Effects of a Whole Plant Extract of Scutellaria rubropunctata var. rubropunctata on Bone Metabolism with Estrogen Receptor Activation.
Misaki WatanabeTadahiro YahagiTakahiro ShirayamaKatsunori MiyakeHitoshi KotaniTakuya OgawaKeiichi MatsuzakiPublished in: Plants (Basel, Switzerland) (2022)
We screened natural resources for estrogen receptor (ER)-activating and bone metabolism-promoting activities with the aim of finding potential treatments for osteoporosis. A screen of 1531 extracts from Ryukyu Arc plants using a luciferase reporter assay identified an 80% MeOH extract of Scutellaria rubropunctata var. rubropunctata (SRE) with dose-dependent ER transcription-promoting activity. Importantly, SRE had no proliferative effect on human breast cancer cells. SRE enhanced the ALP activity of pre-osteoblast MC3T3-E1 cells after 72 h in culture and slightly enhanced mineralization at 14 and 21 d. SRE did not significantly affect the TRAP activity of RAW264.7 cells. Gene expression analysis in MC3T3-E1 cells by quantitative real-time PCR revealed that SRE upregulated the mRNA levels of Runx2 , Osterix ( Osx ), Osteopontin ( Opn ), Osteocalcin ( Ocn ), Smad1 , Smad4 , and Smad5 at 72 h, and those of Runx2 , Osx , Smad1 , Smad4 , and Smad5 at 21 d of osteogenic induction. Analysis of the expression levels of osteogenic markers suggested that SRE may promote osteogenic differentiation by acting at the early stage of differentiation rather than at the late stage of differentiation. These results indicate that SRE activates ER and induces osteoblast differentiation by activating Runx2 and Osx through the BMP/ Smad pathway, suggesting that SRE may be useful for the prevention and treatment of postmenopausal osteoporosis.
Keyphrases
- estrogen receptor
- transforming growth factor
- epithelial mesenchymal transition
- induced apoptosis
- bone mineral density
- mesenchymal stem cells
- breast cancer cells
- early stage
- signaling pathway
- cell cycle arrest
- transcription factor
- oxidative stress
- bone marrow
- bone regeneration
- postmenopausal women
- endothelial cells
- endoplasmic reticulum stress
- real time pcr
- poor prognosis
- high throughput
- crispr cas
- radiation therapy
- copy number
- binding protein
- lymph node
- smoking cessation
- soft tissue
- pi k akt
- combination therapy
- endoplasmic reticulum
- genome wide identification
- rectal cancer