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Updated: Mar 23, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Papaverine inhibits lipopolysaccharide-induced microglial activation by suppressing NF-κB signaling pathway
Yalong Dang1, Yalin Mu2, Kun Wang3
1Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
Objective:
To investigate the effects of papaverine (PAP) on lipopolysaccharide (LPS)-induced microglial activation and its possible mechanisms.
Materials And Methods:
BV2 microglial cells were first pretreated with PAP (0, 0.4, 2, 10, and 50 μg/mL) and then received LPS stimulation. Transcription and production of proinflammatory factors (IL1β, TNFα, iNOS, and COX-2) were used to evaluate microglial activation. The transcriptional changes undergone by M1/M2a/M2b markers were used to evaluate phenotype transformation of BV2 cells. Immunofluorescent staining and Western blot were used to detect the location and expression of P65 and p-IKK in the presence or absence of PAP pretreatment.
Results:
Pretreatment with PAP significantly inhibited the expression of IL1β and TNFα, and suppressed the transcription of M1/M2b markers Il1rn, Socs3, Nos2 and Ptgs2, but upregulated the transcription of M2a markers (Arg1 and Mrc1) in a dose-dependent manner. In addition, PAP pretreatment significantly decreased the expression of p-IKK and inhibited the nuclear translocation of P65 after LPS stimulation.
Conclusion:
PAP not only suppressed the LPS-induced microglial activity by inhibiting transcription/production of proinflammatory factors, but also promoted the transformation of activated BV2 cells from cytotoxic phenotypes (M1/M2b) to a neuroprotective phenotype (M2a). These effects were probably mediated by NF-κB signaling pathway. Thus, it would be a promising candidate for the treatment of neurodegenerative diseases.
Insights
Papaverine (PAP) reduces inflammation in microglial cells by inhibiting pro-inflammatory factors and promoting a shift to a neuroprotective M2a phenotype. This suggests PAP may be beneficial for treating neurodegenerative diseases.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Microglial activation by lipopolysaccharide (LPS) contributes to neuroinflammation.
- Understanding modulators of microglial activation is crucial for neurodegenerative disease research.
Purpose of the Study:
- To investigate the effects of papaverine (PAP) on LPS-induced microglial activation.
- To elucidate the underlying mechanisms of PAP's action on microglial cells.
Main Methods:
- BV2 microglial cells were treated with PAP and LPS.
- Pro-inflammatory factor transcription and production were measured.
- M1/M2a/M2b marker expression was analyzed for phenotype transformation.
- NF-κB signaling pathway components (P65, p-IKK) were assessed via immunofluorescence and Western blot.
Main Results:
- Papaverine significantly inhibited pro-inflammatory factors (IL1β, TNFα) and M1/M2b markers.
- PAP upregulated M2a markers (Arg1, Mrc1) in a dose-dependent manner.
- PAP decreased p-IKK expression and inhibited P65 nuclear translocation.
Conclusions:
- Papaverine suppresses LPS-induced microglial activation and pro-inflammatory factor production.
- PAP promotes a shift from cytotoxic M1/M2b phenotypes to neuroprotective M2a phenotypes.
- The observed effects are likely mediated by the NF-κB pathway, positioning PAP as a potential therapeutic for neurodegenerative diseases.
