Wei-Jan Huang1, Hsin-Jung Lee2, Hon-Lie Chen3, Pi-Chuan Fan4, Yuan-Ling Ku5, Lih-Chu Chiou6. 1. Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan; School of Pharmacy, National Defense Medical Center, Taipei, Taiwan. 2. Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan. 3. Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan. 4. Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan. 5. Medical and Pharmaceutical Industry Technology and Development Center, New Taipei City, Taiwan. 6. Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: lcchiou@ntu.edu.tw.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Previously, we found a patient with an intractable motor tic disorder that could be ameliorated by the ground leaf juice of Clerodendrum inerme (CI). Furthermore, the ethanol extract of CI leaves effectively ameliorated methamphetamine-induced hyperlocomotion (MIH) in mice, an animal model mimicking the hyper-dopaminergic status of tic disorders/Tourette syndrome, schizophrenia, or obsessive-compulsive disorder. Here, we for the first time identified a constituent able to reduce MIH from the CI ethanol extract that might represent a novel lead for the treatment of such disorders. MATERIALS AND METHODS: The ethanol extract of CI was sub-divided into n-hexane, dichloromethane, n-butanol and water fractions. Using MIH alleviation as a bioassay, active compounds were identified in these fractions using silica gel chromatography, recrystallization and proton NMR spectroscopy. RESULTS: The dichloromethane and n-hexane fractions were active in the bioassay. Further subfractionation and re-crystallization resulted in an active compound that was identified to be hispidulin by proton NMR spectroscopy. Hispidulin significantly alleviated MIH in mice at doses that did not affect their spontaneous locomotor activity or performance in the rotarod test, a measure for motor coordination. CONCLUSIONS: Hispidulin is a flavonoid that has been isolated from several plants and reported to have anti-oxidative, anti-inflammatory and anti-cancer activities. Here, we for the very first time found that hispidulin can also alleviate MIH at doses that did not impair motor activity, suggesting a therapeutic potential of hispidulin in hyper-dopaminergic disorders.
ETHNOPHARMACOLOGICAL RELEVANCE: Previously, we found a patient with an intractable motor tic disorder that could be ameliorated by the ground leaf juice of Clerodendrum inerme (CI). Furthermore, the ethanol extract of CI leaves effectively ameliorated methamphetamine-induced hyperlocomotion (MIH) in mice, an animal model mimicking the hyper-dopaminergic status of tic disorders/Tourette syndrome, schizophrenia, or obsessive-compulsive disorder. Here, we for the first time identified a constituent able to reduce MIH from the CI ethanol extract that might represent a novel lead for the treatment of such disorders. MATERIALS AND METHODS: The ethanol extract of CI was sub-divided into n-hexane, dichloromethane, n-butanol and water fractions. Using MIH alleviation as a bioassay, active compounds were identified in these fractions using silica gel chromatography, recrystallization and proton NMR spectroscopy. RESULTS: The dichloromethane and n-hexane fractions were active in the bioassay. Further subfractionation and re-crystallization resulted in an active compound that was identified to be hispidulin by proton NMR spectroscopy. Hispidulin significantly alleviated MIH in mice at doses that did not affect their spontaneous locomotor activity or performance in the rotarod test, a measure for motor coordination. CONCLUSIONS: Hispidulin is a flavonoid that has been isolated from several plants and reported to have anti-oxidative, anti-inflammatory and anti-cancer activities. Here, we for the very first time found that hispidulin can also alleviate MIH at doses that did not impair motor activity, suggesting a therapeutic potential of hispidulin in hyper-dopaminergic disorders.
Authors: Yao Wang; Aiping Wang; Hana Alkhalidy; Jing Luo; Elizabeth Moomaw; Andrew P Neilson; Dongmin Liu Journal: Mol Nutr Food Res Date: 2020-02-03 Impact factor: 5.914
Authors: Marco Treven; David C B Siebert; Raphael Holzinger; Konstantina Bampali; Jure Fabjan; Zdravko Varagic; Laurin Wimmer; Friederike Steudle; Petra Scholze; Michael Schnürch; Marko D Mihovilovic; Margot Ernst Journal: Br J Pharmacol Date: 2017-12-22 Impact factor: 9.473