Background

Indole-3-guanylhydrazone hydrochloride (LQM01) is a new derivative of aminoguanidine hydrochloride, an aromatic aminoguanidine.

Methods

Mice were treated with LQM01 (5, 10, 25 or 50 mg/kg, i.p.), vehicle (0.9% saline i.p.) or a standard drug. The mice were subjected to carrageenan-induced pleurisy, abdominal writhing induced by acetic acid, the formalin test and the hot-plate test. The model of non-inflammatory chronic muscle pain induced by saline acid was also used. Mice from the chronic protocol were assessed for withdrawal threshold, muscle strength and motor coordination. LQM01 or vehicle treated mice were evaluated for Fos protein.

Results

LQM01 inhibits TNF-α and IL-1β production, as well as leukocyte recruitment during inflammation process. The level of IL-10 in LQM01-treated mice increased in pleural fluid. In addition, LQM01 decreased the nociceptive behavior in the acetic acid induced writhing test, the formalin test (both phases) and increased latency time on the hot-plate. LQM01 treatment also decreased mechanical hyperalgesia in mice with chronic muscle pain, with no changes in muscle strength and motor coordination. LQM01 reduced the number of Fos positive cells in the superficial dorsal horn. This compound exhibited antioxidant properties in in vitro assays.

Conclusions

LQM01 has an outstanding anti-inflammatory and analgesic profile, probably mediated through a reduction in proinflammatory cytokines release, increase in IL-10 production and reduction in neuron activity in the dorsal horn of the spinal cord in mice.

General significance

Beneficial effects of LQM01 suggest that it has some important clinical features and can play a role in the management of ‘dysfunctional pain’ and inflammatory diseases.

中文翻译：

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TNF-α，IL-1β和IL-10参与啮齿动物吲哚-3-胍guan盐酸盐（一种芳香族氨基胍）的抗伤害感受和抗炎作用的证据

背景

吲哚-3-胍yl盐酸盐（LQM01）是氨基胍盐酸盐（一种芳香族氨基胍）的新衍生物。

方法

用LQM01（5、10、25或50 mg / kg，腹膜内），溶媒（0.9％生理盐水，腹膜内）或标准药物治疗小鼠。小鼠经受角叉菜胶致胸膜炎，乙酸致腹部扭伤，福尔马林试验和热板试验。还使用了由盐水诱导的非炎性慢性肌肉疼痛模型。评估慢性方案的小鼠的戒断阈值，肌肉力量和运动协调性。评估LQM01或运载体处理的小鼠的Fos蛋白。

结果

LQM01在炎症过程中抑制TNF-α和IL-1β的产生以及白细胞募集。在接受LQM01处理的小鼠中，胸膜液中的IL-10水平升高。此外，LQM01降低了乙酸诱导的扭体试验，福尔马林试验（两个阶段）的伤害性，并增加了热板上的等待时间。LQM01治疗还可以减轻患有慢性肌肉痛的小鼠的机械性痛觉过敏，且肌肉力量和运动协调性均无变化。LQM01减少了浅表背角中Fos阳性细胞的数量。该化合物在体外试验中表现出抗氧化性能。

结论

LQM01具有出色的抗炎和镇痛作用，可能是通过降低小鼠促炎性细胞因子的释放，增加IL-10的产生以及减少脊髓背角神经元活性介导的。

一般意义

LQM01的有益作用表明它具有一些重要的临床特征，并且可以在“功能障碍性疼痛”和炎症性疾病的治疗中发挥作用。