Salidroside Attenuates Adriamycin-Induced Focal Segmental Glomerulosclerosis by Inhibiting the Hypoxia-Inducible Factor-1α Expression Through Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway

Abstract

Background: Focal segmental glomerulosclerosis (FSGS) is a common histologic pattern of kidney injury, which may eventually lead to end-stage renal disease. Objectives: Salidroside (SAL, p-hydroxyphenyl-β-D-glucoside) is an active component isolated from Rhodiolarosea, which has various pharmacological properties including anti-inflammation and antioxidation. SAL may attenuate FSGS, but the underlying mechanism is not clear. Thus, in this study, we focus on the renoprotective role of SAL in FSGS using Adriamycin nephropathy (AN) mouse models. Methods: In C57 BL/6 mice, AN was induced by Adriamycin (10 mg/kg body weight, diluted in normal saline) via a tail vein on day 0. Then they were organized into 6 groups for the animal experiments: AN + saline group; AN + SAL group (40 mg/kg); AN + LY294002 (a selective phosphatidylinositol 3-kinase [PI3K] inhibitors, 50 mg/kg) group; AN + SAL + LY294002 group; AN + YC-1 (a selective hypoxia-inducible factor-1α [HIF-1α] inhibitors, 50 mg/kg) group; and AN + SAL + YC-1 group. All of the drugs were given on the day of Adriamycin injection and continued for 6 weeks, and the drugs were given by intraperitoneally. At 6 weeks, the mice were sacrificed; kidneys and blood samples were collected for further analysis. Results: In FSGS mouse models, SAL treatment could ameliorate proteinuria, renal function, and markers of Nephrotic Syndrome inhibit alpha-smooth muscle actin and fibronectin expression and downregulates the expression of HIF-1α. Besides, the levels of PI3K and p-protein kinase B (Akt) in renal tissues were significantly decreased after SAL injection. Eventually, SAL treatment results reduced inflammatory cytokines and reactive oxygen species production. Conclusions: In summary, SAL ameliorates FSGS mainly by inhibiting the expression of HIF-1α through PI3K/Akt pathway, which might offer an array of hope for ameliorating FSGS.

Salidroside Suppresses IL-1β-Induced Apoptosis in Chondrocytes via Phosphatidylinositol 3-Kinases (PI3K)/Akt Signaling Inhibition

“…In the present study, we been found that cells treated with IL-1b had significantly increased levels of p-PI3K and p-AKT. Previous studies have reported that Salidroside has a negative effect on PI3K/AKT activation [12]. Our data are consistent with previous studies reporting that Salidroside blocks the IL-1 b-induced PI3K/AKT activation.…”

“…Salidroside, the major constituent of a Chinese medicinal herb, Rhodiola rosea L, has been reported to suppress apoptosis in many diseases [11]. Its anti-inflammation effect works on Adriamycin-induced focal segmental glomerulosclerosis through suppressing the PI3K/AKT pathway [12]. Considering its various beneficial effects, Salidroside is thought to protect chondrocytes.…”

Salidroside inhibits platelet function and thrombus formation through AKT/GSK3β signaling pathway

“…As anucleated cells, platelets also express AKT which involves in regulating platelet function, such as platelet aggregation, activation, granule secretion as well as integrin signaling [42,43]. Through inhibition of PI3K/AKT signaling pathway, salidroside have been shown to repress proliferation, migration and invasion of human lung cancer cells [29], induce autophagy in human colorectal cancer cells [28] suppress LPSinduced myocardial injury [44] as well as attenuate Adriamycin-induced focal segmental glomerulosclerosis [45]. Consistent with these, in our present study, we demonstrated that salidroside treatment significantly reduced the phosphorylation of AKT (Thr308/Ser473) AGING after stimulation with thrombin in both human and mouse platelets, indicating that salidroside exerts antiplatelet activities possibly through inhibition of AKT signaling.…”

Argon inhibits reactive oxygen species oxidative stress via the miR-21-mediated PDCD4/PTEN pathway to prevent myocardial ischemia/reperfusion injury

“…Previous studies have shown that MI/R injury is closely related to oxygen-free radical accumulation and mitochondrial dynamics disorder, affecting myocardial cell proliferation and apoptosis [ 13 , 14 ]. MiR-21 can repair MI/R injury by affecting reactive oxygen species (ROS)-mediated oxidative stress [ 15 , 16 ]. Programmed cell death protein 4 (PDCD4) is an important tumor suppressor that plays a vital role in cellular oxidative stress.…”