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)...
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BMC
2023-05-01
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Series: | Chinese Medicine |
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Online Access: | https://doi.org/10.1186/s13020-023-00762-4 |
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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. |
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language | English |
last_indexed | 2024-03-13T10:13:01Z |
publishDate | 2023-05-01 |
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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 |
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