Effect of ginsenoside Rh2 on renal apoptosis in cisplatin-induced nephrotoxicity in vivo

Zeng, Qi; Li, Wei; Tan, Jing; Wang, Cuizhu; Lin, Hongqiang; Zhou, Baisong; Liu, Jinping; Li, Pingya

doi:10.1016/j.phymed.2019.152862

Cited by 48 publications

(40 citation statements)

References 24 publications

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“…VG shares similar chemical constituents with PG regarding protopanaxadiol-and protopanaxatrioltype saponins. Therefore, from VG, some PPD-type less polar ginsenosides, such as G-Rg3, -Rk1, -Rg5, and -Rh2, displayed kidney cell protective effects, which is consistent with previous reports [22,37]. Especially, G-Rh2, a rare PPD-type saponin, exhibited the ability to recover cisplatin-induced kidney cell loss at a surprisingly low dose.…”

Section: Discussionsupporting

confidence: 89%

“…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].…”

Section: Discussionmentioning

confidence: 61%

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

Vu-Huynh

Nguyen

et al. 2019

Molecules

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Cisplatin is a platinum-based anticancer agent used for treating a wide range of solid cancers. One of the side effects of this drug is its severe nephrotoxicity, limiting the safe dose of cisplatin. Therefore, many natural products have been studied and applied to attenuate the toxicity of this compound. In this study, we found that steamed Vietnamese ginseng (Panax vietnamensis) could significantly reduce the kidney damage of cisplatin in an in vitro model using porcine proximal tubular LLC-PK1 kidney cells. From processed ginseng under optimized conditions (120 °C, 12 h), we isolated seven compounds (20(R,S)-ginsenoside Rh2, 20(R,S)-ginsenoside Rg3, ginsenoside Rk1, ginsenoside-Rg5, and ocotillol genin) that showed kidney-protective potential against cisplatin toxicity. By comparing the 50% recovery concentration (RC50), the R form of ginsenoside, Rh2 and Rg3, had RC50 values of 6.67 ± 0.42 µM and 8.39 ± 0.3 µM, respectively, while the S forms of ginsenoside, Rh2 and Rg3, and Rk1, had weaker protective effects, with RC50 ranging from 46.15 to 88.4 µM. G-Rg5 and ocotillol, the typical saponin of Vietnamese ginseng, had the highest RC50 (180.83 ± 33.27; 226.19 ± 66.16, respectively). Our results suggest that processed Vietnamese gingseng (PVG), as well as those compounds, has the potential to improve kidney damage due to cisplatin toxicity.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 61%

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

Vu-Huynh

Nguyen

et al. 2019

Molecules

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“…Reactive oxygen species (ROS) have been associated with cisplatin-induced nephrotoxicity, as ROS can induce massive production of the inflammatory cytokine tumor necrosis factor (TNF-α). Release of TNF-α induces other inflammatory cytokines and leads to inflammatory responses [6,7]. These inflammatory mediators and oxidative stress can cause damage to renal tubular cells and kidney tissue.…”

Section: Introductionmentioning

confidence: 99%

Cordyceps cicadae Mycelia Ameliorate Cisplatin-Induced Acute Kidney Injury by Suppressing the TLR4/NF-κB/MAPK and Activating the HO-1/Nrf2 and Sirt-1/AMPK Pathways in Mice

Deng

Jiang

Chen

et al. 2020

Oxidative Medicine and Cellular Longevity

100

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Acute kidney injury (AKI) is a common clinical problem, characterized by a sudden loss of renal function, a high risk of death, and the eventual development of renal fibrosis and renal failure. Cordyceps cicadae is a traditional Chinese medicine with the potential function of kidney protection. We analyze two sputum extracts, a water extract (WCC), and an ethanol extract (ECC), to assess the potential of treating AKI in an animal model of kidney injury induced by cisplatin. A nephrotoxic mouse model was first established by intraperitoneal injection of cisplatin. Subsequently, WCC and ECC were orally administered in these mice. The results show that WCC and ECC significantly alleviated cisplatin-induced AKI renal histological changes, serum creatinine (CRE) and blood urea nitrogen (BUN) production, and the levels of NO, TNF-α, IL-1β, and IL-6. The levels of malondialdehyde (MDA) and glutathione (GSH) were suppressed by administration of WCC and ECC. However, WCC treatment prevented these changes significantly better than ECC treatment. In addition, Western blot data showed that WCC attenuated the cisplatin-induced protein expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS), as well as inhibiting nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation in the kidney tissues. Furthermore, WCC greatly inhibited the expression of Toll-like receptor 4 (TLR4) and cisplatin-induced NF-κB activation, as well as dramatically increasing the production of antioxidative enzymes (i.e., superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1)), silent information regulator T1 (Sirt1), and p-AMP-activated protein kinase (AMPK) in the kidney tissues. In addition, we found that WCC increased the expression levels of the autophagy-related proteins LC3B and Beclin-1; proapoptotic proteins, including cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) 1; and organic anion transporters 1 (OAT1) and 3 (OAT3) in the kidney tissues. Finally, WCC, ECC, and two bioactive compounds—adenosine and N6-(2-hydroxyethyl) adenosine (HEA)—inhibited the production of nitrite oxide (NO) and intracellular reactive oxygen species (ROS) triggered by lipopolysaccharide- (LPS-) stimulated RAW264.7 macrophages in vitro. Collectively, WCC could provide a potential therapeutic candidate for the prevention of cisplatin-induced kidney injury through the inhibition of oxidative stress and inflammation.

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“…Several studies have demonstrated that ginsenosides can attenuate the cisplatin-induced upregulation of phosphorylation of JNK, P38, and the expression levels of cleaved caspase-3 in proximal tubule cells. Ginsenosides Rb1 [7], Rh2 [8], Rh3 [14], and Rg3 [15,36] provide protection in cisplatin-induced tubular cell damage by suppressing the activation of caspase-3 that activates the extrinsic and intrinsic apoptotic pathways. In addition, ginsenosides Rh3 [14] and Rg3 [15] attenuate cisplatin-induced tubular cell damage by inhibiting phosphorylation of JNK and P38.…”

Section: Discussionmentioning

confidence: 99%

“…In human embryonic kidney epithelial cells (HEK293) and mice, ginsenoside Rb3 reduced renal damage via the regulation of autophagy and inhibition of proximal tubular apoptosis [7]. Reportedly, ginsenosides Rh2, Re, and Rg5 prevent oxidative stress, inflammation, and apoptosis in cisplatin-induced renal damage in mice [8][9][10]. Furthermore, treatment with ginsenosides Rk3, Rh4, and Rd reduced cytotoxicity in the porcine renal proximal tubular cell line LLC-PK1 and improved the renal histology in cisplatin-induced acute kidney injury in rats [11][12][13].…”

mentioning

confidence: 99%

Protective Effect of Panaxynol Isolated from Panax vietnamensis against Cisplatin-Induced Renal Damage: In Vitro and In Vivo Studies

Lee

Vu-Huynh

et al. 2019

Biomolecules

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Polyacetylenic compounds isolated from Panax species are comprised of non-polar C17 compounds, exhibiting anti-inflammatory, antitumor, and antifungal activities. Panaxynol represents the major component of the essential oils of ginseng. We investigated whether panaxynol isolated from Panax vietnamensis (Vietnamese ginseng, VG) could prevent cisplatin-induced renal damage induced in vitro and in vivo. Cisplatin-induced apoptotic cell death was observed by staining with annexin V conjugated with Alexa Fluor 488, and western blotting evaluated the molecular mechanism. Panaxynol at concentrations above 0.25 μM prevented cisplatin-induced LLC-PK1 porcine renal proximal tubular cell death. LLC-PK1 cells treated with cisplatin demonstrated an increase in apoptotic cell death, whereas pretreatment with 2 and 4 μM panaxynol decreased this effect. Cisplatin demonstrated a marked increase in the phosphorylation of c-Jun N-terminal kinase (JNK), P38, and cleaved caspase-3. However, pretreatment with 2 and 4 μM panaxynol reversed the upregulated phosphorylation of JNK, P38, and the expression of cleaved caspase-3. We confirmed that the protective effect of panaxynol isolated from P. vietnamensis in LLC-PK1 cells was at least partially mediated by reducing the cisplatin-induced apoptotic damage. In the animal study, panaxynol treatment ameliorated body weight loss and blood renal function markers and downregulated the mRNA expression of inflammatory mediators.

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Effect of ginsenoside Rh2 on renal apoptosis in cisplatin-induced nephrotoxicity in vivo

Cited by 48 publications

References 24 publications

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

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

Cordyceps cicadae Mycelia Ameliorate Cisplatin-Induced Acute Kidney Injury by Suppressing the TLR4/NF-κB/MAPK and Activating the HO-1/Nrf2 and Sirt-1/AMPK Pathways in Mice

Protective Effect of Panaxynol Isolated from Panax vietnamensis against Cisplatin-Induced Renal Damage: In Vitro and In Vivo Studies

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