Renoprotective effects of Gushen Jiedu capsule on diabetic nephropathy in rats

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Gushen Jiedu capsule (GSJD) is a formula that has been widely used in traditional Chinese medicine for the prevention and treatment of diabetic nephropathy (DN). However, the mechanism underlying the protective effects of GSJD on DN is still unclear. This study was performed to clarify the therapeutic effects of GSJD on DN and its underlying mechanisms. High-fat diet- and streptozotocin-induced DN rats were treated with or without GSJD suspension by gavage for 8 weeks, and biochemical changes in blood and urine were analysed. Kidneys were isolated for histological, TUNEL and Western blot analysis. Compared to the DN group, the GSJD-treated groups exhibited decreased urinary albumin, ameliorated renal dysfunction, including serum creatinine and blood urea nitrogen, and attenuated total cholesterol, triglyceride and total protein levels. However, there were no significant effects of GSJD on body weight, fasting blood glucose or albuminuria. Histology showed that GSJD could retard the progression of DN and decrease the apoptosis rate from 52% to less than 20%. Western blot analysis showed that GSJD could regulate the mitochondrial apoptotic pathway by downregulating the expression of Bax and upregulating the expression of BCL-2 in the kidneys of DN rats. Moreover, the Akt pathway, an upstream signalling pathway of the BCL-2 family, was also ameliorated by GSJD. Further, the podocyte foot process markers podocin and nephrin were upregulated by GSJD in DN rats. This study demonstrated that GSJD might play a renoprotective role by inhibiting apoptosis and regulating the mitochondrial apoptotic and Akt pathways during pathological changes in DN.

Related collections

Most cited references 57

Record: found
Abstract: found
Article: not found

Akt, FoxO and regulation of apoptosis.

Xinbo Zhang, Naimei Tang, Timothy J. Hadden … (2011)

Forkhead box O (FoxO) transcription factors are downstream targets of the serine/threonine protein kinase B (PKB)/Akt. The Akt kinase regulates processes of cellular proliferation and survival. Phosphorylation of FoxOs by Akt inhibits transcriptional functions of FoxOs and contributes to cell survival, growth and proliferation. Emerging evidence suggests involvement of FoxOs in diverse intracellular signaling pathways with critical roles in a number of physiological as well as pathological conditions including cancer. The FoxO signaling is regulated by their interactions with other intracellular proteins as well as their post-translational modifications such as phosphorylation. FoxOs promote cell growth inhibitory and/or apoptosis signaling by either inducing expression of multiple pro-apoptotic members of the Bcl2-family of mitochondria-targeting proteins, stimulating expression of death receptor ligands such as Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), or enhancing levels of various cyclin-dependent kinase inhibitors (CDKIs). Coupled with their ability to cross-talk with p53, FoxOs represent an important class of tumor suppressors in a variety of cancers. This review summarizes our current understanding of mechanisms by which Akt and FoxOs regulate cell growth and survival that in turn offers opportunities for development of novel strategies to combat cancer. This article is part of a Special Issue entitled: P13K-AKT-FOxO axis in cancer and aging. 2011 Elsevier B.V. All rights reserved.

0 comments Cited 373 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Diabetic kidney disease

Merlin Thomas, Michael Brownlee, Katalin Susztak … (2015)

The kidney is arguably the most important target of microvascular damage in diabetes. A substantial proportion of individuals with diabetes will develop kidney disease owing to their disease and/or other co-morbidity, including hypertension and ageing-related nephron loss. The presence and severity of chronic kidney disease (CKD) identify individuals who are at increased risk of adverse health outcomes and premature mortality. Consequently, preventing and managing CKD in patients with diabetes is now a key aim of their overall management. Intensive management of patients with diabetes includes controlling blood glucose levels and blood pressure as well as blockade of the renin-angiotensin-aldosterone system; these approaches will reduce the incidence of diabetic kidney disease and slow its progression. Indeed, the major decline in the incidence of diabetic kidney disease (DKD) over the past 30 years and improved patient prognosis are largely attributable to improved diabetes care. However, there remains an unmet need for innovative treatment strategies to prevent, arrest, treat and reverse DKD. In this Primer, we summarize what is now known about the molecular pathogenesis of CKD in patients with diabetes and the key pathways and targets implicated in its progression. In addition, we discuss the current evidence for the prevention and management of DKD as well as the many controversies. Finally, we explore the opportunities to develop new interventions through urgently needed investment in dedicated and focused research. For an illustrated summary of this Primer, visit: http://go.nature.com/NKHDzg.

0 comments Cited 342 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Regulation of mTORC1 by PI3K signaling.

Christian Dibble, Lewis Cantley (2015)

The class I phosphoinositide 3-kinase (PI3K)-mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signaling network directs cellular metabolism and growth. Activation of mTORC1 [composed of mTOR, regulatory-associated protein of mTOR (Raptor), mammalian lethal with SEC13 protein 8(mLST8), 40-kDa proline-rich Akt substrate (PRAS40), and DEP domain-containing mTOR-interacting protein (DEPTOR)] depends on the Ras-related GTPases (Rags) and Ras homolog enriched in brain (Rheb) GTPase and requires signals from amino acids, glucose, oxygen, energy (ATP), and growth factors (including cytokines and hormones such as insulin). Here we discuss the signal transduction mechanisms through which growth factor-responsive PI3K signaling activates mTORC1. We focus on how PI3K-dependent activation of Akt and spatial regulation of the tuberous sclerosis complex (TSC) complex (TSC complex) [composed of TSC1, TSC2, and Tre2-Bub2-Cdc16-1 domain family member 7 (TBC1D7)] switches on Rheb at the lysosome, where mTORC1 is activated. Integration of PI3K- and amino acid-dependent signals upstream of mTORC1 at the lysosome is detailed in a working model. A coherent understanding of the PI3K-mTORC1 network is imperative as its dysregulation has been implicated in diverse pathologies including cancer, diabetes, autism, and aging.

0 comments Cited 300 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Can Yan: yanc020@126.com

Dan Yan: pharmsci@126.com

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 6 February 2020

Publication date PMC-release: 6 February 2020

Publication date Collection: 2020

Volume: 10

Electronic Location Identifier: 2040

Affiliations

[1 ]ISNI 0000 0004 0369 153X, GRID grid.24696.3f, Beijing Shijitan Hospital, , Capital Medical University, ; Beijing, 100038 China

[2 ]Beijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use, Beijing, 100038 China

[3 ]ISNI 0000 0000 8848 7685, GRID grid.411866.c, Guangzhou University of Chinese Medicine, School of Basic Medical Sciences, ; Guangzhou, 510006 China

Article

Publisher ID: 58781

DOI: 10.1038/s41598-020-58781-2

PMC ID: 7005167

PubMed ID: 32029775

SO-VID: 8d25d9e6-7649-41a8-b6d0-c22a87ed8ce2

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 22 May 2019

Date accepted : 15 January 2020

Funding

Funded by: Beijing Hospitals Authority Youth Programme(QML 20170703),Youth Fund of Beijing Shijitan Hospital (2017-q14)

Funded by: FundRef https://doi.org/10.13039/501100004826, Natural Science Foundation of Beijing Municipality (Beijing Natural Science Foundation);

Award ID: 7194280

Award Recipient : Xinyu Yang

Funded by: FundRef https://doi.org/10.13039/501100009592, Beijing Municipal Science and Technology Commission;

Award ID: Z161100001816025

Award Recipient : Dan Yan

Funded by: the National Great New Drugs Development Project of China (2017ZX09301040)

Custom metadata

ScienceOpen disciplines: Uncategorized

Keywords: chronic kidney disease,kidney diseases

Data availability:

ScienceOpen disciplines: Uncategorized

Keywords: chronic kidney disease, kidney diseases

Comments

Comment on this article

scite_

Cited by 6

See all cited by

Most referenced authors 784

See all reference authors

Renoprotective effects of Gushen Jiedu capsule on diabetic nephropathy in rats

Read this article at

Abstract

Related collections

Karger: Nephrology

Most cited references 57

Akt, FoxO and regulation of apoptosis.

Diabetic kidney disease

Regulation of mTORC1 by PI3K signaling.

Author and article information

Contributors

Journal

Affiliations

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 301

Cited by 6

Most referenced authors 784