Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970, Londrina, Paraná, Brazil; Centro de Pesquisa Em Ciências da Saúde, Universidade Norte Do Paraná, 86041-140, Londrina, Paraná, Brazil.
Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970, Londrina, Paraná, Brazil.
J Ethnopharmacol. 2021 Jun 12;273:113980. doi: 10.1016/j.jep.2021.113980. Epub 2021 Feb 27.
Sphagneticola trilobata (L.) Pruski is a plant species belonging to the Asteraceae family. Kaurenoid acid (KA) is a diterpene metabolite and one of the active ingredients of Sphagneticola trilobata (L.) Pruski. Extracts containing KA are used in traditional medicine to treat pain, inflammation, and infection.
The goal of the present study was to investigate the in vivo effects of KA (1-10 mg/kg, per oral gavage) upon LPS inoculation in mice by intraperitoneal (i.p.) or intraplantar (i.pl.; subcutaneous plantar injection) routes at the dose of 200 ng (200 μL or 25 μL, respectively).
In LPS paw inflammation, mechanical and thermal hyperalgesia MPO activity and oxidative imbalance (TBARS, GSH, ABTS and FRAP assays) were evaluated. In LPS peritonitis we evaluated leukocyte migration, cytokine production, oxidative stress, and NF-κB activation.
KA inhibited LPS-induced mechanical and thermal hyperalgesia, MPO activity and modulated redox status in the mice paw. Pre- and post-treatment with KA inhibited migration of neutrophils and monocytes in LPS peritonitis. KA inhibited the pro-inflammatory/hyperalgesic cytokine (e.g., TNF-α, IL-1β and IL-33) production while enhanced anti-inflammatory/analgesic cytokine IL-10 in peritoneal cavity. In agreement with the effect of KA over pro-inflammatory cytokines it inhibited oxidative stress (total ROS, superoxide production and superoxide positive cells) and NF-κB activation during peritonitis.
KA efficiently dampens LPS-induced peritonitis and hyperalgesia in vivo, suggesting it as a suitable candidate to control excessive inflammation and pain during gram-negative bacterial infections and bringing mechanistic explanation to the ethnopharmacological application of Sphagneticola trilobata (L.) Pruski in inflammation and infection.
三叶鬼针草（L.）Pruski 是菊科植物物种。贝壳杉烯酸（KA）是一种二萜代谢物，也是三叶鬼针草（L.）Pruski 的活性成分之一。含有 KA 的提取物用于传统医学中治疗疼痛、炎症和感染。
本研究旨在通过腹腔内（i.p.）或足底（i.pl.；皮下足底注射）途径以 200ng（200μL 或 25μL，分别）的剂量，研究 KA（1-10mg/kg，口服灌胃）对 LPS 接种后小鼠体内的影响。
在 LPS 足爪炎症中，评估机械性和热痛觉过敏、髓过氧化物酶（MPO）活性以及氧化失衡（TBARS、GSH、ABTS 和 FRAP 测定）。在 LPS 腹膜炎中，评估白细胞迁移、细胞因子产生、氧化应激和 NF-κB 激活。
KA 抑制 LPS 诱导的机械性和热痛觉过敏、MPO 活性，并调节小鼠足爪中的氧化还原状态。KA 的预先和后处理抑制了 LPS 性腹膜炎中的中性粒细胞和单核细胞迁移。KA 抑制促炎/痛觉过敏细胞因子（例如 TNF-α、IL-1β 和 IL-33）的产生，同时增强了腹腔内抗炎/镇痛细胞因子 IL-10 的产生。与 KA 对促炎细胞因子的作用一致，它抑制了腹膜炎期间的氧化应激（总 ROS、超氧化物产生和超氧化物阳性细胞）和 NF-κB 激活。
KA 有效地抑制 LPS 诱导的体内腹膜炎和痛觉过敏，表明它是控制革兰氏阴性菌感染期间过度炎症和疼痛的合适候选物，并为三叶鬼针草（L.）Pruski 在炎症和感染中的民族药理学应用提供了机制解释。
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