A novel limonin derivate modulates inflammatory response by suppressing the TLR4/NF-κB signalling pathway

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Shuwei JinGuoqing Gong

Abstract

In our previous studies, we have demonstrated that a novel water-soluble derivative of limonin, (12S,12aS,Z)-8-((2-(diethylamino)ethoxy)imino)-12-(furan-3-yl)-6,6,8a,12a-tetramethyldodecahydro-1H,3H-oxireno[2,3-d]pyrano[4',3':3,3a]isobenzofuro[5,4-f]isochromene-3,10(9aH)-dione (V-A-4), exhibited strong anti-inflammatory activity both in vitro and in vivo. The purpose of this study was to further explore the underlying mechanisms of such activity demonstrated by V-A-4. The protective effect of V-A-4 on the alleviation of xylene-induced ear swelling and carrageenan-induced subcutaneous air pouch model was detected in vivo. Furthermore, the in vitro effects of V-A-4 and its mechanisms of action were determined by colorimetric COX (ovine) inhibitor-screening assay and in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. This study showed that V-A-4 does not exert anti-inflammatory effect through the inhibition of COX-1 or COX-2. Rather, it is exerted through the suppression of the secretion of nitric oxide (NO) and tumor necrosis factor-α (TNF-α), as well as through the infiltration of inflammatory cells. V-A-4 demonstrated strong inhibition of NF-κB activation through repression of IKKα and IKKβ phosphorylations, which in turn l...Continue Reading

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Citations

Oct 17, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shunming FanLingying Yu
Sep 18, 2020·Chemistry & Biodiversity·Yu-Hong HuYue-Wei Guo
Jan 14, 2021·Immunopharmacology and Immunotoxicology·Maryam NematiMohammad Nouri
Aug 24, 2021·Environmental Toxicology·Tingting XiaChunfang Xu
Sep 3, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Wei XiongJian Gong

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