Neuroprotective and hepatoprotective effects of micronized purified flavonoid fraction (Daflon®) in lipopolysaccharide-treated rats

Abstract

Micronized purified flavonoid fraction (MPFF, Daflon ® ) is a phlebotonic drug widely used in chronic venous or lymphatic insufficiency. We aimed to investigate the effects of MPFF on hepatic and brain oxidative stress and on liver injury caused by lipopolysaccharide (LPS) in rats. MPFF (4.5, 9, or 18 mg/kg) or saline was administered orally for two days prior to intraperitoneal (i.p.) LPS (300 μg/kg) and at time of LPS administration. Rats were euthanized 4 h after LPS injection. The administration of LPS increased oxidative stress in brain and liver tissue. Malondialdehyde (MDA) increased by 193.5 and 191.8%, reduced glutathione (GSH) decreased by 73.8 and 70.8% and nitric oxide increased by 118.2 and 151.7% in the brain and liver, respectively. Serum paraoxonase 1 (PON1) activity decreased by 42.6%. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were raised by 101.8, 93.6, and 223.2%, respectively. Rats treated with MPFF at 9 and 18 mg/kg showed decreased brain MDA (27.5-34%), nitrite (25.5-41%) and increased GSH (27.2-74.1%). In the liver, MDA decreased by 16.4-59.8%, nitrite decreased by 54.7-56.7%, and GSH increased by 15.2-70.5% with MPFF at 4.5, 9, or 18 mg/kg, respectively. Serum PON1 activity showed 41-65.9% increments with MPFF. Significant reductions in serum AST, ALT, and ALP were seen after treatment with MPFF. Moreover, the degree of histological damage, expression of the inducible form of nitric oxide synthase and the apoptotic enzyme caspase-3 in the liver were substantially reduced. MPFF thus prevented the increased oxidative stress and inflammation in brain and liver as well as the liver dysfunction caused by endotoxemia in the rat.

Novel effect of Daflon and low-dose γ-radiation in modulation of thioacetamide-induced hepatic encephalopathy in male albino rats

“…According to the obtained results, pretreatment of rats with Daflon and/or irradiation of rats with fractionated LDR ameliorated liver injury elicited by TAA and recorded a significant decrease in serum AST, ALT, and GGT activities as well as markedly reduced T Bil, ammonia, and manganese serum and brain levels, suggesting that it offers protection by preserving the structural integrity of the hepatocellular membrane against hepatotoxins due to its flavonoids constituents. 37 These results are in harmony with those obtained by Abdel-Salam et al, 38 Hozayen et al, 39 and Fouad et al 40 In addition to its membrane-stabilizing efficacy, Germoush 41 reported that hesperidin supplementation significantly reduced ammonia level in hyperammonemic rats. This might be attributed to the improvement of hepatic microcirculation by diosmin.…”

“…The exhibited effect of Daflon suggests its role in scavenging free radicals generated by TAA, which might be attributed to its flavonoids content. 38 The radical scavenging and antioxidant enhancement properties of hesperidin were reported in several studies. 40,49 The antioxidant activity of hesperidin seems to be correlated to its structure.…”

Natural compounds in the chemoprevention of alcoholic liver disease

“…Based on difference in structure, flavonoids are divided into seven subgroups: flavones, flavanones, flavonols, flavanonols, isoflavones, catechins, and anthocyanidins (Ververidis et al, ). There are reports indicating that some flavonoids exhibit a broad spectrum of biological activities and thus widespread benefits for treatment of various diseases such as cancer, virus infection, and liver injury (Abdel‐Salam et al, ; Cui, Wang, Kokudo, Fang, & Tang, ; Handoussa, Osmanova, Ayoub, & Mahran, ). Here, we emphasize flavonoids as potential therapeutic approaches to prevent and treat ALD (Table ).…”

“…trum of biological activities and thus widespread benefits for treatment of various diseases such as cancer, virus infection, and liver injury(Abdel-Salam et al, 2012;Cui, Wang, Kokudo, Fang, & Tang, 2010;Handoussa, Osmanova, Ayoub, & Mahran, 2009). Here, we emphasize flavonoids as potential therapeutic approaches to prevent and treat ALD(Table 1).…”

Flavonoid-Rich Fraction of Ocimum gratissimum Attenuates Lipopolysaccharide-Induced Sickness Behavior, Inflammatory and Oxidative Stress in Mice

“…Increased oxidative stress in the brain is associated with aging, Parkinson's disease, Alzheimer's disease, as well as psychiatric diseases (e. g., schizophrenia). Flavonoid-rich extracts have been shown to demonstrate neuroprotective and hepatoprotective properties in LPS challenged rodents [19,56]. The neuroprotective and hepatoprotective effects of the flavonoid-rich ethylacetate fraction of O. gratissimum leaf suggests its potential in slowing down LPS-mediated hepatic and neuronal disease processes.…”