Unraveling the superiority of (−)‐gallocatechin gallate to (−)‐epigallocatechin‐3‐gallate in protection of diabetic nephropathy of db/db mice

Abstract GCG ((−)‐gallocatechin gallate) and EGCG ((−)‐epigallocatechin‐3‐gallate) are main biologically active polyphenolic compounds in tea leaves, and EGCG has been studied for its potential effects on alleviating diabetic nephropathy (DN). Previous studies showed that GCG exhibited better hypogl...

Full description

Bibliographic Details
Main Authors: Xin Xiao, Ling Feng, Huijun Cheng, Huifang Ge, Yijun Wang, Xiaochun Wan, Daxiang Li, Zhongwen Xie
Format: Article
Language:English
Published: Wiley 2024-03-01
Series:Food Frontiers
Subjects:
Online Access:https://doi.org/10.1002/fft2.356
_version_ 1797257854753701888
author Xin Xiao
Ling Feng
Huijun Cheng
Huifang Ge
Yijun Wang
Xiaochun Wan
Daxiang Li
Zhongwen Xie
author_facet Xin Xiao
Ling Feng
Huijun Cheng
Huifang Ge
Yijun Wang
Xiaochun Wan
Daxiang Li
Zhongwen Xie
author_sort Xin Xiao
collection DOAJ
description Abstract GCG ((−)‐gallocatechin gallate) and EGCG ((−)‐epigallocatechin‐3‐gallate) are main biologically active polyphenolic compounds in tea leaves, and EGCG has been studied for its potential effects on alleviating diabetic nephropathy (DN). Previous studies showed that GCG exhibited better hypoglycemic and antioxidant efficacy than EGCG. However, the efficacy and molecular mechanisms of GCG in the protection of DN are unknown. In this study, db/db mice were administered with EGCG or GCG orally for 20 weeks to comparatively investigate their effects on DN. These results revealed that GCG was significantly more effective than EGCG in decreasing water intake and urine excretion, reducing fasting blood glucose levels and systolic blood pressure, improving mesenteric artery contractility, enhancing the right renal hemodynamics, and improving key renal function markers. Through transcriptome analysis, S100A8/S100A9, two regulators of interstitial fibrosis, were identified and found to be more sensitive to GCG intervention, which was further confirmed by mRNA and protein expression data. In addition, the molecular docking analysis results demonstrated that GCG displayed a superior binding affinity toward S100A8/S100A9 in comparison to EGCG. Overall, our study found that GCG holds significant potential for the treatment of DN and outperforms EGCG in terms of efficacy.
first_indexed 2024-04-24T22:44:16Z
format Article
id doaj.art-ff6ccb96d659472abbfa9a65e7627cce
institution Directory Open Access Journal
issn 2643-8429
language English
last_indexed 2024-04-24T22:44:16Z
publishDate 2024-03-01
publisher Wiley
record_format Article
series Food Frontiers
spelling doaj.art-ff6ccb96d659472abbfa9a65e7627cce2024-03-18T16:46:15ZengWileyFood Frontiers2643-84292024-03-015277178810.1002/fft2.356Unraveling the superiority of (−)‐gallocatechin gallate to (−)‐epigallocatechin‐3‐gallate in protection of diabetic nephropathy of db/db miceXin Xiao0Ling Feng1Huijun Cheng2Huifang Ge3Yijun Wang4Xiaochun Wan5Daxiang Li6Zhongwen Xie7State Key Laboratory of Tea Plant Biology and Utilization Anhui Agricultural University Hefei ChinaState Key Laboratory of Tea Plant Biology and Utilization Anhui Agricultural University Hefei ChinaSchool of Life Sciences Anhui Agricultural University Hefei ChinaState Key Laboratory of Tea Plant Biology and Utilization Anhui Agricultural University Hefei ChinaState Key Laboratory of Tea Plant Biology and Utilization Anhui Agricultural University Hefei ChinaState Key Laboratory of Tea Plant Biology and Utilization Anhui Agricultural University Hefei ChinaState Key Laboratory of Tea Plant Biology and Utilization Anhui Agricultural University Hefei ChinaState Key Laboratory of Tea Plant Biology and Utilization Anhui Agricultural University Hefei ChinaAbstract GCG ((−)‐gallocatechin gallate) and EGCG ((−)‐epigallocatechin‐3‐gallate) are main biologically active polyphenolic compounds in tea leaves, and EGCG has been studied for its potential effects on alleviating diabetic nephropathy (DN). Previous studies showed that GCG exhibited better hypoglycemic and antioxidant efficacy than EGCG. However, the efficacy and molecular mechanisms of GCG in the protection of DN are unknown. In this study, db/db mice were administered with EGCG or GCG orally for 20 weeks to comparatively investigate their effects on DN. These results revealed that GCG was significantly more effective than EGCG in decreasing water intake and urine excretion, reducing fasting blood glucose levels and systolic blood pressure, improving mesenteric artery contractility, enhancing the right renal hemodynamics, and improving key renal function markers. Through transcriptome analysis, S100A8/S100A9, two regulators of interstitial fibrosis, were identified and found to be more sensitive to GCG intervention, which was further confirmed by mRNA and protein expression data. In addition, the molecular docking analysis results demonstrated that GCG displayed a superior binding affinity toward S100A8/S100A9 in comparison to EGCG. Overall, our study found that GCG holds significant potential for the treatment of DN and outperforms EGCG in terms of efficacy.https://doi.org/10.1002/fft2.356comparisondb/dbdiabetic nephropathyEGCGGCGtranscriptome analysis
spellingShingle Xin Xiao
Ling Feng
Huijun Cheng
Huifang Ge
Yijun Wang
Xiaochun Wan
Daxiang Li
Zhongwen Xie
Unraveling the superiority of (−)‐gallocatechin gallate to (−)‐epigallocatechin‐3‐gallate in protection of diabetic nephropathy of db/db mice
Food Frontiers
comparison
db/db
diabetic nephropathy
EGCG
GCG
transcriptome analysis
title Unraveling the superiority of (−)‐gallocatechin gallate to (−)‐epigallocatechin‐3‐gallate in protection of diabetic nephropathy of db/db mice
title_full Unraveling the superiority of (−)‐gallocatechin gallate to (−)‐epigallocatechin‐3‐gallate in protection of diabetic nephropathy of db/db mice
title_fullStr Unraveling the superiority of (−)‐gallocatechin gallate to (−)‐epigallocatechin‐3‐gallate in protection of diabetic nephropathy of db/db mice
title_full_unstemmed Unraveling the superiority of (−)‐gallocatechin gallate to (−)‐epigallocatechin‐3‐gallate in protection of diabetic nephropathy of db/db mice
title_short Unraveling the superiority of (−)‐gallocatechin gallate to (−)‐epigallocatechin‐3‐gallate in protection of diabetic nephropathy of db/db mice
title_sort unraveling the superiority of gallocatechin gallate to epigallocatechin 3 gallate in protection of diabetic nephropathy of db db mice
topic comparison
db/db
diabetic nephropathy
EGCG
GCG
transcriptome analysis
url https://doi.org/10.1002/fft2.356
work_keys_str_mv AT xinxiao unravelingthesuperiorityofgallocatechingallatetoepigallocatechin3gallateinprotectionofdiabeticnephropathyofdbdbmice
AT lingfeng unravelingthesuperiorityofgallocatechingallatetoepigallocatechin3gallateinprotectionofdiabeticnephropathyofdbdbmice
AT huijuncheng unravelingthesuperiorityofgallocatechingallatetoepigallocatechin3gallateinprotectionofdiabeticnephropathyofdbdbmice
AT huifangge unravelingthesuperiorityofgallocatechingallatetoepigallocatechin3gallateinprotectionofdiabeticnephropathyofdbdbmice
AT yijunwang unravelingthesuperiorityofgallocatechingallatetoepigallocatechin3gallateinprotectionofdiabeticnephropathyofdbdbmice
AT xiaochunwan unravelingthesuperiorityofgallocatechingallatetoepigallocatechin3gallateinprotectionofdiabeticnephropathyofdbdbmice
AT daxiangli unravelingthesuperiorityofgallocatechingallatetoepigallocatechin3gallateinprotectionofdiabeticnephropathyofdbdbmice
AT zhongwenxie unravelingthesuperiorityofgallocatechingallatetoepigallocatechin3gallateinprotectionofdiabeticnephropathyofdbdbmice