Abstract
BackgroundPilea umbrosa (Urticaceae) is used by local communities (district Abbotabad) for liver disorders, as anticancer, in rheumatism and in skin disorders.MethodsMethanol extract of P. umbrosa (PUM) was investigated for the presence of polyphenolic constituents by HPLC-DAD analysis. PUM (150 mg/kg and 300 mg/kg) was administered on alternate days for eight weeks in rats exposed with carbon tetrachloride (CCl4). Serum analysis was performed for liver function tests while in liver tissues level of antioxidant enzymes and biochemical markers were also studied. In addition, semi quantitative estimation of antioxidant genes, endoplasmic reticulum (ER) induced stress markers, pro-inflammatory cytokines and fibrosis related genes were carried out on liver tissues by RT-PCR analysis. Liver tissues were also studied for histopathological injuries.ResultsLevel of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), peroxidase (POD) and glutathione (GSH) decreased (p < 0.05) whereas level of thiobarbituric acid reactive substance (TBARS), H2O2 and nitrite increased in liver tissues of CCl4 treated rat. Likewise increase in the level of serum markers; alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and total bilirubin was observed. Moreover, CCl4 caused many fold increase in expression of ER stress markers; glucose regulated protein (GRP-78), x-box binding protein1-total (XBP-1 t), x-box binding protein1-unspliced (XBP-1 u) and x-box binding protein1-spliced (XBP-1 s). The level of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) was aggregated whereas suppressed the level of antioxidant enzymes; γ-glutamylcysteine ligase (GCLC), protein disulfide isomerase (PDI) and nuclear erythroid 2 p45-related factor 2 (Nrf-2). Additionally, level of fibrosis markers; transforming growth factor-β (TGF-β), Smad-3 and collagen type 1 (Col1-α) increased with CCl4 induced liver toxicity. Histopathological scrutiny depicted damaged liver cells, neutrophils infiltration and dilated sinusoids in CCl4 intoxicated rats. PUM was enriched with rutin, catechin, caffeic acid and apigenin as evidenced by HPLC analysis. Simultaneous administration of PUM and CCl4 in rats retrieved the normal expression of these markers and prevented hepatic injuries.ConclusionCollectively these results suggest that PUM constituted of strong antioxidant chemicals and could be a potential therapeutic agent for stress related liver disorders.
Highlights
Pilea umbrosa (Urticaceae) is used by local communities for liver disorders, as anticancer, in rheumatism and in skin disorders
Naz et al Environmental Health and Preventive Medicine (2020) 25:53 (Continued from previous page). Collectively these results suggest that P. umbrosa (PUM) constituted of strong antioxidant chemicals and could be a potential therapeutic agent for stress related liver disorders
HPLC-DAD analysis of PUM Eight analytes were subjected to HPLC-DAD method
Summary
Pilea umbrosa (Urticaceae) is used by local communities (district Abbotabad) for liver disorders, as anticancer, in rheumatism and in skin disorders. Carbon tetrachloride (CCl4) has been extensively used in animal models to elucidate the mechanism of hepatic injury and for analyzing biomarkers discovery. It stimulates cytochrome P-450 enzyme (CYP) system in endoplasmic reticulum (ER) to metabolize into trichloromethyl radicals (CCl3) and trichloromethyl peroxy radical (CCl3O2). These radicals inaugurate lipid peroxidation and compel oxidative stress that causes liver cell damage. CCl4-induced liver toxicity is accompanied by elevation of inflammatory cytokines such as interleukin (IL-1β), IL-6, tumor necrosis factor (TNF-α), and chemokines e.g. monocyte chemo attractant protein-1 (MCP-1) which causes severe hepatocyte inflammation [7, 8]
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