Effect of Scutellarin on BV-2 Microglial-mediated Apoptosis in PC12 Cells Via JAK2/STAT3 Signalling Pathway

Overview

Journal Sci Rep

Specialty Science

Date 2024 Jun 11

PMID 38862696

Authors

Zhao-Da Duan

Li-Yang Zheng

Qiu-Ye Jia

Hao-Lun Chen

Dong-Yao Xu

Yu-Jia Yang

Zhi Qi

Li Yang

Chun-Yun Wu

Affiliations

Soon will be listed here.

Abstract

Previous studies have shown that scutellarin inhibits the excessive activation of microglia, reduces neuronal apoptosis, and exerts neuroprotective effects. However, whether scutellarin regulates activated microglia-mediated neuronal apoptosis and its mechanisms remains unclear. This study aimed to investigate whether scutellarin can attenuate PC12 cell apoptosis induced by activated microglia via the JAK2/STAT3 signalling pathway. Microglia were cultured in oxygen-glucose deprivation (OGD) medium, which acted as a conditioning medium (CM) to activate PC12 cells, to investigate the expression of apoptosis and JAK2/STAT3 signalling-related proteins. We observed that PC12 cells apoptosis in CM was significantly increased, the expression and fluorescence intensity of the pro-apoptotic protein Bax and apoptosis-related protein cleaved caspase-3 were increased, and expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) was decreased. Phosphorylation levels and fluorescence intensity of the JAK2/STAT3 signalling pathway-related proteins JAK2 and STAT3 decreased. After treatment with scutellarin, PC12 cells apoptosis as well as cleaved caspase-3 and Bax protein expression and fluorescence intensity decreased. The expression and fluorescence intensity of Bcl-2, phosphorylated JAK2, and STAT3 increased. AG490, a specific inhibitor of the JAK2/STAT3 signalling pathway, was used. Our findings suggest that AG490 attenuates the effects of scutellarin. Our study revealed that scutellarin inhibited OGD-activated microglia-mediated PC12 cells apoptosis which was regulated via the JAK2/STAT3 signalling pathway.

Citing Articles

Scutellarin Alleviates Neuronal Apoptosis in Ischemic Stroke via Activation of the PI3K/AKT Signaling Pathway.

Duan Z, Peng Y, Xu D, Yang Y, Wu Y, Wu C Int J Mol Sci. 2025; 26(5).

PMID: 40076795 PMC: 11901123. DOI: 10.3390/ijms26052175.

References

Peng L, Wen L, Shi Q, Gao F, Huang B, Meng J . Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial-mesenchymal transition and inflammation. Cell Death Dis. 2020; 11(11):978. PMC: 7666141. DOI: 10.1038/s41419-020-03178-2. View

Niu R, Xiong L, Zhou H, Xue L, Xia Q, Ma Z . Scutellarin ameliorates neonatal hypoxic-ischemic encephalopathy associated with GAP43-dependent signaling pathway. Chin Med. 2021; 16(1):105. PMC: 8524967. DOI: 10.1186/s13020-021-00517-z. View

Wu C, Fang M, Karthikeyan A, Yuan Y, Ling E . Scutellarin Attenuates Microglia-Mediated Neuroinflammation and Promotes Astrogliosis in Cerebral Ischemia - A Therapeutic Consideration. Curr Med Chem. 2016; 24(7):718-727. DOI: 10.2174/0929867324666161118142045. View

Bolli R, Dawn B, Xuan Y . Role of the JAK-STAT pathway in protection against myocardial ischemia/reperfusion injury. Trends Cardiovasc Med. 2003; 13(2):72-9. DOI: 10.1016/s1050-1738(02)00230-x. View

Wakselman S, Bechade C, Roumier A, Bernard D, Triller A, Bessis A . Developmental neuronal death in hippocampus requires the microglial CD11b integrin and DAP12 immunoreceptor. J Neurosci. 2008; 28(32):8138-43. PMC: 6670768. DOI: 10.1523/JNEUROSCI.1006-08.2008. View

Bal-Price A, Brown G . Inflammatory neurodegeneration mediated by nitric oxide from activated glia-inhibiting neuronal respiration, causing glutamate release and excitotoxicity. J Neurosci. 2001; 21(17):6480-91. PMC: 6763071. View

Simon E, Obst J, Gomez-Nicola D . The Evolving Dialogue of Microglia and Neurons in Alzheimer's Disease: Microglia as Necessary Transducers of Pathology. Neuroscience. 2018; 405:24-34. DOI: 10.1016/j.neuroscience.2018.01.059. View

Back T . Pathophysiology of the ischemic penumbra--revision of a concept. Cell Mol Neurobiol. 1999; 18(6):621-38. PMC: 11560235. DOI: 10.1023/a:1020629818207. View

Martin-Villalba A, Herr I, Jeremias I, Hahne M, Brandt R, Vogel J . CD95 ligand (Fas-L/APO-1L) and tumor necrosis factor-related apoptosis-inducing ligand mediate ischemia-induced apoptosis in neurons. J Neurosci. 1999; 19(10):3809-17. PMC: 6782733. View

10.

Satriotomo I, Bowen K, Vemuganti R . JAK2 and STAT3 activation contributes to neuronal damage following transient focal cerebral ischemia. J Neurochem. 2006; 98(5):1353-68. DOI: 10.1111/j.1471-4159.2006.04051.x. View

11.

Stewart V, Heslegrave A, Brown G, Clark J, Heales S . Nitric oxide-dependent damage to neuronal mitochondria involves the NMDA receptor. Eur J Neurosci. 2002; 15(3):458-64. DOI: 10.1046/j.0953-816x.2001.01878.x. View

12.

Yuan Y, Zha H, Rangarajan P, Ling E, Wu C . Anti-inflammatory effects of Edaravone and Scutellarin in activated microglia in experimentally induced ischemia injury in rats and in BV-2 microglia. BMC Neurosci. 2014; 15:125. PMC: 4247200. DOI: 10.1186/s12868-014-0125-3. View

13.

Chen H, Yang L, Zhang X, Jia Q, Duan Z, Li J . Scutellarin Acts via MAPKs Pathway to Promote M2 Polarization of Microglial Cells. Mol Neurobiol. 2023; 60(8):4304-4323. DOI: 10.1007/s12035-023-03338-3. View

14.

Klampfer L . Signal transducers and activators of transcription (STATs): Novel targets of chemopreventive and chemotherapeutic drugs. Curr Cancer Drug Targets. 2006; 6(2):107-21. DOI: 10.2174/156800906776056491. View

15.

Stuckey S, Ong L, Collins-Praino L, Turner R . Neuroinflammation as a Key Driver of Secondary Neurodegeneration Following Stroke?. Int J Mol Sci. 2021; 22(23). PMC: 8658328. DOI: 10.3390/ijms222313101. View

16.

Bal-Price A, Matthias A, Brown G . Stimulation of the NADPH oxidase in activated rat microglia removes nitric oxide but induces peroxynitrite production. J Neurochem. 2002; 80(1):73-80. DOI: 10.1046/j.0022-3042.2001.00675.x. View

17.

OShea J, Gadina M, Schreiber R . Cytokine signaling in 2002: new surprises in the Jak/Stat pathway. Cell. 2002; 109 Suppl:S121-31. DOI: 10.1016/s0092-8674(02)00701-8. View

18.

Dirnagl U, Iadecola C, Moskowitz M . Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 1999; 22(9):391-7. DOI: 10.1016/s0166-2236(99)01401-0. View

19.

Xu Y, Tang D, Wang J, Wei H, Gao J . Neuroprotection of Andrographolide Against Microglia-Mediated Inflammatory Injury and Oxidative Damage in PC12 Neurons. Neurochem Res. 2019; 44(11):2619-2630. DOI: 10.1007/s11064-019-02883-5. View

20.

He Q, Wang Y, Lin W, Zhang Q, Zhao J, Liu F . Trehalose alleviates PC12 neuronal death mediated by lipopolysaccharide-stimulated BV-2 cells via inhibiting nuclear transcription factor NF-κB and AP-1 activation. Neurotox Res. 2014; 26(4):430-9. DOI: 10.1007/s12640-014-9487-7. View