Jiali Liu, Li Ji, Yue Wang, Xingrui Chen, Yemin Wan, Haihua Qian, Dan Zhang
{"title":"通便煎剂通过PI3K/Akt/mTOR信号通路抑制细胞自噬以治疗便秘大鼠","authors":"Jiali Liu, Li Ji, Yue Wang, Xingrui Chen, Yemin Wan, Haihua Qian, Dan Zhang","doi":"10.1016/j.jep.2024.119139","DOIUrl":null,"url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>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.</p><p><strong>Aim of this study: </strong>To determine the mechanism which underlined the effects of TBD for activating PI3K/AKT/mTOR signaling pathway to inhibit the autophagy in rat.</p><p><strong>Methods: </strong>In this study, we fed the rat with forage containing compound diphenoxylate 8mg/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, 1.3g/mL; TBD-M, 2.7g/mL; TBD-H, 5.3g/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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119139"},"PeriodicalIF":4.8000,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Tongbian Decoction Inhibits Cell Autophagy via PI3K/Akt/mTOR Signaling Pathway to Treat Constipation Rats.\",\"authors\":\"Jiali Liu, Li Ji, Yue Wang, Xingrui Chen, Yemin Wan, Haihua Qian, Dan Zhang\",\"doi\":\"10.1016/j.jep.2024.119139\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Ethnopharmacological relevance: </strong>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.</p><p><strong>Aim of this study: </strong>To determine the mechanism which underlined the effects of TBD for activating PI3K/AKT/mTOR signaling pathway to inhibit the autophagy in rat.</p><p><strong>Methods: </strong>In this study, we fed the rat with forage containing compound diphenoxylate 8mg/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, 1.3g/mL; TBD-M, 2.7g/mL; TBD-H, 5.3g/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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":15761,\"journal\":{\"name\":\"Journal of ethnopharmacology\",\"volume\":\" \",\"pages\":\"119139\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-11-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of ethnopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jep.2024.119139\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jep.2024.119139","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
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 8mg/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, 1.3g/mL; TBD-M, 2.7g/mL; TBD-H, 5.3g/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, p-AKT/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.
期刊介绍：
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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