Salidroside ameliorates Adriamycin nephropathy in mice by inhibiting β‐catenin activity

Abstract

Salidroside is a major phenylethanoid glycoside in Rhodiola rosea L., a traditional Chinese medicine, with multiple biological activities. It has been shown that salidroside possesses protective effects for alleviating diabetic renal dysfunction, contrast‐induced‐nephropathy and other kidney diseases. However, the involved molecular mechanism was still not understood well. Herein, we examined the protective effects of salidroside in mice with Adriamycin (ADR)‐induced nephropathy and the underlying molecular mechanism. The results showed that salidroside treatment ameliorates proteinuria; improves expressions of nephrin and podocin; and reduces kidney fibrosis and glomerulosclerosis induced by ADR. Mechanistically, ADR induces a robust accumulation of β‐catenin in the nucleus and stimulates its downstream target gene expression. The application of salidroside largely abolishes the nuclear translocation of β‐catenin and thus inhibits its activity. Furthermore, the activation of β‐catenin almost completely counteracts the protective roles of salidroside in ADR‐injured podocytes. Taken together, our data indicate that salidroside ameliorates proteinuria, renal fibrosis and podocyte injury in ADR nephropathy, which may rely on inhibition of β‐catenin signalling pathway.

Enhanced effects of salidroside on erectile function and corpora cavernosa autophagy in a cavernous nerve injury rat model

“…This also happens in the CC after CN damage (Kim et al., 2018; Rockey et al., 2015). In our study, we observed the anti‐corporal fibrosis effects of both salidroside and rapamycin on penile tissue, which is in line with the anti‐fibrosis effect on other organ tissues (Chen et al., 2019; Chung et al., 2016; Farrar et al., 2015; Huang et al., 2019).…”

Salidroside protects against diabetes mellitus‐induced kidney injury and renal fibrosis by attenuating TGF‐β1 and Wnt1/3a/β‐catenin signalling

“…This has been also shown previously in high glucose-treated cells and diabetic kidneys of rats. 25,39 Such an unexpected increase in Akt activation could be due to the parallel observed increase in TGF-β1 (described below). Indeed, TGFβ-1 is a potent stimulator of the PI3K/Akt axis.…”

“…21 Interestingly, and independent of its hypoglycaemic effect, Salidroside prevented renal damage and reduces kidney fibrosis and glomerulosclerosis in Adriamycintreated mice by suppressing β-catenin signalling. 25 Also, Salidroside protected renal tubular epithelial cells from hypoxia/ reoxygenation induced apoptosis suppression of ROS, inflammation, and intrinsic cell death. 26 However, the effect of Salidroside on β-catenin signalling pathways in diabetic kidneys is completely lacking.…”

Serum and Glucocorticoid-Inducible Kinase 3/Nedd4-2 Signaling Pathway Participates in Podocyte Injury by Regulating the Stability of Nephrin

“…To the best of our knowledge, this is the first study to have shown that ADR stimulation enhances nephrin ubiquitination, a key component of slit diaphragm membranes ( Oh et al, 2004 ; Qin et al, 2009 ; New et al, 2014 , 2016 ). Previous reports have shown that ADR regulates nephrin protein levels through nuclear transcription ( Yu et al, 2016 ; Huang et al, 2019 ; Wang et al, 2020 ). Meyer-Schwesinger et al (2009) observed that the levels of ubiquitin-modifying enzyme ubiquitin C-terminal hydrolase-L1 in podocytes was increased in the biopsies of patients with membranous nephropathy, focal segmental glomerulosclerosis, and lupus nephritis IV.…”