Protosappanin‐A and oleanolic acid protect injured podocytes from apoptosis through inhibition of AKT‐mTOR signaling

Abstract

Protosappanin‐A (PrA) and oleanolic acid (OA), which are important effective ingredients isolated from Caesalpinia sappan L., exhibit therapeutic potential in multiple diseases. This study focused on exploring the mechanisms of PrA and OA function in podocyte injury. An in vitro model of podocyte injury was induced by the sC5b‐9 complex and assays such as cell viability, apoptosis, immunofluorescence, quantitative real‐time polymerase chain reaction, and western blot were performed to further investigate the effects and mechanisms of PrA and OA in podocyte injury. The models of podocyte injury were verified to be successful as seen through significantly decreased levels of nephrin, podocin, and CD2AP and increased level of desmin. The sC5b‐9‐induced podocyte apoptosis was inhibited in injured podocytes treated with PrA and OA, accompanied by increased protein levels of nephrin, podocin, CD2AP, and Bcl2 and decreased levels of desmin and Bax. The p‐AKT/p‐mTOR levels were also reduced by treatment of PrA and OA while AKT/mTOR was unaltered. Further, the effects of PrA and OA on injured podocytes were similar to that of LY294002 (a PI3K‐AKT inhibitor). PrA and OA were also seen to inhibit podocyte apoptosis and p‐AKT/p‐mTOR levels induced by IGF‐1 (a PI3K‐AKT activator). Our data demonstrate that PrA and OA can protect podocytes from injury or apoptosis, which may occur through inhibition of the abnormal activation of AKT‐mTOR signaling.

Effects of Shenkang Pills on Early-Stage Diabetic Nephropathy in db/db Mice via Inhibiting AURKB/RacGAP1/RhoA Signaling Pathway

“…Ellagic acid prevented the advanced glycation end products-mediated loss of expression nephrin and podocin in diabetic rats (Raghu et al, 2016). Oleanolic acid combined with Protosappanin-A increased protein levels of nephrin, podocin, and CD2AP in sC5b-9-induced podocyte apoptosis (Zheng et al, 2019). Calcitriol treatment resulted in restoration of nephrin signalling in the STZ-diabetic animal model (Trohatou et al, 2017).…”

Protective Effects of Caesalpinia sappan Linn. and Its Bioactive Compounds on Cardiovascular Organs

“…The seeds of C. sappan are rich in diterpenoids, including caesalsappanin A−N, R and S ( Ma et al, 2015 ; Bao et al, 2016 ; Zhu et al, 2017 ; Wang et al, 2020 ); phanginin A−K and R‒T ( Yodsaoue et al, 2008 ; Bao et al, 2016 ); and ester glycosides, namely caesateroside A−C ( Wang et al, 2020 ). Oleanolic acid, a triterpenoid, has also been isolated from the plant ( Zheng et al, 2020 ). These diterpenoids exhibit antiplasmodial ( Zhu et al, 2017 ) and antitumor ( Bao et al, 2016 ; Wang et al, 2020 ) activity.…”

Oleanolic acid mitigates interleukin‐1β‐induced chondrocyte dysfunction by regulating miR‐148‐3p‐modulated FGF2 expression

“…Oleanolic acid (OLA) is a natural pentacyclic triterpenoid compound mainly extracted from Fructus Ligustri Lucidi (the fruit of Ligustrum lucidum ), which is an important Chinese herbal medicine for protecting against inflammation, osteoporosis and endocrine metabolic disorders . Numerous studies reveal that OLA has the ability to block stimuli‐induced cell apoptosis, including podocyte, lung epithelial cell and human umbilical vascular endothelial cells . Several studies suggest that OLA has a beneficial effect on injury‐induced metabolic disorders of articular cartilage .…”