scholarly journals Chemopreventive Efficacy of Punica granatum and Silybum marianum Extracts on Chemically-induced Hepatocellular Carcinoma in Rats

2019 ◽  
Vol 7 (2) ◽  
Author(s):  
Hend Maarof Tag ◽  
Ahlem Bargougui ◽  
Sara Gamal Alshayyal ◽  
Amany Kamal ◽  
Hekmat M. Tantawy ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepg2 Cells ◽  
Punica Granatum ◽  
In Vivo Model ◽  
Control Group ◽  
Albino Rats ◽  
Silybum Marianum ◽  
Chemically Induced

Punica granatum (POM) and Silybum marianum (MT) receiving attention as potential potent anti-oxidant and anti-mutant agents. In this context, the present study was designed to highlight their effects either in vitro as well as in vivo model of induced Hepatocellular carcinoma (HCC). Human hepatoma (HepG2 cells) were treated with MT and POM to explore their antitumor activity then in vivo were carried out on thirty-six male albino rats divided into six groups (n=6). Two weeks after induction of HCC, rats were co-treated with either MT or POM ethanolic extract (500 mg/kg, orally) daily for 8 weeks. The results displayed marked reduction in the viability of HepG2 cells with IC50 equal to 48.4 and 8.6 μg/mL of POM and MT treatment respectively. Considering, in vivo experiment HCC group displayed significant elevation liver function indices (p<0.05). It also elicited depletion of liver reduced glutathione (GSH), and increased content of liver malondialdehyde (MDA) compared to control group. HCC was proved after a significantly elevated alpha-fetoprotein (AFP) level (p<0.05). All of these measurements were diminished significantly after POM and MT treatments, except the GSH level that was increased significantly. Supplementation of pomegranate and milk thistle extracts had a protective effect against chemically induced HCC. 

Effect of Tumor Suppressor MiR-34a Loaded on ZSM-5 Nanozeolite in Hepatocellular Carcinoma: In Vitro and In Vivo Approach

2019 ◽  
Vol 19 (5) ◽  
pp. 342-354 ◽  
Author(s):  
Zeinab Salah ◽  
Eman M. Abd El Azeem ◽  
Hanan F. Youssef ◽  
Amira M. Gamal-Eldeen ◽  
Abdel R. Farrag ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Suppressor ◽  
Hepg2 Cells ◽  
Cloning And Expression ◽  
Great Promise ◽  
Control Group ◽  
Qrt Pcr ◽  
Nano Formulation

Background: MicroRNA modulation therapy has shown great promise to treat hepatocellular carcinoma (HCC), however Efficient tissue-specific and safe delivery remains a major challenge. Objective: We sought to develop an inorganic-organic hybrid vehicle for the systemic delivery of the tumor suppressor miR-34a, and to investigate the efficiency of the delivered miR-34a in the treatment of HCC in vitro and in vivo. Methods: In the present study, pEGP-miR cloning and expression vector, expressing miR-34a, was electrostatically bound to polyethyleneimine (PEI), and then loaded onto ZSM-5 zeolite nanoparticles (ZNP). Qualitative and quantitative assessment of the transfection efficiency of miR-34a construct in HepG2 cells was applied by GFP screening and qRT-PCR, respectively. The expression of miR-34a target genes was investigated by qRT-PCR in vitro and in vivo. Results: ZNP/PEI/miR-34a nano-formulation could efficiently deliver into HepG2 cells with low cytotoxicity, indicating good biocompatibility of generated nanozeolite. Furthermore, five injected doses of ZNP/PEI/miR-34a nano-formulation in HCC induced male Balb-c mice, significantly inhibited tumor growth, and demonstrated improved cell structure, in addition to a significant decrease in alphafetoprotein level and liver enzymes activities, as compared to the positive control group. Moreover, injected ZNP/PEI/miR-34a nano-formulation led to a noticeable decrease in the CD44 and c-Myc levels. Results also showed that ZNP/PEI/miR-34a nano-formulation inhibited several target oncogenes including AEG-1, and SOX-9, in vitro and in vivo. Conclusion: Our results suggested that miR-34a is a powerful candidate in HCC treatment and that AEG-1 and SOX-9 are novel oncotargets of miR-34a in HCC. Results also demonstrated that our nano-formulation may serve as a candidate approach for miR-34a restoration for HCC therapy, and generally for safe gene delivery.

scholarly journals Potential Role of microRNA-183 as a Tumor Suppressor in Hepatocellular Carcinoma

2018 ◽  
Vol 51 (5) ◽  
pp. 2065-2072 ◽  
Author(s):  
Wei Bian ◽  
Hongfei Zhang ◽  
Miao Tang ◽  
Shaojun Zhang ◽  
Lichao Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Metastatic Progression ◽  
Mesenchymal Transition ◽  
Reporter Assays

Background/Aims: Disseminated tumors, known as metastases, are responsible for ninety-percent of mortality due to cancer. Epithelial to mesenchymal transition, a phenomenon required for morphological conversion of non-motile discoid shaped epithelial cells to highly motile spindle-shaped mesenchymal cells, is thought to be a pre-requisite for metastatic progression. Metastasis-associated 1 (MTA1) protein is a prime inducer of EMT and metastatic progression in all solid tumors including hepatocellular carcinoma (HCC). However, the molecular mechanisms that regulate the expression and function of MTA1 in HCC have not been elucidated. Methods: In silico prediction algorithms were used to find microRNAs (miRNAs) that may target MTA1. We examined the relationship between the expression of MTA1 and miR-183 using quantitative real time PCR. We also determined the levels of the MTA1 protein using immunohistochemistry. Reporter assays, in the presence and absence of the miR-183 mimic, were used to confirm MTA1 as a bona fide target of miR183. The effect of miR-183 on HCC pathogenesis was determined using a combination of in vitro migration and invasion assay, together with in vivo xenograft experiments. The correlation between miR-183 and MTA1 expression was also studied in samples from HCC patients, and in The Cancer Genome Atlas dataset. Results: Analysis of the sequence database revealed that MTA1 is a putative target of miR-183. MTA1 protein and RNA expression showed opposite trends to miR-183 expression in breast, renal, prostate, and testicular tissue samples from cancer patients, and in the metastatic HCC cell line HepG2. An inverse correlation was also observed between MTA1 (high) and miR-183 (low) expression within samples from HHC patients and in the TCGA dataset. Reporter assays in HepG2 cells showed that miR-183 could inhibit translation of a reporter harboring the wild-type, but not the mutant miR-183 3’-untranslated region (UTR). In addition, miR-183 significantly inhibited in vitro migration and invasion in HepG2 cells, and in vivo hepatic metastasis. Conclusion: Our results reveal a novel post-transcriptional regulatory mechanism for MTA1 expression via miR-183, which is suppressed during HCC pathogenesis.

scholarly journals IN VITRO ANTIOXIDANT AND IN VIVO ANTIDIABETIC ACTIVITY OF TWO POTENTIAL PROBIOTIC ENTEROCOCCUS SPP. ON ALLOXAN-INDUCED DIABETIC RATS

2021 ◽  
pp. 94-98
Author(s):  
KAMNI RAJPUT ◽  
RAMESH CHANDRA DUBEY
Keyword(s):  
Diabetic Rats ◽  
Antidiabetic Activity ◽  
Control Group ◽  
Albino Rats ◽  
Bacterial Cells ◽  
Bacterial Strains ◽  
Animal Group ◽  
Enterococcus Spp

Objective: In vitro antioxidant activity, in vivo antidiabetic property and intestinal attachment by two potential probiotic bacterial strains, namely, Enterococcus faecium and Enterococcus hirae were studied using albino rats. Methods: Antioxidant the activity was assessed using 2,2-Diphenyl-1-picrylhydrazyl radicals scavenging assay. Alloxan was administered intraperitoneally to induce diabetic conditions in experimental rats. Animals were treated with oral administration of Enterococcus spp., such as E. faecium, and E. hirae isolated from goat and sheep milk. The control animal group received normal saline for the same days. Glibenclamide drug was used as a positive control against probiotic bacterial cells. Results: However, administration of probiotic bacterial strains E. faecium and E. hirae, in albino rats significantly (p<0.05) at varying doses lowered blood glucose levels in diabetic rats as compared to the diabetic control group. Both the species of Enterococcus increased the bodyweight of experimental rats. However, E. faecium was the best antidiabetic strain having the antioxidant activities also in comparison to E. hirae. The attachment of probiotic bacterial cells E. faecium on the rat’s intestine wall against pathogens was examined. Furthermore, E. faecium showed its aggregation with pathogens by attachment of the intestines of albino rats. This showed that both the bacterial strains exhibited in vivo antidiabetic effect. Conclusion: The results of this study showed that probiotic bacteria possess antioxidant, antidiabetic activities, and attachment of intestine.

Pharmacognostical Standardization, Isolation of Phytoconstituents (β-sitosterol), HPTLC analysis of extracts of Operculina turpethum (Linn.) roots and evaluation of cytotoxic, in vitro & in vivo anti-inflammatory activities

2021 ◽  
Vol 18 ◽  
Author(s):  
Akash Ved ◽  
Shweta Gupta ◽  
Namrata Singh ◽  
Karuna S. Shukla ◽  
Om Prakash ◽  
...  
Keyword(s):  
Column Chromatography ◽  
Inflammatory Activity ◽  
Control Group ◽  
Albino Rats ◽  
Cell Viability Assay ◽  
Edema Formation ◽  
Egg Albumin ◽  
Anti Inflammatory

Background: Operculina turpethum (Linn.) Silva Manso, family- convolvulaceae, is an important plant in Indian conventional system of medicine which is extensively employed by different tribes in many countries to cure edema and painful conditions like arthritis, back pain; hyperlipidemia, diabetes mellitus, liver disorders, skin disorders and to regulate bowel functions. Objective: The roots of O. turpethum (Linn.) was subjected to physicochemical, phytochemical standardization, the chromatographic separation which was accomplished by column chromatography, TLC, and HPTLC, further, the acute toxicity, cytotoxic and anti-inflammatory activities of Operculina turpethum roots were estimated by in vivo and in vitro models. Materials and Methods: This study includes percentage yield of extraction, organoleptic evaluation along with the analysis of its physicochemical investigations & preliminary phytochemical estimation. The isolation of active phytoconstituents was done by column chromatography, and the isolated compound was then exposed to TLC and HPTLC analysis. Cytotoxic activity was tested by WST-1 based cell viability assay on HepG2 cells. Anti-inflammatory activity of methanol extract (ME) was evaluated against inflammation occur by both in vitro and in vivo method. Results: The methanolic extract exhibited the presence of most of the phytoconstituents out of all the extracts, the phytoconstituent phytosterol, i.e., β-sitosterol was isolated by column chromatography, identified and quantified by TLC and HPTLC, which is liable for anti-inflammatory activity. The amount of β-sitosterol was estimated to be 14.09 µg in 10.00 mg fraction of MEOT. MEOT is devoid of toxicity up to 2000 mg/kg in Wistar albino rats. It was analysed that in vitro anti-inflammatory activity of MEOT by egg albumin denaturation method exhibited a incredible decrement in turbidity and increasing the percentage inhibition of albumin denaturation (60.52%) in MEOT treated group as compared with control group. In egg albumin-induced edema in rats, MEOT at the dose of 400 mg/kg reduced the edema formation (3.03 ± 0.02) induced by egg albumin at 4th h. In cotton pellet-induced granuloma in rats, MEOT at the dose of 400 mg/kg displayed maximum granuloma inhibition (51.06%) which is similar to that of indomethacin. Conclusion: From the obtained findings it is confirmed that O. turpethum contains β-sitosterol which is responsible for potent anti-inflammatory activity without causing cytotoxicity to the plant. The results suggested that ME of O. turpethum roots had high potential for application as an anti-inflammatory agent. The recognization and confirmation of the plant can be obtaineded from the study and will present data which is aidful in determining the quality and purity of a crude drug which further helps in preventing its adulteration.

scholarly journals Lemon Balm Extract and Its Major Chemical Compound, Rosmarinic Acid, Alleviate Damages of Liver in an Animal Model of Nonalcoholic Steatohepatitis (NASH) (P06-093-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Gyhye Yoo ◽  
Myungsuk Kim ◽  
Ahmad Randy ◽  
Yang-Ju Son ◽  
Chi Rak Hong ◽  
...  
Keyword(s):  
Animal Model ◽  
Chemical Compound ◽  
Rosmarinic Acid ◽  
Hepg2 Cells ◽  
In Vivo Model ◽  
World Population ◽  
Lemon Balm ◽  
Major Chemical

Abstract Objectives The non-alcoholic fatty liver disease (NAFLD) comprises the broad histopathological states of liver, that ranging from asymptomatic hepatic steatosis to non-alcoholic steatohepatitis (NASH) and liver cirrhosis. In some studies, they suppose that almost 25–30% of world population is underlying NAFLD. Lemon balm (Melissa officinalis) is the herb that has some traditional medicinal usages. Also rosmarinic acid (RA; O-caffeoyl-3,4-dihydroxyphenyl lactic acid), the major chemical compound of lemon balm, already reported that it has the potency on anti-obesity and -inflammatory. Hence, we evaluate the whether lemon balm extract (LBE) and RA could suppress the pathogenesis of NASH using an in vitro and in vivo model. Methods In vitro model: The palmitic acid (PA) exposed HepG2 hepatocellular carcinoma cells can imitate the lipid accumulation in hepatocytes. PA exposed HepG2 cells were exposed with or without LBE or RA. In vivo model: The methionine- and choline-deficient (MCD) diet fed db/db C57BL/6 J mice model was used. This model is known as it can mimic well symptoms of human NAFLD. The LBE or RA were treated by oral gavage. Results With the MCD diet only, the severe liver damage was caused by progression of NASH in animal model. LBE and RA treatments alleviated the oxidative stress in the MCD diet-fed db/db mice and PA-exposed HepG2 cells by increasing the expression of antioxidant enzymes (NRF2, SOD) and augmented lipolysis-related gene (PPARα, PGC-1α, CPT-1 L) expression. In addition, LBE and RA treatments inhibited the expression of genes involved in hepatic fibrosis (α-SMA, COL1A1) and fatty acid synthesis (SREBP-1c, CPT-1 L) and activated AMP-activated protein kinase in vitro and in vivo. Also, the histopathological results were ameliorated by treatment of LBE or RA. Conclusions LBE and RA modulate lipid metabolism via AMPK activation and suppress inflammation via changes in NRF2 and NF-κB signalling. Importantly, the extract of lemon balm obtained with 20% EtOH showed effectiveness similar to that of RA at high concentrations. Therefore, LBE may be a good candidate for the treatment and prevention of NASH. Funding Sources This work was supported by the National Research Council of Science & Technology (NST) funded by the Korea Government (MSIP) (grant No. CRC-15-01-KIST). Supporting Tables, Images and/or Graphs

scholarly journals Anti-tumor effect of polysaccharide from Pleurotus ostreatus on H22 mouse Hepatoma ascites in-vivo and hepatocellular carcinoma in-vitro model

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kavish Hasnain Khinsar ◽  
Sattar Abdul ◽  
Akbar Hussain ◽  
Riaz Ud Din ◽  
Liu Lei ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gene Regulation ◽  
Side Effects ◽  
Tumor Suppression ◽  
Pleurotus Ostreatus ◽  
Edible Mushroom ◽  
Malignant Ascites ◽  
In Vivo Model

AbstractHepatocellular carcinoma is one of the leading causes of cancer-associated death across the globe. Malignant ascites are the major clinical attributes in cancer patients. Despite the advancements in HCC treatments such as chemotherapy, radiotherapy, surgery, and hormonal therapy, researchers are pursuing novel natural edible compounds for the treatment of cancer to eliminate dreadful side effects. Pleurotus ostreatus is one of the most edible cuisines in Asia as well as all over the world. It has been a source of nutritious diet since it was classified as an edible mushroom with no or negligible side effects. The present study focused on the natural anti-cancerous and anti-ascites capabilities of polysaccharides extracted from Pleurotus ostreatus in-vivo as well as in-vitro. Administration of polysaccharide Pleurotus ostreatus showed a significant decrease in tumor cell metastasis while the increase in the survival period among mice models of H22 malignant ascites. Downregulation of regenerative genes Foxp3 and Stat3 and secretion of immunological factors such as IL-2, TNF α, and INF γ were observed after treating with the partially pure extracted polysaccharide. Twining with the hypothesis of tumor suppression in-vivo model polysaccharide showed a decrease in invasion and migration abilities and henceforth responsible for the gene regulation such Cytochrome C which supposedly induced the chain of gene regulation process resulting in apoptosis in HCC cell lines observed in-vitro experiments. Collective research findings manifested that polysaccharide extracted from Pleurotus ostreatus bears anti-proliferative activity and thus influence tumor suppression in-vivo and in-vitro against hepatocellular carcinoma and can be used for therapeutic purposes as a potential anti-cancerous source in the future.

scholarly journals Hepatocellular Carcinoma Growth Is Inhibited byEuphorbia helioscopiaL. Extract in Nude Mice Xenografts

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Junsheng Cheng ◽  
Wei Han ◽  
Zheyuan Wang ◽  
Yuan Shao ◽  
Yingzhen Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chromatin Condensation ◽  
Xenograft Model ◽  
Inhibitory Effect ◽  
Control Group ◽  
Potential Candidate ◽  
Invasion And Metastasis ◽  
Mouse Xenograft Model

Euphorbia helioscopiaL. is a traditional Chinese medicine; recently research found that its ethyl acetate extract (EAE) plays an important role on tumor cell proliferation, apoptosis, invasion, and metastasisin vitro. But the effect of EAE for tumor cellsin vivohas not been reported. To explore the inhibitory effect of EAE and molecular mechanism on hepatocellular carcinoma (HCC) SMMC-7721 cellsin vivo, we utilized the nude mouse xenograft model of HCC. Treated with EAE (50, 100, and 200 μg/mL), the volume of xenograft was measured during the entire process of EAE treatment. In EAE treatment group, the volume of xenograft was significantly reduced compared with the control group (P<0.05) and the protein expressions of CyclinD1, bcl-2, and MMP-9 were reduced, while those of bax, caspase-3, and nm23-H1 were increased. A significant change trend with increasing EAE concentrations has presented, compared with controls. Moreover, the ultrastructural morphology of xenografts showed significant changes, including nuclear pyknosis and chromatin condensation, We found that EAE could effectively inhibit tumor growth, induce apoptosis, and inhibit tumor invasion and metastasisin vivo; it is suggested that EAE is a potential candidate for as a new anticancer agent.

GH002: A Novel and Potent Agents for Elevating HDL-Cholesterol

2011 ◽  
Vol 340 ◽  
pp. 337-343
Author(s):  
Guo Lei
Keyword(s):  
Hepg2 Cells ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Control Group ◽  
Vitro Assay ◽  
Cholesterol Levels ◽  
Promoter Effects ◽  
Positive Effect

The aim of this study was to evaluate whether the positive effect of GH002 on high-density lipoprotein (HDL) cholesterol in vitro and in vivo. In vitro assay, effects of GH002 on apolipoprotein (apo) A-I was studied using stable-transfected HepG2 cells with recombinant vector including apoA-I promoter; Effects of GH002 on apoA-I, apoA-II and apoC-III production were determined using HepG2 cells. In vivo assay, Effects of GH002 on lipid profile were investigated in hyperlipidemic rats. The results showed that GH002 can effectively activate apoA-I promoter, enhance apoA-I and apoA-II secretion in vitro, whereas reduce apoC-III production significantly. Furthermore, after in vivo study that the hyperlipidemic rats were treated with GH002, HDL-cholesterol levels were increased significantly (P<0.01) at 2 weeks (100 mg/kg, 28.8%) and 3 weeks (30mg/kg, 19.8% and 100mg/kg, 36.4%, respectively) compared with control group. Triglyceride levels were reduced significantly at 2 and 3 weeks (19.5%, P<0.05 and 28.1%, P<0.01 respectively). Total cholesterol levels also were reduced at 3 weeks (19.1%, P<0.05) after 100mg/kg GH002 administration, but GH002 didn’t increase the ratio of liver/body weight compared with the control group at the end of the experiments. It is therefore reasonable to assume that GH002 is an effectively HDL-cholesterol enhancer by regulating apoA-I gene expression, consequently enhancing apoA-I, apoA-II secretion and reducing apoC-III production.

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