Inhibitory effects of patchouli alcohol on stress-induced diarrhea-predominant irritable bowel syndrome

AIM To elucidate the mechanism of patchouli alcohol (PA) in treatment of rat models of diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS We studied the effects of PA on colonic spontaneous motility using its cumulative log concentration (3 x 10(-7) mol/L to 1 x 10(-4) mol/L). We then determined the responses of the proximal and distal colon seg-ments of rats to the following stimuli: (1) carbachol (1 x 10(-9) mol/L to 1 x 10(5) mol/L); (2) neurotransmitter antagonists including N.-nitro-l-arginine methyl ester hydrochloride (10 mu mol/L) and (1R*, 2S*)-4-[2-Iodo-6-(methylamino)-9H-purin-9-yl]-2-(phosphonooxy)bicyclo[3.1.0] hexane-1methanol dihydrogen phosphate ester tetraammonium salt (1 mu mol/L); (3) agonist alpha,beta-methyleneadenosine 5'-triphosphate trisodium salt (100 mu mol/L); and (4) single KCl doses (120 mmol/L). The effects of blockers against antagonist responses were also assessed by pretreatment with PA (100 mu mol/L) for 1 min. Electrical-field stimulation (40 V, 2-30 Hz, 0.5 ms pulse duration, and 10 s) was performed to observe nonadrenergic, noncholinergic neurotransmitter release in IBS-D rat colon. The ATP level of Kreb's solution was also determined. RESULTS PA exerted a concentration-dependent inhibitory effect on the spontaneous contraction of the colonic longitudinal smooth muscle, and the half maximal effective concentration (EC50) was 41.9 mu mol/L. In comparison with the KCl-treated IBS-D group, the contractile response (mg contractions) in the PA + KCl-treated IBS-D group (11.87 +/- 3.34) was significantly decreased in the peak tension (P < 0.01). Compared with CCh-treated IBS-D rat colon, the cholinergic contractile response of IBS-D rat colonic smooth muscle (EC50 = 0.94 mu mol/L) was significantly decreased by PA (EC50 = 37.43 mu mol/L) (P < 0.05). Lack of nitrergic neurotransmitter release in stress-induced IBS-D rats showed contraction effects on colonic smooth muscle. Pretreatment with PA resulted in inhibitory effect on l-NAME-induced (10 mu mol/L) contraction (P < 0.05). ATP might not be the main neurotransmitter involved in inhibitory effects of PA in the colonic relaxation of stress-induced IBS-D rats. CONCLUSION PA application may serve as a new therapeutic approach for IBS-D.