title: Naturally occurring proteinaceous nanoparticles in Coptidis Rhizoma extract act as concentration-dependent carriers that facilitate berberine absorption.
abstract: Pharmacological activities of some natural products diminish and even disappear after purification. In this study, we explored the mechanisms underlying the decrease of acute oral toxicity of Coptidis Rhizoma extract after purification. The water solubility, in vitro absorption, and plasma exposure of berberine (the major active compound) in the Coptidis Rhizoma extract were much better than those of pure berberine. Scanning electron microscopy, laser scanning confocal microscopy (LSCM), and dynamic light scattering experiments confirmed that nanoparticles attached to very fine precipitates existed in the aqueous extract solution. The LSCM experiment showed that the precipitates were absorbed with the particles by the mouse intestine. High-speed centrifugation of the extract could not remove the nanoparticles and did not influence plasma exposure or acute oral toxicity. However, after extract dilution, the attached precipitates vanished, although the nanoparticles were preserved, and there were no differences in the acute oral toxicity and plasma exposure between the extract and pure berberine. The nanoparticles were then purified and identified as proteinaceous. Furthermore, they could absorb co-dissolved berberine. Our results indicate that naturally occurring proteinaceous nanoparticles in Coptidis Rhizoma extract act as concentration-dependent carriers that facilitate berberine absorption. These findings should inspire related studies in other natural products.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Bing-Liang
authors.initials: BL
authors.lastname: Ma
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Yin
authors.affiliation: Department of Physics, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Bo-Kai
authors.initials: BK
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Yi-Qun
authors.initials: YQ
authors.lastname: Jia
authors.affiliation: Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Shi
authors.affiliation: Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Tian-Ming
authors.initials: TM
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Jia-Sheng
authors.initials: JS
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Li
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Lin
authors.affiliation: Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Yue-Ming
authors.initials: YM
authors.lastname: Ma
mesh_terms: D000818:Animals; D001599:Berberine / Q000493:pharmacokinetics / Q000633:toxicity; D000089042:Coptis chinensis; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000633:toxicity; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity; D010940:Plant Proteins / Q000737:chemistry / Q000633:toxicity
chemical_list: D004365:Drugs, Chinese Herbal; D010940:Plant Proteins; D001599:Berberine; C107393:Coptidis rhizoma extract
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