Hypoglycemic Mechanism of Gegen Qinliantang： An Exploration Based on GPR119/cAMP/GLP-1 Pathway

Jun CHEN; Zi-xing QIAN; Meng-yang ZHU; Xiao LIN; Ya-mei GE

doi:10.13422/j.cnki.syfjx.20220207

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Hypoglycemic Mechanism of Gegen Qinliantang： An Exploration Based on GPR119/cAMP/GLP-1 Pathway

更新时间：2021-12-31

- Hypoglycemic Mechanism of Gegen Qinliantang： An Exploration Based on GPR119/cAMP/GLP-1 Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 28, Issue 3, Pages: 25-30(2022)
- 作者机构：
  
  1.湖北省中医院，武汉 430061
  2.湖北中医药大学，武汉 430061
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20220207
  CLC： R2-0;R22;R285.5;R289;R33
- Received：27 August 2021，
  
  Published Online：23 November 2021，
  
  Published：05 February 2022
- 稿件说明：
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陈俊,钱紫星,朱梦杨等.基于GPR119/cAMP/GLP-1通路探讨葛根芩连汤的降糖机制[J].中国实验方剂学杂志,2022,28(03):25-30.

CHEN Jun,QIAN Zi-xing,ZHU Meng-yang,et al.Hypoglycemic Mechanism of Gegen Qinliantang： An Exploration Based on GPR119/cAMP/GLP-1 Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(03):25-30.
陈俊,钱紫星,朱梦杨等.基于GPR119/cAMP/GLP-1通路探讨葛根芩连汤的降糖机制[J].中国实验方剂学杂志,2022,28(03):25-30. DOI： 10.13422/j.cnki.syfjx.20220207.

CHEN Jun,QIAN Zi-xing,ZHU Meng-yang,et al.Hypoglycemic Mechanism of Gegen Qinliantang： An Exploration Based on GPR119/cAMP/GLP-1 Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(03):25-30. DOI： 10.13422/j.cnki.syfjx.20220207.

摘要

目的

探讨葛根芩连汤（GGQL）对肠道上皮细胞增殖和凋亡的影响，并通过其对细胞环磷酸腺苷（cAMP），G蛋白偶联受体119（GPR119）表达的影响探讨其对胰高血糖素样肽-1（GLP-1）的影响和潜在降糖机制。

方法

对25只Wistar大鼠按生药23 g·kg

-1

，每天2次予以葛根芩连汤灌胃，每只大鼠每天灌胃6 mL，以制备含葛根芩连汤的血清，连续给药7次。用不同浓度葛根芩连汤含药血清（1%，2.5%，5%，7.5%，10%）培养肠道上皮L细胞系NCI-H716细胞；细胞增殖与活性检测（CCK-8）评估细胞增殖水平；流式细胞术检测细胞凋亡水平；酶联免疫吸附测定法（ELISA）检测细胞上清液中GLP-1，cAMP含量；实时荧光定量聚合酶链式反应（Real-time PCR）检测GLP-1，GPR119 mRNA水平；蛋白免疫印迹法（Western blot）检测GLP-1，GPR119蛋白表达水平。

结果

与空白组比较，葛根芩连汤明显减少了NCI-H716细胞的增殖（

0.05），且随着葛根芩连汤浓度的增加，其抑制作用更加明显；每种浓度的葛根芩连汤均明显促进NCI-H716细胞凋亡（

0.05），并且与空白组比较，葛根芩连汤明显提高cAMP，GLP-1，GPR119的表达（

0.05）。葛根芩连汤的作用与其浓度呈正相关，其中10%葛根芩连汤表现出最好的作用。

结论

葛根芩连汤可有效抑制NCI-H716的增殖并促进其凋亡，其可能通过上调cAMP，GPR119的表达而促进GLP-1的分泌。

Abstract

Objective

To explore the effects of Gegen Qinliantang（GGQL） on the proliferation and apoptosis of intestinal epithelial cells as well as on the expression of cyclic adenosine monophosphate （cAMP）， G protein-coupled receptor 119 （GPR119）， and glucagon-like peptide-1 （GLP-1）， so as to explore its potential hypoglycemic mechanism.

Method

Twenty-five Wistar rats were gavaged with GGQL at the dose of 23 g·kg

-1

crude drug， twice a day， which meant that 6 mL was administered into each rat per day for preparing the GGQL-containing serum. After seven consecutive times of administration， the intestinal epithelial L （NCI-H716） cells were cultured with different concentrations （1%， 2.5%， 5%， 7.5%， and 10%） of GGQL. The cell proliferation was evaluated using cell counting kit-8 （CCK-8） and the apoptosis by flow cytometry. The GLP-1 and cAMP contents in cell supernatant were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein GLP-1 and GPR119 levels were assayed by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively.

Result

Compared with the control group， GGQL significantly reduced the proliferation of NCI-H716 cells（

0.05）. As the GGQL concentration increased， its inhibitory effect became more obvious. GGQL at each concentration significantly promoted the apoptosis of NCI-H716 cells （

0.05）. Compared with the control group， GGQL significantly up-regulated the expression of cAMP， GLP-1， and GPR119 （

0.05）. The results showed that the effect of GGQL was positively correlated with its concentration， and 10% GGQL exhibited the best effect.

Conclusion

GGQL effectively inhibits the proliferation of NCI-H716 cells and promotes their apoptosis， and it may promote the secretion of GLP-1 by up-regulating the expression of cAMP and GPR119.

关键词

Keywords

references

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