gingerol and Diarrhea

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.

Topics: Animals; Antimetabolites, Antineoplastic; Catechols; Chemokine CXCL1; Colon; Diarrhea; Disease Models, Animal; Drugs, Chinese Herbal; Fatty Alcohols; Flavonoids; Fluorouracil; Humans; Intestinal Mucosa; Japan; Male; Mice; Mice, Inbred C57BL; Neoplasms; NF-kappa B; RNA, Messenger; Up-Regulation

One of the important medicinal properties of ginger is known to remove chills caused by common cold and to warm body. In the present study, acetone extract of ginger at 100 mg/kg p.o. significantly inhibited serotonin (5-HT) induced hypothermia. Therefore, the active constituents of ginger were further examined. The acetone extract was functioned into 4 fractions by column chromatography. Fractions 1 and 2 showed significant activity. Fraction 2 was further purified and [6]-shogaol which was obtained from fraction 2-2, at 10 mg/kg p.o. was shown to inhibit 5-HT induced hypothermia. Anticathartic activity is known to be one of the medicinal effects of ginger. In the present study, acetone extract of ginger at 75 mg/kg p.o., significantly inhibited 5-HT induced diarrhea. In order to clarify the active constituents, the acetone extract was fractionated into 4 fractions by silica gel chromatography. Fractions 2 and 3, which was especially effective, were further purified and [6]-shogoal, [6]-dehydrogingerdione, [8]- and [10]-gingerol were found to have an anticathartic action. [6]-Shogaol was more potent than [6]-dehydrogingerdione, [8]- and [10]-gingerol.

Topics: Acetone; Animals; Catechols; Diarrhea; Fatty Alcohols; Hypothermia; Ketanserin; Mice; Pindolol; Plant Extracts; Plants, Medicinal; Serotonin