Cargando…

Protective Effects of Total Glycoside From Rehmannia glutinosa Leaves on Diabetic Nephropathy Rats via Regulating the Metabolic Profiling and Modulating the TGF-β1 and Wnt/β-Catenin Signaling Pathway

Rehmannia glutinosa Libosch (RG), is officially listed in the Chinese Pharmacopoeia and is widely used in China. The leaves of RG (LR) is an important vegetative organ of the plant. At present, the total glycosides of RG (TLR) were extracted from RG, and developed a national second class of new drug...

Descripción completa

Detalles Bibliográficos
Autores principales: Dai, Xinxin, Su, Shulan, Cai, Hongdie, Wei, Dandan, Yan, Hui, Zheng, Tianyao, Zhu, Zhenhua, Shang, Er-xin, Guo, Sheng, Qian, Dawei, Duan, Jin-ao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143134/
https://www.ncbi.nlm.nih.gov/pubmed/30271343
http://dx.doi.org/10.3389/fphar.2018.01012
_version_ 1783355928671682560
author Dai, Xinxin
Su, Shulan
Cai, Hongdie
Wei, Dandan
Yan, Hui
Zheng, Tianyao
Zhu, Zhenhua
Shang, Er-xin
Guo, Sheng
Qian, Dawei
Duan, Jin-ao
author_facet Dai, Xinxin
Su, Shulan
Cai, Hongdie
Wei, Dandan
Yan, Hui
Zheng, Tianyao
Zhu, Zhenhua
Shang, Er-xin
Guo, Sheng
Qian, Dawei
Duan, Jin-ao
author_sort Dai, Xinxin
collection PubMed
description Rehmannia glutinosa Libosch (RG), is officially listed in the Chinese Pharmacopoeia and is widely used in China. The leaves of RG (LR) is an important vegetative organ of the plant. At present, the total glycosides of RG (TLR) were extracted from RG, and developed a national second class of new drugs to the Dihuangye total glycoside capsule (DTG). Additionally, DTG has the effect of nourishing yin and tonifying kidney, promoting blood circulation and blood cooling, and applicable to chronic glomerulonephritis mild to Qi and Yin Deficiency. Moreover, diabetic nephropathy (DN) rats model was induced by intraperitoneal injection of a small dose of streptozotocin (45 mg/kg) and high-fat diet and plus 5% glucose drinking water. Over 15 days, after oral administration TLR and DTG in DN rats, samples from serum, urine and kidney were collected for biochemical indicators measurements, pathological analysis, western blotting and metabolomics. Therefore, the analytical results of biochemical indicators, histopathological observations and western blotting showed that TLR and DTG exhibited a significant effect in renal protection. And 27 endogenous metabolites (12 in serum and 15 in urine) could be tentatively identified in the process of DN in rats using metabolomics method. Those endogenous metabolites were chiefly involved in sphingolipid metabolism; pentose, glucuronate interconversion; terpenoid backbone biosynthesis; purine metabolism and retinol metabolism. After drug intervention, these endogenous metabolites turned back to normal level some extent (P < 0.05). Furthermore, TLR and DTG prevent high glucose-induced glomerular mesangial cells (GMCs) by inhibiting TGF-β1 and Wnt/β-catenin signaling pathway, providing a powerful supports to develop a new therapeutic agent for DN. This study paved the way for further exploration of the pathogenesis of DN, early diagnosis and the evaluation of curative effect.
format Online
Article
Text
id pubmed-6143134
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-61431342018-09-28 Protective Effects of Total Glycoside From Rehmannia glutinosa Leaves on Diabetic Nephropathy Rats via Regulating the Metabolic Profiling and Modulating the TGF-β1 and Wnt/β-Catenin Signaling Pathway Dai, Xinxin Su, Shulan Cai, Hongdie Wei, Dandan Yan, Hui Zheng, Tianyao Zhu, Zhenhua Shang, Er-xin Guo, Sheng Qian, Dawei Duan, Jin-ao Front Pharmacol Pharmacology Rehmannia glutinosa Libosch (RG), is officially listed in the Chinese Pharmacopoeia and is widely used in China. The leaves of RG (LR) is an important vegetative organ of the plant. At present, the total glycosides of RG (TLR) were extracted from RG, and developed a national second class of new drugs to the Dihuangye total glycoside capsule (DTG). Additionally, DTG has the effect of nourishing yin and tonifying kidney, promoting blood circulation and blood cooling, and applicable to chronic glomerulonephritis mild to Qi and Yin Deficiency. Moreover, diabetic nephropathy (DN) rats model was induced by intraperitoneal injection of a small dose of streptozotocin (45 mg/kg) and high-fat diet and plus 5% glucose drinking water. Over 15 days, after oral administration TLR and DTG in DN rats, samples from serum, urine and kidney were collected for biochemical indicators measurements, pathological analysis, western blotting and metabolomics. Therefore, the analytical results of biochemical indicators, histopathological observations and western blotting showed that TLR and DTG exhibited a significant effect in renal protection. And 27 endogenous metabolites (12 in serum and 15 in urine) could be tentatively identified in the process of DN in rats using metabolomics method. Those endogenous metabolites were chiefly involved in sphingolipid metabolism; pentose, glucuronate interconversion; terpenoid backbone biosynthesis; purine metabolism and retinol metabolism. After drug intervention, these endogenous metabolites turned back to normal level some extent (P < 0.05). Furthermore, TLR and DTG prevent high glucose-induced glomerular mesangial cells (GMCs) by inhibiting TGF-β1 and Wnt/β-catenin signaling pathway, providing a powerful supports to develop a new therapeutic agent for DN. This study paved the way for further exploration of the pathogenesis of DN, early diagnosis and the evaluation of curative effect. Frontiers Media S.A. 2018-09-11 /pmc/articles/PMC6143134/ /pubmed/30271343 http://dx.doi.org/10.3389/fphar.2018.01012 Text en Copyright © 2018 Dai, Su, Cai, Wei, Yan, Zheng, Zhu, Shang, Guo, Qian and Duan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Dai, Xinxin
Su, Shulan
Cai, Hongdie
Wei, Dandan
Yan, Hui
Zheng, Tianyao
Zhu, Zhenhua
Shang, Er-xin
Guo, Sheng
Qian, Dawei
Duan, Jin-ao
Protective Effects of Total Glycoside From Rehmannia glutinosa Leaves on Diabetic Nephropathy Rats via Regulating the Metabolic Profiling and Modulating the TGF-β1 and Wnt/β-Catenin Signaling Pathway
title Protective Effects of Total Glycoside From Rehmannia glutinosa Leaves on Diabetic Nephropathy Rats via Regulating the Metabolic Profiling and Modulating the TGF-β1 and Wnt/β-Catenin Signaling Pathway
title_full Protective Effects of Total Glycoside From Rehmannia glutinosa Leaves on Diabetic Nephropathy Rats via Regulating the Metabolic Profiling and Modulating the TGF-β1 and Wnt/β-Catenin Signaling Pathway
title_fullStr Protective Effects of Total Glycoside From Rehmannia glutinosa Leaves on Diabetic Nephropathy Rats via Regulating the Metabolic Profiling and Modulating the TGF-β1 and Wnt/β-Catenin Signaling Pathway
title_full_unstemmed Protective Effects of Total Glycoside From Rehmannia glutinosa Leaves on Diabetic Nephropathy Rats via Regulating the Metabolic Profiling and Modulating the TGF-β1 and Wnt/β-Catenin Signaling Pathway
title_short Protective Effects of Total Glycoside From Rehmannia glutinosa Leaves on Diabetic Nephropathy Rats via Regulating the Metabolic Profiling and Modulating the TGF-β1 and Wnt/β-Catenin Signaling Pathway
title_sort protective effects of total glycoside from rehmannia glutinosa leaves on diabetic nephropathy rats via regulating the metabolic profiling and modulating the tgf-β1 and wnt/β-catenin signaling pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143134/
https://www.ncbi.nlm.nih.gov/pubmed/30271343
http://dx.doi.org/10.3389/fphar.2018.01012
work_keys_str_mv AT daixinxin protectiveeffectsoftotalglycosidefromrehmanniaglutinosaleavesondiabeticnephropathyratsviaregulatingthemetabolicprofilingandmodulatingthetgfb1andwntbcateninsignalingpathway
AT sushulan protectiveeffectsoftotalglycosidefromrehmanniaglutinosaleavesondiabeticnephropathyratsviaregulatingthemetabolicprofilingandmodulatingthetgfb1andwntbcateninsignalingpathway
AT caihongdie protectiveeffectsoftotalglycosidefromrehmanniaglutinosaleavesondiabeticnephropathyratsviaregulatingthemetabolicprofilingandmodulatingthetgfb1andwntbcateninsignalingpathway
AT weidandan protectiveeffectsoftotalglycosidefromrehmanniaglutinosaleavesondiabeticnephropathyratsviaregulatingthemetabolicprofilingandmodulatingthetgfb1andwntbcateninsignalingpathway
AT yanhui protectiveeffectsoftotalglycosidefromrehmanniaglutinosaleavesondiabeticnephropathyratsviaregulatingthemetabolicprofilingandmodulatingthetgfb1andwntbcateninsignalingpathway
AT zhengtianyao protectiveeffectsoftotalglycosidefromrehmanniaglutinosaleavesondiabeticnephropathyratsviaregulatingthemetabolicprofilingandmodulatingthetgfb1andwntbcateninsignalingpathway
AT zhuzhenhua protectiveeffectsoftotalglycosidefromrehmanniaglutinosaleavesondiabeticnephropathyratsviaregulatingthemetabolicprofilingandmodulatingthetgfb1andwntbcateninsignalingpathway
AT shangerxin protectiveeffectsoftotalglycosidefromrehmanniaglutinosaleavesondiabeticnephropathyratsviaregulatingthemetabolicprofilingandmodulatingthetgfb1andwntbcateninsignalingpathway
AT guosheng protectiveeffectsoftotalglycosidefromrehmanniaglutinosaleavesondiabeticnephropathyratsviaregulatingthemetabolicprofilingandmodulatingthetgfb1andwntbcateninsignalingpathway
AT qiandawei protectiveeffectsoftotalglycosidefromrehmanniaglutinosaleavesondiabeticnephropathyratsviaregulatingthemetabolicprofilingandmodulatingthetgfb1andwntbcateninsignalingpathway
AT duanjinao protectiveeffectsoftotalglycosidefromrehmanniaglutinosaleavesondiabeticnephropathyratsviaregulatingthemetabolicprofilingandmodulatingthetgfb1andwntbcateninsignalingpathway