PMID- 32917140
OWN - NLM
STAT- MEDLINE
DCOM- 20200929
LR  - 20231112
IS  - 1347-4715 (Electronic)
IS  - 1342-078X (Print)
IS  - 1342-078X (Linking)
VI  - 25
IP  - 1
DP  - 2020 Sep 11
TI  - Pilea umbrosa ameliorate CCl(4) induced hepatic injuries by regulating 
      endoplasmic reticulum stress, pro-inflammatory and fibrosis genes in rat.
PG  - 53
LID - 10.1186/s12199-020-00893-2 [doi]
LID - 53
AB  - 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 (CCl(4)). 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), 
      H(2)O(2) and nitrite increased in liver tissues of CCl(4) 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, CCl(4) 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-alpha 
      (TNF-alpha), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) was 
      aggregated whereas suppressed the level of antioxidant enzymes; 
      gamma-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-beta (TGF-beta), Smad-3 and collagen type 1 
      (Col1-alpha) increased with CCl(4) induced liver toxicity. Histopathological scrutiny 
      depicted damaged liver cells, neutrophils infiltration and dilated sinusoids in 
      CCl(4) intoxicated rats. PUM was enriched with rutin, catechin, caffeic acid and 
      apigenin as evidenced by HPLC analysis. Simultaneous administration of PUM and 
      CCl(4) 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.
FAU - Naz, Irum
AU  - Naz I
AD  - Faculty of Biological Sciences, Department of Biochemistry, Quaid-i-Azam 
      University, Islamabad, Pakistan.
FAU - Khan, Muhammad Rashid
AU  - Khan MR
AUID- ORCID: 0000-0003-2956-3264
AD  - Faculty of Biological Sciences, Department of Biochemistry, Quaid-i-Azam 
      University, Islamabad, Pakistan. mrkhanqau@yahoo.com.
FAU - Zai, Jawaid Ahmed
AU  - Zai JA
AD  - Faculty of Biological Sciences, Department of Biochemistry, Quaid-i-Azam 
      University, Islamabad, Pakistan.
FAU - Batool, Riffat
AU  - Batool R
AD  - Faculty of Biological Sciences, Department of Biochemistry, Quaid-i-Azam 
      University, Islamabad, Pakistan.
FAU - Zahra, Zartash
AU  - Zahra Z
AD  - Faculty of Biological Sciences, Department of Biochemistry, Quaid-i-Azam 
      University, Islamabad, Pakistan.
FAU - Tahir, Aemin
AU  - Tahir A
AD  - Faculty of Biological Sciences, Department of Biochemistry, Quaid-i-Azam 
      University, Islamabad, Pakistan.
LA  - eng
PT  - Journal Article
DEP - 20200911
PL  - Japan
TA  - Environ Health Prev Med
JT  - Environmental health and preventive medicine
JID - 9609642
RN  - 0 (Protective Agents)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
SB  - IM
MH  - Animals
MH  - Carbon Tetrachloride/*adverse effects
MH  - Chemical and Drug Induced Liver Injury/*drug therapy/etiology/pathology
MH  - Endoplasmic Reticulum Stress/*drug effects
MH  - Fibrosis/*drug therapy/genetics
MH  - Inflammation/*drug therapy/genetics
MH  - Liver/drug effects/enzymology/metabolism
MH  - Male
MH  - Protective Agents/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Urticaceae/*chemistry
PMC - PMC7488709
OTO - NOTNLM
OT  - Antioxidant
OT  - Cytokines
OT  - ER stress
OT  - Liver
OT  - RT-PCR
COIS- The authors declare that they have no competing interests.
EDAT- 2020/09/13 06:00
MHDA- 2020/09/30 06:00
PMCR- 2020/09/11
CRDT- 2020/09/12 05:22
PHST- 2019/10/23 00:00 [received]
PHST- 2020/09/01 00:00 [accepted]
PHST- 2020/09/12 05:22 [entrez]
PHST- 2020/09/13 06:00 [pubmed]
PHST- 2020/09/30 06:00 [medline]
PHST- 2020/09/11 00:00 [pmc-release]
AID - 10.1186/s12199-020-00893-2 [pii]
AID - 893 [pii]
AID - 10.1186/s12199-020-00893-2 [doi]
PST - epublish
SO  - Environ Health Prev Med. 2020 Sep 11;25(1):53. doi: 10.1186/s12199-020-00893-2.