Protective Effects And Molecular Mechanisms Of Ginseng Fruit Anthocyanin On Drug-induced Liver And Kidney Injury In Mice

Ginseng[Panax ginseng Meyer]is a famous traditional Chinese herbal medicine,and it is a precious traditional Chinese herbal medicine in our country.The fruits of P.ginseng contain many chemicals that have significant pharmacological activities.These chemicals include ginseng saponin?ginsenoside?,flavonoids,polysaccharides,alkaloids and volatile oil.Anthocyanin is a type of water-soluble natural constituent that shows a variety of pharmacological effects such as antioxidant,antibacterial,anti-inflammatory,anti-ageing and anticancer effects and can protect cardiovascular,cerebrovascular and vision systems from damage.Although the liver and kidney protective activity of ginsenosides is frequently reported,it is not clear whether the GFA have the protective effect on liver and kidney injury.In this experiment,the effect of anti-oxidation,inhibition of nitrification stress,reduction of inflammatory reaction and inhibition of apoptosis of GFA prove that GFA has protective effect on kidney and liver injury and provide theoretical reference in the clinical application.In recent years,with the intake of chemicals such as medicines,health products and various food additives,unreasonable intake has threatened the health of the body.“It is a drug that kills three points,”and the drug can also cause damage to the organs while treating the disease.In particular,the incidence of liver and kidney damage increases year by year.Acetaminophen?APAP?,is known as paracetamol,is widely used clinically for analgesia and antipyretics.APAP is safe in the treatment range,but excessive intake can lead to acute liver injury.To investigate the protective effect of Ginseng fruit anthocyanin?GFA?against APAP-induced liver damage in mice and its possible mechanism,we established the model of APAP induced liver injury,and observe the GFA protection for liver damage.32 male ICR mice were randomly divided into normal group,APAP group,GFA with 200 mg·kg^-1 dose group,and GFA with 400 mg·kg^-1 group.Colorimetric method was used to assay the contents of serum Alanine Aminotransferase?ALT?and Aspartate Aminotransferase?AST?,activity of Glutathione?GSH?and Malondialdehyde?MDA?content of liver homogenate in mice,and observe liver tissue pathological section.GFA obviously reduced the level of ALT in serum,inhibited the level of MDA,and enhanced activity of GSH in liver tissue.The H&E and Hoechst 33258 staining results indicate that GFA can obviously improve the degree of liver tissue necrosis and apoptosis,narrowed the scope of necrosis,relieved the inflammatory cell infiltration.By inflammatory factor of iNOS,COX-2immunohistochemical staining and nitrification stress index of 3-NT immunofluorescence,GFA can inhibit nitration stress and the expression of inflammatory cytokines.GFA has certain protective effect on APAP-induced acute liver injury and its mechanism may relate to antioxidant effect,inhibition of nitrification stress,alleviation inflammation reaction and inhibiting apoptosis.Cisplatin?cis-diamminedchloroplatinum,CDDP?isaneffectiveanticancer chemotherapeutic agent,but the use of cisplatin in the clinic is severely limited by side effects.Nephrotoxicity is a major factor that contributes to the side effects of cisplatin chemotherapy.The aim of this research was to survey the nephroprotective effects of anthocyanin from the fruits of Panax ginseng?GFA?in a murine model of cisplatin-induced acute kidney injury.We observed that pretreatment with GFA attenuated cisplatin-induced elevations in blood urea nitrogen?BUN?and creatinine?Cre?levels and histopathological injury induced by cisplatin.The formation of kidney malondialdehyde?MDA?,heme oxygenase-1?HO-1?,cytochrome P450 E1?CYP2E1?and4-hydroxynonenal?4-HNE?with a concomitant reduction in reduced glutathione was also inhibited by GFA,while the activities of kidney superoxide dismutase?SOD?and catalase?CAT?were all increased.GFA also inhibited the increase in serum tumour necrosis factor-??TNF-??and interleukin-1??IL-1??induced by cisplatin.In addition,the levels of induced nitric oxide synthase?iNOS?and cyclooxygenase-2?COX-2?were suppressed by GFA.Furthermore,GFA supplementation inhibited the activation of apoptotic pathways by increasing Bcl-2 and decreasing Bax protein expression levels.In conclusion,the findings from the present investigation demonstrates that GFA pre-administration can significantly prevent cisplatin-induced nephrotoxicity,which may be related to its antioxidant,anti-apoptotic and anti-inflammatory effects.In summary,our results suggest that GFA exerts an obvious protective effect against liver damage induced by APAP and kidney damage induced by cisplatin.The protective effects of GFA were demonstrated by the inhibition of oxidative stress,inflammation and apoptosis accompanied by an improvement in the regulation of oxidative balance,anti-inflammatory effects and anti-apoptosis effects.