AIM　To observe the effect of intravenous injection of erythromycin (EM) on interdigestive migrating motor complex (MMC) and postprandial gastrointestinal contraction in conscious dogs , and to study its possible mechanism. METHODS　Gastrointestinal contractile activity was recorded using low compliance capillary water perfusion manometric system. EM was administered intravenously during phaseⅠ and after meal, and blood samples were drawn for measuring plasma motilin concentrations. RESULTS　①Plasma motilin levels showed cyclical fluctuations in different phases of MMC, and plasma motilin reached peak during phaseⅢ and lowest during phaseⅠ.②EM induced phaseⅢ-like contractions in the antrum and duodenum, which was not accompanied by a peak in plasma motilin level. The optimum dose of EM for resulting in a premature phaseⅢ with the same characteristics as the spontaneously occurring phaseⅢ was established to be 0.5 mg*kg-1. The dose of 10 mg*kg-1 EM induced gastrointestinal continuous contractions and duodeno-gastric retrograde peristalsis which was associated with retching and vomiting. ③Atropine obviously inhibited EM-induced phaseⅢ activity in the antrum and duodenum. ④EM powerfully enhanced postprandial gastrointestinal contractile activity. CONCLUSIONS The results suggests that EM is a potent prokinetic agent. The mechanism is not related to the release of motilin, but may be mediated partially by cholinergic pathway.

AIM To observe the effect of intra- venous injection of erythromycin (EM) on interdigestive migrating motor complex (MMC) and postprandial gastrointestinal contraction in conscious dogs, and to study its possible mechanism. METHODS Gastrointestinal contractile activity was recorded using low compliance capillary water per fusion manometric system. EM was administered intravenously during phase I and after meal, and blood samples were drawn for measuring plasma motilin concentra- tions. RESULTS ①Plasma motilin levels showed cyclical fluctuations in different phases of MMC, and plasma motilin reached peak during phaseⅢ and lowest during phase Ｉ. ②EM induced phase Ⅲ -like contractions in the antrum and duodenum, which was not accompanied by a peak in plasma motilin level. The optimum dose of EM for resulting in a premature phaseⅢ with the same characteristics as the spontaneously occurring phaseⅢ was established to be 0. 5 mg.kg-1. The dose of 10 mg.kg-1 EM induced gas- trointestinal continuous contractions and duodeno-gas-tric retrograde peristalsis which was associated with retching and vomiting. ③Atropine obviously inhibited EM-induced phase Ⅲ activity in the antrum and duodenum. GEM powerfully enhanced postprandial gastrointestinal contractile activity. CONCLUSIONS The results suggests that EM is a potent prokinetic agent. The mechanism is not related to the release of motilin, but may be mediated partially by cholinergic pathway.

ObjectiveTo investigate the mechanism of action and main active components of Xiaoyaosan in the treatment of diabetic mellitus-induced erectile dysfunction （DMED）. MethodStreptozotocin （STZ） was used to induce a diabetic rat model. The therapeutic efficacy of Xiaoyaosan was evaluated by measuring intracavernous pressure/mean arterial pressure （ICP/MAP） and using Masson's trichrome staining. The main active components， key targets， and potential signaling pathways of Xiaoyaosan for the treatment of DMED were predicted by network pharmacology and molecular docking. The predicted results were then validated by in vitro and in vivo experiments. ResultThe ICP/MAP measurements and Masson's staining results showed that compared with the results in the control group， the erectile function of rats in the model group was significantly reduced （P<0.01）， and the ratio of smooth muscle/collagen fibers was significantly reduced （P<0.01）. After treatment with Xiaoyaosan， compared with the results in the model group， the ICP/MAP value of the diabetic rats was significantly elevated （P<0.01）， and the ratio of smooth muscle/collagen fibers was significantly higher （P<0.01）. The results of network pharmacology showed that Xiaoyaosan acted on key targets such as albumin （ALB）， protein kinase B1 （Akt1）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF） through its main active components， including quercetin， kaempferol， β-sitosterol， and stigmasterol. These components were involved in the regulation of the advanced glycation end-products/receptor for advanced glycation end-products （AGE/RAGE） signaling pathway and the phosphoinositide 3-kinases（PI3K）/Akt signaling pathway in diabetic complications. The results of molecular docking showed that the key components of Xiaoyaosan had good binding capabilities with core targets， with β-sitosterol showing the strongest binding affinity with ALB. In vivo experiments demonstrated that Xiaoyaosan could significantly increase the protein and mRNA expression of ALB and Akt1 in serum， and inhibit the expression of IL-6 and TNF-α. It also significantly upregulated the expression of protein and mRNA of phosphorylation（p）-PI3K and p-Akt， and inhibited the RAGE expression. The results of cellular thermal shift assay （CETSA） showed that β-sitosterol could significantly inhibit the degradation of ALB protein. ConclusionXiaoyaosan may restore erectile function in diabetic rats by modulating targets such as ALB， Akt1， IL-6， and TNF， and through the RAGE/PI3K/Akt signaling pathway， and its main active component is likely β-sitosterol.