☆ 4.6 Article

Regulation of Nrf2 and NF-κB activities may contribute to the anti-inflammatory mechanism of xylopic acid

INFLAMMOPHARMACOLOGY (2022)

Journal

INFLAMMOPHARMACOLOGY

Volume 30, Issue 5, Pages 1835-1841

Publisher

SPRINGER BASEL AG

DOI: 10.1007/s10787-022-00950-y

Keywords

HO-1 protein; Inflammation; NF-kappa B; Nrf2; VCAM-1; Xylopic acid

Funding

Society of Medicinal Plants and Natural Products Research

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Abstract

Xylopic acid (XA), a kaurene diterpene found in African plants, has been shown to possess acute and chronic anti-inflammatory activities. This study investigates the potential molecular target(s) of XA, revealing an inhibitory effect on NF-kappa B activity and an increased activity of Nrf2, accompanied by changes in the expression of related proteins.

Xylopic acid (XA) is a kaurene diterpene which naturally exists in African plants such as Xylopia aethiopica. It has been established to exhibit acute and chronic anti-inflammatory activities from our earlier studies. This current work sets out to shed light on the potential molecular target(s) of xylopic acid. Selection of investigated targets (NF-kappa B, Nrf2 and PTP1B) was based on an unbiased approach, using the SPiDER in silico prediction tool, and a candidate approach, examining well-known anti-inflammatory targets. Reporter gene assays were used to test for altered NF-kappa B and Nrf2 activities in transfected HEK or CHO cells, respectively, and immunoblot and flow cytometric analyses examined protein expression of the Nrf2/NF-kB target genes HO-1 and VCAM-1 in HUVEC. An effect of XA on PTP1B activity assay was studied using an in vitro enzyme assay with recombinant human enzyme and pNPP as substrate as well as by looking at insulin receptor phosphorylation in HepG2 cells. XA at 30 mu M significantly (p < 0.001) inhibited the NF-kappa B-dependent reporter gene expression and enhanced activation of Nrf2 in a concentration-dependent manner when compared to the control. XA also marginally increased HO-1 protein expression levels while expression of VCAM-1 was reduced to 70% in XA-treated endothelial cells. However, XA did not show any sign of inhibition of PTP1B or a related phosphatase. Our findings suggest that the anti-inflammatory mechanism of XA entails the inhibitory effect on NF-kappa B and an increased activity of Nrf2, accompanied by increased expression of HO-1 and reduced expression of VCAM-1.

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Gossypin exert lipopolysaccharide induced lung inflammation via alteration of Nrf2/HO-1 and NF-κB signaling pathway

Hao Huang, Jian Wang, Shaik Althaf Hussain, Venkata Subba Reddy Gangireddygari, Yingying Fan

Summary: This study aimed to investigate the preventive effect of gossypin against LPS-induced lung inflammation and explore the underlying mechanism. Rats were orally administered different doses of gossypin and various parameters were measured. The results showed that gossypin significantly reduced lung tissue wet to dry weight ratio, inflammatory cells, total protein, macrophages, and neutrophils in bronchoalveolar lavage fluid. Gossypin also affected the levels of inflammatory cytokines, antioxidants, and inflammatory parameters, as well as Nrf2 and HO-1 expression. The findings suggest that gossypin can improve the severity of ALI by enhancing lung tissue integrity, decreasing alveolar wall thickness, reducing pulmonary interstitial edema and inflammatory cell infiltration.

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