Salvianolic acid A attenuates kidney injury and inflammation by inhibiting NF-κB and p38 MAPK signaling pathways in 5/6 nephrectomized rats

Abstract

Salvianolic acid A (SAA) is a minor phenolic carboxylic acid extracted from Salviae miltiorrhizae Bunge (Danshen). SAA exhibits a variety of pharmacological activities, such as antioxidative, anti-thrombotic, neuroprotective, and anti-fibrotic effects, as well as protection from myocardial ischemia and prevention of diabetes and other diseases. Furthermore, SAA has shown renal-protective effects in doxorubicin-induced nephropathy. However, there has been limited research regarding the effects of SAA and underlying mechanisms in chronic kidney disease (CKD). Here, we examined the effects and molecular mechanisms of SAA in an established animal model of 5/6 nephrectomized (5/6Nx) rats. The rats were injected with SAA (2.5, 5, and 10 mg/kg per day, intraperitoneally (ip)) for 28 days. SAA dose-dependently lowered the levels of urine protein, blood urea nitrogen, serum creatinine, plasma total cholesterol, and plasma triglycerides in 5/6Nx rats. Histological examination revealed that SAA dose-dependently attenuated renal pathological lesions, evidenced by reduced renal tubulointerstitial fibrosis by decreasing the expression levels of tumor growth factor-β1 and α-smooth muscle actin in 5/6Nx rats. Moreover, SAA dose-dependently inhibited the activation of nuclear factor-κB (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signaling pathways, subsequently attenuating the secretion of tumor necrosis factor-α and interleukin-1β and inhibiting the expression of monocyte chemotactic protein-1, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in kidneys of 5/6Nx rats. The above results were consistent with those obtained in lipopolysaccharide-induced HK-2 cells in vitro (a recognized in vitro inflammatory model). In conclusion, our results demonstrated that SAA effectively attenuates kidney injury in 5/6Nx rats. The therapeutic effects of SAA on kidney injury can be attributed to its anti-inflammatory activities through inhibition of the activation of the NF-κB and p38 MAPK signaling pathways.

Oridonin Attenuates Lipopolysaccharide‐Induced ROS Accumulation and Inflammation in HK‐2 Cells

“…Similar protective effects were reported for berberine against chronic renal failure mediated via tumor necrosis factor receptor associated factor 5-(TRAF5-) induced activation of the NF-κB signaling pathway in mouse podocytes [30]. Consistent with the results of the previous studies [28,31], we proposed that traditional Chinese medicine regularly used in clinical patients may provide protective effects against kidney injury.…”

“…Similar patterns of JNK activation are evident in animal models of acute and chronic renal injury [26]. NF-κB nuclear translocation is an indicator of chronic inflammation and ROS accumulation during the progression and development of CKD [27,28]. erefore, the inhibition of inflammation and oxidative stress may serve as a good strategy for the treatment of CKD.…”

Deciphering the Pharmacological Mechanisms of Taohe-Chengqi Decoction Extract Against Renal Fibrosis Through Integrating Network Pharmacology and Experimental Validation In Vitro and In Vivo

“…Salvia miltiorrhiza Bunge, Astragalus mongholicus Bunge, and Rheum palmatum L.) and active components (e.g. tanshinone, salvianolic acid, and emodin) reportedly possess antirenal fibrosis effect (Wang et al, 2015;Ma et al, 2017;Zhang et al, 2018). Unlike the one drug-one target concept of Western medicine, TCM emphasizes that the human body is an organic whole.…”

Danhong injection in cardiovascular and cerebrovascular diseases: Pharmacological actions, molecular mechanisms, and therapeutic potential

“…Salviae Miltiorrhizae has many pharmacological activities, such as anti-oxidation, suppressing platelet adhesion and aggregation, improving microcirculation, improving hemorheology, and regulating blood lipids [16][17][18]. The main bioactive ingredients of Salviae Miltiorrhizae injection include several water-soluble bioactive compounds (Danshensu, salvianolic acids, protocatechuic aldehyde, rosmarinic acid, and caffeic acid) [16,[19][20][21][22][23]. Salviae Miltiorrhizae injection also contains trace amount of lipophilic compounds, such as tanshinone II A and cryptotanshinone.…”

“…Salviae Miltiorrhizae injection also contains trace amount of lipophilic compounds, such as tanshinone II A and cryptotanshinone. The cardiovascular actions of Danshensu, and salvianolic acids have been intensively investigated in the past decade, which supports the clinical utility of these compounds against platelet aggregation and thrombus formation, promoting fibrin degradation, protecting against myocardial ischemia, and improving the microcirculation [16,[19][20][21][22][23]. Protocatechuic aldehyde is another hydrophilic component of DHI.…”