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Am J Chin Med. 2018;46(6):1263-1279. doi: 10.1142/S0192415X18500660. Epub 2018 Aug 27.

Neferine, a Bisbenzylisoquinoline Alkaloid, Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis.

Author information

1
* State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, P. R. China.
2
† Key Lab for Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical College, Zunyi, P. R. China.
3
‡ Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.

Abstract

Both the incidence and prevalence of ulcerative colitis (UC) are increasing throughout the world. Neferine, a natural alkaloid, demonstrated a variety of biological activities. In this study, the anti-inflammatory effect of neferine was investigated. Raw264.7 cells were stimulated with lipopolysaccharide (LPS) or LPS plus Z-VAD-fmk (Z-VAD). The inhibitory effect of neferine on secretion of nitrite, cytokines tumor necrosis factor alpha (TNF-[Formula: see text]) and interleukin 6 (IL-6), expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was determined. The protective effect of neferine was investigated in dextran sulfate sodium (DSS)-induced UC mouse model. Neferine significantly inhibited LPS and LPS plus Z-VAD induced secretion of nitrite, cytokines, and expression of iNOS and COX-2. Oral administration of neferine (10[Formula: see text]mg/kg and 25[Formula: see text]mg/kg) significantly reduced DSS-induced mouse weight loss, decreased disease activity index (DAI) scores, improved colon pathological changes, and decreased plasma cytokines. In addition, neferine significantly inhibited the protein expression of iNOS, COX-2, receptor-interacting protein 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL), and increased the protein expression of caspase-8 in colon tissues. These data suggest that neferine was a potent anti-inflammatory agent against LPS and DSS induced inflammation both in vitro and in vivo.

KEYWORDS:

Inflammation; Neferine; Ulcerative Colitis

PMID:
30149754
DOI:
10.1142/S0192415X18500660
[Indexed for MEDLINE]

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