Nymphaeol-C, a prenylflavonoid from Macaranga tanarius, suppresses the expression of fibroblast growth factor 18

• Published in: Phytomedicine (Stuttgart) Vol. 36; pp. 238 - 242
• Main Authors: Yoshimura, Kazuki, Hosoya, Takahiro, Fujinami, Misa, Ohta, Toshiro, Kumazawa, Shigenori
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.12.2017
• Subjects: Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; beta Catenin - metabolism; Cell Line, Tumor; Drug Screening Assays, Antitumor - methods; Euphorbiaceae - chemistry; Fibroblast growth factor 18; Fibroblast Growth Factors - antagonists & inhibitors; Fibroblast Growth Factors - genetics; Fibroblast Growth Factors - metabolism; Flavanones - pharmacology; Humans; Macaranga tanarius; MAP Kinase Signaling System - drug effects; Mitogen-activated protein kinase cascade; Mitogen-Activated Protein Kinases - metabolism; Molecular Targeted Therapy; Nymphaeol-C; Phosphorylation - drug effects; Plant Leaves - chemistry; Wnt Signaling Pathway - drug effects; Wnt/β-catenin pathway; FGF; MeCN; Nymphaeol-C; PVDF; TFA; D-PBS (–); DMEM; SDS-PAGE; ERK1/2; WST-8; MAPK cascade; MeOH; FBS; FGF18; Mitogen-activated protein kinase cascade; Fibroblast growth factor 18; Macaranga tanarius; Wnt/β-catenin pathway; RIPA buffer; FGFRs; GAPDH; Foxp1
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2017.10.009

Fibroblast growth factor 18 (FGF18) is one of the key factors in human signaling pathways and has been reported to be associated with the formation of various tissues. Additionally, FGF18 has been reported to maintain the telogen stage of the hair cycle, and its over-expression has also been observed in cancer cells. We searched for natural compounds that inhibit the expression of FGF18 expression in vitro and evaluated their inhibitory mechanisms. Various plant samples were screened using a luciferase assay targeting FGF18. One active compound was selected by the screening, isolated and identified. The active compound was isolated using chromatographic techniques and identified by specific rotation measurements, LC-MS and NMR. Additionally, its inhibitory mechanism was evaluated using real-time RT-PCR and Western blotting. As a result of screening various plant leaf samples, Macaranga tanarius was identified as the most active plant and a prenylflavonoid nymphaeol-C was isolated as the active compound. Using real-time RT-PCR and Western blotting analysis, this compound was confirmed to strongly suppress the expression of FGF18. The compound lowered the β-catenin level in the Wnt/β-catenin pathway. Thus, it was suggested that nymphaeol-C suppresses the expression of FGF18 by suppressing β-catenin expression. Additionally, the compound lowered the extracellular signal-regulated kinase1/2 (ERK1/2) phosphorylation level in the mitogen-activated protein kinase cascade (MAPK cascade). Therefore, nymphaeol-C suppressed downstream signals of FGF18 by suppressing the expression of FGF18. We isolated and identified prenylflavonoid nymphaeol-C from M. tanarius. The compound suppresses the expression of FGF18 and affects FGF18 related signals. [Display omitted]