Penehyclidine hydrochloride attenuates LPS-induced iNOS production by inhibiting p38 MAPK activation in endothelial cells

Zhan, Jianghua; Zhang, Zongze; Chen, Chang; Chen, Kai; Wang, Yanlin

doi:10.1007/s11033-011-0857-4

Cited by 12 publications

(5 citation statements)

References 20 publications

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“…13 Another study was to investigate the inhibitory effect of PHC on LPS-induced NO and inducible nitric oxide synthase (iNOS) production. 33 LPS treatment significantly induced p38 MAPK activation, iNOS expression, and NO production, which could be attenuated by PHC pretreatment. Furthermore, LPS-induced NO production and iNOS expression were suppressed by p38 MAPK inhibitor SB203580 pretreatment.…”

Section: Discussionmentioning

confidence: 89%

Penehyclidine hydrochloride suppressed peripheral nerve injury-induced neuropathic pain by inhibiting microglial MAPK/p-p38/IL-1β pathway activation

et al. 2019

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Background: Millions of people suffered from neuropathic pain, which is related to neuroinflammation in the central nervous system. Penehyclidine hydrochloride is a premedication of general anesthesia, which has been confirmed possessing neuroprotective effects against various neurodegenerative or neuroinflammatory diseases. However, it is not clear that whether penehyclidine hydrochloride could suppress neuropathic pain through its anti-neuroinflammatory effects. Methods: This study investigated the effects of penehyclidine hydrochloride on rat spinal nerve ligation injury-induced neuropathic pain with behavioral, morphological, and molecular biological methods in animals. Results: The results indicated that penehyclidine hydrochloride could attenuate spinal nerve ligation-induced neuropathic pain without any motor impairment and had no effect on sham-operated animals after repeated intraperitoneal administration. Intraperitoneal penehyclidine hydrochloride could suppress spinal nerve ligation-induced ipsilateral spinal dorsal horn microglial activation with downregulation of OX42 expression. Moreover, intraperitoneal penehyclidine hydrochloride inhibited spinal nerve ligation-induced spinal p-p38 mitogen-activated protein kinase expression, which was specially colocalized with the spinal dorsal horn microglia. Furthermore, intraperitoneal penehyclidine hydrochloride could depress spinal neuroinflammation by suppressing spinal nerve ligation-induced interleukin (IL)-1b over-expression. Conclusion: These results indicated that the anti-allodynic effects of penehyclidine hydrochloride on spinal nerve ligationinduced neuropathic pain did not rely on motor impairment. Inhibiting spinal microglial p-p38/IL-1b pathway activation might contribute to the anti-allodynic effect of penehyclidine hydrochloride on nerve injury-induced neuropathic pain.

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Section: Discussionmentioning

confidence: 89%

Penehyclidine hydrochloride suppressed peripheral nerve injury-induced neuropathic pain by inhibiting microglial MAPK/p-p38/IL-1β pathway activation

et al. 2019

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“…This suggests that the therapeutic potential of PHC might be related to its inhibition of the p38 signalling pathway. A previous study indicated that PHC exerted its protective effects against lipopolysaccharide-induced endothelial cell injury by suppressing the activation of the p38 MAPK pathway (Zhan et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Penehyclidine hydrochloride attenuates the cerebral injury in a rat model of cardiopulmonary bypass

Cao

Sun

Zhang

et al. 2013

Can. J. Physiol. Pharmacol.

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This study investigated the effect of penehyclidine hydrochloride (PHC) on regulatory mediators during the neuroinflammatory response and cerebral cell apoptosis following cardiopulmonary bypass (CPB). Forty-eight rats were randomly divided among 4 groups as follows: sham-operation, vehicle, low-dose PHC (0.6 mg·(kg body mass)(-1)), and high-dose PHC (2.0 mg·(kg body mass)(-1)). CPB was performed in the latter 3 groups. The plasma levels of neuron specific enolase (NSE) and S-100B were tested with ELISA. Real-time PCR and Western blotting were used to evaluate the expression levels of matrix metalloproteinase-9 (MMP-9), IL-10, caspase-3, Bcl-2, and p38 in brain tissue. The ultrastructure of hippocampus tissue was examined under an electron microscope. PHC attenuated the increase of plasma NSE and S-100B following CPB. MMP-9, cleaved caspase-3, and phosphorylated p38 expression were substantially increased in the vehicle group compared with the sham-operation group and gradually diminished with increasing doses of PHC. IL-10 and Bcl-2 expression were markedly lower in the vehicle group than in the sham-operation group and gradually recovered with increasing doses of PHC. PHC attenuated the histopathological changes of cerebral injury following CPB. PHC favorably regulates the inflammatory response and reduces markers of neuronal injury following CPB, potentially by reducing p38 and caspase-3 activation.

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“…As an important narcotic, propofol can reduce the occurrence of awareness, protect the heart in patients with surgery ( 25 ), has the potential to treat sepsis ( 26 , 27 ), and can protect important organs in ischemia reperfusion injury ( 28 - 30 ). Some reports suggest that propofol can inhibit the release of many early inflammatory cytokines in mononuclear macrophages after LPS stimulation ( 14 - 16 ). However, it is unclear whether propofol inhibits the expression and release of HMGB1 in mononuclear macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…Monocytes/macrophages are stimulated by lipopolysaccharide (LPS), TNF, or IL-1, and secrete HMGB1 as a delayed response ( 4 , 13 ). Studies have indicated that propofol (2,6-diisopropylphenol) inhibits the release of many early inflammatory cytokines in LPS-stimulated mononuclear macrophages ( 14 , 15 ), as well as pressure-stimulated macrophage phagocytosis ( 16 ). However, the effects of propofol on the expression and release of HMGB1 in mononuclear macrophages are unclear.…”

Section: Introductionmentioning

confidence: 99%

Effects of propofol on lipopolysaccharide-induced expression and release of HMGB1 in macrophages

Wang

Wei

Liu

et al. 2015

Braz J Med Biol Res

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This study aimed to determine the effects of different concentrations of propofol (2,6-diisopropylphenol) on lipopolysaccharide (LPS)-induced expression and release of high-mobility group box 1 protein (HMGB1) in mouse macrophages. Mouse macrophage cell line RAW264.7 cells were randomly divided into 5 treatment groups. Expression levels of HMGB1 mRNA were detected using RT-PCR, and cell culture supernatant HMGB1 protein levels were detected using enzyme-linked immunosorbent assay (ELISA). Translocation of HMGB1 from the nucleus to the cytoplasm in macrophages was observed by Western blotting and activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus was detected using ELISA. HMGB1 mRNA expression levels increased significantly in the cell culture supernatant and in cells after 24 h of stimulating RAW264.7 cells with LPS (500 ng/mL). However, HMGB1 mRNA expression levels in the P2 and P3 groups, which received 500 ng/mL LPS with 25 or 50 μmol/mL propofol, respectively, were significantly lower than those in the group receiving LPS stimulation (P<0.05). After stimulation by LPS, HMGB1 protein levels were reduced significantly in the nucleus but were increased in the cytoplasm (P<0.05). Simultaneously, the activity of NF-κB was enhanced significantly (P<0.05). After propofol intervention, HMGB1 translocation from the nucleus to the cytoplasm and NF-κB activity were inhibited significantly (each P<0.05). Thus, propofol can inhibit the LPS-induced expression and release of HMGB1 by inhibiting HMGB1 translocation and NF-κB activity in RAW264.7 cells, suggesting propofol may be protective in patients with sepsis.

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Penehyclidine hydrochloride attenuates LPS-induced iNOS production by inhibiting p38 MAPK activation in endothelial cells

Cited by 12 publications

References 20 publications

Penehyclidine hydrochloride suppressed peripheral nerve injury-induced neuropathic pain by inhibiting microglial MAPK/p-p38/IL-1β pathway activation

Penehyclidine hydrochloride suppressed peripheral nerve injury-induced neuropathic pain by inhibiting microglial MAPK/p-p38/IL-1β pathway activation

Penehyclidine hydrochloride attenuates the cerebral injury in a rat model of cardiopulmonary bypass

Effects of propofol on lipopolysaccharide-induced expression and release of HMGB1 in macrophages

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