Preventive Effects of a Natural Anti-Inflammatory Agent, Astragaloside IV, on Ischemic Acute Kidney Injury in Rats

Abstract

This study investigated the anti-inflammatory effects of astragaloside IV(AS-IV) on ischemia/reperfusion (IR) induced acute kidney injury (AKI) in rats. Experimental model of ischemic AKI was induced in rats by bilateral renal artery clamp for 45 min followed by reperfusion of 12 h and 24 h, respectively. AS-IV was orally administered once a day to rats at 10 and 20 mg·kg−1·d−1 for 7 days prior to ischemia. AS-IV pretreatment significantly decreased serum urea, creatinine, and cystatin C levels at 12 h and 24 h of reperfusion in AKI rats. AS-IV pretreatment also ameliorated tubular damage and suppressed the phosphorylation of p65 subunit of NF-κB in AKI rats. Moreover, NF-κB and MPO activity as well as serum and tissue levels of TNF-α, MCP-1, and ICAM-1 were elevated in AKI rats. All of these abnormalities were prevented by AS-IV. Furthermore, AS-IV downregulated the mRNA expression of NF-κB, TNF-α, MCP-1, and ICAM-1 in AKI rats. These results suggest that AS-IV might be developed as a novel therapeutic approach to prevent ischemic AKI through inhibition of NF-κB mediated inflammatory genes expression.

Anti-Fibrotic Effects of Astragaloside IV in Systemic Sclerosis

“…Interestingly, Astragaloside IV, one of the most active compounds isolated from a Chinese medical herb [30], could decrease the expression of collagen and fibronectin in a dose- and time-dependent manner. Further, this drug displayed a strong anti-fibrosis effect in vivo , consistent with previous studies [10,11,15,16].…”

Astragaloside IV Alleviates Lipopolysaccharide-Induced Acute Kidney Injury Through Down-Regulating Cytokines, CCR5 and p-ERK, and Elevating Anti-Oxidative Ability

“…In rat models of ischemia and reperfusion, AS-IV prevented ischemia-induced AKI through inhibiting nuclear factor-kappa B (NF-κB)-mediated expression of inflammatory genes and upregulating p53-upregulated modulator of apoptosis (PUMA) [14,15]. Studies also found that AS-IV protected against ischemia-induced AKI by inhibiting oxidative stress and apoptosis pathways [16].…”

Administration of hydrogen sulfide protects ischemia reperfusion-induced acute kidney injury by reducing the oxidative stress

“…Renal ischemia reperfusion injury (IRI) is well known as a main cause of AKI [2] that may occur because of an abrupt decrease of renal blood flow, low flow state, diverse surgical procedures, or during the organ transplantation [3]. IRI can be an early outcome of a transplanted organ that may lead to acute rejection of graft and has adverse effects on long term graft survival [4,5].…”

“…Renal IRI induces renal dysfunction characterized by increasing levels of creatinine (Cr) and blood urea nitrogen (BUN) [6]. The search for a treatment to recover IRI is ongoing, but unfortunately, innovative interventions beyond supportive therapy are not currently available for IRI [3,4].…”