Ginger Extract and [6]-Gingerol Inhibit Contraction of Rat Entire Small Intestine

Abstract

This study aims to investigate the effect of oral administration and the direct action of ginger extract or [6]-gingerol on small intestinal contractility. The direct effect of 10 minutes preincubation of ginger ethanolic extract (10, 100 and 300 μg/mL) or [6]-gingerol (1, 30, and 100 μM) on 0.01 to 30 μM ACh-induced contractions of all parts of the small intestine isolated from normal rats was investigated using the organ bath technique. For in vivo study, the rats were orally administered with extract (10, 20, and 100 mg/kg/d) or [6]-gingerol (2 mg/kg/d) for 7 days, followed by determining the contractile responses to ACh of rat isolated duodenum, jejunum, and ileum and their histology were assessed. Direct application of the extract or [6]-gingerol attenuated ACh-induced contractions in each small intestinal segment, E_max was reduced by 40% to 80%, while EC₅₀ increased 3- to 8-fold from control. Similarly, in the in vivo study ACh-induced contractions were reduced in all parts of the small intestine isolated from rats orally treated with ginger extract (20 and 100 mg/kg/d) or [6]-gingerol (2 mg/kg/d). E_max decreased 15% to 30%, while EC₅₀ increased 1- to 3-fold compared to control. No discernable changes in the histology of intestinal segments were detectable. Thus, the results support the clinical application of ginger for disorders of gastrointestinal motility.

Keywords: [6]-gingerol; contraction; ginger; small intestine.

Figure 1.

HPLC chromatogram of active compounds in the ginger extract. Column: Luna C₁₈ 4.6 × 150 mm; Mobile phase: water/acetonitrile (gradient).

Figure 2.

Inhibitory effect of ginger extract or [6]-gingerol on spontaneous contraction of rat isolated duodenum, jejunum, and ileum. (A) Representative tracing of the duodenum, jejunum, and ileum spontaneous contraction before and after 10 minutes preincubation with DMSO, 300 μg/mL ginger extract, or 100 μM [6]-gingerol. (B) Contraction expressed as percentage to high K⁺ (80 mM) solution-induced maximum contraction of isolated duodenum, jejunum, and ileum before (control) and after incubation with DMSO, 10 to 300 μg/mL ginger extract, or 1 to 100 μM [6]-gingerol. All data were expressed as means ± SEM (n = 5). ***P < .001 versus the control or DMSO; ^††† P < .001 versus the 10 μg/mL ginger extract; ^‡‡‡ P < .001 versus the 1 μM [6]-gingerol.

Figure 3.

Inhibitory effect of ginger extract (A) and [6]-gingerol (B) on cumulative ACh-induced contractions of rat isolated duodenum, jejunum, and ileum. Small intestinal segments were preincubated with either DMSO, 10 to 300 μg/mL ginger extract, or 1 to 100 μM [6]-gingerol for 10 minutes, and then concentration-contraction responses to ACh were obtained. Contractions were expressed as percentage of 80 mM K⁺ solution-induced maximum response. All data were expressed as means ± SEM (n = 5-6). ***P < .001 versus the control; ^### P < .001 versus the DMSO; ^††† P < .001 versus the 10 μg/mL ginger extract; ^‡‡‡ P < .001 versus the 1 μM [6]-gingerol.

Figure 4.

Concentration response curves of ACh-induced contraction in duodenum (A), jejunum (B), and ileum (C) isolated from rats orally administered with 10 to 100 mg/kg/d ginger extract or 2 mg/kg/d [6]-gingerol for 7 days. Values are means ± SEM (n = 6). ***P < .001 versus the control; ^# P < .05, ^### P < .001 versus the 10 mg/kg ginger extract group.

Figure 5.

(A) Typical histological cross-section images of rat duodenum, jejunum, and ileum isolated from rats orally administered with PG (control), 10 to 100 mg/kg/d ginger extract, or 2 mg/kg/d [6]-gingerol for 7 days (H&E; ×100 original magnification, insets ×400 original magnification of the area indicated by black arrows). (B) The lengths of the villi and crypts, and thicknesses of the circular and longitudinal muscle layers of duodenum, jejunum, or ileum. Values are means ± SEM (n = 5).