Parthenolide modulates cerebral ischemia-induced microglial polarization and alleviates neuroinflammatory injury via the RhoA/ROCK pathway

Zhang, Yehao; Miao, Lei; Peng, Qing; Fan, Xiaodi; Song, Wenting; Yang, Bin; Zhang, Peng; Li, Guangyu; Liu, Jianxun

doi:10.1016/j.phymed.2022.154373

Cited by 20 publications

(7 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies have shown that the RhoA/p38MAPK pathway promotes the activation of microglia 18,34 . In this study, microglial trajectory analysis and GMI‐R1 cell experiments confirmed that the RhoA/p38MAPK pathway can lead to the M1 polarization of microglial cells.…”

Section: Discussionsupporting

confidence: 80%

Paeonol alleviates neuropathic pain by modulating microglial M1 and M2 polarization via the RhoA/p38MAPK signaling pathway

Shi

Zhang

et al. 2023

CNS Neurosci Ther

View full text Add to dashboard Cite

Background This study aimed to investigate the potential mechanism of paeonol in the treatment of neuropathic pain. Methods Relevant mechanisms were explored through microglial pseudotime analysis and the use of specific inhibitors in cell experiments. In animal experiments, 32 SD rats were randomly divided into the sham operation group, the chronic constrictive injury (CCI) group, the ibuprofen group, and the paeonol group. We performed behavioral testing, ELISA, PCR, Western blotting, immunohistochemistry, and immunofluorescence analysis. Results The pseudotime analysis of microglia found that RhoA, Rock1, and p38MAPK were highly expressed in activated microglia, and the expression patterns of these genes were consistent with the expression trends of the M1 markers CD32 and CD86. Paeonol decreased the levels of M1 markers (IL1β, iNOS, CD32, IL6) and increased the levels of M2 markers (IL10, CD206, ARG‐1) in LPS‐induced microglia. The expression of iNOS, IL1β, RhoA, and Rock1 was significantly increased in LPS‐treated microglia, while paeonol decreased the expression of these proteins. Thermal hyperalgesia occurred after CCI surgery, and paeonol provided relief. In addition, paeonol decreased the levels of IL1β and IL8 and increased the levels of IL4 and TGF‐β in the serum of CCI rats. Paeonol decreased expression levels of M1 markers and increased expression levels of M2 markers in the spinal cord. Paeonol decreased IBA‐1, IL1β, RhoA, RhoA‐GTP, COX2, Rock1, and p‐p38MAPK levels in the spinal dorsal horn. Conclusion Paeonol relieves neuropathic pain by modulating microglial M1 and M2 phenotypes through the RhoA/p38 MAPK pathway.

show abstract

Section: Discussionsupporting

confidence: 80%

Paeonol alleviates neuropathic pain by modulating microglial M1 and M2 polarization via the RhoA/p38MAPK signaling pathway

Shi

Zhang

et al. 2023

CNS Neurosci Ther

View full text Add to dashboard Cite

show abstract

“…This restorative process typically occurs around 2 weeks after the initial damage ( Niu et al, 2021 ). As mentioned previously, activation of the RhoA-ROCK signaling pathway in microglia results in polarization of macrophages to the M1 type and the production of inflammatory factors ( Zhang et al, 2022 ). Inhibition of myelin formation by Nogo-A has also been associated with activation of OLs and the RhoA-ROCK signaling pathway, and activation of RhoA inhibits differentiation of OPCs to OLs ( Wang et al, 2021 ).…”

Section: Pathophysiological Process Of Scimentioning

confidence: 78%

Biomaterials targeting the microenvironment for spinal cord injury repair: progression and perspectives

Gao,

Wang,

et al. 2024

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Spinal cord injury (SCI) disrupts nerve pathways and affects sensory, motor, and autonomic function. There is currently no effective treatment for SCI. SCI occurs within three temporal periods: acute, subacute, and chronic. In each period there are different alterations in the cells, inflammatory factors, and signaling pathways within the spinal cord. Many biomaterials have been investigated in the treatment of SCI, including hydrogels and fiber scaffolds, and some progress has been made in the treatment of SCI using multiple materials. However, there are limitations when using individual biomaterials in SCI treatment, and these limitations can be significantly improved by combining treatments with stem cells. In order to better understand SCI and to investigate new strategies for its treatment, several combination therapies that include materials combined with cells, drugs, cytokines, etc. are summarized in the current review.

show abstract

“…In recent years, natural products have made significant advances in managing ischemic stroke [ 30 ], with many exhibiting anti-inflammatory and antioxidative properties in cerebral ischemia models [ 31 , 32 ]. Hydrogen peroxide, a powerful oxidant, can trigger an intracellular oxidative stress response, resulting in cellular damage.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effect of acetoxypachydiol against oxidative stress through activation of the Keap1-Nrf2/HO-1 pathway

Qi,

Liu,

Jin

et al. 2024

BMC Complement Med Ther

View full text Add to dashboard Cite

Background Excessive oxidative stress in the brain is an important pathological factor in neurological diseases. Acetoxypachydiol (APHD) is a lipophilic germacrane-type diterpene extracted as a major component from different species of brown algae within the genus Dictyota. There have been no previous reports on the pharmacological activity of APHD. The present research aims to explore the potential neuroprotective properties of APHD and its underlying mechanisms. Methods The possible mechanism of APHD was predicted using a combination of molecular docking and network pharmacological analysis. PC12 cells were induced by H2O2 and oxygen–glucose deprivation/reoxygenation (OGD/R), respectively. Western blot, flow cytometry, immunofluorescence staining, and qRT-PCR were used to investigate the antioxidant activity of APHD. The HO-1 inhibitor ZnPP and Nrf2 gene silencing were employed to confirm the influence of APHD on the signaling cascade involving HO-1, Nrf2, and Keap1 in vitro. Results APHD exhibited antioxidant activity in both PC12 cells subjected to H2O2 and OGD/R conditions by downregulating the release of LDH, the concentrations of MDA, and ROS, and upregulating SOD, GSH-Px, and GSH concentrations. APHD could potentially initiate the Keap1-Nrf2/HO-1 signaling cascade, according to the findings from network pharmacology evaluation and molecular docking. Furthermore, APHD was observed to increase Nrf2 and HO-1 expression at both mRNA and protein levels, while downregulating the protein concentrations of Keap1. Both Nrf2 silencing and treatment with ZnPP reversed the neuroprotective effects of APHD. Conclusions APHD activated antioxidant enzymes and downregulated the levels of LDH, MDA, and ROS in two cell models. The neuroprotective effect is presumably reliant on upregulation of the Keap1-Nrf2/HO-1 pathway. Taken together, APHD from brown algae of the genus Dictyota shows potential as a candidate for novel neuroprotective agents.

show abstract

Parthenolide modulates cerebral ischemia-induced microglial polarization and alleviates neuroinflammatory injury via the RhoA/ROCK pathway

Cited by 20 publications

References 48 publications

Paeonol alleviates neuropathic pain by modulating microglial M1 and M2 polarization via the RhoA/p38MAPK signaling pathway

Paeonol alleviates neuropathic pain by modulating microglial M1 and M2 polarization via the RhoA/p38MAPK signaling pathway

Biomaterials targeting the microenvironment for spinal cord injury repair: progression and perspectives

Neuroprotective effect of acetoxypachydiol against oxidative stress through activation of the Keap1-Nrf2/HO-1 pathway

Contact Info

Product

Resources

About