Sanqi Oral Solution Ameliorates Renal Ischemia/Reperfusion Injury via Reducing Apoptosis and Enhancing Autophagy: Involvement of ERK/mTOR Pathways

Abstract

Ischemia-reperfusion (I/R) induced acute kidney injury (AKI) is a significant health problem with high morbidity and mortality, yet prophylaxis strategies and effective drugs are limited. Sanqi oral solution (SQ) is a formulated medicine widely used in clinical settings to treat various renal diseases via enriching qi and activating blood circulation while its role on I/R-AKI remains unclear. Herein, by establishing rat I/R-AKI models, we intended to investigate the effect of SQ on the prevention of I/R-AKI and explore its underlying mechanisms. We demonstrated that SQ treatment significantly attenuated renal dysfunction of I/R-AKI, alleviated histological damages, inhibited renal apoptosis, and enhanced autophagy. Further investigation proved that SQ could significantly inhibit the activation of ERK and mTOR signaling pathways. Moreover, its renoprotective effect can be abolished by autophagy inhibitor 3-methyladenine (3-MA). Collectively, our results suggest that SQ exerts renoprotective effects on renal I/R injury via reducing apoptosis and enhancing autophagy, which are associated with regulating ERK/mTOR pathways.

Renal-Protective Effects and Potential Mechanisms of Traditional Chinese Medicine after Ischemia-Reperfusion Injury

“…Most TCMs were reported to alleviate renal histological changes and decrease renal tubular injury score, caused by I/R injury. Furthermore, TCMs, such as Sanqi oral solution, hydroxysafflor yellow A, and total glucosides of paeony, showed dose-dependent effects, such that higher concentrations showed greater alleviating effects [ 4 , 7 , 23 ]. In contrast, ATG played a detrimental role in renal I/R injury since renal function and histology worsened with increasing concentration [ 3 ].…”

“…Treatment with Sanqi (SQ) oral solution showed decrease in apoptosis and increase in autophagy [ 7 ]. Lower Bax and caspase-3 levels and higher Bcl-2 level were observed in the SQ treatment group in a dose-dependent manner, demonstrating the antiapoptotic activity of SQ.…”

“…Several signaling pathways were considered to be involved in the renoprotective effects of TCMs, especially the anti-inflammation effect, antioxidative effect, antiapoptotic activity, and some others. These pathways included the NF- κ B/TLR4, NF- κ B-p65, NF- κ B-p MAPK, Nrf2-NLRP3, Nrf2-HO-1, Shh signaling pathway, PI3K-Akt [ 30 ], ERK/mTOR [ 7 ], Akt/mTOR/4EBP1 [ 21 ], OMA1-OPA1 [ 18 ], XIST/MicroRNA-124-3p/ITGB1 [ 23 ], etc. The most important pathways involved in renal I/R injury are discussed below.…”

“…Increase in blood urea nitrogen (BUN) and creatinine (Cr) [ 3 ] and a higher urinary total protein level are reported to occur after renal I/R injury [ 6 ]. Histopathology of renal I/R injury shows luminal narrowing, intraluminal necrotic cellular debris, tubular basal membrane rupture, tubular vacuolization, interstitial congestion, apparent cell swelling and nuclear infiltration in the H&E staining of renal tissues [ 7 ], and higher Kim-1 expression, thus causing a higher renal tubular injury score [ 2 ].…”

“…In the theory of TCM, renal I/R injury is attributed to Qi and blood deficiency and blood stasis syndrome [ 8 ]. From the perspective of TCM, renal I/R injury should be treated through the replenishment of Qi and activation of blood circulation [ 7 ]. Several TCMs have been applied for the prevention and treatment of renal I/R, and they show different renal-protective effects in Table 1 , including anti-inflammation ( Cordyceps sinensis , cordycepin, Yisheng injection, cryptotanshinone, Panax notoginseng , total glucosides of paeony, hydroxysafflor yellow A, farnesiferol B, anemoside B4, etc.…”