Beneficial effects of fermented black ginseng and its ginsenoside 20(S)-Rg3 against cisplatin-induced nephrotoxicity in LLC-PK1 cells

Abstract

BackgroundNephrotoxicity is a common side effect of medications. Panax ginseng is one of the best-known herbal medicines, and its individual constituents enhance renal function. Identification of its efficacy and mechanisms of action against drug-induced nephrotoxicity, as well as the specific constituents mediating this effect, have recently emerged as an interesting research area focusing on the kidney protective efficacy of P. ginseng.MethodsThe present study investigated the kidney protective effect of fermented black ginseng (FBG) and its active component ginsenoside 20(S)-Rg3 against cisplatin (chemotherapy drug)-induced damage in pig kidney (LLC-PK1) cells. It focused on assessing the role of mitogen-activated protein kinases as important mechanistic elements in kidney protection.ResultsThe reduced cell viability induced by cisplatin was significantly recovered with FBG extract and ginsenoside 20(S)-Rg3 dose-dependently. The cisplatin-induced elevated protein levels of phosphorylated c-Jun N-terminal kinase (JNK), p53, and cleaved caspase-3 were decreased after cotreatment with FBG extract or ginsenoside 20(S)-Rg3. The elevated percentage of apoptotic LLC-PK1 cells induced by cisplatin treatment was significantly abrogated by cotreatment with FBG and the ginsenoside 20(S)-Rg3.ConclusionFBG and its major ginsenoside 20(S)-Rg3, ameliorated cisplatin-induced nephrotoxicity in LLC-PK1 cells by blocking the JNK–p53–caspase-3 signaling cascade.

Natural remedies for non‐steroidal anti‐inflammatory drug‐induced toxicity

“…The impaired renal function was observed by increases in the total protein level and renal enzyme markers. Panax ginseng extract was analyzed to restore the level of alteration caused by cisplatin (Han et al, 2016). Nordihydroguaiaretic acid is a natural product, which was known to have potential activity against inflammation, cancer and oxidation activity, and was reported to treat cisplatin-administered renal toxicity in rats (Mundhe et al, 2015).…”

20(S)-Ginsenoside Rg3 Protects Kidney from Diabetic Kidney Disease via Renal Inflammation Depression in Diabetic Rats

“…Moreover, 20(S)-Rg3 is more suitable for application in clinical medicine, such as a novel inhibitor of autophagy [15] or protecting INS-1 cell death from intermittent high glucose [16]. It also has been confirmed that 20(S)-Rg3 is a compound that has many pharmacological effects such as anticancer [17], inhibition of brain injury [18], and diabetic kidney injury resistance [19]. Thus, 20(S)-Rg3 therapy has now become a nontraditional therapy for diabetes and its complications treatment.…”

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

“…There are many reports about the differences in bioactivity of the isomers of a single compound, for example, G-Rg3, -Rh2, -Rk1, and -Rg5 are isomeric compounds. However, previous studies report their nephroprotective effect as a mixture of the two isomers or only the S form of those compounds [22,35,40]. In this study, we investigated the kidney cell protective effect of the isomers of these compounds.…”

“…Many types of processed Korean ginseng were previously reported to protect kidney cells from cisplatin toxicity. White ginseng could be steamed at 120 • C for 3 h or fermented with a microorganism, such as Saccharomyces cerevisiae, to obtain the less polar saponins [31,35]. In our study, the kidney cell protective effect increased gradually with the increase of time and reached a maximum at 12 h. Most of the less polar saponins possessing the kidney cell protective effect are protopanaxadiol-type saponins, including G-Rg3, -Rk1, -Rg5, -Rh2, and -Rh3 [22,[35][36][37].…”

“…White ginseng could be steamed at 120 • C for 3 h or fermented with a microorganism, such as Saccharomyces cerevisiae, to obtain the less polar saponins [31,35]. In our study, the kidney cell protective effect increased gradually with the increase of time and reached a maximum at 12 h. Most of the less polar saponins possessing the kidney cell protective effect are protopanaxadiol-type saponins, including G-Rg3, -Rk1, -Rg5, -Rh2, and -Rh3 [22,[35][36][37]. Only a few studies of the kidney protective effect of protopanaxatriol-type saponins (G-Rk3 and -Rh4) and ocotillol-type saponins (pseudoginsenoside F11) have been reported [30,31].…”