Effects of natural compounds in treatment and prevention ofhepatotoxicity and hepatocellular carcinoma

Liver diseases are most common disorders in the world and characterized by rapid changes from steatosis to chronic hepatitis,fi brosis,cirrhosis,and hepatocellular carcinoma(HCC).Natural products that attained great attention is to be used in the prevention and treatment of multiple diseases in humans.Several researches have been reported numerous natural and phytochemical compounds that may counteract or prevent the hepatic injury and primary liver cancer.The conservative treatment of liver toxicity and HCC may face awkward challenges in chemotherapy such as therapeutic failure or drug resistance.Accordingly,there is an actual need for safe and effective therapeutic and preventive modalities for liver disorders.The present review aims to focus on the potential protective and therapeutic effects of natural compounds in the prevention and treatment of hepatotoxicity and HCC.It also demonstrates the mechanism of the natural products in enzymatic regulation of antioxidants and its role in apoptosis and proliferation of cancerous lesions of hepatocytes.Accordingly,it highlights the promising role of natural bioactive compounds and provides the rational for further transitional researches,and emphasize on the scientifi c validation of natural compounds for therapeutic portfolio for clinical use in liver diseases.

Protective effects of Amaranthus hybridus against aflatoxin B1 and fumonisin B1-induced genotoxicity in H4IIE-luc cells

Aim:Protective effects of aqueous extract of Amaranthus hybridus against afl atoxin B1(AFB_(1))and/or fumonisin B1(FB_(1))on the H4IIE-luc cell line were determined by use of the methyl thiazol tetrazolium viability assay and disruption of DNA integrity.Methods:H4IIE-luc cells were incubated with different concentrations of AFB_(1) and/or FB_(1) for 24 and 48 h with or without aqueous extract of A.hybridus.Results:AFB_(1) decreased the viability of cells after 24 and 48 h of exposure.EC_(50)values for AFB_(1) were 10.5 and 1.8μmol/L for the two periods,respectively.When the 48 h exposure to mycotoxin repeated with a pre-treatment of 20 and 40μg/mL extract of A.hybridus,the EC_(50)changed to 3.88 and 7.67μmol/L,respectively.H4IIE-luc cells exposed to FB_(1) for 24 h responded more than those incubated for 48 h.Cells treated with a combination of AFB_(1) and FB_(1) were less viable with a signifi cant decrease in the greater concentration.The mixture of AFB_(1) and FB_(1) resulted in a signifi cant threat to H4IIE-luc as indicated by the absence or appearance of new bands in random amplifi ed polymorphic DNA analysis,which demonstrated damage to DNA.The protective effects were probably due to greater content of total phenolics,carotenoids,β-carotene,folic-,linolenic-,linoleic and palmitic acids,as well as calcium,magnesium,iron,zinc,and selenium observed in the extract.Conclusion:Exposure to 40μg/mL of extract of A.hybridus protected cells from damage to DNA by stabilizing DNA.

Dietary incorporation of jojoba extract eliminates oxidative damage in livers of rats fed fumonisin-contaminated diet

Aim:This study aimed to determine the composition of ethanol extract of jojoba seeds,and to evaluate its hepatoprotective effects in rats fed fumonisin B1(FB1)-contaminated diet.Methods:Jojoba seeds were extracted in 95%ethanol,and the chemical composition was determined.Male rats were divided into six groups and treated for 8 weeks as follows:(1)Untreated control;(2)FB1-contaminated diet(80 mg/kg diet);(3)low dose(0.5 mg/kg b.w.)jojoba extract;(4)high dose(1.0 mg/kg b.w.)jojoba extract;(5)low dose jojoba extract plus FB1;and(6)high dose jojoba extract plus FB1.Blood and liver samples were collected for different biochemical analyses and histological examinations.Results:The results indicated that the ethanolic extract of jojoba is rich in protein,phenolic compounds,phytic acid,and considerable amounts of simmondsin.Animals fed FB1-contaminated diet showed severe biochemical and histological changes typical to those reported in literature.Treatment with jojoba seed extract alone at the two tested doses did not induce significant alterations in all parameters tested.Combined treatment of jojoba seed extract with FB1 eliminated hepatotoxicity induced by FB1,especially at low dose of jojoba seed extract.Conclusion:The authors concluded that jojoba seed extract can be incorporated in FB1-contaminated feed to eliminate FB1-induced hepatotoxicity.

Aqueous extract of Corchorus olitorius decreases cytotoxicityof aflatoxin B1 and fumonisin B1 in H4IIE-luc cells

Aim:Afl atoxin B1(AFB1)and fumonisin B1(FB1)are important food-borne mycotoxins.Co-contamination of foodstuffs with these two mycotoxins is well-known and has been implicated in a possible development of hepatocellular carcinoma in humans living in regions of the world where exposures to these mycotoxins in grain are greatest.The aim of the current study was to evaluate the potential protective effects of an aqueous extract of Cochorus olitorius(C.olitorius,moroheiya)against cytotoxicity of AFB1 and/or FB1 in H4IIE-luc rat hepatoma cells,using assays to measure cell viability and disruption of DNA integrity.Although this transactivation assay was originally developed to specifi cally respond to aryl hydrocarbon agonists,this cell line was used because of its hepatic origin.Methods:H4IIE-luc cells were incubated with different concentrations of AFB1 and/or FB1 for 24 and 48 h with or without aqueous extract of C.olitorius.Results:Both mycotoxins decreased cell viability and increased DNA damage.Cytotoxicity was more pronounced when cells were exposed simultaneously to AFB1 and FB1.Conclusion:Aqueous extract of C.olitorius protected cells against cytotoxicity of mycotoxins.C.olitorius contains a water-soluble,natural chemo-preventative agent for cancer that should be isolated and identifi ed.

Natural products and hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a major health problem,with more than 500,000 cases diagnosed annually.It is also an important cause of human mortality in the world.The incidence of HCC is rising due to the widespread of hepatitis and alcoholism,which may be caused by infection,injury,exposure to drugs or toxic compounds,autoimmunity,or genetic defect that leads to the deposition of harmful substances.