Academic Journal
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
| العنوان: | 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 |
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| المؤلفون: | Hsin-Ling Yang, Ting-Yu Yang, Yugandhar Vudhya Gowrisankar, Chun-Huei Liao, Jiunn-Wang Liao, Pei-Jane Huang, You-Cheng Hseu |
| المصدر: | Oxidative Medicine and Cellular Longevity, Vol 2020 (2020) |
| بيانات النشر: | Hindawi Limited |
| سنة النشر: | 2020 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Cytology, QH573-671 |
| الوصف: | 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1942-0900 1942-0994 |
| Relation: | http://dx.doi.org/10.1155/2020/3476212; https://doaj.org/toc/1942-0900; https://doaj.org/toc/1942-0994; https://doaj.org/article/2b1132413c634bfeab0df274ed5ab8b1 |
| DOI: | 10.1155/2020/3476212 |
| الاتاحة: | https://doi.org/10.1155/2020/3476212 https://doaj.org/article/2b1132413c634bfeab0df274ed5ab8b1 |
| رقم الانضمام: | edsbas.3CCF38CC |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 19420900 19420994 |
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| DOI: | 10.1155/2020/3476212 |