Liu Jiali, Ji Li, Wang Yue, Chen Xingrui, Wan Yemin, Qian Haihua, Zhang Dan
Department of Anorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Department of Anorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
J Ethnopharmacol. 2025 Jan 13;339:119139. doi: 10.1016/j.jep.2024.119139. Epub 2024 Nov 19.
Tongbian Decoction (TBD) is a traditional Chinese botanical drug preparation which has been reported to improve constipation in patients. Due to the lack of a well-understood action mechanism of TBD, we examined the effects of TBD in cell autophagy via phosphatidylinositol 3-kinase/protein kinase B/mammalian aimed of rapamycin (PI3K/Akt/mTOR) signaling pathway associated with constipation.
To determine the mechanism which underlined the effects of TBD for activating PI3K/Akt/mTOR signaling pathway to inhibit the autophagy in rat.
In this study, we fed the rat with forage containing compound diphenoxylate 8 mg/kg/day for 120 days, to finish the establishment of a constipation rat model. Subsequently, The constipation rats from all TBD group (TBD-Low group, TBD-Medium group, TBD-High group) were intragastrically administered with different dose (TBD-L, 1.3 g/mL; TBD-M, 2.7 g/mL; TBD-H, 5.3 g/mL) for 28 days, and their general condition, fecal moisture percentage, intestinal propulsion and pathological morphology were observed. In addition, Neuropeptid and Gastrointestinal hormones were detected by ELISA, and the inspection of protein 1A/1B-light chain 3 (LC3) -II/I, Beclin1, p62, and PI3K/Akt/mTOR was done with the utility of western blotting and qPCR.
In this study, TBD was shown to be able to improve general condition, intestinal function, and reduce inflammatory cell infiltration, whereas ELISA indicated that TBD can regulate the levels of gastrointestinal hormones, increase5-hydroxytryptamine (5-HT), substance P (SP) and decrease neuropeptide Y(NPY), calcitonin gene related peptide(CGRP) morphology. Meanwhile, TBD can also decrease Beclin 1 level and LC3II/I ratio, and increase p62 level, which inhibit the cell autophagy, and increase the phosphorylation level of p-PI3/PI3K, p-Akt/Akt and p-mTOR/mTOR in colon tissue.
These results found that TBD can regulate the expression of Neuropeptid and Gastrointestinal hormones to activate PI3K/Akt/mTOR signaling pathway, and inhibit the cell autophagy to enhance the function of intestinal transmission.
通便汤（TBD）是一种传统的中药制剂，据报道可改善患者便秘。由于对TBD的作用机制了解不足，我们通过与便秘相关的磷脂酰肌醇3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白（PI3K/Akt/mTOR）信号通路研究了TBD对细胞自噬的影响。
确定TBD激活PI3K/Akt/mTOR信号通路以抑制大鼠自噬的作用机制。
在本研究中，我们给大鼠喂食含复方地芬诺酯8mg/kg/天的饲料，持续120天，以完成便秘大鼠模型的建立。随后，将所有TBD组（TBD低剂量组、TBD中剂量组、TBD高剂量组）的便秘大鼠分别灌胃不同剂量（TBD-L，1.3g/mL；TBD-M，2.7g/mL；TBD-H，5.3g/mL），持续28天，并观察其一般状况、粪便水分百分比、肠道推进情况和病理形态。此外，通过酶联免疫吸附测定法检测神经肽和胃肠激素，并用蛋白质免疫印迹法和定量聚合酶链反应检测微管相关蛋白1A/1B轻链3（LC3）-II/I、Beclin1、p62以及PI3K/Akt/mTOR。
在本研究中，TBD被证明能够改善一般状况、肠道功能，并减少炎症细胞浸润，而酶联免疫吸附测定法表明TBD可调节胃肠激素水平，增加5-羟色胺（5-HT）、P物质（SP），并降低神经肽Y（NPY）、降钙素基因相关肽（CGRP）水平。同时，TBD还可降低Beclin 1水平和LC3II/I比率，并增加p62水平，从而抑制细胞自噬，并增加结肠组织中p-PI3/PI3K、p-Akt/Akt和p-mTOR/mTOR的磷酸化水平。
这些结果发现，TBD可调节神经肽和胃肠激素的表达，激活PI3K/Akt/mTOR信号通路，并抑制细胞自噬以增强肠道传输功能。
