PMID- 34492273
OWN - NLM
STAT- MEDLINE
DCOM- 20220106
LR  - 20220106
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 193
DP  - 2021 Nov
TI  - Oroxylin A reduces osteoclast formation and bone resorption via suppressing 
      RANKL-induced ROS and NFATc1 activation.
PG  - 114761
LID - S0006-2952(21)00377-4 [pii]
LID - 10.1016/j.bcp.2021.114761 [doi]
AB  - Excessive bone erosion by osteoclasts is associated with osteoporosis, rheumatoid 
      arthritis, and periprosthetic osteolysis. Targeting osteoclasts may serve as an 
      effective treatment for osteolytic diseases. Although drugs are currently 
      available for the treatment of these diseases, exploring potential 
      anti-osteoclast natural compounds with safe and effective treatment remains 
      needed. Oroxylin A (OA), a natural flavonoid isolated from the root of 
      Scutellaria baicalensis Georgi, has numerous beneficial pharmacological 
      characteristics, including anti-inflammatory and antioxidant activity. However, 
      its effects and mechanisms on osteoclast formation and bone resorption have not 
      yet been clarified. Our research showed that OA attenuated the formation and 
      function of osteoclast induced by RANKL in a time- and concentration-dependent 
      manner without any cytotoxicity. Mechanistically, OA suppressed intracellular 
      reactive oxygen species (ROS) levels through the Nrf2-mediated antioxidant 
      response. Moreover, OA inhibited the activity of NFATc1, the master 
      transcriptional regulator of RANKL-induced osteoclastogenesis. OA exhibited 
      protective effects in mouse models of post-ovariectomy (OVX)- and 
      lipopolysaccharide (LPS)-induced bone loss, in accordance with its in vitro 
      anti-osteoclastogenic effect. Collectively, our findings highlight the potential 
      of OA as a pharmacological agent for the prevention of osteoclast-mediated 
      osteolytic diseases.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Xian, Yansi
AU  - Xian Y
AD  - Guangxi Key Laboratory of Regenerative Medicine, Research Centre for Regenerative 
      Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi 
      Collaborative Innovation Center for Biomedicine, Guangxi Medical University, 
      Nanning, Guangxi, China.
FAU - Su, Yuangang
AU  - Su Y
AD  - Guangxi Key Laboratory of Regenerative Medicine, Research Centre for Regenerative 
      Medicine, Guangxi Medical University, Nanning, Guangxi, China.
FAU - Liang, Jiamin
AU  - Liang J
AD  - Guangxi Key Laboratory of Regenerative Medicine, Research Centre for Regenerative 
      Medicine, Guangxi Medical University, Nanning, Guangxi, China.
FAU - Long, Feng
AU  - Long F
AD  - Guangxi Key Laboratory of Regenerative Medicine, Research Centre for Regenerative 
      Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi 
      Collaborative Innovation Center for Biomedicine, Guangxi Medical University, 
      Nanning, Guangxi, China.
FAU - Feng, Xiaoliang
AU  - Feng X
AD  - Guangxi Key Laboratory of Regenerative Medicine, Research Centre for Regenerative 
      Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi 
      Collaborative Innovation Center for Biomedicine, Guangxi Medical University, 
      Nanning, Guangxi, China.
FAU - Xiao, Yu
AU  - Xiao Y
AD  - Medical College of Guangxi University, Nanning, Guangxi, China.
FAU - Lian, Haoyu
AU  - Lian H
AD  - Guangxi Key Laboratory of Regenerative Medicine, Research Centre for Regenerative 
      Medicine, Guangxi Medical University, Nanning, Guangxi, China.
FAU - Xu, Jiake
AU  - Xu J
AD  - School of Biomedical Sciences, the University of Western Australia, Perth, 
      Australia.
FAU - Zhao, Jinmin
AU  - Zhao J
AD  - Guangxi Key Laboratory of Regenerative Medicine, Research Centre for Regenerative 
      Medicine, Guangxi Medical University, Nanning, Guangxi, China; Orthopaedic 
      Department, the First Affiliated Hospital of Guangxi Medical University, Guangxi, 
      China.
FAU - Liu, Qian
AU  - Liu Q
AD  - Guangxi Key Laboratory of Regenerative Medicine, Research Centre for Regenerative 
      Medicine, Guangxi Medical University, Nanning, Guangxi, China. Electronic 
      address: liuqian@gxmu.edu.cn.
FAU - Song, Fangming
AU  - Song F
AD  - Guangxi Key Laboratory of Regenerative Medicine, Research Centre for Regenerative 
      Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi 
      Collaborative Innovation Center for Biomedicine, Guangxi Medical University, 
      Nanning, Guangxi, China. Electronic address: songfangming@gxmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210904
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Flavonoids)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Nfatc1 protein, mouse)
RN  - 0 (RANK Ligand)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tnfsf11 protein, mouse)
RN  - 53K24Z586G (5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one)
SB  - IM
MH  - Animals
MH  - Bone Resorption/*prevention & control
MH  - Cell Differentiation
MH  - Cell Survival/drug effects
MH  - Female
MH  - Flavonoids/chemistry/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Macrophages/*drug effects/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NFATC Transcription Factors/genetics/*metabolism
MH  - Osteoclasts/*drug effects
MH  - Podosomes
MH  - RANK Ligand
MH  - Random Allocation
MH  - Reactive Oxygen Species/*metabolism
OTO - NOTNLM
OT  - NFATc1
OT  - Oroxylin A
OT  - Osteoclast
OT  - ROS
EDAT- 2021/09/08 06:00
MHDA- 2022/01/07 06:00
CRDT- 2021/09/07 20:12
PHST- 2021/07/13 00:00 [received]
PHST- 2021/09/02 00:00 [revised]
PHST- 2021/09/02 00:00 [accepted]
PHST- 2021/09/08 06:00 [pubmed]
PHST- 2022/01/07 06:00 [medline]
PHST- 2021/09/07 20:12 [entrez]
AID - S0006-2952(21)00377-4 [pii]
AID - 10.1016/j.bcp.2021.114761 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2021 Nov;193:114761. doi: 10.1016/j.bcp.2021.114761. Epub 2021 
      Sep 4.