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Environmental Health and Preventive Medicine

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Open Access 01-12-2020 | Cytokines | Research article

Pilea umbrosa ameliorate CCl₄ induced hepatic injuries by regulating endoplasmic reticulum stress, pro-inflammatory and fibrosis genes in rat

Authors: Irum Naz, Muhammad Rashid Khan, Jawaid Ahmed Zai, Riffat Batool, Zartash Zahra, Aemin Tahir

Published in: Environmental Health and Preventive Medicine | Issue 1/2020

Abstract

Background

Pilea umbrosa (Urticaceae) is used by local communities (district Abbotabad) for liver disorders, as anticancer, in rheumatism and in skin disorders.

Methods

Methanol 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.

Results

Level 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.

Conclusion

Collectively these results suggest that PUM constituted of strong antioxidant chemicals and could be a potential therapeutic agent for stress related liver disorders.

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Title: Pilea umbrosa ameliorate CCl4 induced hepatic injuries by regulating endoplasmic reticulum stress, pro-inflammatory and fibrosis genes in rat
Authors: Irum Naz
Muhammad Rashid Khan
Jawaid Ahmed Zai
Riffat Batool
Zartash Zahra
Aemin Tahir
Publication date: 01-12-2020
Publisher: BioMed Central
Keyword: Cytokines
Published in: Environmental Health and Preventive Medicine / Issue 1/2020
Print ISSN: 1342-078X
Electronic ISSN: 1347-4715
DOI: https://doi.org/10.1186/s12199-020-00893-2

At a glance: The STEP trials

Springer Medicine

Pilea umbrosa ameliorate CCl₄ induced hepatic injuries by regulating endoplasmic reticulum stress, pro-inflammatory and fibrosis genes in rat

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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