Effect of Boswellia serrata on intestinal motility in rodents: inhibition of diarrhoea without constipation

Abstract

Clinical studies suggest that the Ayurvedic plant Boswellia serrata may be effective in reducing diarrhoea in patients with inflammatory bowel disease. In the present study, we evaluated the effect of a Boswellia serrata gum resin extract (BSE) on intestinal motility and diarrhoea in rodents. BSE depressed electrically-, acetylcholine-, and barium chloride-induced contractions in the isolated guinea-pig ileum, being more potent in inhibiting the contractions induced by acetylcholine and barium chloride. The inhibitory effect of BSE on acetylcholine-induced contractions was reduced by the L-type Ca(2+) channel blockers verapamil and nifedipine, but not by the sarcoplasmic reticulum Ca(2+)-ATPase inhibitor cyclopiazonic acid, by the phosphodiesterase type IV inhibitor rolipram or by the lipoxygenase inhibitor zileuton. 3-acetyl-11-keto-beta-boswellic acid, one of the main active ingredients of B. serrata, inhibited acetylcholine-induced contractions. BSE inhibited upper gastrointestinal transit in croton oil-treated mice as well as castor oil-induced diarrhoea. However, BSE did not affect intestinal motility in control mice, both in the small and in the large intestine. It is concluded that BSE directly inhibits intestinal motility with a mechanism involving L-type Ca(2+) channels. BSE prevents diarrhoea and normalizes intestinal motility in pathophysiological states without slowing the rate of transit in control animals. These results could explain, at least in part, the clinical efficacy of this Ayurvedic remedy in reducing diarrhoea in patients with inflammatory bowel disease.

Figure 1

Inhibitory effect of B. serrata gum resin extract (BSE, 1–1000 μg ml⁻¹) on the contractile response induced by exogenous acetylcholine (ACh, 10⁻⁶ M), barium chloride (BaCl₂, 10⁻⁴ M), or electrical field stimulation (EFS, 10 Hz for 0.3 s, 100 mA, 0.5 ms pulse duration) in the isolated guinea-pig ileum. Each point represents mean±s.e.m. of six to eight experiments. ^***P<0.001 vs ACh (significance between the two dose–response curves).

Figure 2

Typical trace showing inhibitory effect of B. serrata gum resin extract (BSE, 1–1000 μg ml⁻¹) on contractions produced by acetylcholine in isolated guinea-pig ileum. Dots indicate contractions induced by acetylcholine (10⁻⁶ M), arrows indicate the administrations of BSE in the organ bath.

Figure 3

Acetylcholine-induced contractions in isolated guinea-pig ileum: effect of B. serrata gum resin extract (BSE, 1–1000 μg ml⁻¹) alone (vehicle) or in the presence of verapamil (10⁻⁶ M), nifedipine (10⁻⁶ M) or cyclopiazonic acid (10⁻⁵ M). Each point represents mean±s.e.m. of six to eight experiments. ^**P<0.01 and ^***P<0.001 vs vehicle (significance between the two dose–response curves).

Figure 4

Inhibitory effect of 3-acetyl-11-keto-β-boswellic acid (2 × 10⁻⁷–2 × 10⁻⁴ M) on the contractions induced by acetylcholine (10⁻⁶ M) in the isolated guinea-pig ileum. Each point represents mean±s.e.m. of six to eight experiments.

Figure 5

Effect of B. serrata gum resin extract (BSE, 100–400 mg kg⁻¹) and atropine (AT, 1 mg kg⁻¹) on upper gastrointestinal transit (a) and colonic propulsion in mice (b). Results are mean±s.e.m. of 10–12 animals for each experimental group. ^**P<0.01 vs control.

Figure 6

Effect of B. serrata gum resin extract (BSE, 100–400 mg kg⁻¹) on upper gastrointestinal transit in mice treated with croton oil (20 μl mouse⁻¹). Results are mean±s.e.m. of 10–12 animals for each experimental group. ^#P<0.01 vs control; ^*P<0.05 vs croton oil.

Figure 7

Effect of B. serrata gum resin extract (BSE, 100–400 mg kg⁻¹) on castor oil-induced diarrhoea. The effect of BSE was assessed 2 h after castor oil (0.2 ml mouse⁻¹) administration (n=10–12). ^*P<0.05 and ^**P<0.01 vs control.