RESUMO
BACKGROUND AND PURPOSE: Microglial activation plays an important role in the onset and progression of neuropathic pain by producing a variety of pro-inflammatory cytokines that interact with neurons to enhance neuronal hyperexcitability. Corydalis decumbens (Thunb.) pers., a traditional Chinese medicine has been used to treat mild cancer pain, dementia and to remit cerebral ischemia in clinics. Phenylphthalide isoquinolines are the major type of metabolites of C. decumbens and one of the derivatives, Corydecumine G (Cor G) has been shown to inhibit neuronal excitability. The present study aims to investigate the analgesic efficacy of Cor G in neuropathic pain rat model, the effects of Cor G on microglia activation and the possible mechanisms. EXPERIMENTAL APPROACH: Neuropathic pain was modeled using chronic constriction sciatic nerve injury (CCI) in rats. Western blot, immunofluorescence, and qRT-PCR were used to evaluate the levels of protein and mRNA. KEY RESULTS: Intraperitoneal administration of Cor G concentration-dependently ameliorates mechanical and thermo allodynia, suppresses CCI-induced p38/ERK phosphorylation and spinal cord microglia activation, and attenuates the expression levels of NO, inos, Tnf-α, Pge2 in dorsal horn of L4-L6 spinal cord on the ligation side in CCI rats. Pretreatment with 30 µM Cor G decreased LPS-induced BV2 microglia activation, which occurred via the inos, Tnf-α, Il-1ß, Il-6 and phospho-p38/ERK pathways. CONCLUSIONS AND IMPLICATIONS: Taken together, we suggest that Cor G, the specific phthalide isoquinoline from traditional Chinese medicine Corydalis Decumbentis Rhizoma, may be promising for treatment of neuropathic pain.
Assuntos
Microglia , Neuralgia , Piperidinas/farmacologia , Animais , Hiperalgesia/metabolismo , Sistema de Sinalização das MAP Quinases , Microglia/metabolismo , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Ratos , Ratos Sprague-Dawley , Medula Espinal/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/farmacologiaRESUMO
Fifteen new water-soluble alkaloids were obtained from the fresh herbs of Portulaca oleracea L. The structures of 15 alkaloids 1-15 were established according to spectroscopic data, and the stereoconfigurations were determined based on experimental and calculated electronic circular dichroism (ECD) data and single crystal X-ray diffraction. Alkaloids 1-15 were found to display good anti-inflammatory activity at 10 µM and could significantly reduce the interleukin-6 (IL-6) and nitric oxide (NO) levels induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages.
Assuntos
Alcaloides/química , Anti-Inflamatórios/química , Portulaca/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Cristalografia por Raios X , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/patologia , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Conformação Molecular , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Portulaca/metabolismo , Células RAW 264.7 , Solubilidade , Água/químicaRESUMO
Two previously undescribed flavonols with phenylpropanoid or benzyl substitution, named alangsine A (1), and alangsine B (2), together with four known compounds (3-6) were isolated from the leaves of Alangium chinense. Alangsine A was a racemic mixture, which was further separated into two enantiomers via high-performance liquid chromatography on a chiral column. The absolute configurations of the enantiomer pairs were deduced from the circular dichroism (CD) spectra. The activity of the isolated compounds towards neuronal excitability was examined.