Protective effect and possible mechanisms of Salvia miltiorrhiza Bge. for the treatment of diabetic nephropathy: A systematic review and meta-analysis of animal studies

Abstract

To explore the protective effect and potential mechanisms of danshen root ( Salvia miltiorrhiza Bge., S . miltiorrhiza ) and its extracts for the treatment of diabetic nephropathy (DN). Preclinical studies of S . miltiorrhiza and its extracts on DN were systematically searched in nine databases. The primary outcomes were blood glucose, kidney function, proteinuria, and renal histopathology. The secondary outcomes included the related mechanisms. The methodological quality of animal studies was assessed based on the risk of bias tool of the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) for animal studies. Meta-analysis was performed using R software (version 4.1.2). Twenty-nine animal experimental studies that met the eligibility criteria were included in this study. Compared to the control group, S . miltiorrhiza reduced the serum creatinine, blood urea nitrogen, 24-h urine protein, 24-h urine albumin, blood glucose, and kidney index (kidney weight/body weight), and alleviated renal pathological damage. In terms of the mechanism of action, compared to the control group, S . miltiorrhiza reduced the levels of transforming growth factor β1, collagen IV, malondialdehyde, tumor necrosis factor α, interleukin-6, and monocyte/macrophage (ED-1), and increased the levels of superoxide dismutase, glutathione peroxidase, nuclear factor E2–related factor 2, and heme oxygenase-1. The existing evidence shows that S . miltiorrhiza has beneficial effects on the animal model of DN, and its mechanism is mainly related to improving kidney fibrosis, oxidative stress, and inflammatory response.