Xiaoke Decoction Inhibits COX-2-Mediated LDLr Pathway Dysfunction and Protects Renal Function in Diabetic Nephropathy Rats

Abstract

Objective

Traditional Chinese medicine exhibits positive therapeutic effects as a primary or adjunctive treatment for diabetic nephropathy (DN). This study aimed to evaluate the impact and mechanism of action of Xiaoke decoction (XKD), a traditional Chinese medicine, on renal function in DN rats.

Methods

A rat model of DN was established, and the rats were divided into five groups (n = 7 per group): normal control group (NC), DN model group (DN), low-dose XKD treatment group (DN + XKD-L, 1.5 g/kg/d), high-dose XKD treatment group (DN + XKD-H, 6 g/kg/d), and cyclooxygenase-2 (COX-2) inhibitor (NS398) treatment group (DN + NS398, 8 mg/kg/d). Medications were administered via gavage for 12 consecutive weeks, while equal volumes of normal saline were given to the NC and DN groups. A glucometer was used to detect changes in blood glucose (BG). Enzyme-linked immunosorbent assay (ELISA) and an automatic biochemical analyzer were employed to measure levels of insulin, serum creatinine (Scr), blood urea nitrogen (BUN), triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and 24-h urine protein quantity (UP/24 h) in rats. Renal tissue sections from different treatment groups were prepared, with tissue lesions examined via periodic acid-Schiff (PAS) and hematoxylin–eosin (HE) staining. Tissue inflammation and lipid deposition were evaluated using ELISA and Oil Red O staining. Immunohistochemistry and Western blotting were used to detect changes in the expression levels of COX-2 and low-density lipoprotein receptor (LDLr) in tissues, and to clarify the regulatory mechanism of XKD on renal function in DN rats.

Results

XKD, particularly at the high dose (XKD-H, 6 g/kg/d), significantly reduced BG, insulin levels, renal weight ratio, Scr, BUN, and UP/24 h in DN rats. DN rats showed significant renal lesions, and XKD gavage (especially XKD-H) markedly improved these pathological changes. In DN rats, XKD significantly decreased the protein expression levels of COX-2 and LDLr, downregulated the levels of inflammatory factors and lipid factors, reduced lipid deposition in renal tissues, and ameliorated structural abnormalities in glomeruli, basement membranes, and renal tubules.

Conclusions

XKD alleviates renal tissue damage by regulating the COX-2-mediated LDLr pathway, thereby reducing the release of inflammatory factors and lipid accumulation in DN rats and protecting renal function.

Graphical Abstract

XKD improves renal function in streptozotocin (STZ)-induced DN rats by regulating the COX-2-mediated LDLr pathway, reducing inflammatory factors and lipid deposition, and alleviating renal tissue damage.

Keywords

Xiaoke decoction / Cyclooxygenase-2 / Low-density lipoprotein receptor / Diabetic nephropathy / Renal function

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Funding

Budget project of Shanghai University of Traditional Chinese Medicine(18LK058)

RIGHTS & PERMISSIONS

The Author(s), under exclusive licence to the Huazhong University of Science and Technology