Department of Pharmacology, Anhui Medical University, Hefei 230032, PR China.
Pharmacol Biochem Behav. 2012 Sep;102(3):465-70. doi: 10.1016/j.pbb.2012.06.007. Epub 2012 Jun 12.
Iridoid glycosides of Paederia scandens (IGPS) is a major active component isolated from traditional Chinese herb P. scandens (LOUR.) MERRILL (Rubiaceae). The aim of the present study was to investigate the analgesic effect of IGPS on spared nerve injury (SNI) model of neuropathic pain. The SNI model in rats was established by complete transection of the common peroneal and tibial distal branches of the sciatic nerve, leaving the sural branch intact. The mechanical withdrawal threshold (MWT) in response to mechanical stimulation was measured by electronic von Frey filaments on day 1 before operation and on days 1, 3, 5, 7, 10, and 14 after operation, respectively. Nitric oxide synthase (NOS) activity and nitric oxide (NO) production of spinal cord were measured by spectrophotometry and its cyclic guanosine monophosphate (cGMP) content by radioimmunoassay, mRNA expression of inducible NOS (iNOS) and protein kinase G type I (PKG-I, including PKG Ια and PKG Iβ) of spinal cord were analyzed by RT-PCR. There was a marked mechanical hypersensitivity response observed on day 1 after operation in SNI model, which accompanied with decreased MWT. Treatment with IGPS (70, 140, 280 mg/kg) significantly alleviated SNI-induced mechanical hypersensitivity response evidenced by increased MWT; as well as markedly decreased NOS activity, NO and cGMP levels. At the same time, IGPS (70, 140, 280 mg/kg) could also inhibit mRNA expression of iNOS, PKG Ια and PKG Iβ in the spinal cord. The results suggested that IGPS possesses antinociceptive effect, which may be partly related to the inhibition of NO/cGMP/PKG signaling pathway in the rat SNI model of neuropathic pain.
鸡矢藤中裂环烯醚萜总苷(IGPS)是从传统中药鸡矢藤(茜草科)中分离得到的主要活性成分。本研究旨在探讨 IGPS 对神经病理性疼痛 spared nerve injury(SNI)模型的镇痛作用。大鼠 SNI 模型通过坐骨神经的腓总神经和胫神经的完全横断建立,保留腓肠神经完整。在手术前第 1 天及第 1、3、5、7、10 和 14 天,通过电子 von Frey 细丝测量机械刺激的机械撤回避反应阈值(MWT)。通过分光光度法测量脊髓中一氧化氮合酶(NOS)活性和一氧化氮(NO)的产生,通过放射免疫法测量其环鸟苷酸(cGMP)含量,通过 RT-PCR 分析脊髓中诱导型 NOS(iNOS)和蛋白激酶 G 型 I(PKG-I,包括 PKG Ια 和 PKG Iβ)的 mRNA 表达。在 SNI 模型中,手术后第 1 天观察到明显的机械性超敏反应,MWT 降低。IGPS(70、140、280mg/kg)治疗可显著缓解 SNI 引起的机械性超敏反应,MWT 增加;NOS 活性、NO 和 cGMP 水平明显降低。同时,IGPS(70、140、280mg/kg)还可抑制脊髓中 iNOS、PKG Ια 和 PKG Iβ的 mRNA 表达。结果表明,IGPS 具有镇痛作用,可能部分与抑制 NO/cGMP/PKG 信号通路有关。