Protective effects of formononetin against oxygen-glucose deprivation/ reperfusion injury in BV2 microglia and associated mechanism

Wei Dingling, Wang Mei, Wang Wenxiu, Cao Liping, He Qiansong

PDF(2545 KB)
PDF(2545 KB)
Journal of Chongqing Medical University ›› 2025, Vol. 50 ›› Issue (02) : 244-249. DOI: 10.13406/j.cnki.cyxb.003701
Basic research

Protective effects of formononetin against oxygen-glucose deprivation/ reperfusion injury in BV2 microglia and associated mechanism

Author information +
History +

Abstract

Objective To investigate the effects of formononetin on the PARP1/PARG signaling pathway and neuroinflammation in BV2 microglia activated by oxygen-glucose deprivation/reperfusion（OGD/R）. Methods An OGD/R model was established with BV2 cells. These microglia were divided into blank control group，OGD/R group，formononetin（10 μm） group，OGD/R+formononetin（10 μm） group，OGD/R+PJ34（PARP1 inhibitor，10 μm） group，and OGD/R+ethacridine lactate（PARG inhibitor，7.5 μm） group. We measured the nuclear translocation of nuclear factor-kappa B（NF-κB） p65 and the expression of p53，apoptosis-inducing factor （AIF），and Toll-like receptor 4（TLR4） proteins in BV2 cells by immunofluorescence assay；measured the expression of PARP1/PARG pathway-related proteins by Western blot；and determined the content of interferon（INF）-γ，interleukin（IL）-1β，and tumor necrosis factor-α（TNF-α） by enzyme-linked immunosorbent assay（ELISA）. Results Western blot results showed that compared with the control group，the expression of PARP1 and PARG in cells was significantly increased after 6-hour oxygen-glucose deprivation followed by 1-hour reperfusion（P<0.05）； compared with the OGD/R group，the OGD/R+formononetin group had significantly decreased expression of PARP1 and PARG proteins（P<0.05） and significantly increased expression of Iduna protein（P<0.05）；the OGD/R+PJ34 group had significantly decreased expression of PARP1 protein（P<0.05），but the expression of PARG and Iduna proteins had no significant changes（P>0.05）；the OGD/R+ethacridine lactate group had significantly decreased expression of PARG protein（P<0.05），but had no significant changes in the expression of PARP1 and Iduna proteins（P>0.05）. Immunofluorescence assay results showed that compared with the OGD/R group，formononetin significantly reduced the expression of p53，AIF，TLR4，and NF-κB p65 and the nuclear translocation of NF-κB p65 in OGD/R cells； and both PJ34 and ethacridine lactate significantly reduced the expression of p53，AIF，and TLR4 and the nuclear translocation of NF-κB p65 in OGD/R cells. ELISA results showed that compared with the OGD/R group，formononetin significantly decreased the expression of IL-1β and TNF-α（P<0.05），but did not significantly affect INF-γ levels in OGD/R cells （P>0.05）； and both PJ34 and ethacridine lactate significantly decreased the expression levels of the proinflammatory factors INF-γ，IL-1β，and TNF-α in OGD/R cells （P<0.05）. Conclusion Formononetin can inhibit neuroinflammation in BV2 microglia deprived of glucose and oxygen，through regulating the PARP1/PARG signaling pathway.

Key words

formononetin / BV2 microglia / oxygen-glucose deprivation/reperfusion / PARP1 inhibitor / PARG inhibitor

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations
Wei Dingling , Wang Mei , Wang Wenxiu , et al . Protective effects of formononetin against oxygen-glucose deprivation/ reperfusion injury in BV2 microglia and associated mechanism. Journal of Chongqing Medical University. 2025, 50(02): 244-249 https://doi.org/10.13406/j.cnki.cyxb.003701

References

List( Publishing order | Descend order by publishing year | Descend order by cited within ) Chart analysis
1
Herpich F， Rincon F. Management of acute ischemic stroke[J]. Crit Care Med，2020，48（11）：1654-1663.
本文引用 [1]
2
Zhang P， Cui J. Neuroprotective effect of fisetin against the cerebral ischemia-reperfusion damage via suppression of oxidative stress and inflammatory parameters[J]. Inflammation，2021，44（4）：1490-1506.
本文引用 [1]
3
Xu Q， Guohui M， Li DD，et al. lncRNA C2dat2 facilitates autophagy and apoptosis via the miR-30d-5p/DDIT4/mTOR axis in cerebral ischemia-reperfusion injury[J]. Aging，2021，13（8）：11315-11335.
本文引用 [1]
4
Slade D. PARP and PARG inhibitors in cancer treatment[J]. Genes Dev，2020，34（5/6）：360-394.
本文引用 [1]
5
McGurk L， Rifai OM， Bonini NM. Poly（ADP-ribosylation） in age-related neurological disease[J]. Trends Genet，2019，35（8）：601-613.
本文引用 [1]
6
Zhu HF， Tang YD， Zhan GQ，et al. The critical role of PARPs in regulating innate immune responses[J]. Front Immunol，2021，12：712556.
本文引用 [1]
7
Liu LB， Li JX， Ke YS，et al. The key players of parthanatos：opportunities for targeting multiple levels in the therapy of parthanatos-based pathogenesis[J]. Cell Mol Life Sci，2022，79（1）：60.
本文引用 [1]
8
Karpova Y， Johnson SJ， Bordet G，et al. Upregulation of PARG in prostate cancer cells suppresses their malignant behavior and downregulates tumor-promoting genes[J]. Biomedecine Pharmacother，2022，153：113504.
本文引用 [1]
9
Peng JL， Wang HX， Gong Z，et al. Idebenone attenuates cerebral inflammatory injury in ischemia and reperfusion via dampening NLRP3 inflammasome activity[J]. Mol Immunol，2020，123：74-87.
本文引用 [1]
10
Kanazawa M， Ninomiya I， Hatakeyama M，et al. Microglia and monocytes/macrophages polarization reveal novel therapeutic mechanism against stroke[J]. Int J Mol Sci，2017，18（10）：2135.
本文引用 [1]
11
Var SR， Shetty AV， Grande AW，et al. Microglia and macrophages in neuroprotection，neurogenesis，and emerging therapies for stroke[J]. Cells，2021，10（12）：3555.
本文引用 [1]
12
Ma XY， Wang JJ. Formononetin：a pathway to protect neurons[J]. Front Integr Neurosci，2022，16：908378.
本文引用 [2]
13
Luo J， Cai YD， Wei DL，et al. Formononetin alleviates cerebral ischemia-reperfusion injury in rats by targeting the PARP-1/PARG/Iduna signaling pathway[J]. Brain Res，2024，1829：148845.
本文引用 [1]
14
Jia WC， Liu G， Zhang CD，et al. Formononetin attenuates hydrogen peroxide （H2O2）-induced apoptosis and NF-κB activation in RGC-5 cells[J]. Eur Rev Med Pharmacol Sci，2014，18（15）：2191-2197.
本文引用 [1]
15
Liang K， Ye Y， Wang Y，et al. Formononetin mediates neuroprotection against cerebral ischemia/reperfusion in rats via downregulation of the Bax/Bcl-2 ratio and upregulation PI3K/Akt signaling pathway[J]. J Neurol Sci，2014，344（1/2）：100-104.
本文引用 [1]
16
Morihara R， Yamashita T， Kono S，et al. Reduction of intracerebral hemorrhage by rivaroxaban after tPA thrombolysis is associated with downregulation of PAR-1 and PAR-2[J]. J Neurosci Res，2017，95（9）：1818-1828.
本文引用 [1]
17
Mamontova EM， Clément MJ， Sukhanova MV，et al. FUS RRM regulates poly（ADP-ribose） levels after transcriptional arrest and PARP-1 activation on DNA damage[J]. Cell Rep，2023，42（10）：113199.
本文引用 [1]
18
Yang XX， Cheng JH， Gao YB，et al. Downregulation of Iduna is associated with AIF nuclear translocation in neonatal brain after hypoxia-ischemia[J]. Neuroscience，2017，346：74-80.
本文引用 [1]
19
Stoica BA， Loane DJ， Zhao ZR，et al. PARP-1 inhibition attenuates neuronal loss，microglia activation and neurological deficits after traumatic brain injury[J]. J Neurotrauma，2014，31（8）：758-772.
本文引用 [2]
20
Li WH， Wang F， Song GY，et al. PARP-1：a critical regulator in radioprotection and radiotherapy-mechanisms，challenges，and therapeutic opportunities[J]. Front Pharmacol，2023，14：1198948.
本文引用 [1]
21
Sun SC. The non-canonical NF-κB pathway in immunity and inflammation[J]. Nat Rev Immunol，2017，17（9）：545-558.
本文引用 [1]
22
Ganbold T， Bao QM， Zandan J，et al. Modulation of microglia polarization through silencing of NF-κB p65 by functionalized curdlan nanoparticle-mediated RNAi[J]. ACS Appl Mater Interfaces，2020，12（10）：11363-11374.
本文引用 [1]

Comments

PDF(2545 KB)

Accesses

Citation

Detail
Sections
Recommended
Copyright © Journal of Chongqing Medical University, All Rights Reserved.
Powered by Beijing Magtech Co. Ltd.

/

〈 〉