclear ability to penetrate inside the eye. Therefore, before recognizing EBHM as a neuroprotectant in glaucoma for further clinical studies and practice, its active constituents and their pharmacokinetics (systemic as well as ocular) need to be explored.Neuroprotection as a pharmacological strategy to shield retinal ganglion cell death has been a popular approach adopted by many researchers. Yet, its effectiveness in preventing retinal ganglion cell death and thereby preserving vision in patients with primary open-angle glaucoma has not been demonstrated. [1] Mitochondria are abundant in the unmyelinated part of the retinal ganglion cell axons to meet the higher energy demand for nerve conduction and for the maintenance of optimum neuronal function. [2] Ischemia to the optic nerve head region can cause ganglion cell death at different rates. Therefore, effective intraocular pressure (IOP) control and blocking intracellular death triggers are both viable options. The right pharmacologic agent with a meaningful intraocular penetration would rationalize the neuroprotection strategy in glaucoma.For the last three decades, several attempts have been made to establish a successful neuroprotectant for glaucoma using various in vitro and in vivo models. A comprehensive PubMed search with the MeSH terms ''glaucoma'' and ''neuroprotection'' revealed the following compounds, factors and plant extracts: NMDA receptor antagonists (memantine, dexanabinol), an a2-adrenergic receptor agonist (brimonidine), an a 1 -and b-adrenergic receptor antagonist with a nitric oxide donor (nipradilol), an angiotensin II type 1 receptor blocker (candesartan), a prostaglandin-related compound (tafluprost), calcium channel blockers (nilvadipine and cilnidipine), a sodium channel blocker (phenytoin), a dual COMMENTARY Drugs R D 2010; 10 (2): 93-96

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Pharmacokinetics and Metabolism of the Flavonoid Scutellarin in Humans After a Single Oral Administration

Cited by 99 publications

References 36 publications

Development of ionic-complex-based nanostructured lipid carriers to improve the pharmacokinetic profiles of breviscapine

Development of ionic-complex-based nanostructured lipid carriers to improve the pharmacokinetic profiles of breviscapine

Metabolic and pharmacokinetic studies of scutellarin in rat plasma, urine, and feces

Closed Gateways — Can Neuroprotectants Shield the Retina in Glaucoma?

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