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Rhoifolin Alleviates Inflammation of Acute Inflammation Animal Models and LPS-Induced RAW264.7 Cells via IKKβ/NF-κB Signaling Pathway

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Abstract

Rhoifolin (ROF) is a main effective component in Citrus grandis ‘Tomentosa’. ROF has a potential anti-inflammatory activity, but its specific effects and mechanisms have not been studied. This study investigated the anti-inflammatory activity of ROF and searched for its possible molecular mechanisms. A mouse model of acute inflammation was induced by lipopolysaccharide, and the effects of ROF on pathological damages of the lung and liver were observed. Carrageenan-induced paw edema rat model was used to evaluate the effect of ROF on the volume of swelling paw. In LPS-induced RAW264.7 macrophages, the expression levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α were measured using ELISA. Real-time PCR was used to measure the mRNA levels of iNOS and CCL2. Western blot was used to detect the activation of IκBα and IKKβ in NF-κB signaling pathways. The results showed that ROF accelerated the recoveries of liver and lung tissue damages in acute inflammation mice and inhibited carrageenan-induced paw edema in rats; in addition, ROF significantly suppressed the secretion of TNF-α, IL-1β, and IL-6 in the serum of rats and mouse model. In LPS-induced RAW264.7 cells, 100 μmol/L ROF enhanced cell viability and suppressed the production of TNF-α, IL-6, and IL-1β significantly. ROF also decreased the mRNA expression of iNOS and CCL2 and inhibited IκBα and IKKβ phosphorylation. In summary, ROF had a potential therapeutic value for inflammation. Our research provided experimental basis for the further development of ROF as an anti-inflammatory drug and for clarifying the anti-inflammatory substance basis of Citrus grandis ‘Tomentosa’.

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Funding

This study was supported by Chinese medicine standardization project from the National Development and Reform Commission and National Administration of Traditional Chinese Medicine (ZYBZH-Y-GD-13), Science Program for Overseas Scholar of Guangzhou University of Chinese Medicine (Torch Program) (XH20170109), and the Innovation Team Construction Project with Agricultural Products as the Unit of Modern Agricultural Industry Technology System of Guangdong Province (2019KJ148).

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Author notes

  1. Jiaqi Fang and Zelin Cao contributed to the work equally and should be regarded as co-first authors.

Authors and Affiliations

  1. School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China

    Jiaqi Fang, Zelin Cao, Xiaoxin Song, Xiaoying Zhang, Baoyu Mai, Tingfang Wen, Jingran Lin, Jialan Chen, Yuguang Chi & Fengxia Xiao

  2. Proteomics and Metabolomics Core Facility, Weill Cornell Medicine, New York, NY, 10021, USA

    Taojunfeng Su

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  1. Jiaqi Fang
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Contributions

Concept and design: Fengxia Xiao and Xiaoxin Song; data collection: Xiaoxin Song and Zelin Cao; data analysis and interpretation: Jiaqi Fang and Xiaoxin Song; generating the manuscript: Jiaqi Fang, Taojunfeng Su, Yuguang Chi, Baoyu Mai, Tingfang Wen, Jingran Lin, Xiaoying Zhang, and Jialan Chen

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Correspondence to Fengxia Xiao.

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Fang, J., Cao, Z., Song, X. et al. Rhoifolin Alleviates Inflammation of Acute Inflammation Animal Models and LPS-Induced RAW264.7 Cells via IKKβ/NF-κB Signaling Pathway. Inflammation 43, 2191–2201 (2020). https://doi.org/10.1007/s10753-020-01286-x

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