Suppression of LPS-Induced Inflammation by Chalcone Flavokawain A through Activation of Nrf2/ARE-Mediated Antioxidant Genes and Inhibition of ROS/NFκB Signaling Pathways in Primary Splenocytes. (13th June 2020)

• Record Type: Journal Article
• Authors: Yang, Hsin-Ling; Yang, Ting-Yu; Gowrisankar, Yugandhar Vudhya; Liao, Chun-Huei; Liao, Jiunn-Wang; Huang, Pei-Jane; Hseu, You-Cheng
• Other Names: Lillig Christopher Horst Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2020(2020)
• Publication Date: 2020-06-13
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2020/3476212
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : Oxidative stress is an important contributing factor for inflammation. Piper methysticum, also known as Kava - kava, is a shrub whose root extract has been consumed as a drink by the pacific islanders for a long time. Flavokawain A (FKA) is a novel chalcone derived from the kava plant that is known to have medicinal properties. This study was aimed at demonstrating the antioxidant molecular mechanisms mediated by FKA on lipopolysaccharide- (LPS-) induced inflammation in BALB/c mouse-derived primary splenocytes. In vitro data show that the nontoxic concentrations of FKA (2-30 μ M) significantly suppressed the proinflammatory cytokine (TNF- α, IL-1 β, and IL-6) release but induced the secretion of interleukin-10 (IL-10), an anti-inflammatory cytokine. It was also shown that FKA pretreatment significantly downregulated the LPS-induced ROS production and blocked the activation of the NF κ B (p65) pathway leading to the significant suppression of iNOS, COX-2, TNF- α, and IL-1 β protein expressions. Notably, FKA favored the nuclear translocation of Nrf2 leading to the downstream expression of antioxidant proteins HO-1, NQO-1, and γ -GCLC via the Nrf2/ARE signaling pathway signifying the FKA's potent antioxidant mechanism in these cells. Supporting the in vitro data, the ex vivo data obtained from primary splenocytes derived from the FKA-preadministered BALB/c mice (orally) show that FKA significantly suppressed the proinflammatory cytokine (TNF- α, IL-1 β, and IL-6) secretion in control-, LPS-, or Concanavalin A- (Con A-) stimulated cells. A significant decrease in the ratios of pro- and anti-inflammatory cytokines (IL-6/IL-10; TNF- α /IL-10) showed that FKA possesses strong anti-inflammatory properties. Furthermore, BALB/c mice induced with experimental pancreatitis using cholecystokinin- (CCK-) 8 showed decreased serum lipase levels due to FKA pretreatment. We conclude that with its potent antioxidant and anti-inflammatory properties, chalcone flavokawain A could be a novel therapeutic agent in the treatment of inflammation-associated diseases.