title: Two-Armed Activation of Bone Mineral Deposition by the Flavones Baicalin and Baicalein, Encapsulated in Polyphosphate Microparticles.
abstract: In this study, we investigated the effect of the two flavonoids, baicalin (baicalein 7-O-[Formula: see text]- d-glucuronic acid) and its aglycone, baicalein (5,6,7-trihydroxyflavone), after encapsulation into amorphous calcium polyphosphate (Ca-polyP) microparticles on mineralization of primary human osteoblasts (phOSB). Both flavonoids, which come from root extracts of Scutellaria baicalensis Georgi, are used in Traditional Chinese Medicine, and are nontoxic in cells up to a concentration of 3[Formula: see text][Formula: see text]g/ml. The morphogenetically active, energy-rich Ca-polyP particles with a stoichiometric P:Ca ratio of 1:2 are degraded by cellular alkaline phosphatase (ALP) to ortho-phosphate used for bone hydroxyapatite formation. Here we show that the flavone-loaded Ca-polyP microparticles are readily taken up by phOSB, resulting in the accumulation of polyP around the nuclei and the formation of intracellular vesicles containing the ALP. In addition, we demonstrate that baicalin/baicalein causes a rise of the intracellular calcium [Ca[Formula: see text]]ia level which markedly is augmented after encapsulation into Ca-polyP, through activation of the phospholipase C. Moreover, both flavones, either alone or associated with Ca-polyP microparticles, upregulate the expression of the osteoblast calcium efflux channel, the plasma membrane Ca[Formula: see text]-ATPase (PMCA), while the expression of ALP, which promotes bone mineralization, is induced by Ca-polyP and by the flavones only if present in the Ca-polyP-microparticle-associated form. As a result, the extent of bone mineralization is markedly enhanced. Based on the two-armed activating function, new applications of baicalin/baicalein as a component of nutriceuticals for osteoporosis prevention or bone implants can be envisaged.
authors.affiliation: * ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, D-55128 Mainz, Germany.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Wang
authors.affiliation: † State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Yue-Wei
authors.initials: YW
authors.lastname: Guo
authors.affiliation: * ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, D-55128 Mainz, Germany.
authors.forename: Emad
authors.initials: E
authors.lastname: Tolba
authors.affiliation: ‡ Max Planck Institute for Polymer Research, D-55128 Mainz, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Kokkinopoulou
authors.affiliation: * ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, D-55128 Mainz, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Wiens
authors.affiliation: * ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, D-55128 Mainz, Germany.
authors.forename: Heinz C
authors.initials: HC
authors.lastname: Schröder
authors.affiliation: * ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, D-55128 Mainz, Germany.
authors.forename: Werner E G
authors.initials: WEG
authors.lastname: Müller
mesh_terms: D002113:Calcification, Physiologic / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002130:Calcium Phosphates; D002214:Capsules; D002470:Cell Survival; D002478:Cells, Cultured; D017886:Durapatite / Q000378:metabolism; D044950:Flavanones / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D010006:Osteoblasts / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000517:prevention & control; D008517:Phytotherapy; D018517:Plant Roots / Q000737:chemistry*; D031364:Scutellaria baicalensis / Q000737:chemistry*; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D002130:Calcium Phosphates; D002214:Capsules; D044950:Flavanones; D005419:Flavonoids; C519480:amorphous calcium phosphate; C038044:baicalin; C006680:baicalein; D017886:Durapatite; D010738:Type C Phospholipases; D002118:Calcium
keywords: Alkaline Phosphatase; Baicalein; Baicalin; Bone Mineralization; Calcium Efflux/Transport; Phospholipase C; Polyphosphate Microparticles; Primary Human Osteoblasts