Tongbian decoction inhibits cell autophagy via PI3K/Akt/mTOR signaling pathway to treat constipation rats

Ethnopharmacological relevance: 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. Aim of This Study: To determine the mechanism which underlined the effects of TBD for activating PI3K/Akt/ mTOR signaling pathway to inhibit the autophagy in rat. Methods: 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. Results: 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, pAkt/Akt and p-mTOR/mTOR in colon tissue. Conclusion: 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.