Inhibitory effects of patchouli alcohol on stress-induced diarrhea-predominant irritable bowel syndrome.
World J Gastroenterol. 2018 Feb 14 ;24(6):693-705. PMID: 29456408
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× 10mol/L to 1× 10mol/L). We then determined the responses of the proximal and distal colon segments of rats to the following stimuli: (1) carbachol (1× 10mol/L to 1× 10mol/L); (2) neurotransmitter antagonists including N-nitro-L-arginine methyl ester hydrochloride (10μmol/L) and (1R*, 2S*)-4-[2-Iodo-6-(methylamino)-9H-purin-9-yl]-2-(phosphonooxy)bicyclo[3.1.0]hexane-1-methanol dihydrogen phosphate ester tetraammonium salt (1 μmol/L); (3) agonist α,β-methyleneadenosine 5'-triphosphate trisodium salt (100 μmol/L); and (4) single KCl doses (120 mmol/L). The effects of blockers against antagonist responses were also assessed by pretreatment with PA (100 μmol/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 ATPlevel 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 (EC) was 41.9μmol/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 (<0.01). Compared with CCh-treated IBS-D rat colon, the cholinergic contractile response of IBS-D rat colonic smooth muscle (EC= 0.94μmol/L) was significantly decreased by PA (EC= 37.43μmol/L) (<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 (10μmol/L) contraction (<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.