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石蒜科千里光属倍半萜内酯:治疗急性痛风的抗伤害感受、抗炎和抗氧化作用途径。

Sesquiterpene lactones from Lychnophora species: Antinociceptive, anti-inflammatory, and antioxidant pathways to treat acute gout.

机构信息

Laboratório de Plantas Medicinais (LAPLAMED), Programa de Pós-Graduação Em Ciências Farmacêutica (CiPharma), Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, 35400-000, Brazil.

Laboratório de Imunopatologia, Núcleo de Pesquisas Em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, 35400-000, Brazil.

出版信息

J Ethnopharmacol. 2021 Apr 6;269:113738. doi: 10.1016/j.jep.2020.113738. Epub 2020 Dec 24.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Lychnophora trichocarpha and Lychnophora passerina are species used in folk medicine to treat inflammation, pain, and rheumatism. Previous studies have demonstrated the anti-inflammatory effect of ethanol extracts of these species and identified that sesquiterpene lactones contribute to this activity.

AIM OF THE STUDY

Gout is an acute inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals in joints. Inflammation in joints induces oxidative stress in defense cells, releasing pro-inflammatory mediators. This study has three objectives: (1) to demonstrate the effects of sesquiterpene lactones lychnopholide and eremantholide C isolated from L. trichocarpha and goyazensolide isolated from L. passerina on arthritis induced by MSU crystals in C57BL6 mice; (2) to determine whether or not these compounds can inhibit the migration of neutrophils and the release of TNF-α and IL-1β cytokines in the inflammation region; and (3) to evaluate the effects of sesquiterpene lactones on the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in the cartilage of C57BL/6 mice with gouty arthritis.

MATERIALS AND METHODS

The anti-inflammatory, antinociceptive, and antioxidant activities of sesquiterpene lactones in C57BL/6 mice with MSU crystal-induced arthritis were evaluated. In our experimental model, the mice were injected with MSU crystals in the tibiofemoral joint to induce arthritis and then treated with indomethacin, vitamin C, and sesquiterpene lactones. Nociception was evaluated before and after inflammation induction and treatments, neutrophil migration, IL-1β and TNF-α concentrations, and SOD and CAT activities.

RESULTS

Sesquiterpene lactones exerted an anti-inflammatory effect by inhibiting neutrophil migration and TNF-α production. These compounds also demonstrated antinociceptive and antioxidant activities.

CONCLUSION

Lychnopholide, eremantholide C, and goyazensolide improved the inflammation induced by MSU crystals by inhibiting the migration of neutrophils to the inflamed area and by blocking the release of the pro-inflammatory cytokine TNF-α. In addition, sesquiterpene lactones reduced oxidative stress by activating SOD and CAT. These results suggest that sesquiterpene lactones have anti-gout activity through the inflammation, pain, and oxidative stress pathways.

摘要

民族药理学相关性

Lychnophora trichocarpha 和 Lychnophora passerina 是用于民间医学治疗炎症、疼痛和风湿病的物种。先前的研究已经证明了这些物种的乙醇提取物的抗炎作用,并确定了倍半萜内酯对这种活性的贡献。

研究目的

痛风是一种由单钠尿酸盐(MSU)晶体在关节中沉积引起的急性炎症性关节炎。关节中的炎症会在防御细胞中引起氧化应激,释放促炎介质。本研究有三个目标:(1)证明从 Lychnophora trichocarpha 中分离出的倍半萜内酯 lychnopholide 和 eremantholide C 以及从 Lychnophora passerina 中分离出的 goyazensolide 对 C57BL6 小鼠 MSU 晶体诱导的关节炎的影响;(2)确定这些化合物是否可以抑制炎症部位中性粒细胞的迁移以及 TNF-α 和 IL-1β 细胞因子的释放;(3)评估倍半萜内酯对 MSU 晶体诱导的 C57BL/6 小鼠痛风性关节炎软骨中超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性的影响。

材料和方法

在 C57BL/6 小鼠 MSU 晶体诱导关节炎模型中评估倍半萜内酯的抗炎、镇痛和抗氧化活性。在我们的实验模型中,将 MSU 晶体注射到膝关节以诱导关节炎,然后用吲哚美辛、维生素 C 和倍半萜内酯治疗。在炎症诱导和治疗前后评估痛觉和中性粒细胞迁移,IL-1β 和 TNF-α 浓度以及 SOD 和 CAT 活性。

结果

倍半萜内酯通过抑制中性粒细胞迁移和 TNF-α 产生发挥抗炎作用。这些化合物还具有镇痛和抗氧化活性。

结论

lychnopholide、eremantholide C 和 goyazensolide 通过抑制中性粒细胞迁移到炎症区域并阻断促炎细胞因子 TNF-α 的释放,改善了 MSU 晶体诱导的炎症。此外,倍半萜内酯通过激活 SOD 和 CAT 减轻氧化应激。这些结果表明,倍半萜内酯通过炎症、疼痛和氧化应激途径具有抗痛风活性。

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