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Biol Pharm Bull. 2017;40(12):2134-2139. doi: 10.1248/bpb.b17-00479.

Active Ingredients of Hange-shashin-to, Baicalelin and 6-Gingerol, Inhibit 5-Fluorouracil-Induced Upregulation of CXCL1 in the Colon to Attenuate Diarrhea Development.

Author information

1
Department of Analytical Pathophysiology, Division of Pharmacy Professional Development and Research, Hoshi University.
2
Division of Cancer Pathophysiology, National Cancer Center Research Institute.
3
Department of Pharmacology, Hoshi University.
4
Division of Supportive Cancer Research, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center.
5
Innovation Center for Supportive, Palliative and Psychosocial Care, National Cancer Center Hospital.

Abstract

5-Fluorouracil (5-FU) is widely used as an anti cancer drug and is known to cause severe diarrhea. Recently we suggested that levels of chemokine (C-X-C motif) ligand 1 (CXCL1) and neutrophil recruitment in the colonic mucosa were drastically increased by the 5-FU administration in mice. Hange-shashin-to (HST) is prescribed in Japan for treat gastritis, stomatitis, and inflammatory diarrhea. We therefore examined the effects of HST and its active ingredients on 5-FU-induced CXCL1 upregulation in cultured colon tissue, and also examined the effects of HST on 5-FU-induced diarrhea development in the mouse. The distal colon isolated from the mouse was incubated with 5-FU and HST. Mice were given 5-FU (50 mg/kg, intraperitoneally (i.p.)) daily for four days. HST (300 mg/kg, per os (p.o.)) was administered 30 min before mice received 5-FU. mRNA levels of CXCL1 in the colon were examined using quantitative RT-PCR. 5-FU enhanced CXCL1 mRNA in the colon but the effect by 5-FU was markedly suppressed by application of HST and its active ingredients, baicalein and 6-gingerol. Nuclear factor kappa B (NF-κB) was activated by 5-FU treatment in cultured colon tissue, which was also suppressed by HST and the combination of baicalein and 6-gingerol. Furthermore, HST reduced 5-FU-induced diarrhea development. Under such experimental condition, CXCL1 gene, protein levels of neutrophil elastase and myeloperoxidase upregulation induced by 5-FU in the colon was attenuated by HST. These findings suggest that HST, especially baicalein and 6-gingerol, prevent the development of neutrophil recruitment and diarrhea by the inhibition of NF-κB activity.

KEYWORDS:

5-fluorouracil; 6-gingerol; baicalein; chemokine (C-X-C motif) ligand 1; diarrhea; hange-shashin-to

PMID:
29199237
DOI:
10.1248/bpb.b17-00479
[Indexed for MEDLINE]
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