Study on the effects and mechanism of luteolin on osteogenic repair of bone defects
- VernacularTitle:木犀草素对骨缺损成骨修复的作用及机制研究
- Author:
Shengyao TANG
1
;
Minhua HU
1
;
Ruoyu ZHOU
1
;
Weipeng SUN
1
;
Xintao TANG
1
;
Haixiong LIN
2
,
3
;
Ziwei JIANG
4
Author Information
1. The First Clinical Medical College，Guangzhou University of Chinese Medicine，Guangzhou 510405，China
2. Ningxia Hui Autonomous Region Hospital of Traditional Chinese Medicine&Academy of Traditional Chinese Medicine，Yinchuan 750021，China
3. Institute of Tissue Engineering and Regenerative Medicine，the Chinese University of Hong Kong，Hong Kong 999077，China
4. Dept. One of Orthopedics，the First Affiliated Hospital of Guangzhou University of Chinese Medicine，Guangzhou 510405，China
- Publication Type:Journal Article
- Keywords:
luteolin;
bone defect;
osteogenic repair;
angiogenesis;
network pharmacology;
molecular docking
- From:
China Pharmacy
2023;34(7):807-813
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the effects and mechanism of luteolin on osteogenic repair of bone defects. METHODS The targets and potential pathways of luteolin in the treatment of bone defects were screened by network pharmacology method， and then the top 2 targets were selected by Hub gene screening for molecular docking verification， with binding energy as the evaluation standard. In vitro experiments were conducted on rat bone mesenchymal stem cells （BMSC） and rat umbilical vein endothelial cells （RUVEC）. Phenotypic validation was performed using alkaline phosphatase staining， alizarin red S staining， and in vitro angiogenesis experiments. Western blot assay was used to detect the protein expressions of phosphatidylinositol 3 kinase （PI3K） and protein kinase 1 （Akt1）， so as to validate the mechanism of luteolin on osteogenic differentiation of BMSC and angiogenesis of RUVEC in vitro. RESULTS The results of network pharmacology showed that the effects of luteolin on vascular formation and bone repair in bone defects were mainly related to Akt1， SRC， estrogen receptor 1， epidermal growth factor receptor， cyclooxygenase 2， matrix metalloproteinase 9 targets， and were closely related to PI3K-Akt signaling pathway. The results of molecular docking showed that luteolin binding to Akt1 and SRC proteins was stable. The results of in vitro experiments showed that luteolin could significantly improve the expressions and activities of alkaline phosphatase in BMSC， increased the number of calcium salt deposits and calcified nodules， and promoted calcification of BMSC. Compared with luteolin 0 μmol/L group， the angiogenesis ability of RUVEC was enhanced significantly in luteolin 1， 10 μmol/L groups， the length of blood vessels and the protein expressions of PI3K and Akt1 were significantly increased （P＜0.05 or P＜0.01）； the higherthe concentration， the better the effect. CONCLUSIONS Luteolin may play a role in promoting angiogenesis and bone repair at the fracture site by activating PI3K/Akt signaling pathway and promoting the protein expressions of PI3K and Akt1.
