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Suppression of LPS-Induced Inflammation by Chalcone Flavokawain A through Activation of Nrf2ARE-Mediated Antioxidant Genes and Inhibition of ROSNFκB Signaling Pathways in Primary Splenocytes
Joint Authors
Hseu, You Cheng
Liao, Jiunn-Wang
Yang, Hsin-Ling
Huang, Pei-Jane
Gowrisankar, Yugandhar Vudhya
Yang, Ting-Yu
Liao, Chun-Huei
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-06-13
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
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 μM) significantly suppressed the proinflammatory cytokine (TNF-α, IL-1β, 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 NFκB (p65) pathway leading to the significant suppression of iNOS, COX-2, TNF-α, and IL-1β 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-1β, 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.
American Psychological Association (APA)
Yang, Hsin-Ling& Yang, Ting-Yu& Gowrisankar, Yugandhar Vudhya& Liao, Chun-Huei& Liao, Jiunn-Wang& Huang, Pei-Jane…[et al.]. 2020. Suppression of LPS-Induced Inflammation by Chalcone Flavokawain A through Activation of Nrf2ARE-Mediated Antioxidant Genes and Inhibition of ROSNFκB Signaling Pathways in Primary Splenocytes. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1204264
Modern Language Association (MLA)
Yang, Hsin-Ling…[et al.]. Suppression of LPS-Induced Inflammation by Chalcone Flavokawain A through Activation of Nrf2ARE-Mediated Antioxidant Genes and Inhibition of ROSNFκB Signaling Pathways in Primary Splenocytes. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-14.
https://search.emarefa.net/detail/BIM-1204264
American Medical Association (AMA)
Yang, Hsin-Ling& Yang, Ting-Yu& Gowrisankar, Yugandhar Vudhya& Liao, Chun-Huei& Liao, Jiunn-Wang& Huang, Pei-Jane…[et al.]. Suppression of LPS-Induced Inflammation by Chalcone Flavokawain A through Activation of Nrf2ARE-Mediated Antioxidant Genes and Inhibition of ROSNFκB Signaling Pathways in Primary Splenocytes. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1204264
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1204264