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Journal of Chinese Pharmaceutical Sciences ›› 2020, Vol. 29 ›› Issue (12): 868-879.DOI: 10.5246/jcps.2020.12.077

• Original articles • Previous Articles     Next Articles

Intestinal anti-inflammatory effects of main components of the fruits of Euodia rutaecarpa in a co-culture model of the human colorectal adenocarcinoma cells and RAW264.7 macrophages

Shi Wang, Lu Liu, Youbo Zhang*(), Wei Xu, Xiuwei Yang*()   

  1. State Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2020-08-26 Revised:2020-10-10 Accepted:2020-11-06 Online:2020-12-30 Published:2020-12-30
  • Contact: Youbo Zhang, Xiuwei Yang
  • About author:
    Dr. Youbo Zhang received his Ph.D. and was a staff fellow of Peking University at the year 2010. He went Natural Institutes of Health to complete his postdoctoral training in Dr. Frank J. Gonzalez’s laboratory during the year 2015-2016. Dr. Zhang’s research interests include chemistry of natural products, drug metabolism, drug-induced liver injury, and toxicometabolomics. He has published more than 40 papers on Free Radical and Biology and Medicine, Drug Metabolism and Disposition, and some other journals by now.
    Dr. Xiuwei Yang got his doctorate in Toyama Medical and Pharmaceutical University of Japan in 1992. He worked as a postdoctoral research fellow at School of Pharmaceutical Sciences from Beijing Medical University in 1992–1994. In 1994.9, he joined Peking University School of Pharmaceutical Sciences and worked as a professor. His major research interests are the absorption, distribution, metabolism, excretion, toxicity and activity of drugs (ADMET/Act.), complex system exploration of traditional Chinese Medicine, biological transformation of natural drug and/or Chinese medicinal chemical compositions, innovative drug discovery and natural medicinal chemistry. His group has established human intestinal bacteria biological transformation system, human Caco-2 cell monolayer absorption model, modified rat everted intestinal sac model, blood brain barrier absorption cell model, liver microsomal transformation and metabolism, and tissue distribution of drugs. He has published more than 450 papers in journals, and edited more than 20 works. He serves as the editorial board member of Journal of Asian Natural Products Research, Journal of Chinese Pharmaceutical Sciences, China Journal of Chinese Medica and Chinese Journal of Pharmaceutical Analysis , etc.

Abstract:

Alkaloids are the main active constituents of the nearly ripe fruits of Euodia rutaecarpa (Juss.) Benth., which possesses antitumor, anti-inflammatory, analgesic and antimicrobial activities. In this study, we aimed to assess the potential anti-inflammatory effects of six main components, evodiamine, rutaecarpine, dehydroevodiamine, evocarpine, dihydroevocarpine and 1-methyl-2-undecyl-4-(1H)-quinolone, in the nearly ripe fruits of E. rutaecarpa. In the co-culture system consisting of the human colorectal adenocarcinoma (Caco-2) cells and RAW264.7 macrophages, inflammation was induced in RAW264.7 cells with 2 μg/mL lipopolysaccharide. The results indicated that evodiamine, rutaecarpine, and dehydroevodiamine significantly down-regulated the mRNA expressions of pro-inflammatory cytokines (Il-6, Il-1β and Tnf-α) and inflammatory mediators, such as cyclooxygenase-2 (Cox-2) and inducible nitric oxide synthase (iNos). Besides, the drug administration group showed a higher transepithelial electrical resistance and a lower tight junction permeability compared with the model group. Taken together, the tested compounds possessed anti-inflammatory effects. Our findings laid the foundation for further research on the anti-inflammatory mechanism of the nearly ripe fruits of E. rutaecarpa.

Key words: Euodia rutaecarpa, Anti-inflammation, Tight junction, Caco-2, RAW264.7

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