scholarly journals Ziziphus spina-christi leaves methanolic extract alleviates diethylnitrosamine-induced hepatocellular carcinoma in rats

2019 ◽  
Vol 97 (4) ◽  
pp. 437-445 ◽  
Author(s):  
Manar Salah El-Din ◽  
AlShaimaa Mohamed Taha ◽  
Ahmed Abdel-Aziz Sayed ◽  
Ahmed Mohamed Salem
Keyword(s):  
Oxidative Stress ◽  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Methanolic Extract ◽  
Essential Fatty Acids ◽  
B Cell Lymphoma ◽  
Cytotoxic Activities ◽  
Male Wistar Rats ◽  
Metalloproteinase 9

This study evaluated the antitumor activity of a methanolic extract from the leaves of Ziziphus spina-christi (ZSCL) against diethylnitrosamine (DENA)-induced hepatocarcinoma in rats. The phytochemical constituents, in vitro antioxidant and cytotoxic activities of ZSCL extract were investigated. Male Wistar rats were distributed among 6 groups: (i) normal control; (ii) ZSCL1-treated rats (100 mg/kg body mass; “b.m.”); (iii) ZSCL2-treated rats (300 mg/kg b.m.); (iv) rats with DENA-induced hepatocarcinoma; (v and vi) rats with hepatocarcinoma that were treated with either (v) ZSCL1 or (vi) ZSCL2. Serum liver function and levels of oxidative stress were assayed. The expression of hepatocyte growth factor, insulin-like growth factor-1 receptor, B cell lymphoma-2, and matrix metalloproteinase-9 oncogenes were quantified in liver samples. Histological examination of the liver tissues was performed. The ZSCL was rich in essential fatty acids, phytol, and polyphenolic flavones (luteolin and quercetin) with strong free-radical and peroxide scavenging activities and cytotoxic activity. Administration of ZSCL1 and ZSCL2 to the rats produced no toxic effects. DENA induced hepatocellular carcinoma and cholangioma by producing oxidative stress and upregulating the expression of hepatic oncogenes. Treatment of DENA-induced hepatocarcinoma with ZSCL2 ameliorated all of the abnormalities induced by DENA except for cholangioma. In conclusion, the ZSCL (300 mg/kg b.m.) displayed strong therapeutic activity against DENA-induced hepatocellular carcinoma via targeting oxidative stress and oncogenes.

CISSAMPELOS PAREIRA: PROTEIN-LIGAND DOCKING TO IDENTIFY SUITABLE TARGETS FOR HEPATOCELLULAR CARCINOMA (HCC) BY IN-SILICO TECHNIQUES AND TOOLS

2015 ◽  
Vol 77 (2) ◽  
Author(s):  
B. Samuel Thavamani ◽  
Molly Mathew ◽  
Dhanabal S. Palaniswamy
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
In Silico ◽  
B Cell Lymphoma ◽  
Aurora Kinase ◽  
Pharmacological Action ◽  
Ligand Docking ◽  
Ligand Interaction

Protein-ligand interaction plays a major role in identification of the possible mechanism by which a ligand can bind with the target and exerts the pharmacological action. The present study aims to identify new possible candidates for treating Hepatocellular Carcinoma (HCC) by docking the reported phytochemicals present in Cissampelos pareira with the well known HCC targets using in-silico techniques. Although C. pareira demonstrated in vitro and in vivo anti-heptatocellular carcinoma activities, the mechanism remains uncertain. Selected compounds from C. pareira were docked using GLIDE software with known targets of hepatocellular carcinoma viz. Aurora Kinase, c-Kit, Fibroblast Growth Factor (FGF), Nuclear Factor kappa B (NF-kB), B-cell lymphoma-extra large (Bcl-xL) and Vascular Endothelial Growth Factor (VEGF). Among the compounds docked, pareitropone and pareirubrine B exhibited good hydrogen bonding interactions and binding energy with the targets of HCC taken in the study. Hence these compounds deserve consideration for further studies towards HCC.

scholarly journals Effect of Shuangdan Mingmu capsule, a Chinese herbal formula, on oxidative stress-induced apoptosis of pericytes through PARP/GAPDH pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fujiao Nie ◽  
Jiazhao Yan ◽  
Yanjun Ling ◽  
Zhengrong Liu ◽  
Chaojun Fu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Oxidative Damage ◽  
Damage Model ◽  
B Cell Lymphoma ◽  
Cell Counting ◽  
Network Pharmacology ◽  
Diabetic Patients ◽  
Induced Apoptosis

Abstract Background Diabetic retinopathy (DR) has become a worldwide concern because of the rising prevalence rate of diabetes mellitus (DM). Despite much energy has been committed to DR research, it remains a difficulty for diabetic patients all over the world. Since apoptosis of retinal microvascular pericytes (RMPs) is the early characteristic of DR, this study aimed to reveal the mechanism of Shuangdan Mingmu (SDMM) capsule, a Chinese patent medicine, on oxidative stress-induced apoptosis of pericytes implicated with poly (ADP-ribose) polymerase (PARP) / glyceraldehyde 3-phosphate dehydrogenase (GAPDH) pathway. Methods Network pharmacology approach was performed to predict biofunction of components of SDMM capsule dissolved in plasma on DR. Both PARP1 and GAPDH were found involved in the hub network of protein-protein interaction (PPI) of potential targets and were found to take part in many bioprocesses, including responding to the regulation of reactive oxygen species (ROS) metabolic process, apoptotic signaling pathway, and response to oxygen levels through enrichment analysis. Therefore, in vitro research was carried out to validate the prediction. Human RMPs cultured with media containing 0.5 mM hydrogen oxide (H2O2) for 4 h was performed as an oxidative-damage model. Different concentrations of SDMM capsule, PARP1 inhibitor, PARP1 activation, and GAPDH inhibitor were used to intervene the oxidative-damage model with N-Acetyl-L-cysteine (NAC) as a contrast. Flow cytometry was performed to determine the apoptosis rate of cells and the expression of ROS. Cell counting kit 8 (CCK8) was used to determine the activity of pericytes. Moreover, nitric oxide (NO) concentration of cells supernatant and expression of endothelial nitric oxide synthase (eNOS), superoxide dismutase (SOD), B cell lymphoma 2 (BCL2), vascular endothelial growth factor (VEGF), endothelin 1 (ET1), PARP1, and GAPDH were tested through RT-qPCR, western blot (WB), or immunocytochemistry (ICC). Results Overproduction of ROS, high apoptotic rate, and attenuated activity of pericytes were observed after cells were incubated with media containing 0.5 mM H2O2. Moreover, downregulation of SOD, NO, BCL2, and GAPDH, and upregulation of VEGFA, ET1, and PARP1 were discovered after cells were exposed to 0.5 mM H2O2 in this study, which could be improved by PARP1 inhibitor and SDMM capsule in a dose-dependent way, whereas worsened by PARP1 activation and GAPDH inhibitor. Conclusions SDMM capsule may attenuate oxidative stress-induced apoptosis of pericytes through downregulating PARP expression and upregulating GAPDH expression.

scholarly journals Effect of Caffeic Acid Phenethyl Ester Provision on Fibroblast Growth Factor-2, Matrix Metalloproteinase-9 Expression, Osteoclast and Osteoblast Numbers during Experimental Tooth Movement in Wistar Rats (Rattus norvegicus)

2021 ◽  
Author(s):  
Ida Bagus Narmada ◽  
Paristyawati Dwi Putri ◽  
Lucky Lucynda ◽  
Ari Triwardhani ◽  
I Gusti Aju Wahju Ardani ◽  
...  
Keyword(s):  
Growth Factor ◽  
Matrix Metalloproteinase ◽  
Rattus Norvegicus ◽  
Wistar Rats ◽  
Tooth Movement ◽  
Caffeic Acid Phenethyl Ester ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Male Wistar Rats ◽  
Metalloproteinase 9

Abstract Objectives To investigate the effect of caffeic acid phenethyl ester (CAPE) provision on matrix metalloproteinase-9 (MMP-9), fibroblast growth factor-2 (FGF-2) expression, osteoclast and osteoblast numbers during experimental orthodontic tooth movement (OTM) in male Wistar rats (Rattus norvegicus). Materials and Methods Forty-eight healthy male Wistar rats (R. norvegicus), 16 to 20 weeks old with 200 to 250 g body weight (bw) were divided into several groups as follows: K1: OTM for 3 days; K2: OTM for 7 days; K3: OTM for 14 days; KP1: OTM and CAPE for 3 days; KP2: OTM and CAPE for 7 days; and KP3: OTM and CAPE for 14 days. A nickel titanium closed coil spring 8.0 mm long with 10 g/mm2 was installed between the upper left first molar and upper central incisor to move molar mesially. CAPE provision with a dose of 20 mg/kg bw of animal studies was done per orally. Immunohistochemistry was done to examine MMP-9 expression and osteoclast number in compression side as well as FGF-2 expression and osteoblast number in tensile side of the OTM. Statistical Analysis One-way analysis of variance test and Tukey’s honest significant difference test were performed to determine the difference between the groups (p < 0.05). Results MMP-9 expression and osteoclast numbers in the compression side were significantly different between the groups. Similarly, FGF-2 expression and osteoclast numbers in the tensile side were significantly different between the groups. Conclusions CAPE provision during OTM increases the number of osteoblasts and the FGF-2 expression significantly in the tensile side. Osteoclast numbers and MMP-9 expression significantly decrease in the compression side.

Oxidative stress in primary culture hepatocytes isolated from partially hepatectomized rats

2007 ◽  
Vol 85 (10) ◽  
pp. 1047-1051 ◽  
Author(s):  
Daniel Francés ◽  
M. Teresa Ronco ◽  
Elena Ochoa ◽  
M. Luján Alvarez ◽  
Ariel Quiroga ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Primary Culture ◽  
Cell Injury ◽  
Cultured Cells ◽  
Male Wistar Rats ◽  
Metabolic Activities ◽  
Stress Oxidative ◽  
Species Production

The aim of this study was to evaluate the influence of partial hepatectomy prior to cell isolation on hepatocytes in vitro. We characterized the possible changes of various stress oxidative parameters within the first 24 h after seeding. Male Wistar rats served as donors. Hepatocytes were isolated by collagenase digestion from either liver of simulated surgery (SH) or from liver 1 h after 70% hepatectomy (PH), and the changes in stress parameters were analyzed after 1, 3, 18, and 24 h in culture. At 24 h, only hepatocytes from PH maintained significantly increased reactive oxygen species production, oxidized glutathione percentage, and Cu/Zn superoxide dismutase and catalase activities. Our results show that hepatocytes suffer significant cell injury as a result of the isolation procedure, but primary cultured cells from SH metabolically recover from this stress after 18 h. After this time, primary culture hepatocytes primed by PH maintain their in vivo-like metabolic activities (increase in both oxidative stress and antioxidant status).

92 INSULIN-LIKE GROWTH FACTOR-1 PROTECTS BOVINE PRE-IMPLANTATION EMBRYOS PRODUCED IN VITRO FROM ANTI-DEVELOPMENTAL ACTIONS OF MENADIONE

2016 ◽  
Vol 28 (2) ◽  
pp. 176
Author(s):  
N. A. S. Rocha-Frigoni ◽  
B. C. S. Leão ◽  
P. C. Dall'Acqua ◽  
M. Ambrogi ◽  
G. Z. Mingoti
Keyword(s):  
Oxidative Stress ◽  
Growth Factor ◽  
Molecular Probes ◽  
Insulin Like Growth Factor ◽  
Blastocyst Development ◽  
Chi Square ◽  
Fluorescent Intensity ◽  
Chi Square Test ◽  
Student’S T

The objective of this study was to evaluate the protective effect of insulin-like growth factor (IGF-1) on blastocyst development and cryotolerance of bovine embryos in in vitro culture (IVC) under oxidative stress induced by menadione (MD). Cumulus-oocyte complexes (n = 1421) were matured in TCM-199 with bicarbonate, hormones, and 10% FCS for 22 h. After fertilization, the presumptive zygotes were cultured up to 7 days in SOF medium with 2.5% FCS and 0.5% BSA (control), and also supplemented with 100 μM IGF-1 (IGF). At Day 6, MD was included in the culture medium (0 μM, control; or 5.0 μM, MD) during 24 h. Cultures were conducted at 38.5°C in 5% CO2 in air. The cleavage and blastocysts rates were evaluated, respectively, at Days 3 and 7 (IVF = Day 0). At Day 7, a sample of the blastocysts was stained with 5 μM H2DCFDA (Molecular Probes, Canada) to evaluate the intracellular ROS levels or was stained for TUNEL (In Situ Cell Death Detection Kit, Roche, Indianapolis, IN, USA). Stained embryos were immediately evaluated under an epifluorescence microscope (excitation 495/550 nm and emission 404/590 nm, respectively, for ROS and TUNEL), and the images of embryos stained with H2DCFDA were analysed by Q-Capture Pro image software for determining the fluorescent intensity. Other blastocysts were vitrified (Ingámed®, Maringá-PR, Brazil), and after warming, they were cultured for 24 h to evaluate the re-expansion rates. The results were compared by ANOVA followed by Student’s t-test (mean ± s.e.M) and re-expansion rates by chi-square test (P < 0.05). The cleavage rates did not differ (P > 0.05) among groups (77.1 ± 1.9% to 82.75 ± 2.2%). The blastocyst rates were similar between control (35.4 ± 2.0%) and IGF (34.5 ± 3.7%), and both were higher (P < 0.05) than MD (21.3 ± 2.7%); the IGF+MD group (28.3 ± 1.6%) was similar (P > 0.05) to all groups. The intracellular levels of ROS were higher (P < 0.05) for the MD group (21.7 ± 0.7) than for control (17.0 ± 1.6), and both were similar (P > 0.05) to the IGF (19.2 ± 0.6) and IGF+MD (18.0 ± 1.0) groups. The highest rates of apoptosis were found in the MD group (22.3% ± 2.3) and the smallest in IGF (9.1% ± 0.7), and both differed (P < 0.05) from control (12.8% ± 1.0), and IGF+MD (15.6% ± 1.6). The re-expansion rates were similar between control (77.4%) and IGF (69.2%), and both were higher (P < 0.05) than MD (49.1%); however, the IGF+MD group (57.6%) was similar (P > 0.05) to IGF and MD groups. In conclusion, the supplementation with IGF-1 during IVC reversed the detrimental effects of MD on embryonic levels of ROS and apoptosis, as well as improved the embryo development and cryotolerance of blastocysts under oxidative stress. Financial support was provided by FAPESP (#2012/10083–8 and #2013/07382–6).

scholarly journals LongShengZhi Capsule Attenuates Alzheimer-Like Pathology in APP/PS1 Double Transgenic Mice by Reducing Neuronal Oxidative Stress and Inflammation

2020 ◽  
Vol 12 ◽  
Author(s):  
Zequn Yin ◽  
Xuerui Wang ◽  
Shihong Zheng ◽  
Peichang Cao ◽  
Yuanli Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transgenic Mice ◽  
Amyloid Β ◽  
B Cell Lymphoma ◽  
Acanthopanax Senticosus ◽  
Neuroprotective Effects ◽  
Long Term Treatment ◽  
Double Transgenic Mice ◽  
The Brain

Alzheimer’s disease (AD) is the most common form of dementia in the elderly. It may be caused by oxidative stress, inflammation, and cerebrovascular dysfunctions in the brain. LongShengZhi Capsule (LSZ), a traditional Chinese medicine, has been approved by the China Food and Drug Administration for treatment of patients with cardiovascular/cerebrovascular disease. LSZ contains several neuroprotective ingredients, including Hirudo, Astmgali Radix, Carthami Flos (Honghua), Persicae Semen (Taoren), Acori Tatarinowii Rhizoma (Shichangpu), and Acanthopanax Senticosus (Ciwujia). In this study, we aimed to determine the effect of LSZ on the AD process. Double transgenic mice expressing the amyloid-β precursor protein and mutant human presenilin 1 (APP/PS1) to model AD were treated with LSZ for 7 months starting at 2 months of age. LSZ significantly improved the cognition of the mice without adverse effects, indicating its high degree of safety and efficacy after a long-term treatment. LSZ reduced AD biomarker Aβ plaque accumulation by inhibiting β-secretase and γ-secretase gene expression. LSZ also reduced p-Tau expression, cell death, and inflammation in the brain. Consistently, in vitro, LSZ ethanol extract enhanced neuronal viability by reducing L-glutamic acid-induced oxidative stress and inflammation in HT-22 cells. LSZ exerted antioxidative effects by enhancing superoxide dismutase and glutathione peroxidase expression, reduced Aβ accumulation by inhibiting β-secretase and γ-secretase mRNA expression, and decreased p-Tau level by inhibiting NF-κB-mediated inflammation. It also demonstrated neuroprotective effects by regulating the Fas cell surface death receptor/B-cell lymphoma 2/p53 pathway. Taken together, our study demonstrates the antioxidative stress, anti-inflammatory, and neuroprotective effects of LSZ in the AD-like pathological process and suggests it could be a potential medicine for AD treatment.

scholarly journals In VitroandIn VivoAntimalarial Evaluations of Myrtle Extract, a Plant Traditionally Used for Treatment of Parasitic Disorders

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Farzaneh Naghibi ◽  
Somayeh Esmaeili ◽  
Noor Rain Abdullah ◽  
Mehdi Nateghpour ◽  
Mahdieh Taghvai ◽  
...  
Keyword(s):  
Cell Lines ◽  
Mammalian Cell ◽  
Methanolic Extract ◽  
Cytotoxic Activities ◽  
Traditional Use ◽  
Aerial Parts ◽  
Mammalian Cell Lines ◽  
Phytochemical Investigation

Based on the collected ethnobotanical data from the Traditional Medicine and Materia Medica Research Center (TMRC), Iran,Myrtus communisL. (myrtle) was selected for the assessment ofin vitroandin vivoantimalarial and cytotoxic activities. Methanolic extract of myrtle was prepared from the aerial parts and assessed for antiplasmodial activity, using the parasite lactate dehydrogenase (pLDH) assay against chloroquine-resistant (K1) and chloroquine-sensitive (3D7) strains ofPlasmodium falciparum. The 4-day suppressive test was employed to determine the parasitemia suppression of the myrtle extract againstP. berghei  in vivo. The IC50values of myrtle extract were 35.44 µg/ml against K1 and 0.87 µg/ml against 3D7. Myrtle extract showed a significant suppression of parasitaemia (84.8 ± 1.1% at 10 mg/kg/day) in mice infected withP. bergheiafter 4 days of treatment. Cytotoxic activity was carried out against mammalian cell lines using methyl thiazol tetrazolium (MTT) assay. No cytotoxic effect on mammalian cell lines up to 100 µg/mL was shown. The results support the traditional use of myrtle in malaria. Phytochemical investigation and understanding the mechanism of action would be in our upcoming project.

scholarly journals Anthelmintic and Cytotoxic Activities of Two Medicinal Plants: Polygonum viscosum and Aphanamixis polystachya Growing in Bangladesh

2014 ◽  
Vol 6 (2) ◽  
pp. 339-345 ◽  
Author(s):  
M. N. Amin ◽  
M. S. Majumder ◽  
M. M. R. Moghal ◽  
S. Banik ◽  
A. Kar ◽  
...  
Keyword(s):  
Methanolic Extract ◽  
Anthelmintic Activity ◽  
Cytotoxic Activities ◽  
Dependent Manner ◽  
Reference Standard ◽  
Cytotoxic Potential ◽  
Lc50 Value ◽  
Vincristine Sulphate ◽  
Dose Dependent

The present study was designed to investigate in vitro anthelmintic and cytotoxic activities of crude methanolic extract of two plants(Polygonum viscosum and Aphanamixis polystachya) grown in Bangladesh. Evaluation of cytotoxic activity was done using the brine shrimp lethality bioassay. The crude methanolic extract of Polygonum viscosum showed significant cytotoxic potential (LC50 value of 6.34 ?g/ml) among all the fractions comparing with that of standard vincristine sulphate (0.825 ?g/ml). Besides, the LC50 values of crude methanolic extract, pet ether and chloroform extracts of Aphanamixis polystachya showed good cytotoxic activities 11, 10.36, and 16.45 µg/ml, respectively. The other study was undertaken to evaluate anthelmintic activity (using Pheretima posthuma model) where piperazine was used as reference standard. The crude methanolic extract of Polygonum viscosum leaves produced a significant anthelmintic activity in dose dependent manner and the activity of crude extract was comparable with that of standard drugs. Besides, the Aphanamixis polystachya extract revealed moderate anthelmintic activity. Here, the anova testing was done with the P < 0.05. Further studies are suggested to determine the active compounds responsible for the anthelmintic and cytotoxic activities of these two plant extracts.   Keywords: Anthelmintic; Cytotoxic; Medicinal plant; Aphanamixis polystachya; Polygonum viscosu.  © 2014 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved.   doi: http://dx.doi.org/10.3329/jsr.v6i2.17299 J. Sci. Res. 6 (2), 339-345 (2014) 

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