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A high-fat diet (HFD) is one of the most prominent causative factors for obesity and metabolic inflammation. The effects of HFD overconsumption on intestinal histology, expression of haem oxygenase-1 (HO-1), and transferrin receptor-2 (TFR2) remain elusive. The present study was conducted to analyze the effect of HFD on these parameters. To develop the HFD-induced obese model, rat colonies were divided into 3 groups; the control group was reared on normal rat chow, whereas groups I and II were given HFD for 16 weeks. Hematoxylin and eosin (H & E) staining revealed marked epithelial changes, inflammatory cell infiltrates, and destruction of mucosal architecture in both experimental groups as compared to the control group. Sudan Black B staining showed a high triglyceride deposition in the intestinal mucosa of animals fed on HFD. Atomic absorption spectroscopy revealed a decrease in tissue copper (Cu) and selenium (Se) concentration in both HFD experimental groups. Whereas the cobalt (Co) and manganese (Mn) levels were comparable to controls. The mRNA expression levels of HO-1 and TFR2 were found to be significantly upregulated in HFD groups compared to the control group. Hence, HFD consumption leads to histopathological changes and altered gene expression in the rodent intestine. So, one should remove HFD from daily meals to avoid related metabolic complications.

Idiopathic generalized epilepsy (IGE) is the most prevalent type of epilepsy with genetic origin. Mutations in ion channel genes have been identified as a common cause of IGE. Several studies have reported various epilepsy risk variants of GABRG2 (gamma-aminobutyric acid type A receptor subunit gamma2 subunit) gene in different ethnic groups, but the results are inconsistent. The purpose of this case-control research is to determine if GABRG2 polymorphisms contribute to IGE susceptibility and antiepileptic drug resistance in Pakistani population. For this purpose, we genotyped exon2, exon5 (C540T and C588T), exon7 (T813C), exon8 (K289M), and exon9 of GABRG2 gene by restriction fragment length polymorphism and Sanger’s sequencing in 87 drug-responsive idiopathic generalized epilepsy patients, 55 drug-resistant epilepsy patients, and 83 healthy controls. Restriction fragment length polymorphism (RFLP) and sequencing results indicated only C588T polymorphism in the studied subjects. The comparison of genotypic and allelic frequencies showed significant differences between IGE patients and control groups ( P = 0.008 and odds ratio = 4.2 ) and nonsignificant association of C588T polymorphism in antiseizure medication-resistant patients ( P = 0.9 ). Our findings showed that C588T polymorphism of GABRG2 is a risk variant for IGE in Pakistani population. Further studies are required to validate the results.

Bisphenol S (BPS), an analog of bisphenol A (BPA), has been frequently detected in consumer products, food wrappers, plastics, and thermal papers. Since the liver is a hub of metabolic and detoxification pathways, thus intimately related to BPS presence in the environment and body. The current study was designed to investigate the effects of BPS administration in an animal model. Twenty-five male Wistar rats weighing 175 ± 25 g were randomly divided into control and treated groups. The control group was further divided into group I (no treatment) and group II (corn oil), whereas the treatment group was divided into D-I (40 mg/kg/day), D-II (200 mg/kg/day), and D-III (400 mg/kg/day) groups, getting oral doses of BPS for 15 days. Data analysis showed a significant statistical increase in hepatic enzymes ALT (33.4%), AST (25.4%), and ALP (529.6%) in the D-III group along with the development of hypercholesterolemia and hypertriglyceridemia in all BPS groups. Aberrant mRNA expressions of some key hepatic iron regulatory genes and inflammatory mediators were evident through qRT-PCR. Bisphenol S caused congestion of central vein from mild to moderate in hepatic sections. In conclusion, our investigation insinuates BPS intoxication potential and therefore may not be a safe alternative to BPA.

Background: The cryptic diversity of bat fauna in Pakistan demands to incorporate an efficient and reliable approach for morphological species identification. The traditional taxonomic approaches are effective in exploring variations of characters but have proved to be less efficient in quantifying the interspecific and intraspecific differences. Geometric morphometric method has recently act as an efficient tool to analyze the overall changes in shape and size of biological features. The present study is therefore conducted to exploit the use of geometric morphometric methods along with traditional morphological measurements to examine the size and shape differences among four geographically isolated population groups of insectivorous bat species (Pipistrellus coromandra). Methods: Specimens were collected from different locations of Punjab, Pakistan. Twelve well-defined landmarks to quantify the variation in right wing of bats were analyzed using geometric morphometric tools and wing measurements of 5 selected parameters were also taken using traditional morphological measurements. Results: The results of external measurements for wing overlapped for most part among the different studied population groups. Fur colour photographs displayed in the inter-population had shown visible change from dark brown to light brown giving an indication of more morphological differences. Regarding the geometric morphometric results, wing-shape differences were found to dominate in inter-population as compared to intra-population for bats species (Pipistrellus coromandra) which clearly reflects the effects of habitat factors on different populations phenotypically. The wireframe for the first two PCs indicated an overall shape change trend with the displacement of landmark points representing the expansion along the upper wing margins in PC1 compared to PC2. Conclusion: The current study has successfully explored the power of geometric morphometric in reflecting the variations in wing shape among different populations of bats species (Pipistrellus coromandra).

Background: Migraine is a severe neurovascular disease with some temporary symptoms like unilateral headache attacks associated with sensory and autonomic disturbances. It affects 12% of the general population worldwide. Females are more susceptible to migraine than males. The genetic and environmental factors contribute as a causative agent to its symptomatology. Gamma-aminobutyric acid (GABA) neurotransmitter plays a potential role in migraine pathophysiology that prompted us to evaluate the association between gamma-aminobutyric acid type a receptor gamma two subunit gene (GABRG2) polymorphisms and the risk of a migraine attack. Methods The present case-control study included 220 subjects (100 control; 120 patients). Blood samples were taken from all the participants and DNA was isolated. The selected SNPs (rs211037, rs121909672, and T813C) of exons 5, 7, and 8 of the GABRG2 gene were genotyped for cases and controls. Results: A silent polymorphism was found at the rs211037 polymorphic site, while no variation was found on other targeted sites either in the case or control population. Statistical analysis indicated significant differences in genotypic (p=

In recent years, nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions. Characteristic findings in NAFLD patients are elevated iron stores, as iron plays an important role in the pathophysiology of chronic liver disease. The current study was aimed at investigating the possible protective effects of N. sativa seeds and P. ovata husks on the regulation of iron homeostasis in NAFLD.Two age groups of Wistar rats (four weeks and twelve weeks old), further subdivided into four groups were fed on high fat/high sucrose (HF/SF) diet for sixteen weeks to induce NAFLD and randomized into three groups (HF/SF diet control (Group I), HF/SF diet with N. sativa seeds (Group II) and HF/SF diet with P. ovata husks (Group III) and normal diet, serving as negative control (Group 0). At the end of the experiment, histochemical analysis of hepatic sections, biochemical evaluates of the blood, and gene expression analysis were conducted.The results revealed that both N. sativa seeds and P. ovata husks possess the capacity to maintain iron homeostasis by regulating the level of blood hemoglobin, serum iron contents, expression of key genes involved in iron metabolism, and iron deposition in hepatic sections. While N. sativa seeds proved more effective.N. sativa seeds are a more potent iron regulator compared to P. ovata husks at reducing the iron overburden associated with NAFLD.

Autophagy is an evolutionary conserved catabolic process that plays physiological and pathological roles in a cell. Its effect on cellular metabolism, the proteome, and the number and quality of organelles, diversely holds the potential to alter cellular functions. It acts paradoxically in cancer as a tumor inhibitor as well as a tumor promoter. In the early stage of tumorigenesis, it prevents tumor initiation by the so-called “quality control mechanism” and suppresses cancer progression. For late-staged tumors that are exposed to stress, it acts as a vibrant process of degradation and recycling that promotes cancer by facilitating metastasis. Despite this dichotomy, the crucial role of autophagy is evident in cancer, and associated with mammalian targets of rapamycin (mTOR), p53, and Ras-derived major cancer networks. Irrespective of the controversy regarding autophagic manipulation, promotion and suppression of autophagy act as potential therapeutic targets in cancer treatment and may provide various anticancer therapies.

Background: Amongst the industrial hubs in Pakistan, Wazirabad is renowned for its cutlery industry. Cutlery industry generates heaps of multi-metallic dust in whetting units during the processing of stain fewer steel tools. This dust comprises certain potentially toxic and even carcinogenic constituents, thus pose a serious health threat to the workers involved in its processing. Laborers health and safety is something quite non-seriously considered in most of the developing countries, no different is Pakistan. Present exploration was aimed at searching for the differences, in blood profile and quantitative serum protein profile of a group of laborers in cutlery industry that are directly and regularly exposed to multi-metallic dust. Materials and Methods: After taking written consent from the participants, blood samples were drawn for hematological analysis and serum analysis. Hematological analysis was performed with hematological analyzer and serum was subjected to SDS gel electrophoresis for protein profiling. Results: Statistically significant changes were observed in the number of RBCs, MCV, HCT and RDW, whereas platelet count was decreased in experimental groups when compared to control group. Serum protein profiling using SDS-PAGE revealed the protein fractions ranging from 73 to 287 kDa. Densitometric analysis has shown changes in the serum proteins of the subjects exposed to metal dust. Conclusion: Chronic exposure to the metal dust induce changes in the hematological parameters as well as serum proteins. The industrial workers should ensure the use of industry specific personal safety equipment. Key words: Health hazard, Hematology, Metals, Metal dust, Proteins, SDS-PAGE.

Extracellular Vesicles (EVs) are membrane-derived messengers which have been playing an important role in the inflammation and pathogenesis of lung diseases. EVs contain varieties of DNA, RNA, and membrane receptors through which they work as a delivery system for bioactive molecules as well as intracellular communicators. EV signaling mediates tumor progression and metastasis. EVs are linked with many diseases and perform a diagnostic role in lung injury and inflammation so are used to diagnose the severity of diseases. EVs containing a variety of biomolecules communicate with the recipient cells during pathophysiological mechanisms thereby acquiring the attention of clinicians toward the diagnostic and therapeutic potential of EVs in different lung diseases. In this review, we summarise the role of EVs in inflammation with an emphasis on their potential as a novel candidate in the diagnostics and therapeutics of chronic obstructive pulmonary disease (COPD), asthma, and sarcoidosis.

Background Citrullinated proteins formed by peptidyl arginine deiminases (PADIs) deimination of arginine residues in proteins are of particular interest in arthritis pathogenesis. Polymorphisms on the PADI-4 gene lead to the malfunctioning of PADIs leading to the onset of arthritis. Objective The present study was conducted to determine the polymorphisms on the PADI-4 gene and their association with rheumatoid arthritis (RA) as well as Osteoarthritis (OA). Methodology To achieve the above-mentioned objective a case-control study was conducted. Blood samples were collected from RA, OA, and control subjects. DNA was extracted from each blood sample by modified organic method and was quantified as well as qualified by DNA gel electrophoresis and Nanodrop. Patients were tested for rs874881, rs11203366, rs11203367, rs2240336, rs2240337, rs2240339, rs1748033 and rs2240340 polymorphic sites by amplifying targeted regions through PCR with site-specific primers. Genotyping was performed by Restriction Fragment Length Polymorphism and direct sequencing method. Mutations were identified by analyzing sequences on BioEdit software. Allelic, genetic, and multiple site analysis were performed by SHEsis and PLINK software. Change in the amino acid sequence was identified by MEGA 6.0 software. Results Polymorphisms were identified on all targeted polymorphic sites except rs2240337 in both RA and OA individuals. In addition, two novel mutations were also identified in exon 4 identified i-e SCV000804840: c.218T > C and SCV000807675: c.241G > T. All the SNPs except rs11203366 were found to be significantly associated with RA at an allelic level whereas all SNP’s have been significant risk factors in the onset of OA. At genotypic level rs874881, rs11203366, rs2240339, SCV000804840 and SCV000807675 were significantly associated to RA development whereas rs874881, rs11203366, rs11203367, rs2240339, SCV000804840 and SCV000807675 were genetic risk factors in OA onset. Haplotype analysis indicated that GACCACGCC and GACCACGCT were highly significant in disease development. Polymorphisms identified altered the functioning of PADIs by altering their amino acid sequence. Conclusion In conclusion, it was found that PADI-4 gene polymorphism was not only involved in the onset of RA but was also found to be a significant risk factor in OA onset.

Supplementary Figure S1 - Study schema

Sipuleucel-T is an autologous cellular therapy for asymptomatic, or minimally symptomatic, metastatic castrate-resistant prostate cancer, designed to stimulate an immune response against prostate cancer. In a recent clinical trial (NCT00715104), we found that neoadjuvant sipuleucel-T increased the number of activated T cells within the tumor microenvironment. The current analysis examined whether sipuleucel-T altered adaptive T-cell responses by expanding pre-existing T cells or by recruiting new T cells to prostate tissue. Next-generation sequencing of the T-cell receptor (TCR) genes from blood or prostate tissue was used to quantitate and track T-cell clonotypes in these treated subjects with prostate cancer. At baseline, there was a significantly greater diversity of circulating TCR sequences in subjects with prostate cancer compared with healthy donors. Among healthy donors, circulating TCR sequence diversity remained unchanged over the same time interval. In contrast, sipuleucel-T treatment reduced circulating TCR sequence diversity versus baseline as measured by the Shannon index. Interestingly, sipuleucel-T treatment resulted in greater TCR sequence diversity in resected prostate tissue in sipuleucel-T–treated subjects versus tissue of nonsipuleucel-T–treated subjects with prostate cancer. Furthermore, sipuleucel-T increased TCR sequence commonality between blood and resected prostate tissue in treated versus untreated subjects with prostate cancer. The broadening of the TCR repertoire within the prostate tissue supports the hypothesis that sipuleucel-T treatment facilitates the recruitment of T cells into the prostate. Our results highlight the importance of assessing T-cell response to immunotherapy both in the periphery and in tumor tissue. Cancer Res; 76(13); 3711–8. ©2016 AACR.

Lipids are integral cellular components that act as substrates for energy provision, signaling molecules, and essential constituents of biological membranes along with a variety of other biological functions. Despite their significance, lipid accumulation may result in lipotoxicity, impair autophagy, and lysosomal function that may lead to certain diseases and metabolic syndromes like obesity and even cell death. Therefore, these lipids are continuously recycled and redistributed by the process of selective autophagy specifically termed as lipophagy. This selective form of autophagy employs lysosomes for the maintenance of cellular lipid homeostasis. In this review, we have reviewed the current literature about how lipid droplets (LDs) are recruited towards lysosomes, cross-talk between a variety of autophagy receptors present on LD surface and lysosomes, and lipid hydrolysis by lysosomal enzymes. In addition to it, we have tried to answer most of the possible questions related to lipophagy regulation at different levels. Moreover, in the last part of this review, we have discussed some of the pathological states due to the accumulation of these LDs and their possible treatments under the light of currently available findings.

Background: Nonalcoholic fatty liver disease (NAFLD) is a developing liver problem mainly linked with the consumption of an ‘energy-rich-diet (ERD) in Asian countries including both females and males. NAFLD is associated with fibrosis in advanced stages. Medicinal herbs are being used to cut down the excessive fat of the body conventionally. Therefore, the current study was aimed to evaluate the lipid lowering factor against ERD induced fibrosis. Materials and methods: 40 female (F) and 40 male (M) Rattus norvegicus, subdivided as four groups Groups 0, I, II and III according to their nutritional content. Group-0 received 100% rat chow and Group-I received ERD. Group-II and Group-III received ERD supplemented with 5% Nigella sativa seeds/Plantago. ovata husk per kg ERD, respectively. Results: Histopathological evaluation of the liver showed pericellular and portal and fibrosis in both F-I and F-II. Radial fibrosis was detected in the M-II group, and peri lobular as well as bridging fibrosis between portal triads in the M-III and F-III groups. Conclusion: In the light of the present findings, it is inferred that male livers were more susceptible to DRE-induced fibrosis. N. sativa seeds proved auspicious in minimizing fibrosis, whereas P. ovata pods caused advanced liver fibrosis with DRE.

Background Acute myeloid leukemia (AML) is a bone marrow malignancy having multiple molecular pathways driving its progress. In recent years, the main causes of AML considered all over the world are genetic variations in cancerous cells. The RUNX1 and FLT3 genes are necessary for the normal hematopoiesis and differentiation process of hematopoietic stem cells into mature blood cells, therefore they are the most common targets for point mutations resulting in AML. Methods We screened 32 CN-AML patients for FLT3-ITD (by Allele-specific PCR) and RUNX1 mutations (by Sanger sequencing). The FLT3 mRNA expression was assessed in all AML patients and its subgroups. Results Eight patients (25%) carried RUNX1 mutation (K83E) while three patients (9.37%) were found to have internal tandem duplications in FLT3 gene. The RUNX1 mutation data were correlated with clinical parameters and FLT3 gene expression profile. The RUNX1 mutations were observed to be significantly prevalent in older males. Moreover, RUNX1 and FLT3-mutated patients had lower complete remission rate, event-free survival rate, and lower overall survival rate than patients with wild-type RUNX1 and FLT3 gene. The RUNX1 and FLT3 mutant patients with up-regulated FLT3 gene expression showed even worse prognosis. Bradford Assay showed that protein concentration was down-regulated in RUNX1 and FLT3 mutants in comparison to RUNX1 and FLT3 wild-type groups. Conclusion This study constitutes the first report from Pakistan reporting significant molecular mutation analysis of RUNX1 and FLT3 genes including FLT3 expression evaluation with follow-up. This provides an insight that aforementioned mutations are markers of poor prognosis but the study with a large AML cohort will be useful to further investigate their role in disease biology of AML.

Introduction: In Pakistan, for the patients of Hepatitis C virus (HCV), Direct-Acting Antiviral (DAA) therapy for 12 weeks and 24 weeks had been reported to be highly efficacious for genotype 3. We currently carried out an observational study to predict the rate of efficacy of sofosbuvir and ribavirin in hepatitis C patients to establish concrete or authentic data on this combination of DAA for long-term treatment. Materials and Method: Among 2000 subjects who attended tertiary care unit in Lahore-Pakistan from November 2018 to February 2019, 1990 satisfied the criteria set for the present investigation i.e. SVR12 after being treated with sofosbuvir and ribavirin combination. Results: It was noted that genotype 3a were more common among all the subjects under observation with 50.65 % (1008/1990) in females and 49.35% (982/1990) in males. Overall efficacy analysis was found to be 95.4% (1900/1990) in patients while the moderate response was noted in elderly subjects including both genders (61-90 years). DAA responders (male: female percentages) shown the following stats; 66.63 (42/66):36.36 (24/66) in 11-20 years, 56.6(240/424):43.39 (184/424) in 21-30 years and 44.73(272/608):55.27(336/608) in 31-40 years. Conclusion: Collectively, this combinational drug therapy was observed to be successful among the Pakistani population. However, more comprehensive follow-up studies are needed on a larger pool of population nationwide to check only this combinational therapy (sofosbuvir and ribavirin) would be beneficial or not? Or next-generation DAA regimes would be the choice for the Pakistani population.

Background Migraine is a chronic neurovascular condition characterized by recurring attacks of pulsating headaches. Genome-wide association studies (GWAS) identified many potential loci associated with migraine. To check the association of polymorphisms of PRDM16 (rs2651899), LRP1 (rs11172113), and TRPM8 (rs10166942) with migraine, the first time a case-control study was conducted in understudied Pakistani population. Methods The study included 127 migraine patients (21 in migraine with aura and 106 with migraine without aura group) and 120 healthy control subjects from different areas of Punjab, Pakistan. Blood samples were collected from all the participants, and DNA was isolated from the lymphocytes by the modified organic method. Sanger's sequencing was done for PRDM16 (rs2651899), LRP1 (rs11172113), and TRPM8 (rs10166942) in all the samples to check the genotype. Logistic regression analysis was done using SPSS 20.0 to check the association of these SNPs with migraine susceptibility. Results We found statistically significant differences between case and control group for PRDM16 (rs2651899) at genotypic level (p

The trend of consuming food high in calories, fat, and sugar with little nutritional value and reduced physical exercise has resulted in an alarming ratio of overweight and obese subjects worldwide. Low-grade chronic inflammation is the key feature of obesity that causes an increase in pro-inflammatory cytokines and decrease in anti-inflammatory cytokines in circulation. The current study was aimed to investigate the effect of high-fat diet on the architecture of spleen, liver, and skeletal muscle and changes in the expression of hepatic cytokines. Two groups of experimental rats were established, against control that were given different percentage of fats in their diet. After a period of sixteen weeks, rats were dissected and their organs were excised out and processed accordingly. Spleen sections of experimental groups, revealed increased recruitment of lymphocytes, sinusoidal dilatations, necrotic lymphocytes, increased ratio of white-to-red pulp, and hemosiderin and iron deposits in red pulp indicating immune system activation. Hepatic sections showed enlarged sinusoidal spaces, disruptive hepatocytes, necrosis and dilation of portal veins. Sections of skeletal muscle showed degenerating fibers, increased fat accumulation, and recruitment of macrophages. Elevated expression of IFN-γ and decreased expression of IFN-α and IFN-β cytokines verified the adverse effect of high-fat diet on immune system as well. Fats tend to accumulate in organs due to increased intake of fat-rich diet disturbing their normal function and histology. In addition, gene expression analysis of cytokines confirmed the effect of high-fat diet as an inflammatory agent.

Juvenile myoclonic epilepsy (JME) is the most prevalent and genetically heterogeneous form of epilepsy and accounts for 10–30% of all the cases worldwide. Ef-hand domain- (c-terminal-) containing protein 1 (EFHC1) encodes for a nonion channel protein and mutations in this gene have been extensively reported in different populations to play a causative role in JME. Linkage between JME and 6p11-12 locus has already been confirmed in Mexican and Dutch families. A case-control study was conducted on Pakistani JME patients for the first time, aimed at finding out EFHC1 mutations that have been reported in different populations. For this purpose, 66 clinically diagnosed JME patients and 108 control subjects were included in the study. Blood samples were collected from all the participants, and DNA was isolated from the lymphocytes by the modified organic method. Total 3 exons of EFHC1, harboring extensively reported mutations, were selected for genotypic analysis. We identified three heterozygous variants, R159W, V460A, P436P, and one insertion in the current study. V460A, an uncommon variant identified herein, has recently been reported in public databases in an unphenotyped American individual. This missense variant was found in 3 Pakistani JME patients from 2 unrelated families. However, in silico analysis showed that V460A may possibly be a neutral variant. While the absence of a majority of previously reported mutations in our population suggests that most of the mutations of EFHC1 are confined to particular ethnicities and are not evenly distributed across the world. However, to imply the causation, the whole gene and larger number of JME patients should be screened in this understudied population.

Platelet-rich plasma (PRP) is proven a cost-effective therapeutic choice for different ailments. The current study was designed to highlight the effects of heterologous platelet-rich plasma (PRP) on deteriorated hepatic tissues and impaired glucose metabolism in alloxan-induced diabetic mice. A total of thirty (30) male mice were selected and grouped as control (CG), PRP group (PG), diabetic group (DG), treated group 1 (T1G), and treated group 2 (T2G). PG was given a subcutaneous dose of PRP (0.5 ml/kg body weight) twice a week for four weeks. DG, T1G, and T2G were first given a single dose of alloxan intraperitoneally (150 mg/kg) to induce diabetes. PRP (0.5 ml/kg body weight) was given twice a week to T1G and T2G for two and four weeks respectively. After four weeks, all the mice were sacrificed to excise liver for histological observations and gene expression analysis. Hepatic histo-morphological analysis revealed ballooning of hepatocytes, dilatation of sinusoids, and collagen deposition in the alloxan-induced diabetic group (DG) and it was significantly reduced in both T1G and T2G. Additionally, a significant change in the expression of several hepatic genes was observed. Fbp1, G6pc, and Pklr showed an upregulation while a downregulation was detected in the expression of Pck1 in DG. A significant restoration was observed in Fbp1, and G6pc after PRP treatment but no change was observed in Pklr expression. Genes of glycolytic pathway, Hk1 and Gck, were downregulated significantly in DG compared to CG and PRP treatment restore the expression in both treated groups T1G and T2G. Moreover, Wnt2, Wnt4, and Wnt9a genes of the Wnt signaling pathway were also upregulated in DG, conversely, downregulate in T1G and T2G. No significant change in expression of Wnt5b and Wnt9b was observed in DG compared to control. Current study revealed that PRP anticipates a reduction in glucose production and glucose consumption by ameliorating hepatic tissue and modulating the glucose metabolism. So, it may use as one of the adjunctive therapies to treat T2DM in future but further more detailed investigations are suggested.

Hepatitis C virus (HCV) causes persistent infection and invades host's innate and adaptive immune systems. During the eradication of this pathogen, the components of immune system may cause bystand...

The Hedgehog (Hh) pathway has emerged as a potential target for effectual hepatic repair based on convincing clinical and preclinical evidence that proves its significance in regulating hepatic damage. The purpose of this study is to probe the effect of quercetin on liver fibrosis through the modulation of the Hh pathway. Healthy male Wistar rats were divided into four groups (n = 10). The control group was treated with saline, rats in the remaining three groups received twice a week intoxication with intraperitoneal injections of thioacetamide (200 mg/kg) for the induction of hepatic fibrosis for 6 weeks. After 28 days of quercetin and silymarin treatment, histological changes, serum biochemical index, antioxidant enzyme activity, key mediators of Hh pathway and inflammation were analyzed. Serological analysis showed statistically improved cholesterol, H.D.L-Cholesterol, and L.D.L-Cholesterol in the treatment groups. Superoxide dismutase and glutathione levels were found to be increased after the treatment with quercetin and silymarin. mRNA expression of important mediators of the Hh signaling, and inflammation including Shh, Ihh, Ptch-1, Smo, Hhip, Gli-3, TNF-α, NFκ-β, and Socs-3 were significantly downregulated after the use of quercetin and silymarin. Quercetin also minimized the thioacetamide-induced histopathological changes, as confirmed by a lower degree of hepatic lobule degeneration, the intralobular occurrence of inflammatory cells, and a lower degree of hepatocytic necrosis. Sudan Black B staining showed remarked lipids improvements in the treatment groups. Taken together, these findings demonstrate that quercetin could ameliorate hepatic fibrosis by antagonizing the hedgehog pathway and also suggest the hedgehog pathway as a potential therapeutic target for the treatment of liver fibrosis.