Anti-inflammatory activity of 3-cinnamoyltribuloside and its metabolomic analysis in LPS-activated RAW 264.7 cells

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(2020) 20:329

BMC Complementary Medicine and Therapies

RESEARCH ARTICLE

Open Access

Anti-inflammatory activity of 3cinnamoyltribuloside and its metabolomic analysis in LPS-activated RAW 264.7 cells Zhennan Wang1,2†, Ying Guan3†, Rui Yang1, Junjian Li2, Junsong Wang1 and Ai-Qun Jia1,2*

Abstract Background: Inflammation is a response to tissue injuries, which is indispensable and important for human health, but excessive inflammation can potentially cause damage to the host organisms. Camellia nitidissima Chi, one traditional medicinal and edible plant in China, was reported to exhibit anti-inflammation capability. Hence, this study was conducted to isolate the bioactive compounds from the flowers of C. nitidissima Chi and evaluate their anti-inflammatory activity. Methods: The phytochemicals from the flowers of C. nitidissima Chi were isolated and purified by silica gel, Sephadex LH-20 gel, C18 reversed silica gel, semi-preparative HPLC, and identified by the spectrum technologies. The anti-inflammatory activity of isolated compounds was evaluated using cultured macrophage RAW 264.7 cells. Whereafter the potential metabolic mechanism of the anti-inflammatory activity of the bioactive compound was investigated by a 1H-NMR based metabolomics approach. The metabolites in 1H-NMR spectra were identified by querying the Human Metabolome Database and Madison Metabolomics Consortium Database online. And the multivariate statistical analysis was performed to evaluate the variability of metabolites among samples and between sample classes. Results: The compound isolated from the flowers of C. nitidissima Chi was identified as 3-cinnamoyltribuloside (3CT). 3-CT could inhibit the NO production and the mRNA expression of iNOS involved in lipopolysaccharide (LPS)activated RAW 264.7 cells. Moreover, 3-CT could inhibit the expression of a series of inflammatory cytokines, including TNF-α, IL-1β, and IL-6, both at the mRNA level and protein level. The 1H-NMR based metabolomics approach was applied to investigate the potential metabolic mechanism of the anti-inflammatory activity of 3-CT. Thirty-five metabolites were identified and assigned. Orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) of the 1H-NMR data showed 3-CT could balance the significant changes in many endogenous metabolites (e.g., choline, glucose, phenylalanine) induced by LPS in RAW 264.7 cells, which related to cholinergic anti-inflammatory pathway, oxidative stress, energy metabolism, and amino acids metabolism. (Continued on next page)

* Correspondence: [email protected] † Zhennan Wang and Ying Guan contributed equally to this work. 1 School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, China 2 School of Life and Pharmaceutical Sciences, Key Laboratory of Tropical Biological Resources of Ministry Education, Hainan University, Haikou 570228, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article