Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
J Pharmacol Exp Ther. 2010 Dec;335(3):735-42. doi: 10.1124/jpet.110.170852. Epub 2010 Sep 21.
Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) (PL) is a naturally occurring yellow pigment found in the plants of the Plumbaginaceae, Droseraceae, Ancistrocladaceae, and Dioncophyllaceae families. It has been reported that PL exhibits anticarcinogenic, anti-inflammatory, and analgesic activities. However, the mechanism underlying its anti-inflammatory action remains unknown. In the current study, we investigated and characterized the anti-inflammatory and analgesic effects of PL orally administrated in a range of dosages from 5 to 20 mg/kg. We also examined the role of nuclear factor κB (NF-κB) and proinflammatory cytokines and mediators in this effect. The results showed that PL significantly and dose-dependently suppressed the paw edema of rats induced by carrageenan and various proinflammatory mediators, including histamine, serotonin, bradykinin, and prostaglandin E(2). PL reduced the number of writhing episodes of mice induced by the intraperitoneal injection of acetic acid, but it did not reduce the writhing episode numbers induced by MgSO(4) in mice or prolong the tail-flick reaction time of rats to noxious thermal pain. Mechanistic studies showed that PL effectively decreased the production of the proinflammatory cytokines interleukin 1β, interleukin 6, and tumor necrosis factor α. It also inhibited the expression of the proinflammatory mediators inducible nitric-oxide synthase and cyclooxygenase 2, whereas it did not inhibit the expression of cyclooxygenase 1. Further studies demonstrated that PL suppressed inhibitor of κBα phosphorylation and degradation, thus inhibiting the phosphorylation of the p65 subunit of NF-κB. This study suggests that PL has a potential to be developed into an anti-inflammatory agent for treating inflammatory diseases.
白花丹素（5-羟基-2-甲基-1,4-萘醌）（PL）是一种天然存在的黄色色素，存在于白花丹科、茅膏菜科、安息香科和 Dioncophyllaceae 科的植物中。据报道，PL 具有抗癌、抗炎和镇痛作用。然而，其抗炎作用的机制尚不清楚。在本研究中，我们研究并表征了 PL 以 5-20mg/kg 不同剂量口服给药的抗炎和镇痛作用。我们还研究了核因子 κB（NF-κB）和促炎细胞因子和介质在这种作用中的作用。结果表明，PL 显著且剂量依赖性地抑制了角叉菜胶和各种促炎介质（包括组胺、血清素、缓激肽和前列腺素 E2）诱导的大鼠足肿胀。PL 减少了腹腔注射醋酸引起的小鼠扭体次数，但不减少 MgSO4 诱导的小鼠扭体次数或延长大鼠对有害热痛的尾巴摆动反应时间。机制研究表明，PL 有效降低了促炎细胞因子白细胞介素 1β、白细胞介素 6 和肿瘤坏死因子 α 的产生。它还抑制了诱导型一氧化氮合酶和环氧化酶 2 的促炎介质的表达，而不抑制环氧化酶 1 的表达。进一步的研究表明，PL 抑制了 IκBα 的磷酸化和降解，从而抑制了 NF-κB 的 p65 亚基的磷酸化。这项研究表明，PL 具有开发成治疗炎症性疾病的抗炎剂的潜力。
