Arginyl-fructosyl-glucose, a Major Maillard Reaction Product of Red Ginseng, Attenuates Cisplatin-Induced Acute Kidney Injury by Regulating Nuclear Factor κB and Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Pathways

Abstract

Recently, although ginseng (Panax ginseng C. A. Meyer) and its main component saponins (ginsenosides) have been reported to exert protective effects on cisplatin (CDDP)-induced acute kidney injury (AKI), the beneficial activities of non-saponin on CDDP-induced AKI is little known. This research was designed to explore the protective effect and underlying mechanism of arginyl-fructosyl-glucose (AFG), a major and representative non-saponin component generated during the process of red ginseng, on CDDP-caused AKI. AFG at doses of 40 and 80 mg/kg remarkably reversed CDDP-induced renal dysfunction, accompanied by the decreased levels of serum creatinine and blood urea nitrogen. Interestingly, all of oxidative stress indices were ameliorated after pretreatment with AFG continuously for 10 days. Importantly, AFG relieved CDDP-induced inflammation and apoptosis in part by mitigating the cascade initiation steps of nuclear factor κB signals and regulating the participation of the phosphatidylinositol 3-kinase/protein kinase B signal pathway. In conclusion, these results clearly provide strong rationale for the development of AFG to prevent CDDP-induced AKI.

Protective effect of ginsenoside Rk1, a major rare saponin from black ginseng, on cisplatin‐induced nephrotoxicity in HEK‐293 cells

“…Apoptosis is a major cause of cisplatin‐induced nephrotoxicity 36 . To elucidate the nephroprotective mechanism of Rk1 on cisplatin‐induced nephrotoxicity, we investigated the expressions of various apoptosis related proteins in HEK‐293 cells.…”

Antidiabetic Effects of Arginyl‐Fructosyl‐Glucose, a Nonsaponin Fraction from Ginseng Processing in Streptozotocin‐Induced Type 2 Diabetic Mice through Regulating the PI3K/AKT/GSK‐3β and Bcl‐2/Bax Signaling Pathways

“…AFG was synthesized in the laboratory using the method of Li et al [ 22 ], and the purity was 95.0% by the HPLC method. Commercial assay kits for aspartate transaminase (AST) and alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC), malondialdehyde (MDA), glutathione disulfide (GSSG), superoxide dismutase (SOD), reduced glutathione (GSH) assay kit, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), protein extraction kits, and Hematoxylin-eosinstaining (HE staining) were got from Nanjing Jiancheng Bioengineering Co., Ltd (Nanjing, China).…”

“…Arginyl-fructosyl-glucose (AFG, Figure 1(a) ) is an important nonsaponin active substance belonging to arginine derivatives [ 17 – 19 ], with good antioxidant activity [ 20 ], anti-inflammatory effects [ 21 ], etc. At the same time, research indicates that AFG has a strong protective effect on kidney injury [ 22 ]. Furthermore, it was reported to have hypoglycemic activity [ 23 ], but only the level of carbohydrate metabolizing enzymes in the serum has been initially studied, while the mechanism of its antihyperglycemia is still unclear.…”

Increase in Protective Effect of Panax vietnamensis by Heat Processing on Cisplatin-Induced Kidney Cell Toxicity

“…Processing Panax ginseng at high temperatures and pressure generates not only less polar ginsenosides, such as G-Rk3, -Rh4, -Rg3, -Rg5, and -Rk1, but also non-ginsenoside compounds, such as the Maillard reaction product. These mentioned components can significantly reduce porcine proximal tubular kidney LLC-PK1 (Lilly Laboratories Cell-Porcine Kidney 1) cell damage by cisplatin through the regulation of inflammatory and apoptotic procedures [22,23].Vietnamese ginseng (Panax vietnamensis Ha et Grushv., Araliaceae, VG) was first discovered in Ngọc Linh mountain, Quang Nam province, Vietnam in 1978 and since then has been considered the most southern and most recently found Panax species, with high commercial value on the herbal market. Chemical constituents of VG have been reported, with at least 52 saponins, including protopanaxadiol and protopanaxatriol-type saponins, such as G-Rb1, -Rd, -Rg1, and -Re, similar to Panax ginseng.…”

“…Processing Panax ginseng at high temperatures and pressure generates not only less polar ginsenosides, such as G-Rk3, -Rh4, -Rg3, -Rg5, and -Rk1, but also non-ginsenoside compounds, such as the Maillard reaction product. These mentioned components can significantly reduce porcine proximal tubular kidney LLC-PK1 (Lilly Laboratories Cell-Porcine Kidney 1) cell damage by cisplatin through the regulation of inflammatory and apoptotic procedures [22,23].…”