Yi-Ling Sheng1, Jing-Hua Xu2, Cai-Hong Shi3, Wei Li3, Hai-Yan Xu4, Ning Li5, Yu-Qing Zhao5, Xiang-Rong Zhang6. 1. School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Box 51, 103 Wenhua Road, Shenyang 110016, China. 2. School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China. 3. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Box 51, 103 Wenhua Road, Shenyang 110016, China. 4. School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. 5. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Box 51, 103 Wenhua Road, Shenyang 110016, China; Key Laboratory of Research and Design of "drug targets based on the Ministry of Education", Shenyang Pharmaceutical University, Shenyang 110016, China. 6. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Box 51, 103 Wenhua Road, Shenyang 110016, China; Key Laboratory of Research and Design of "drug targets based on the Ministry of Education", Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: zhangxr@vip.sina.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Magnolia officinalis is one of the commonly used in traditional Chinese medicine for the treatment of fever, chronic bronchitis and stomach ailments. Magnolol and honokiol are isomers with hydroxylated biphenol compound in the extract of Magnolia officinalis. This study aims to determine the isomers in rat plasma and evaluate their pharmacokinetic pattern after administration emulsion. MATERIALS AND METHODS: Sprague Dawley male rats received either an intravenous (i.v.25, mg/kg) or oral (50mg/kg) dose of the emulsion of the isomer. A sensitive and specific ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed for the investigation of the pharmacokinetics of magnolol and honokiol in rats. Kaempferol was employed as an internal standard. RESULTS: The plasma samples were deproteinized with acetonitrile, the post-treatment samples were analyzed on an Agela C18 column interfaced with a triple quadrupole tandem mass spectrometer in negative electrospray ionization mode. Acetonitrile and 5 mmol/L ammonium acetate buffer solution (65: 35, v/v) was used as the mobile phase at a flow rate of 0.2 mL/min. Following oral administration of emulsion to rats, magnolol attained mean peak plasma concentrations of 426.4 ± 273.8 ng/mL at 1.20 h, whereas honokiol reached peak plasma concentrations of 40.3 ± 30.8 ng/mL at 0.45 h. The absolute bioavailability of magnolol and honokiol is 17.5 ± 9.7% and 5.3 ± 11.7%. By comparison, the AUC0-∞ of magnolol was 5.4 times higher than that of honokiol after intravenous administration, but AUC0-∞ of magnolol was about 18-fold higher than honokiol after oral administration.
ETHNOPHARMACOLOGICAL RELEVANCE: Magnolia officinalis is one of the commonly used in traditional Chinese medicine for the treatment of fever, chronic bronchitis and stomach ailments. Magnolol and honokiol are isomers with hydroxylated biphenol compound in the extract of Magnolia officinalis. This study aims to determine the isomers in rat plasma and evaluate their pharmacokinetic pattern after administration emulsion. MATERIALS AND METHODS: Sprague Dawley male rats received either an intravenous (i.v.25, mg/kg) or oral (50mg/kg) dose of the emulsion of the isomer. A sensitive and specific ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed for the investigation of the pharmacokinetics of magnolol and honokiol in rats. Kaempferol was employed as an internal standard. RESULTS: The plasma samples were deproteinized with acetonitrile, the post-treatment samples were analyzed on an Agela C18 column interfaced with a triple quadrupole tandem mass spectrometer in negative electrospray ionization mode. Acetonitrile and 5 mmol/L ammonium acetate buffer solution (65: 35, v/v) was used as the mobile phase at a flow rate of 0.2 mL/min. Following oral administration of emulsion to rats, magnolol attained mean peak plasma concentrations of 426.4 ± 273.8 ng/mL at 1.20 h, whereas honokiol reached peak plasma concentrations of 40.3 ± 30.8 ng/mL at 0.45 h. The absolute bioavailability of magnolol and honokiol is 17.5 ± 9.7% and 5.3 ± 11.7%. By comparison, the AUC0-∞ of magnolol was 5.4 times higher than that of honokiol after intravenous administration, but AUC0-∞ of magnolol was about 18-fold higher than honokiol after oral administration.