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      Pharmacokinetic profile of phytoconstituent(s) isolated from medicinal plants—A comprehensive review

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          Abstract

          Herbal medicine, the backbone of traditional medicine, has played an important role in human health and welfare for a long period. Traditional therapeutic approaches of regional significance are found in Africa, South and Central America, China, India, Tibet, Indonesia, and the Pacific Islands. The considerable scientific significance and commercial potential of traditional medicines have resulted in increased international attention and global market demands for herbal medicines, especially Chinese herbal medicines. Herbal medicines currently are the primary form of health care for the poor in the developing countries, and also are widely used as a supplement or substitute for conventional drugs in developed countries. These traditional medicines have a pivotal role in the treatment of various ailments and more than 50% of drugs used in Western pharmacopoeia are isolated from herbs or derived from modifications of chemicals found in plants. Herbal medicines usually contain a complex mixture of various bioactive molecules, which make its standardization complicated, and there is little information about all compounds responsible for pharmacological activity. Several research papers have been published that claim pharmacological activity of herbal medicines but few are discussing the role of the exact phytoconstituent. Understanding the pharmacokinetic profile of such phytoconstituents is essential. Although there are research papers that deal with pharmacokinetic properties of phytoconstituents, there are a number of phytoconstituents yet to be explored for their kinetic properties. This article reviews the pharmacokinetic profile of 50 different therapeutically effective traditional medicinal plants from the year 2003 onward.

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            Analysis of silibinin in rat plasma and bile for hepatobiliary excretion and oral bioavailability application.

            Silibinin is an herbal ingredient isolated from milk thistle. The aim of this study was to develop a simple liquid chromatographic system to assay silibinin in plasma and bile for pharmacokinetic study. Silibinin was given oral and intravenously. The plasma sample (25 microL) was vortex-mixed with 50 microL of internal standard solution (naringenin 10 microg/mL in acetonitrile) to achieve protein precipitation. Silibinin in the rat plasma and bile was separated using a reversed-phase C18 column (250 mm x 4.6 mm, 5 microm) with a mobile phase of acetonitrile -10 mM monosodium phosphate (pH 5.45 adjusted with orthophosphoric acid) (50:50, v/v) and the flow-rate of 1 mL/min. The UV detection wavelength was 288 nm. The concentration-response relationship from the present method indicated linearity over a concentration range of 0.5-100 microg/mL. Intra- and inter-assay precision and accuracy of silibinin fell well within the predefined limits of acceptability (<15%). An ultrafiltration method was used in this experiment and the protein binding of silibinin was 70.3+/-4.6%. After silibinin administration in rats, the disposition of silibinin in the plasma and bile fluid was due to rapid distribution and equilibration between the blood and hepatobiliary system, and the bile levels of unconjugated silibinin and total silibinin were greater than those in the plasma. The oral bioavailability of silibinin in rats was estimated to be 0.73%.
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              Pharmacokinetics and metabolism of ligustilide, a major bioactive component in Rhizoma Chuanxiong, in the rat.

              Ligustilide is the most abundant bioactive ingredient in Rhizoma Chuanxiong, a Chinese medicinal herb commonly used for the treatment of cardiovascular ailments. The present study reported, for the first time, the pharmacokinetics of ligustilide, administered in its pure form and in an herbal extract, in rats. After i.v. administration of pure ligustilide, it was distributed extensively (V(d), 3.76 +/- 1.23 l/kg) and eliminated rapidly (t(1/2), 0.31 +/- 0.12 h). The i.v. clearance (CL) of ligustilide after Chuanxiong extract administration was significantly higher than that dosed in its pure form [CL, 20.35 +/- 3.05 versus 9.14 +/- 1.27 l/h/kg, p < 0.01; area under the curve (AUC), 0.79 +/- 0.10 versus 1.81 +/- 0.24 mg x h/l, p < 0.01], suggesting significant interaction between ligustilide and components present in the extract. Dose-dependent pharmacokinetics was observed after i.p. administration, and a significantly higher dose-normalized AUC (1.77 +/- 0.23 mg x h/l) at 52 mg/kg was obtained than that at 26 mg/kg (0.93 +/- 0.07 mg x h/l, p < 0.05). Oral bioavailability of ligustilide was low (2.6%), which was partly because of extensive first-pass metabolism in the liver. Seven metabolites of ligustilide were identified, and three of them were unequivocally characterized as butylidenephthalide, senkyunolide I, and senkyunolide H. These three compounds also occurred naturally in the herb and were reported to be bioactive.
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                Author and article information

                Contributors
                Journal
                J Tradit Complement Med
                J Tradit Complement Med
                Journal of Traditional and Complementary Medicine
                Elsevier
                2225-4110
                28 January 2015
                October 2015
                28 January 2015
                : 5
                : 4
                : 207-227
                Affiliations
                [a ]Department of Quality Assurance, Bharati Vidyapeeth University, Poona College of Pharmacy, Erandwane, Pune, Maharashtra, India
                [b ]School of Life Sciences, University of Bradford, Bradford, West Yorkshire, UK
                [c ]Department of Pharmaceutical Chemistry, Bharati Vidyapeeth University, Poona College of Pharmacy, Erandwane, Maharashtra, India
                Author notes
                []Corresponding author. Department of Pharmaceutical Chemistry, Bharati Vidyapeeth Deemed University Poona College of Pharmacy, Pune 411 038, Maharashtra, India. pharmsathiya@ 123456gmail.com
                Article
                S2225-4110(14)00055-8
                10.1016/j.jtcme.2014.11.041
                4624361
                26587392
                219b454d-12dd-42ed-8e32-1089f4c1f91e
                Copyright © 2014, Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC. All rights reserved.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

                History
                : 26 September 2014
                : 12 October 2014
                : 24 November 2014
                Categories
                Review Article

                pharmacokinetics,phytoconstituents,traditional chinese medicines (tcm),traditional medicinal systems (tms),adme

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