Manshenkang granules alleviate fibrosis in chronic renal failure rats by regulating the PDE4b/cAMP pathway

Abstract

Ethnopharmacological relevance

Manshenkang granules (MSKG) is a traditional Chinese medicinal formula used to treat chronic renal failure, comprising Rheum tanguticum Maxim. ex Balf., Salvia miltiorrhiza Bunge, Citrus × aurantium L., Codonopsis pilosula (Franch.) Nannf., Polygonatum cyrtonema Hua, Smilax glabra Roxb., Ostrea rivularis Gould, and Glycyrrhiza uralensis Fisch. However, their efficacies and mechanisms of action require further investigation.

Aim of the study

This study explored the role and underlying mechanisms of MSKG in alleviating adenine-induced renal fibrosis in chronic renal failure rats.

Materials and methods

Serum and urine indicators were assessed. Alpha smooth muscle actin (α-SMA), phosphodiesterase 4b (PDE4b), and exchange protein directly activated by cyclic adenosine monophosphate (cAMP) 1 (Epac1) protein expression levels were determined by western blotting. Molecular docking and dynamics simulations were performed to evaluate the binding of the main components of MSKG to PDE4b.

Results

Compared with the model group, the serum levels of creatinine, urea nitrogen, K⁺, P³⁺ and Ca²⁺ in rats treated with MSKG were significantly reduced, and the urine levels of creatinine, urea nitrogen, K⁺ and P³⁺ were significantly increased. The creatinine clearance rate in the MSKG group was significantly higher than that in the model group. MSKG increases mean blood flow and decreases the resistance index in chronic renal failure rats. MSKG increases cAMP and Epac1 levels and decreases PDE4b expression in renal tissues. The components of MSKG have a high binding affinity for PDE4b.

Discussion and conclusion

MSKG effectively alleviated renal fibrosis in rats with adenine-induced chronic renal failure, and its mechanism may be related to regulation of the PDE4b/cAMP/Epac1 pathway.