Protective Effect of Ginsenoside Rb1 against Intestinal Ischemia-Reperfusion Induced Acute Renal Injury in Mice

Abstract

Ginsenoside Rb1 (RB1), the most clinically effective constituent of ginseng, possesses a variety of biological activities. The objectives of this study were to investigate the protective effects of RB1 and its underlying mechanism on renal injury induced by intestinal ischemia-reperfusion (IIR) in mice. RB1 was administered prior to inducing IIR achieved by occluding the superior mesenteric artery for 45 min followed by 120 min of reperfusion. All-trans-retinoic acid (ATRA) was used as an inhibitor of NF-E2-related factor-2 (Nrf2) signaling. Adult male C57BL/6J mice were randomly divided into six groups: (1) sham group, (2) IIR group, (3) RB1 group, (4) sham + ATRA group, (5) IIR + ATRA group, and (6) RB1 + ATRA group. Intestinal histology and pathological injury score were observed. Intestinal mucosal injury was also evaluated by measuring serum diamine oxidase (DAO). Renal injury induced by IIR was characterized by increased levels of histological severity score, blood urea nitrogen (BUN), serum creatinine (Scr) and neutrophil gelatinase-associated lipocalin (NGAL), which was accompanied with elevated renal TUNEL-positive cells and the Bcl-2/Bax expression ratio. RB1 significantly reduced renal injury and apoptosis as compared with IIR group, which was reversed by ATRA treatment. Immunohistochemistry and Western blot analysis demonstrated that RB1 significantly upregulated the protein expression of heme oxygenase-1 (HO-1) and Nrf2, which were attenuated by ATRA treatment. Taken together, these results suggest that the protective effects of RB1 pretreatment against renal injury induced by IIR are associated with activation of the Nrf2/ anti-oxidant response element (ARE) pathway.

Cellular stress response mechanisms as therapeutic targets of ginsenosides

“…Upon activation, Nrf2 is relieved from Keap1-directed degradation, followed by nuclear translocation and subsequent binding to the antioxidant responsive element (ARE), eventually leading to the activation of a series of antioxidant and phase II enzymes. 107,108 To date, several ginsenosides, including Rb1, [109][110][111][112][113][114][115][116] Rg3, 95,[117][118][119][120] Rg1, 115,121,122 Rd, 123 Rh1, 124 and 20(S)protopanaxatriol, 115 were found to activate the Nrf2 pathway, whereas Rg3 was also shown to inhibit the Nrf2 pathway 125 (Fig. 4).…”

“…To date, several ginsenosides, including Rb1, Rg3, Rg1, Rd, Rh1, and 20( S )‐protopanaxatriol, were found to activate the Nrf2 pathway, whereas Rg3 was also shown to inhibit the Nrf2 pathway (Fig. ).…”

Ginsenoside Rb1 ameliorates CKD‐associated vascular calcification by inhibiting the Wnt/β‐catenin pathway

“…Ginsenosides are major components of the traditional herbal medicine ginseng, and ginsenosides can be classified into panaxadiols (PPD) and panaxatriols (PPT) by chemical structure. Rb1, the most abundant constituent of panaxadiol, has recently been reported to exert protective properties in vascular diseases and kidney diseases . A clinical study indicated that Rb1 alleviated creatine and inflammatory cytokine levels in CKD patients .…”

“…Rb1, the most abundant constituent of panaxadiol, has recently been reported to exert protective properties in vascular diseases and kidney diseases. [14][15][16][17] A clinical study indicated that Rb1 alleviated creatine and inflammatory cytokine levels in CKD patients. 18 Furthermore, it has been reported that Rb1 reduced type I collagen expression through PPAR-δ, which is considered an osteogenic profile marker of VSMC.…”

Protective effects of curcumin on acute gentamicin-induced nephrotoxicity in rats

“…Nrf2-mediated HO-1 induction contributes to antioxidant capacity has been demonstrated by multiple disease models, including cardiomyopathy in type 2 diabetic mice (Zhang et al 2014b), rat model of transient global cerebral ischaemia (Lee et al 2014), and endotoxic shock-induced acute lung injury in rabbits (Yu et al 2014). Recently, Nrf2/HO-1 activation also shows protective effect in aristolochic acid-induced acute kidney injury (Wu et al 2014a) and intestinal ischemia-reperfusion induced acute renal injury (Sun et al 2013). …”