RESUMO
BACKGROUND: Nephrotoxicity 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. METHODS: The 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. RESULTS: The 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. CONCLUSION: FBG and its major ginsenoside 20(S)-Rg3, ameliorated cisplatin-induced nephrotoxicity in LLC-PK1 cells by blocking the JNK-p53-caspase-3 signaling cascade.
RESUMO
A series of sulforaphane analogues were synthesized with various amines by treatment of carbon disulfide followed by Boc2O and DMAP. These synthesized sulforaphane analogues were tested on cisplatin treated cultured LLC-PK1 kidney cell line. Among these analogues, several compounds including SF5 show a potent effect on kidney cell protection assay at the concentration of 2.5 µM. Further studies with compound SF5 revealed that the kidney cell protection effect was related by inhibiting the apoptosis pathway through JNK-p53-caspase apoptotic cascade. Compound SF5 may be considered as a promising candidate for the development of new kidney protection agent against drug induced acute kidney disease.
Assuntos
Cisplatino/toxicidade , Isotiocianatos/síntese química , Rim/efeitos dos fármacos , Substâncias Protetoras/síntese química , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Cisplatino/antagonistas & inibidores , Relação Dose-Resposta a Droga , Isotiocianatos/farmacologia , Rim/fisiologia , Células LLC-PK1 , Substâncias Protetoras/farmacologia , Sulfóxidos , SuínosRESUMO
Ginsenoside Re is a triol type triterpene glycoside and is abundantly present in ginseng berry. In the present study, we verified that ginsenoside Re can be transformed into less-polar ginsenosides, namely, Rg2, Rg6, and F4, by heat-processing. The products of heat-processed ginsenoside Re inhibited phosphorylation of CDK2 at Thr160 by upregulation of p21 level, resulting in S phase arrest. The products of heat-processed ginsenoside Re also activated caspase-8, caspase-9, and caspase-3, followed by cleavage of PARP, a substrate of caspase-3, in a dose-dependent manner. Concurrently, alteration of mitochondrial factors such as Bcl-2 and Bax was also observed. Moreover, pretreatment with Z-VAD-fmk abrogated caspase-8, -9, and -3 activations by the products of heat-processed ginsenoside Re. We further confirmed that the anticancer effects of the products of heat-processed ginsenoside Re in AGS cells are mainly mediated via generation of less-polar ginsenosides Rg6 and F4.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Ginsenosídeos/farmacologia , Panax/química , Extratos Vegetais/farmacologia , Neoplasias Gástricas/genética , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Caspase 8/genética , Caspase 8/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Frutas/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/química , Temperatura Alta , Humanos , Extratos Vegetais/química , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
The structural change of ginsenoside and the generation of Maillard reaction products (MRPs) are important to the increase in the biological activities of Panax ginseng. This study was carried out to identify the renoprotective active component of P. ginseng using the Maillard reaction model experiment with ginsenoside Re and leucine. Ginsenoside Re was gradually converted into less-polar ginsenosides Rg2, Rg6 and F4 by heat-processing, followed by separation of the glucosyl moiety at carbon-20. The free radical-scavenging activity of the ginsenoside Re-leucine mixture was increased by heat-processing. The improved free radical-scavenging activity by heat-processing was mediated by the generation of MRPs from the reaction of glucose and leucine. The cisplatin-induced LLC-PK1 renal cell damage was also significantly reduced by treatment with MRPs. Moreover, the heat-processed glucose-leucine mixture (major MRPs from the ginsenoside Re-leucine mixture) showed protective effects against cisplatin-induced oxidative renal damage in rats through the inhibition of caspase-3 activation.
Assuntos
Ginsenosídeos/farmacologia , Rim/efeitos dos fármacos , Leucina/química , Panax/química , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ginsenosídeos/química , Temperatura Alta , Humanos , Rim/citologia , Rim/metabolismo , Reação de Maillard , Masculino , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Substâncias Protetoras/química , Ratos , Ratos WistarRESUMO
Reactive oxygen species play critical role in kidney damage. Free radical-scavenging activities of Panax ginseng are known to be increased by heat-processing. The structural change of ginsenoside and the generation of Maillard reaction products (MRPs) are closely related to the increased free radical-scavenging activities. In the present study, we have demonstrated the Maillard reaction model experiment using ginsenoside Re and glycine mixture to identify the renoprotective effect of MRPs from ginseng or ginsenosides. Ginsenoside Re was transformed into less-polar ginsenosides, namely Rg2, Rg6 and F4 by heat-processing. The free radical-scavenging activity of ginsenoside Re-glycine mixture was increased in a temperature-dependant manner by heatprocessing. The improved free radical-scavenging activity by heat-processing was mediated by the generation of antioxidant MRPs which led to the protection of LLC-PK1 renal epithelial cells from oxidative stress. Although the free radical scavenging activities of less-polar ginsenosides were weak, they could protect LLC-PK1 cells from oxidative stress. Therefore, MRPs and less-polar ginsenosides contributed to the combined renoprotective effects against oxidative renal damage.
RESUMO
This study has found that dimethyl cardamonin (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone; DMC), a naturally occurring chalcone, showed potent anti-inflammatory effects in vitro and in vivo. In a cellular model of inflammation, DMC inhibited production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) and attenuated expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-1 beta, inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). DMC prevented nuclear translocation of the nuclear factor-kappaB (NF-kappaB) p65 subunit by reducing inhibitor of kappaB alpha (I-kappaB alpha) phosphorylation and degradation, which resulted in a suppression of NF-kappaB activities for its target genes. In a mouse model of endotoxin shock, the intraperitoneal injection (i.p.) of DMC (1-50mg/kg) suppressed TNF-alpha, IL-6 and IL-1 beta secretion in LPS-induced mouse blood serum. These results suggest that DMC exerts anti-inflammatory effects through blocking NF-kappaB activation, therefore, DMC may act as an effective therapeutic strategy against a variety of inflammatory diseases.