Berberis integerrima hydro-alcoholic root extract and its constituent berberine protect against cisplatin-induced nephro- and hepato-toxicity.

BACKGROUND: This study determined the potential hepato- and renal protective role of berberine and hydroalcohol extract of Berberis integerrima (barberry) against cisplatin-induced acute liver and kidney injury. METHODS: Animals were dedicated into six groups (n = 7 per group): control, control+Ber (berberine, 0.4 mg/kg/day during 10 days, i.p.), control+B.E (barberry extract, 160 mg/kg/day during 10 days, i.p.), Cis (cisplatin, 8 mg/kg on 7th day, i.p.), Cis+Ber (berberine, 100 mg/kg/day during 10 days; cisplatin, 8 mg/kg on 7th day), Cis+B.E (barberry extract, 160 mg/kg/day during 10 days; cisplatin, 8 mg/kg on 7th day). After placing the rats in metabolic cages for 24 h, blood, urine, liver and kidney tissue samples were collected. RESULTS: Compared to control, control+Ber and control+B.E groups, cisplatin administration led to kidney and liver dysfunction. These happened with diminished activities of antioxidant enzymes, increased levels of malondialdehyde, Toll-like receptor 4 gene expression and histological damages in hepatic and renal tissues. Berberine and barberry extract administration decreased all the changes. CONCLUSIONS: An intensification in enzymatic oxidant status, decrease in lipid peroxidation with decrease in TLR4 gene expression level indicate that barberry extract may be a potential candidate in combating cisplatin-induced oxidative stress and inflammation in liver and kidney tissues through its constituent berberine.

The distinctive role of tau and amyloid beta in mitochondrial dysfunction through alteration in Mfn2 and Drp1 mRNA Levels: A comparative study in Drosophila melanogaster.

Alzheimer's disease (AD) is one of the most common forms of neurodegenerative diseases. Aggregation of Aß42 and hyperphosphorylated tau are two major hallmarks of AD. Whether different forms of tau (soluble or hyperphosphorylated) or Aß are the main culprit in the events observed in AD is still under investigation. Here, we examined the effect of wild-type, prone to hyperphosphorylation and hyperphosphorylated tau, and also Aß42 peptide on the brain antioxidant defense system and two mitochondrial genes, Marf (homologous to human MFN2) and Drp1 involved in mitochondrial dynamics in transgenic Drosophila melanogaster. AD is an age associated disease. Therefore, the activity of antioxidant agents, CAT, SOD, and GSH levels and the mRNA levels of Marf and Drp1 were assessed in different time points of the flies lifespan. Reduction in cognitive function and antioxidant activity was observed in all transgenic flies at any time point. The most and the least effect on the eye phenotype was exerted by hyperphosphorylated tau and Aß42, respectively. In addition, the most remarkable alteration in Marf and Drp1 mRNA levels was observed in transgenic flies expressing hyperphosphorylated tau when pan neuronal expression of transgenes was applied. However, when the disease causing gene expression was confined to the mushroom body, Marf and Drp1 mRNA levels alteration was more prominent in tauWT and tauE14 transgenic flies, respectively. In conclusion, in spite of antioxidant deficiency caused by different types of tau and Aß42, it seems that tau exerts more toxic effect on the eye phenotype and mitochondrial genes regulation (Marf and Drp1). Moreover, different mechanisms seem to be involved in mitochondrial genes dysregulation when Aß or various forms of tau are expressed.