| Platycodon grandif1orum(Jacq.)A.DC(PG)is a typical traditional Chinese medicine with a homology of medicine and food.Due to Shennong's Herbal Classic of Materia Medica,PG is flat in nature,bitter and pungent in taste,and belongs to lung channel.PG exerts abundant effects including expectorant antitussive,anti-inflammatory analgesic,cardiovascular protection,liver protection,anti-obesity,anti-tumor,antioxidant and cosmetic.PG contains abundant chemical components including saponins,polysaccharides and flavonoids.Saponins from PG(PGS)are the most important active andl characteristic components.Recent studies have shown that PGS have rich pharmacological activities,such as anti-inflammatory,antioxidant,immunomodulatory and anti-tumor,which is of great significance for enhancing cellular immunity and improving the generation of specific antibodies,and also have strong anti-inflammatory effects on acute and chronic inflammation models.Platycodon D(PD)is a characteristic component with high content as the object of quality control and it has rich pharmacological activities.In this paper,a model of nephrotoxicity induced by CDDP was established to investigate and discuss the protective effects and potential mechanism of the effect of PGS and PD in vivo and vitro.This investigation provides scientific theoretical basis for clinical application of PG and better assists treatment of diseases in clinic.First,the renal protective effect and its mechanism of PGS were studied by establishing an model of acute nephrotoxicity induced by cisplatin in mice.PGS was preadministrated by gavage for 10 days and intraperitoneal injection of CDDP(25 mg/kg)at 1h on day 7 resulted in acute nephrotoxicity.The experimental results showed that the renal index,blood urea nitrogen(BUN)and blood creatinine(CRE)levels were significantly increased in the CDDP model group.The histopathological observation indicated that a large number of inflammatory infiltration and necrosis by H&E staining.These results were remarkly alleviated in the PGS group.Immunohistochemical staining and western blot analysis demonstrated that the PGS group could effectively suppress the expressions of Bcl-2 and Caspase family and other proteins related to apoptosis after CDDP administration.Meanwhile,TUNEL staining results demonstrated that PGS can significantly inhibit CDDP induced renal cell death.In addition,PGS obviously improved the excessive expressions of inflammatory markers caused by CDDP,such as the tumor necrosis factor(TNF-?),interleukins(IL-1?),inducible nitric oxide synthase(iNOS)cyclooxygenase-2(COX-2),and nuclear factor(NF-?B)pathway related proteins and it showed that PGS can significantly mitigate the inflammatory response in mice.Finally,the results showed that PGS remarkly reversed the decreased PI3K/Akt pathway by western blot analysis.Secondly,the renal protective effect of PD and its potential mechanism were studied by establishing an model of renal toxicity induced by cisplatin in human embryonic kidney cells(HEK-293).The experimental results showed that the final administration and modeling time and concentrations were determined through the time-dependent and concentration-dependent experiments.It was found that MDA was increased and GSH was decreased significantly after CDDP,and cells treated with PD were greatly improved in cell homogenates after treatment.Meanwhile,ROS fluorescence staining further proved that PD could remarkly extenuate oxidative stress evoked by CDDP.Levels of inflammatory cytokines including TNF-? and IL-1? in cells were detected by ELISA,and NF-?B pathway related proteins were detected by western blot analysis,indicating that PD can remarkly suppress CDDP-induced inflammatory response.In addition,the apoptosis-related proteins,such as Bcl-2 and Caspase family were evaluated via western blot analysis,CDDP treatment significantly elevated pro-apoptotic proteins,reduced anti-apoptotic proteins.These results were reversed by PD,indicating that PD effectively inhibited CDDP-induced apoptosis.Finally,the upstream target of PI3K/Akt was selected and treated with the PI3 K inhibitor LY294002,indicating that the PI3K/Akt pathway was involved in PD antagonistic effect of CDDP-induced nephrotoxicity.In conclusion,PD inhibited CDDP-induced oxidative stress,inflammatory response and apoptosis by regulating NF-?B and PI3K/Akt signaling pathways.To sum up,the results of this study has shown that PGS and PD can obviously alleviate the acute renal toxicity induced by CDDP by inhibiting oxidative stress,inflammation,apoptosis activity.Its potential mechanisms may be that the PGS and PD were involved in the regulation of PI3K/Akt signaling pathway and its mediated the NF-?B signaling pathway. |
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