title: Lignans from the fruits of Schisandra chinensis (Turcz.) Baill inhibit proprotein convertase subtilisin/kexin type 9 expression.
abstract: Bioactivity-guided fractionation of the fruits of Schisandra chinensis, using the proprotein convertase subtilisin-kexin type 9 (PCSK9) mRNA expression screening assay, led to isolation of two previously unknown lignans, 14-tigloylschinlignan D and rel-(7R, 8R, 7'R, 8'R)-manglisin E, along with 28 known compounds. All structures were established by NMR spectroscopic data as well as CD and MS analysis. All isolates were tested for their inhibitory activities on the mRNA expression of PCSK9. Of the tested compounds, four of the compounds rel-(7R, 8R, 7'R, 8'R)-manglisin E, (-)-schisandrin C, schinlignan D, and (+)-schisandrol B potently inhibited PCSK9 mRNA expression with IC50values of 3.15, 3.85, 0.36, and 1.10 μM, respectively. Furthermore, schinlignan D and (+)-schisandrol B were found to suppress PCSK9 protein expressions and schinlignan D deemed to increase low density lipoprotein receptor expression.
authors.affiliation: College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, 32, Dongguk-lo, Goyang-si, Gyeonggi-do 10326, Republic of Korea.
authors.forename: Pisey
authors.initials: P
authors.lastname: Pel
authors.affiliation: College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, 32, Dongguk-lo, Goyang-si, Gyeonggi-do 10326, Republic of Korea.
authors.forename: Hee-Sung
authors.initials: HS
authors.lastname: Chae
authors.affiliation: College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, 32, Dongguk-lo, Goyang-si, Gyeonggi-do 10326, Republic of Korea.
authors.forename: Piseth
authors.initials: P
authors.lastname: Nhoek
authors.affiliation: College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Woojin
authors.initials: W
authors.lastname: Yeo
authors.affiliation: College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, 32, Dongguk-lo, Goyang-si, Gyeonggi-do 10326, Republic of Korea.
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, 32, Dongguk-lo, Goyang-si, Gyeonggi-do 10326, Republic of Korea. Electronic address: f2744@dongguk.edu.
authors.forename: Young-Won
authors.initials: YW
authors.lastname: Chin
mesh_terms: D034242:Cyclooctanes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004149:Dioxoles; D005638:Fruit / Q000737:chemistry*; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D015394:Molecular Structure; D011083:Polycyclic Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000071449:Proprotein Convertase 9; D011973:Receptors, LDL; D032141:Schisandra / Q000737:chemistry*; D012697:Serine Endopeptidases / Q000378:metabolism; D013381:Subtilisins / Q000378:metabolism
chemical_list: C000614641:14-tigloylschinlignan D; D034242:Cyclooctanes; D004149:Dioxoles; C573412:LDLR protein, human; D017705:Lignans; D011083:Polycyclic Compounds; D011973:Receptors, LDL; C000614640:schizandrol D; C033585:schizandrol B; C031409:schizandrin C; D000071449:Proprotein Convertase 9; D012697:Serine Endopeptidases; D013381:Subtilisins
keywords: (+)-schisandrol B; Lignan; Proprotein convertase subtilisin/kexin type 9 (PCSK9); Schinlignan D; Schisandra chinensis; Schisandraceae