Eleutheroside B‐loaded poly (lactic‐co‐glycolic acid) nanoparticles protect against renal fibrosis via Smad3‐dependent mechanism

Abstract

Although renal fibrosis is a common complication of chronic kidney disease (CKD), effective options for its treatment are currently limited. In this study, we evaluated the renal protective effect and possible mechanism of eleutheroside B. In order to solve the allergic reactions, side effects, and low oral bioavailability of eleutheroside B, we successfully prepared PLGA (poly [lactic-co-glycolic acid])eleutheroside B nanoparticles (NPs) with the diameter of about 128 nm. In vitro and in vivo results showed that eleutheroside B could inhibit expression levels of α-smooth muscle actin (α-SMA) and collagen I. Molecular docking results showed that eleutheroside B bound to Smad3 and significantly decreased the expression of phospho-Smad3 (p-Smad3). Silencing Smad3 reversed the fibrotic protective effect of eleutheroside B in HK2 cells. Furthermore, small animal imaging showed that NPs can selectively accumulate in the UUO kidneys of mice, and retention time reached as long as 7 days. In conclusion, our results suggested that eleutheroside B is a potential drug to protect renal fibrosis and PLGA-eleutheroside B NPs could facilitate specific targeted therapy for renal fibrosis.

The Effect of Aspalathin on SMAD2, SMAD3, TGF-β - A Major Contributor of Inflammation – An In-silico Approach

“…Eleutheroside B was shown to bind to Smad3 molecular docking studies, resulting in a significant decrease in phosphorylated Smad3 (p-Smad3) expression. Eleutheroside B's fibrotic protective effect in HK2 cells was undone by silencing Smad3 [24].…”

Nanoparticles in the diagnosis and treatment of vascular aging and related diseases

“…Researchers have employed PLGA nanoparticles for eleutheroside B delivery and enhanced eleutheroside B bioavailability, with small animal imaging revealing that eleutheroside B-PLGA nanoparticles can selectively accumulate in mice kidneys for up to 7 days. 437 …”

Renal tissue engineering for regenerative medicine using polymers and hydrogels

“…The authors, however, concluded that the membrane replacement did not contribute to adversity for patients undergoing haemodialysis. 71,72 In other reported studies, further fabrication of cellulose into cellulose triacetate 73 or cellulose diacetate 74 reduced platelet activation, making it closer to the commercial dialyser membrane properties in terms of biocompatibility for a more feasible product.…”

“…It is widely used as a drug vehicle for its tailorable erosion capability, 70 which includes research to treat kidney fibrosis. 71,72…”

“…It is widely used as a drug vehicle for its tailorable erosion capability, 70 which includes research to treat kidney fibrosis. 71,72 An assessment of PLGA as a polymer scaffold for kidney tissue engineering was done by Basu et al, who compared it with PCL. 57 A week after injection of neat PLGA particles into the medulla and cortex of the kidney of living Lewis rats, no necrosis, embolism, or infarction was observed; however, there was chronic inflammation and formation of granulomatous cells (giant cells) around PLGA at the medulla.…”