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Penehyclidine hydrochloride inhibits the LPS-induced inflammatory response in microglia
Changshun Huang1, Jianguo He1, Yijun Chen1
1Department of Anesthesia, First Hospital of Ningbo City, Ningbo, Zhejiang, China.
Background:
Activated microglia play an important role in neuroinflammation, which contributes to the neuronal damage found in many neurodegenerative diseases. Penehyclidine hydrochloride (PHC) is an anesthetic used before surgical operations, but also exhibits anti-inflammatory effects on the respiratory and digestive system. In the present study, we investigated whether PHC produces similar anti-inflammatory effects in activated microglia in the central nervous system.
Materials And Methods:
Microglial cells were incubated with lipopolysaccharide (LPS) in the presence or absence of various concentrations of PHC, SB203580 (p38 mitogen-activated protein kinase [MAPK] inhibitor), and pyrrolidine dithiocarbamate (nuclear factor-kappa B [NF-κB] inhibitor). Markers of inflammation and oxidative stress were measured using enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction. The effect of PHC on NF-κB activity was assessed with a NF-κB p50/p65 transcription factor assay kit. The involvement of p38 MAPK phosphorylation in the anti-inflammatory effects of PHC was evaluated with a specific enzyme-linked immunosorbent assay kit for phospho-p38.
Results:
PHC significantly inhibited the release of nitric oxide, prostaglandin E2, interleukin 1β, and tumor necrosis factor α while upregulating the expression of inducible nitric oxide synthase messenger RNA in LPS-activated microglia. Moreover, PHC effectively inhibited the translocation of NF-κB from the cytoplasm to the nucleus and the phosphorylation of p38 MAPK. The activities of NF-κB and p38 MAPK in LPS-treated microglia were significantly lowered after pretreatment of PHC.
Conclusions:
PHC inhibited the LPS-induced release of inflammatory mediators in microglia. These inhibitory effects of PHC may be mediated by blocking p38 MAPK and NF-κB pathways in microglia. These preclinical findings may offer a novel therapeutic option to confine microglial overactivation in neurodegenerative diseases.
Insights
Penehyclidine hydrochloride (PHC) reduces neuroinflammation by inhibiting inflammatory mediators in activated microglia. This effect is mediated by blocking p38 MAPK and NF-κB pathways, offering potential for neurodegenerative disease treatment.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Activated microglia contribute to neuroinflammation and neuronal damage in neurodegenerative diseases.
- Penehyclidine hydrochloride (PHC), an anesthetic, shows anti-inflammatory effects in other systems.
- This study investigates PHC's anti-inflammatory potential in central nervous system microglia.
Purpose of the Study:
- To determine if Penehyclidine hydrochloride (PHC) exhibits anti-inflammatory effects in activated microglia.
- To elucidate the molecular mechanisms underlying PHC's action in the central nervous system.
- To explore PHC as a potential therapeutic agent for neurodegenerative diseases.
Main Methods:
- Microglial cells were stimulated with lipopolysaccharide (LPS) and treated with PHC, p38 MAPK inhibitor, or NF-κB inhibitor.
- Inflammatory markers (nitric oxide, prostaglandin E2, IL-1β, TNF-α) and iNOS mRNA were quantified.
- NF-κB activity, p38 MAPK phosphorylation, and translocation were assessed.
Main Results:
- PHC significantly inhibited the release of key inflammatory mediators (NO, PGE2, IL-1β, TNF-α) in LPS-activated microglia.
- PHC suppressed the nuclear translocation of NF-κB and phosphorylation of p38 MAPK.
- PHC effectively reduced NF-κB and p38 MAPK activities in LPS-treated microglia.
Conclusions:
- Penehyclidine hydrochloride (PHC) effectively inhibits LPS-induced inflammatory mediator release in microglia.
- PHC's anti-inflammatory effects are likely mediated through the blockade of p38 MAPK and NF-κB pathways.
- These findings suggest PHC as a potential therapeutic strategy for managing microglial overactivation in neurodegenerative conditions.
