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Journal of Natural Medicines

, Volume 73, Issue 1, pp 124–130 | Cite as

Identification of β-carboline and canthinone alkaloids as anti-inflammatory agents but with different inhibitory profile on the expression of iNOS and COX-2 in lipopolysaccharide-activated RAW 264.7 macrophages

  • Pan Liu
  • Huixiang Li
  • Ruiling Luan
  • Guiyan Huang
  • Yanan Liu
  • Mengdi Wang
  • Qiuli Chao
  • Liying Wang
  • Danna Li
  • Huaying Fan
  • Daquan Chen
  • Linyu Li
  • Keiichi Matsuzaki
  • Wei LiEmail author
  • Kazuo Koike
  • Feng ZhaoEmail author
Original Paper
  • 190 Downloads

Abstract

A compound library, which consists of 75 natural β-carboline-type or canthinone-type alkaloids from Simaroubaceae plants and their chemical synthetic analogues, was screened for the anti-inflammatory activity by inhibition of the overproduction of inflammatory mediator nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage cells. Six compounds, namely, benzalharman (23), kumujian (27), 1-ethyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (37), 1-acetophenone-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (42), cathin-6-one (46), and 9-methoxy-cathin-6-one (57), exhibited significant inhibitory activity on the overproduction of NO with good dose dependency. Further investigation demonstrated that all of the six compounds down-regulated the high expression of inducible nitric oxide synthase (iNOS) protein. Among them, two canthinone-type alkaloids (46 and 57) potently down-regulated cyclooxygenase-2 (COX-2) protein expression in a dose-dependent manner and also inhibited the overproduction of inflammatory mediator prostaglandin E2 (PGE2). However, the β-carboline-type alkaloids (23, 27, 37, and 42) exhibited no obvious inhibition on the overproduction of PGE2 and the expression of COX-2 protein. The results suggested that β-carboline-type alkaloids and canthinone-type alkaloids may exert an anti-inflammatory effect through different mechanism.

Keywords

β-Carboline alkaloid Canthinone alkaloid Anti-inflammatory activity NO PGE2 iNOS COX-2 

Notes

Acknowledgements

The research of the present study was supported by the National Natural Science Foundation of China Programs (grant nos. 81102781, 81274039, and 81573614), the Shandong Provincial Natural Science Foundation (grant no. ZR2016HL54), the National college students’innovation and entrepreneurship training program (201811066014), and the Undergraduate Scientific and Technological Innovation Project of Yantai University (201811066025).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

11418_2018_1251_MOESM1_ESM.pdf (543 kb)
Supplementary data included: Chemical structures of seventy-five alkaloids, the primary screening results and cell viability

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Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  • Pan Liu
    • 1
  • Huixiang Li
    • 1
  • Ruiling Luan
    • 3
  • Guiyan Huang
    • 1
  • Yanan Liu
    • 1
  • Mengdi Wang
    • 1
  • Qiuli Chao
    • 1
  • Liying Wang
    • 1
  • Danna Li
    • 1
  • Huaying Fan
    • 1
  • Daquan Chen
    • 1
  • Linyu Li
    • 1
  • Keiichi Matsuzaki
    • 4
  • Wei Li
    • 2
    Email author return OK on get
  • Kazuo Koike
    • 2
  • Feng Zhao
    • 1
    Email author
  1. 1.Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, School of PharmacyYantai UniversityYantaiPeople’s Republic of China
  2. 2.Faculty of Pharmaceutical SciencesToho UniversityFunabashiJapan
  3. 3.Pharmacy Dispensing CenterThe Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityYantaiPeople’s Republic of China
  4. 4.School of PharmacyNihon UniversityFunabashiJapan

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