Anti-inflammatory and Analgesic Effect of Plumbagin through Inhibition of Nuclear Factor-κB Activation

Abstract

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 B (NF-B) 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 1␤, interleukin 6, and tumor necrosis factor ␣. It also inhibited the expression of the proinflammatory mediators inducible nitricoxide synthase and cyclooxygenase 2, whereas it did not inhibit the expression of cyclooxygenase 1. Further studies demonstrated that PL suppressed inhibitor of B␣ phosphorylation and degradation, thus inhibiting the phosphorylation of the p65 subunit of NF-B. This study suggests that PL has a potential to be developed into an anti-inflammatory agent for treating inflammatory diseases.

Proteomics Analyses ofBacillus subtilisafter Treatment with Plumbagin, a Plant-Derived Naphthoquinone

“…It has a wide range of activities, including anticancer (Acharya et al, 2008;Gomathinayagam et al, 2008), anti-malarial (Krungkrai et al, 2002), anti-fungal (Curreli, et al, 2001), anti-inflammatory (Luo et al, 2010), and antimutagenic activity (Edenharder and Tang, 1997). It also possesses anti-bacterial activity by generating reactive oxygen species, affecting respiratory process (Imlay and Fridovich, 1992), inhibiting NADH dehydrogenase (Imlay and Fridovich, 1992), and lactose carriers (Neuhaus and Wright, 1983).…”

CRM1 Is a Direct Cellular Target of the Natural Anti-cancer Agent Plumbagin

“…The inhibition of NF-kB activation was accompanied by the inhibition of IkBa degradation. However, the mechanism of blocking IkBa degradation by plumbagin is unclear (3,4,9). IkBa exports from the nucleus in a CRM1-dependent manner.…”

The cellular and molecular mechanisms providing therapeutic efficiency of gistokhrom

“…Не исключено также, что, хелатируя [Са 2+ ] i , эхинохром А предотвращает выброс медиа-торов воспаления и подавляет развитие воспали-оригинальные исследования тельной реакции. Более того, в различных модель-ных системах показано, что структурно родственные эхинохрому А полигидрокси-1,4-нафтохиноны снижают продукцию ряда провоспалительных ци-токинов, угнетая тем самым экссудативную фазу воспаления [48,82,83]. Модулируя активность генных мишеней, природные ПГНХ подавляют экс-прессию NO-синтетазы и циклооксигеназы второго типа (ЦОГ-2) [65,82,84,95,99].…”

“…Модулируя активность генных мишеней, природные ПГНХ подавляют экс-прессию NO-синтетазы и циклооксигеназы второго типа (ЦОГ-2) [65,82,84,95,99]. И наконец, единич-ные сообщения указывают на анальгетический эф-фект полигидрокси-1,4-нафтохинонов [82]. Высока вероятность, что гистохром обладает антиэкссуда-тивным действием, опосредованным одним или не-сколькими механизмами, свойственными его струк-турным аналогам.…”