Objective: To observe the efficacy of Danggui Buxue decoction (, DBD) on diabetic nephropathy-induced renal fibrosis in rats, and to study the possible mechanism.
Methods: Sixty male Goto Kakizaki (GK) rats were randomly assigned to the model group, gliquidone group, astragaloside IV group, and high-, medium- and low-doses DBD groups. After 8 weeks, changes in body weight, blood glucose, serum creatinine, serum urea nitrogen, and total cholesterol were observed. Changes in transforming growth factor-β1 (TGF-β1), Smad3, and Smad5 pathways and the expression of the fibrosis-related proteins collagen IV (col IV), α-smooth muscle actin (α-SMA), and vimentin were assessed. The degree of renal fibrosis was observed by immunohistochemistry and Mason staining. The expression of interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor (TNF-α), and C-reactive protein (CRP) in the kidneys was assessed using enzyme linked immunosorbent assay.
Results: Our experiments showed that DBD effectively reduced blood glucose, blood urea nitrogen, and creatinine levels after 8 weeks of administration, improved renal function in diabetic rats, alleviated renal fibrosis, and reduced the renal tissue levels of IL-6, IL-10, TNF-α, and CRP. Furthermore, DBD decreased the expression of TGF-β1, Smad3, col IV, α-SMA, and vimentin in renal tissues and increased the expression of Smad5.
Conclusions: DBD ameliorates diabetic renal interstitial fibrosis by modulating the TGF-β1/Smads pathway.
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http://dx.doi.org/10.19852/j.cnki.jtcm.20230214.004 | DOI Listing |
Endocr Metab Immune Disord Drug Targets
January 2025
Department of Internal Medicine, Division of Nephrology and Hypertension, Faculty of Medicine, Dr. Cipto Mangunkusumo Hospital, Universitas Indonesia, Jakarta, Indonesia.
Chronic kidney disease (CKD) is a major complication of type 2 diabetes mellitus (T2D), which often leads to diabetic kidney disease (DKD). Traditional therapies, including renin- angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter-2 inhibitors, are effective in slowing CKD progression. However, these approaches are insufficient to comprehensively inhibit mineralocorticoid receptor (MR) overactivation in the kidneys, which remains a significant driver of inflammation, fibrosis, and oxidative stress.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Basic Medical Sciences, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310058, China.
Background: The partial epithelial-mesenchymal transition (EMT) is emerging as a significant mechanism in diabetic nephropathy (DN). LOX is a copper amine oxidase conventionally thought to act by crosslinking collagen. However, the role of LOX in partial EMT and fibrotic progression in diabetic nephropathy has not been investigated experimentally.
View Article and Find Full Text PDFZhong Nan Da Xue Xue Bao Yi Xue Ban
August 2024
Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008.
Renal fibrosis is the common pathological basis for the progressive development of chronic kidney disease (CKD) caused by various etiologies. It is characterized by the persistent deposition of extracellular matrix, leading to renal tissue damage and impaired renal function, and ultimately progressing to kidney failure. Current clinical treatments for CKD mainly focus on managing the primary diseases, with no specific drugs targeting renal fibrosis.
View Article and Find Full Text PDFZhong Nan Da Xue Xue Bao Yi Xue Ban
July 2024
Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha 410013, China.
IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder that can affect multiple organs throughout the body, predominantly in middle-aged and elderly males, with a male-to-female ratio of 2꞉1 to 3꞉1. IgG4-related retroperitoneal fibrosis (IgG4-RPF), a rare subtype of IgG4-RD, has an unclear etiology, and its comorbidity with type 2 diabetes mellitus is also uncommon. A lack of awareness of this condition in clinical practice can easily lead to misdiagnosis.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
January 2025
Department of Pediatric Nephrology and Rheumatism and Immunology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; Department of Pediatric Nephrology and Rheumatism and Immunology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, China. Electronic address:
Renal interstitial fibrosis is the main factor determining chronic kidney disease (CKD) progression, and renal tubular epithelial cells are the key drivers of this pathological process. Herein, we revealed significantly increased ubiquitin-specific peptidase 10 (USP10) expression in the kidney tissues of both patients with CKD and mice induced by unilateral ureteral obstruction, as well as in transforming growth factor-beta 1 (TGFβ1)-induced renal tubular epithelial cells. In vivo, treatment with the USP10 small molecule inhibitor Spautin-1, which inhibits its deubiquitinating activity, weakened renal interstitial fibrosis progression and alleviated the subsequent inflammatory response and oxidative stress in male mice.
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