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首页> 外文期刊>Biochemical Pharmacology >St. John's Wort reduces neuropathic pain through a hypericin-mediated inhibition of the protein kinase Cgamma and epsilon activity.
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St. John's Wort reduces neuropathic pain through a hypericin-mediated inhibition of the protein kinase Cgamma and epsilon activity.

机译：圣约翰草通过金丝桃素介导的蛋白激酶Cgamma和epsilon活性抑制作用减轻神经性疼痛。

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摘要

Current pharmacological treatments for neuropathic pain have limited efficacy and severe side-effect limitations. St. John's Wort (SJW) is a medicinal plant, mainly used as antidepressant, with a favourable side-effect profile. We here demonstrate the ability of SJW to relieve neuropathic pain in rat models. The antihyperalgesic profile and mechanism of action of SJW and its main components were studied in two rat models of neuropathic pain: the chronic constriction injury and the repeated administration of oxaliplatin. SJW, acutely administered at low doses (30-60 mg kg(-1) p.o.), reversed mechanical hyperalgesia with a prolonged effect, being effective up to 180 min after injection. Further examinations of the SJW main components revealed that hyperforin and hypericin were responsible for the antihyperalgesic properties whereas flavonoids were ineffective. The effect of SJW on the PKC expression and activation was investigated in the periaqueductal grey (PAG) area by immunoblotting experiments. Mechanistic studies showed a robust over-expression and hyperphosphorylation of the PKCgamma (227.0+/-15.0% of control) and PKCepsilon (213.9+/-17.0) isoforms in the rat PAG area. A single oral administration of SJW produced a significant decrease of the PKCgamma (131.8+/-10.0) and PKCepsilon (105.2+/-12.0) phosphorylation in the PAG area due to the presence of hypericin. Furthermore, SJW showed a dual mechanism of action since hyperforin antinociception involves an opioid-dependent pathway. Rats undergoing treatment with SJW and purified components did not show any behavioural side effects or signs of altered locomotor activity. Our results indicate SJW as a prolonged antihyperalgesic treatment through inhibition of PKC isoforms and their phosphorylation.
机译：当前用于神经性疼痛的药物治疗具有有限的疗效和严重的副作用局限性。圣约翰草（SJW）是药用植物，主要​​用作抗抑郁药，具有良好的副作用。我们在这里证明了SJW能够减轻大鼠模型的神经性疼痛。在两种神经性疼痛大鼠模型中研究了SJW及其主要成分的镇痛作用，作用机制：慢性收缩性损伤和奥沙利铂的重复给药。 SJW低剂量（30-60 mg kg（-1）p.o.）急性给药，可逆转机械痛觉过敏，效果延长，在注射后180分钟内有效。 SJW主要成分的进一步检查显示，hyperforin和hypericin负责抗痛觉过敏特性，而类黄酮无效。通过免疫印迹实验，研究了SJW对PKC表达和激活的影响。机理研究表明，大鼠PAG区域中PKCgamma（对照组的227.0 +/- 15.0％）和PKCepsilon（213.9 +/- 17.0）同工型具有较强的过表达和过度磷酸化作用。由于金丝桃素的存在，单次口服SJW可使PAG区域的PKCgamma（131.8 +/- 10.0）和PKCepsilon（105.2 +/- 12.0）磷酸化显着降低。此外，SJW显示出双重作用机制，因为超forin抗伤害感受涉及阿片样物质依赖性途径。接受SJW和纯化成分治疗的大鼠未显示任何行为副作用或运动能力改变的迹象。我们的结果表明，SJW是通过抑制PKC亚型及其磷酸化来延长抗痛觉过敏的治疗方法。

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