Identification of the Main Chemical constituents and mechanism of Renshen Guben oral liquid against Renal Fibrosis

Abstract Background Renal fibrosis is the late stage of many chronic kidney diseases (CKD). Clinically, there is almost no effective treatment for renal fibrosis except dialysis. Renshen Guben oral liquid (RSGB) is a Chinese patent medicine approved by National Medical Products Administration (NMPA)...

Full description

Bibliographic Details
Main Authors: Junhong Zhang, Juqin Peng, Tong Zhang, Hong Jiang, Yuewen Qin, Hong Chen, Xiaofang Deng, Junguo Ren, Ping Wang, Haiyu Xu
Format: Article
Language:English
Published: BMC 2023-05-01
Series:Chinese Medicine
Subjects:
Online Access:https://doi.org/10.1186/s13020-023-00762-4
_version_ 1797822701092470784
author Junhong Zhang
Juqin Peng
Tong Zhang
Hong Jiang
Yuewen Qin
Hong Chen
Xiaofang Deng
Junguo Ren
Ping Wang
Haiyu Xu
author_facet Junhong Zhang
Juqin Peng
Tong Zhang
Hong Jiang
Yuewen Qin
Hong Chen
Xiaofang Deng
Junguo Ren
Ping Wang
Haiyu Xu
author_sort Junhong Zhang
collection DOAJ
description Abstract Background Renal fibrosis is the late stage of many chronic kidney diseases (CKD). Clinically, there is almost no effective treatment for renal fibrosis except dialysis. Renshen Guben oral liquid (RSGB) is a Chinese patent medicine approved by National Medical Products Administration (NMPA), which is suitable for clinical patients with chronic nephritis. Currently, the chemical constituents of RSGB remains unclear, and its efficacy and mechanism on renal fibrosis have not been reported. Methods In our research, ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was employed to describe the chemical profile of RSGB, unilateral ureteral obstruction (UUO) model in mice was established to evaluate the beneficial effect of RSGB on renal fibrosis by biochemical indexes, HE and Masson staining. RNA sequencing and “constituents-targets-pathways” multi-dimensional network was established to mine the mechanisms of RSGB. Key targets were verified by quantitative real-time PCR (qRT-PCR) and western bolt (WB). Results A total of 201 constituents were identified or tentatively characterized, 15 of which were confirmed with standards. The number of triterpenes was the highest with 49, followed by phenols with 46. RSGB ameliorated the blood urea nitrogen (BUN) and serum creatinine (Scr) levels in serum, normalizing pathological structure of kidney tissue. RNA sequencing revealed that RSGB regulates 226 differential genes, which were involved in kidney development. According to the “constituents-targets-pathways” network, 26 key active constituents may mainly regulate the inflammatory immune system through 88 corresponding targets. qRT-PCR and WB results showed that RSGB inhibited the activation of the Tgfβ1/Smad2/3 pathway, Wnt4/β-Catenin pathway and NGFR/NF-κB pathway. Conclusions Overall, our study, for the first time, characterized 201 chemical constituents in RSGB, and 26 of them were screened out to alleviates renal fibrosis mainly through Tgfβ1/Smad2/3 pathway, Wnt4/β-catenin pathway and NGFR/NF-κB pathway, which may provide a new research strategy for research on the mechanism of traditional Chinese Medicine.
first_indexed 2024-03-13T10:13:01Z
format Article
id doaj.art-e00f59dc22b447f59446ecf36dd54819
institution Directory Open Access Journal
issn 1749-8546
language English
last_indexed 2024-03-13T10:13:01Z
publishDate 2023-05-01
publisher BMC
record_format Article
series Chinese Medicine
spelling doaj.art-e00f59dc22b447f59446ecf36dd548192023-05-21T11:27:17ZengBMCChinese Medicine1749-85462023-05-0118111410.1186/s13020-023-00762-4Identification of the Main Chemical constituents and mechanism of Renshen Guben oral liquid against Renal FibrosisJunhong Zhang0Juqin Peng1Tong Zhang2Hong Jiang3Yuewen Qin4Hong Chen5Xiaofang Deng6Junguo Ren7Ping Wang8Haiyu Xu9Institute of Chinese Materia Medica, China Academy of Chinese Medical SciencesBeijing Key Laboratory of Pharmacology of Traditional Chinese Medicine, Institute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical SciencesInstitute of Chinese Materia Medica, China Academy of Chinese Medical SciencesInstitute of Chinese Materia Medica, China Academy of Chinese Medical SciencesInstitute of Chinese Materia Medica, China Academy of Chinese Medical SciencesInstitute of Chinese Materia Medica, China Academy of Chinese Medical SciencesInstitute of Chinese Materia Medica, China Academy of Chinese Medical SciencesBeijing Key Laboratory of Pharmacology of Traditional Chinese Medicine, Institute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical SciencesInstitute of Chinese Materia Medica, China Academy of Chinese Medical SciencesInstitute of Chinese Materia Medica, China Academy of Chinese Medical SciencesAbstract Background Renal fibrosis is the late stage of many chronic kidney diseases (CKD). Clinically, there is almost no effective treatment for renal fibrosis except dialysis. Renshen Guben oral liquid (RSGB) is a Chinese patent medicine approved by National Medical Products Administration (NMPA), which is suitable for clinical patients with chronic nephritis. Currently, the chemical constituents of RSGB remains unclear, and its efficacy and mechanism on renal fibrosis have not been reported. Methods In our research, ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was employed to describe the chemical profile of RSGB, unilateral ureteral obstruction (UUO) model in mice was established to evaluate the beneficial effect of RSGB on renal fibrosis by biochemical indexes, HE and Masson staining. RNA sequencing and “constituents-targets-pathways” multi-dimensional network was established to mine the mechanisms of RSGB. Key targets were verified by quantitative real-time PCR (qRT-PCR) and western bolt (WB). Results A total of 201 constituents were identified or tentatively characterized, 15 of which were confirmed with standards. The number of triterpenes was the highest with 49, followed by phenols with 46. RSGB ameliorated the blood urea nitrogen (BUN) and serum creatinine (Scr) levels in serum, normalizing pathological structure of kidney tissue. RNA sequencing revealed that RSGB regulates 226 differential genes, which were involved in kidney development. According to the “constituents-targets-pathways” network, 26 key active constituents may mainly regulate the inflammatory immune system through 88 corresponding targets. qRT-PCR and WB results showed that RSGB inhibited the activation of the Tgfβ1/Smad2/3 pathway, Wnt4/β-Catenin pathway and NGFR/NF-κB pathway. Conclusions Overall, our study, for the first time, characterized 201 chemical constituents in RSGB, and 26 of them were screened out to alleviates renal fibrosis mainly through Tgfβ1/Smad2/3 pathway, Wnt4/β-catenin pathway and NGFR/NF-κB pathway, which may provide a new research strategy for research on the mechanism of traditional Chinese Medicine.https://doi.org/10.1186/s13020-023-00762-4RSGBUPLC-QTOF-MS/MSUUO modelRNA sequencing“Constituents-targets-pathways” network
spellingShingle Junhong Zhang
Juqin Peng
Tong Zhang
Hong Jiang
Yuewen Qin
Hong Chen
Xiaofang Deng
Junguo Ren
Ping Wang
Haiyu Xu
Identification of the Main Chemical constituents and mechanism of Renshen Guben oral liquid against Renal Fibrosis
Chinese Medicine
RSGB
UPLC-QTOF-MS/MS
UUO model
RNA sequencing
“Constituents-targets-pathways” network
title Identification of the Main Chemical constituents and mechanism of Renshen Guben oral liquid against Renal Fibrosis
title_full Identification of the Main Chemical constituents and mechanism of Renshen Guben oral liquid against Renal Fibrosis
title_fullStr Identification of the Main Chemical constituents and mechanism of Renshen Guben oral liquid against Renal Fibrosis
title_full_unstemmed Identification of the Main Chemical constituents and mechanism of Renshen Guben oral liquid against Renal Fibrosis
title_short Identification of the Main Chemical constituents and mechanism of Renshen Guben oral liquid against Renal Fibrosis
title_sort identification of the main chemical constituents and mechanism of renshen guben oral liquid against renal fibrosis
topic RSGB
UPLC-QTOF-MS/MS
UUO model
RNA sequencing
“Constituents-targets-pathways” network
url https://doi.org/10.1186/s13020-023-00762-4
work_keys_str_mv AT junhongzhang identificationofthemainchemicalconstituentsandmechanismofrenshengubenoralliquidagainstrenalfibrosis
AT juqinpeng identificationofthemainchemicalconstituentsandmechanismofrenshengubenoralliquidagainstrenalfibrosis
AT tongzhang identificationofthemainchemicalconstituentsandmechanismofrenshengubenoralliquidagainstrenalfibrosis
AT hongjiang identificationofthemainchemicalconstituentsandmechanismofrenshengubenoralliquidagainstrenalfibrosis
AT yuewenqin identificationofthemainchemicalconstituentsandmechanismofrenshengubenoralliquidagainstrenalfibrosis
AT hongchen identificationofthemainchemicalconstituentsandmechanismofrenshengubenoralliquidagainstrenalfibrosis
AT xiaofangdeng identificationofthemainchemicalconstituentsandmechanismofrenshengubenoralliquidagainstrenalfibrosis
AT junguoren identificationofthemainchemicalconstituentsandmechanismofrenshengubenoralliquidagainstrenalfibrosis
AT pingwang identificationofthemainchemicalconstituentsandmechanismofrenshengubenoralliquidagainstrenalfibrosis
AT haiyuxu identificationofthemainchemicalconstituentsandmechanismofrenshengubenoralliquidagainstrenalfibrosis