Mechanism of aqueous fructus aurantii immaturus extracts in neuroplexus of cathartic colons.

AIM: To examine the effect of aqueous fructus aurantii immaturus (FAI) extracts on the intestinal plexus of cathartic colons. METHODS: Cathartic colons were induced in rats with dahuang, a laxative used in traditional Chinese medicine. Once the model was established (after approximately 12 wk), rats were administered mosapride (1.54 mg/kg) or various doses of aqueous FAI extracts (1-4 g/kg) for 14 d. Transit function was assessed using an ink propulsion test. Rats were then sacrificed, and the ultramicrostructure of colonic tissue was examined using transmission electron microscopy. The expression of the 5-hydroxytryptamine receptor 4 (5-HTR4) and neurofilament-H was assessed in colon tissues using real-time PCR, Western blot, and immunohistochemistry. RESULTS: Mosapride and high dose (4 g/kg) of aqueous FAI extracts significantly improved the bowel movement in cathartic colons compared to untreated model colons as measured by the intestinal transit rate (70.06 ± 7.25 and 72.02 ± 8.74, respectively, vs 64.12 ± 5.19; P < 0.05 for both). Compared to controls, the ultramicrostructure of cathartic colons showed signs of neural degeneration. Treatment with mosapride and aqueous FAI extracts resulted in recovery of ultrastructural pathology. Treatment with mosapride alone upregulated the gene and protein expression of 5-HTR4 compared to untreated controls (P < 0.05 for both). Treatment with aqueous FAI extracts (≥ 2 g/kg) increased 5-HTR4 mRNA levels (P < 0.05), but no change in protein level was observed by Western blot or immunohistochemistry. The mRNA and protein levels of neurofilament-H were significantly increased with mosapride and ≥ 2 g/kg aqueous FAI extracts compared to controls (P < 0.05 for all). CONCLUSION: Aqueous FAI extracts and mosapride strengthen bowel movement in cathartic colons via increasing the expression of 5-HTR4 and neurofilament-H.

Long-term mucosal alterations by sennosides and related compounds.

Sennosides and related compounds are presumed to be severe cell poisons after prolonged ingestion. Some histological and ultrastructural studies in animals and man with such laxative misuse have revealed myenteric plexus and colonic epithelium injuries; but others have failed to point out identical data. In a first histological and ultrastructural study in mouse, we were unable to find any intestinal mucosa injury after long-term sennoside ingestion. In a second long-term experiment, we compared the effects of sennosides and 1,8-dihydroxyanthraquinone (synthetic anthracene derivative) on the mouse jejunum and colon. Electron microscopic observations showed nervous myenteric plexus abnormalities only in 1,8-dihydroxyanthraquinone-treated animals. These results suggest that sennosides have a good intestinal mucosa tolerance as opposed to aglycosidic-related compounds.

A unique population of uranaffin-positive intrinsic nerve endings in the small intestine.

A positive uranaffin reaction was observed in the small (40-60 nm) diameter vesicles of some intestinal axons. There was no change in the number of reactive axons or the intensity of reaction after reserpine (5 mg/kg) or after interruption of axons reaching the intestine through the mesentery. The axons were found in the myenteric, submucous and deep muscular plexuses and in the circular muscle. Some uranaffin-positive axons formed synapses with neurons of the myenteric and submucous plexuses. It is concluded that these axons are not noradrenergic. The axons must represent one of the several nerve types which are known to be intrinsic to the intestine, but are as yet unidentified at an ultrastructural level. If, as has been postulated, the reaction localizes amine storage vesicles, the uranaffin-positive axons are probably the intrinsic amine-handling axons previously demonstrated histochemically.