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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.

We have investigated the protective potential of methanol extract of Iphiona aucheri (IAM) on the expression of endoplasmic reticulum (ER) stress associated genes and inflammatory genes on carbon tetrachloride (CCl4) induced hepatic toxicity in rats. Hepatic damage markers: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin were elevated while the content of antioxidants: catalase (CAT), superoxide dismutase (SOD), peroxidase (POD) and reduced glutathione (GSH) were decreased significantly (p &lt; 0.05) in CCl4 treated rats as compared to the control group. The CCl4 intoxication induced a higher expression of glucose-regulated protein 78 kDa (GRP78), X-box-binding protein 1 total (XBP1t), spliced X-box-binding protein 1 (XBP1s), unspliced X-box-binding protein 1 (XBP1u), C/EBP homologous protein (CHOP) and genes involved in inflammation and fibrosis: tumor necrosis factor alpha (TNF-α), transforming growth factor-beta (TGF-β), mothers against DPP homolog 3 (SMAD3), alpha skeletal muscle actin (αSMA) and collagen type I alpha 1 chain (COL1A1). The intoxicated rats showed a low expression of the glutamate–cysteine ligase catalytic subunit (GCLC), protein disulfide isomerase (PDI) and nuclear factor (erythroid-derived 2) like-2 (Nrf2). The administration of IAM to intoxicated rats restored the expression of ER stress, inflammatory, fibrosis and antioxidant genes in a dose dependent manner. Our results indicated that IAM can impede the ER stress and inflammatory genes and it could be a complementary and alternative therapeutic agent for oxidative stress associated disorders.

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Introduction: The study was designed to identify the genetic mutation in families with autosomal recessive primary microcephaly (MCPH). Methodology: The present study was cross-sectional and conducted at the Department of Biochemistry, Quaid-e-Azam University, Islamabad in 2017. The two families (A and B) with MCPH phenotype randomly selected from Hyderabad and Tando Adam districts respectively. Informed written consent was taken, physical parameters were measured and blood samples were collected from both families. DNA was extracted from whole blood and PCR was performed. The ASPM gene located on chromosome 1 is known to play a vital role in mitotic spindle fiber regulation during neurogenesis, and also is the most probable causative agent of microcephaly. Therefore targeted Sanger sequencing method for the ASPM gene was selected for variant identification in both families. Results: The Sanger sequencing result showed the novel missense variant (c.5841T/C; p. K1862E) in 18 exon of ASPM gene in Family A  and this variant predicted as damaging in mutation tester, and provean and also exhibited deleterious in Polyphen 2 and SIFT public database. Similarly in family B we found a previously reported protein pre termination variant (c.3978G/A; p.Trp1326*) (rs137852995) in exon 17 of ASPM gene. The later mutation was most predominant cause of microcephaly in KPK families. Conclusion: Therefore it is concluded that mutation in the ASPM gene is the most prominent genetic player of Microcephaly in Pakistani families. The current study aids in the genetic analysis of MCPH phenotype families in Pakistan alongwith the counseling of MCPH families.