Ginsenoside Rg5 Ameliorates Cisplatin-Induced Nephrotoxicity in Mice through Inhibition of Inflammation, Oxidative Stress, and Apoptosis

Abstract

Although cisplatin is an effective anti-cancer agent that is widely used for treating various types of malignant solid tumors, the nephrotoxicity induced by cisplatin severely limits its clinical application. The present study was designed to explore the potential protective effect of ginsenoside Rg5, a rare ginsenoside generated during steaming ginseng, on cisplatin-induced nephrotoxicity in a mouse experimental model. The possible mechanisms underlying this nephroprotective effect were also investigated for the first time. Rg5 was given at doses of 10 and 20 mg/kg for 10 consecutive days. On Day 7, a single nephrotoxic dose of cisplatin (25 mg/kg) was injected to mice. Cisplatin administration resulted in renal dysfunction as evidenced by increase in serum creatinine (CRE) and blood urea nitrogen (BUN) levels. In addition, cisplatin increased the level of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), the makers of lipid peroxidation, and depleted glutathione (GSH) content and superoxide dismutase (SOD) activity in renal tissues. These effects were associated with the significantly increased levels of cytochrome P450 E1 (CYP2E1), 4-hydroxynonenal (4-HNE), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, nuclear factor-kappa B (NF-κB) p65, and cyclooxygenase-2 (COX-2) in renal tissues. However, pretreatment with ginsenoside Rg5 significantly attenuated the renal dysfunction, oxidative stress and inflammation response induced by cisplatin. Furthermore, ginsenoside Rg5 supplementation inhibited activation of apoptotic pathways through increasing Bcl-2 and decreasing Bax expression levels. Histopathological examination further confirmed the nephroprotective effect of Rg5. Collectively, these results clearly suggest that Rg5-mediated alleviation of cisplatin-induced nephrotoxicity may be related to its anti-oxidant, anti-apoptotic and anti-inflammatory effects.

Supplementation of American ginseng berry extract mitigated cisplatin-evoked nephrotoxicity by suppressing ROS-mediated activation of MAPK and NF-κB signaling pathways

“…In addition, it is important to develop new prophylactic strategies for preventing and treating cisplatin-induced nephrotoxicity, and to determine their mechanisms of action. Though the same experimental methods and thinking were applied with previous reports in our laboratory (Ma et al, 2017) (Li et al, 2016) , the broader molecular mechanisms and deeper signaling pathways were presented in our study. As a non-traditional medicinal part of P. quinquefolium, the extracts from its berries are relative with no difficulty and cost less.…”

Ethnic Differences in Susceptibility to the Effects of Platinum- Based Chemotherapy

“…GSTA4 plays an important role for the detoxification of 4-hydroxynonenal [53], a toxic product of lipid peroxidation, increasing immensely under oxidative stress conditions (e.g., overproduction of ROS), including cisplatin treatment [54,55]. The role of epoxide hydrolases (EPXHs) in cisplatin-induced toxicity appears to be also related to the effects of oxidative stress.…”

Ginsenoside-Rg5 Inhibits Retinoblastoma Proliferation and Induces Apoptosis through Suppressing BCL2 Expression

“…Furthermore, the cell cycle of human hepatoma SK-HEP-1 cells can be blocked by ginsenoside-Rg5 via decreasing cyclin E-dependent kinase activity [17]. In addition, ginsenoside-Rg5 ameliorates cisplatin-induced nephrotoxicity [18]. However, it remains elusive whether ginsenoside-Rg5 has an anti-retinoblastoma activity.…”