Naringin alleviates methotrexate-induced liver injury in male albino rats and enhances its antitumor efficacy in HepG2 cells

Abstract Methotrexate (MTX) is an efficient chemotherapeutic and immunosuppressant drug, but the hepatotoxicity of MTX limits its clinical use. Naringin (Nar) is a flavonoid derived from Citrus paradise, and has been shown to possess several pharmacological activities, including free-radical scavenging and antioxidant properties. In the present study, we first tested the possible protective effects of multiple doses of Nar against MTX-induced acute hepatotoxicity in rats, and then we investigated the growth inhibition and apoptotic effects of MTX and/or Nar against the HepG2 hepatocarcinoma cell line. Our in vivo results showed that Nar significantly reduced MTX-induced increases in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin levels. Nar also reduced MTX-induced oxidative stress by significantly reducing liver malondialdehyde (MDA) and nitric oxide (NO) content and increasing superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH). In addition, Nar significantly counteracted MTX-induced increases in hepatic interleukin-6 and tumor necrosis factor-α (TNF-α). Further, Nar greatly protected hepatocyte ultrastructure against MTX-induced injury. In contrast, in vitro MTX and/or Nar treatment of HepG2 cells for 48 h exhibited a cytotoxic effect and induced apoptosis in a dose-dependent manner mediated by a significant increase in the Bax/Bcl-2 protein expression ratio. Noticeably, Nar potentiated the MTX effect on the Bax/Bcl-2 ratio. In conclusion, Nar decreased MTX-induced functional and ultrastructural liver damage in a tumor-free animal model. Also, our data introduce MTX and Nar as promising antiproliferative agents with a distinctive mode of action, inducing apoptosis in HepG2 tumor cells through activation of Bax and down-regulation of Bcl-2 protein expression.

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Strong antihemolytic and antioxidant properties of aqueous extract from Algerian Hammada elegans (Bge.) Botsch (Chenopodiaceae)

Current Enzyme Inhibition ◽

10.2174/1573408017666210419115739 ◽

2021 ◽

Vol 17 ◽

Author(s):

Brahim Asseli ◽

Reguia Mahfoudi ◽

Amar Djeridane ◽

Mohamed Yousfi

Keyword(s):

Free Radical ◽

Aqueous Extract ◽

Radical Scavenging Activity ◽

Condensed Tannin ◽

Antioxidant Properties ◽

Radical Scavenging ◽

Total Phenolic ◽

Dependent Manner ◽

Vitro Assay

Background: Research on medicinal plant antioxidants has emerged as a potential therapeutic to prevent free radical generated damage in the human body. Hammada elegans Botsch (popularly known as “Ajram”) is a xerophytic plant widely found in Laghouat region, but there are only a few reports about the biological or chemical properties of these species. Hence, the aim of this study is to investigate the antioxidant and the antihemolytic activities of hexanic, acetonic, methanolic and aqueous extracts of aerial parts of Algerian Hammada elegans Botsch by employing different in vitro assay systems. Methods: The total phenolic content, the flavonoid content and the condensed tannin amount were analyzed using Folin-Ciocalteu, aluminum chloride and vanillin assays, respectively. The in vitro antioxidant capacity of extracts was assessed by CUPRAC, iron chelating, ABTS•+and antihemolytic assays, and was expressed as EC50 values. Results: Among the analyzed extracts, the aqueous extract had the highest phenolic, flavonoid and tannin contents. Also, this extract displayed the highest antioxidant capacities compared to the other extracts and standards. Its EC50 value for ABTS radical-scavenging activity was 0.265 ± 0.003 mg/L. Moreover, this extract showed high iron (II) chelating ability (EC50 = 0.958 ± 0.001 mg/L), and good antioxidant activity in the cupric ion reducing activity (CUPRAC) in a concentration dependent manner (EC50 were 0.709 ± 0.002 mg/L). Additionally, this extract had the best antihemolytic activity against AAPH-induced hemolysis (EC50=0.090 ± 0.004 mg/L). Conclusion: Our study revealed that the aqueous extract of Hammada elegans Botsch, is a potential source of antioxidants which possess a high protective effect of membrane against free radical.

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In vitro inhibitory potentials of ethanolic extract of Moringa oleifera flower against enzymes activities linked to diabetes

Journal of Herbmed Pharmacology ◽

10.34172/jhp.2021.48 ◽

2021 ◽

Vol 10 (4) ◽

pp. 408-414

Author(s):

Oluwaseun Ruth Olasehinde ◽

Olakunle Bamikole Afolabi ◽

Benjamin Olusola Omiyale ◽

Oyindamola Adeniyi Olaoye

Keyword(s):

Free Radical ◽

Moringa Oleifera ◽

Antioxidant Properties ◽

Radical Scavenging ◽

Ethanolic Extract ◽

Antidiabetic Activity ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Antioxidant Power

Introduction: Diabetes mellitus (DM) has been recognized as the seventh leading cause of global mortality; however, researchers seek alternative means to manage the menace. The current study sought to investigate antioxidant potentials, α-amylase, and α-glucosidase inhibitory activities of ethanolic extract of Moringa oleifera flower in vitro. Methods: Antioxidant properties of the extract were appraised by assessing its inhibition against 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl (OH•), and hydrogen peroxide (H2O2) free radicals, as well as ferric reducing antioxidant power (FRAP), the antidiabetic activity was evaluated by α-amylase and α-glucosidase inhibition.Results: In this study, ethanolic extract of M. oleifera flower demonstrated a significant (P < 0.05) inhibition against DPPH free radical (43.57–83.56%) in a concentration-dependent manner, while FRAP (101.76 ± 1.63 mg/100 g), OH• scavenging ability (71.62 ± 0.95 mg/100 g), and H2O2 free radical scavenging capacity (15.33 ± 1.20 mg/100 g) were also observed. In the same manner, ethanolic extract of M. oleifera flower revealed a significant (P < 0.05) inhibition against α-amylase (IC50= 37.63 mg/mL) and α-glucosidase activities (IC50= 38.30 mg/mL) in the presence of their respective substrates in a concentration-dependent manner in comparison with acarbose. Conclusion: Ethanoic extract of M. oleifera flower could be useful as an alternative phytotherapy in the management of DM, having shown a strong antioxidative capacity and substantial inhibition against the activities of key enzymes involved in carbohydrate hydrolysis in vitro.

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In vitro Cancer Cell Growth Inhibition and Antioxidant Activity of Bombax ceiba (Bombacaceae) Flower Extracts

Natural Product Communications ◽

10.1177/1934578x1400900527 ◽

2014 ◽

Vol 9 (5) ◽

pp. 1934578X1400900 ◽

Cited By ~ 3

Author(s):

Rosa Tundis ◽

Khaled Rashed ◽

Ataa Said ◽

Francesco Menichini ◽

Monica R. Loizzo

Keyword(s):

Cancer Cell ◽

Antiproliferative Activity ◽

Human Cancer ◽

Radical Scavenging Activity ◽

Antioxidant Properties ◽

Radical Scavenging ◽

Dependent Manner ◽

Bleaching Test ◽

Β Carotene

The flowers of Bombax ceiba were investigated for their chemical composition, antioxidant effects and antiproliferative activity against seven human cancer cell lines. The antiproliferative responses of diethyl ether (DE) and light petroleum (PE) extracts were evaluated by sulforhodamine B (SRB) assay against MCF-7, HeLa, COR-L23, C32, A375, ACHN, and LNCaP cells in comparison with a human normal cell line, 142BR. Moreover, extracts were characterized by GC-MS analysis and tested for their antioxidant properties by different in vitro systems, namely DPPH, Fe-chelating activity and β-carotene bleaching test. Both PE and DE extracts showed the highest antiproliferative activity against human renal adenocarcinoma (ACHN) in a concentration-dependent manner. PE extract showed the highest radical scavenging activity against the DPPH radical, while DE extract was more active in the β-carotene bleaching test. The presence of β-sitosterol and some fatty acids may contribute to the bioactivity of B. ceiba flower extracts.

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Evaluation of the Potential Cardioprotective Activity of Some Saudi Plants against Doxorubicin Toxicity

Zeitschrift für Naturforschung C ◽

10.1515/znc-2012-5-609 ◽

2012 ◽

Vol 67 (5-6) ◽

pp. 297-307 ◽

Cited By ~ 6

Author(s):

Osama M. Ashour ◽

Ashraf B. Abdel-Naim ◽

Hossam M. Abdallah ◽

Ayman A. Nagy ◽

Ahmed M. Mohamadin ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Activities ◽

Histopathological Examination ◽

Antioxidant Properties ◽

Radical Scavenging ◽

Serum Markers ◽

Protective Effects ◽

Medicinal Uses ◽

Cordia Myxa

Doxorubicin (DOX) is an anthracycline antibiotic widely used as a chemotherapeutic agent in the treatment of several tumours. However, its cardiac toxicity limits its use at maximum therapeutic doses. Most studies implicated increased oxidative stress as the major determinant of DOX cardiotoxicity. The local Saudi flora is very rich in a variety of plants of quite known folkloric or traditional medicinal uses. Tribulus macropterus Boiss., Olea europaea L. subsp. africana (Mill.) P. S. Green, Tamarix aphylla (L.) H. Karst., Cynomorium coccineum L., Cordia myxa L., Calligonum comosum L’ Hér, and Withania somnifera (L.) Dunal are Saudi plants known to have antioxidant activities. The aim of the current study was to explore the potential protective effects of methanolic extracts of these seven Saudi plants against DOX-induced cardiotoxicity in rats. Two plants showed promising cardioprotective potential in the order Calligonum comosum > Cordia myxa. The two plant extracts showed potent in vitro radical scavenging and antioxidant properties. They significantly protected against DOX-induced alterations in cardiac oxidative stress markers (GSH and MDA) and cardiac serum markers (CK-MB and LDH activities). Additionally, histopathological examination indicated a protection against DOX-induced cardiotoxicity. In conclusion, C. comosum and C. myxa exerted protective activity against DOX-induced cardiotoxicity, which is, at least partly, due to their antioxidant effect

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In Vitro Antihepatoma Activity of Novel 3D-Copper Cyanide Supramolecular Coordination Polymers

Journal of AOAC International ◽

10.5740/jaoacint.16-0141 ◽

2016 ◽

Vol 99 (5) ◽

pp. 1240-1246

Author(s):

Noura M Darwish ◽

Ahmed S Sultan ◽

Ahmed M Malki ◽

Hossam Khamis ◽

Mohamed El-Ziady

Keyword(s):

Protein Expression ◽

Western Blot ◽

Coordination Polymers ◽

Hepg2 Cells ◽

Inhibitory Effect ◽

Dependent Manner ◽

Invasive Potential ◽

Dna Ladder ◽

Supramolecular Coordination

Abstract This study aimed to investigate the inhibitory effect of novel 3D-organocopper supramolecular coordination polymers (SCPs) on the invasive potential of HepG2 cells. Chemoprevention could represent an important means to inhibit the process of hepatocarcinogenesis. The inhibitory effect of an SCP compound on the proliferation of HepG2 hepatoma cells was evaluated by cell vibility assay. DNA ladder bands were observed by DNA agarose gel electrophoresis. The influence of the SCP compound on phosphorylated ERK1/2, Bcl-2, and β-catenin protein expression of HepG2 cells was analyzed by Western blot. The SCP compound exerted an inhibitory effect on HepG2 cell proliferation in a dose-dependent manner. This inhibitory effect was confirmed by examination of cell morphology and DNA fragmentation. Furthermore, Western blot analysis revealed that phosphorylated ERK1/2 and β-catenin protein expression was inhibited after 24 h of treatment with the SCP compound, and that this event was associated with decreased Bcl-2 expression. We concluded that SCP can effectively inhibit the invasive potential of the ERK signaling pathway in HepG2 cells by altering apoptosis and by inhibiting Bcl-2 and β-catenin, which may play a significant role in this process.

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Investigation of invitro Antioxidant and invivo Protective Effects of Hypericum triquetrifolium Seed Methanol Extracts against Cyclophosphamide-Induced Acute Myelotoxicity, Hemotoxicity and Hepatotoxicity in Rats

10.20944/preprints201803.0148.v1 ◽

2018 ◽

Author(s):

Songul Cetik Yildiz ◽

Cumali Keskin ◽

Adnan Ayhanci

Keyword(s):

Antioxidant Activities ◽

Antioxidant Properties ◽

Radical Scavenging ◽

Stress Index ◽

Total Phenolic ◽

Rat Tissues ◽

Protective Effects ◽

Methanol Extracts

The aim of this study was to investigate in-vitro antioxidant properties and in-vivo protective effects of different concentrations of Hypericum triquetrifolium Turra. (HT) seed methanol extracts against acute hepatotoxicity, myelotoxicity and hematotoxicity in rats exposed to overdose of cyclophosphamide (CP). HT seed methanol extracts were tested in view of its in-vitro antioxidant activities as total phenolic contents and DPPH free radical-scavenging activity. To investigate in-vivo protective effects of HT seed methanol extracts on rat tissues; tested animals were divided into nine groups. Three groups only were treated with HT extracts (25, 50 and 100 mg/kg HT) for 6 days. Three groups were pre-treated with the extract of HT (25, 50 and 100 mg/kg HT) for 6 days and on the last day they were injected with single dose of CP (150-mg/kg body weight). Two groups were used as control groups and one group was only treated with CP (150 mg/kg) on the 6th day. The toxic effects of CP and protective effects of HT extracts on the nucleated cells which were produced by bone marrow and serum alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), oxidative stress index (OSI) levels were investigated biochemically. Additionally, liver tissue samples were examined histopathologically. Our results show that HT seed methanol extract has high total phenolic content and antioxidant activity. Over dose CP administration caused hepatotoxicity, myelotoxicity and hematotoxicity on rat. Whereas, 25, 50 and 100 mg/kg HT plus CP administered groups showed significant protective effects on nucleated cells. And 25, 50, 100 mg/kg HT plus CP treated groups showed an important decrease on serum ALT, ALP, LDH and OSI levels when compared with CP treated group. Our results showed that the administration of different HT doses with high doses of CP significantly reduced hepatotoxicity, myelotoxicity and hematoxicity on rats.

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Protective Effect of Schisandrin on Hydrogen Peroxide-Induced Damage in PC12 Cells

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.750-752.1545 ◽

2013 ◽

Vol 750-752 ◽

pp. 1545-1548

Author(s):

Kuang Ren ◽

Yan Chun Wang ◽

Hong Yan Fan

Keyword(s):

Protein Expression ◽

Pc12 Cells ◽

Antioxidant Properties ◽

Immunocytochemical Staining ◽

Potential Candidate ◽

Protective Effects ◽

Neuroprotective Effects ◽

Pre Treatment ◽

Vitro Model

In this study, schisandrin was assessed for potential protective effects on pheochromocytoma cell line (PC12 cells). Using PC12 cells damage induced by H2O2(25μmol/L) as in vitro model. After pre-treatment with different concentration of schisandrin (0.3, 0.6, 1.2μM) for 24h, MTT assay was used to detect the cell viability, the supernatant of cells was collected to examine the levels of nitric oxide (NO) in each sample, and immunocytochemical staining was adopted to observe the expression levels of bcl-2. Results showed that schisandrin at different concentrations could increase the viability of PC12 cells and decrease the levels of NO in the culture medium. There were significant differences between schisandrin group and H2O2group (P<0.05,P<0.01). Immunocytochemical staining result revealed that schisandrin could upregulate bcl-2 protein expression. In summary, schisandrin shown significant neuroprotective effects on H2O2-injured PC12 cells through antioxidant properties and upregulate bcl-2 protein expression, and could be a potential candidate for intervention in neurodegenerative diseases.

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Hepatoprotective activity of the methanolic leaf extract of Moringa oleifera (Lam) against chemically-induced Liver Toxicity

International Journal of Pharmacology and Toxicology ◽

10.14419/ijpt.v4i1.5123 ◽

2016 ◽

Vol 4 (1) ◽

pp. 40

Author(s):

Herbert Mbagwu ◽

Etok Nsikan ◽

Ekpo Emem

Keyword(s):

Acute Toxicity ◽

Leaf Extract ◽

Moringa Oleifera ◽

Liver Toxicity ◽

Radical Scavenging ◽

Toxicity Tests ◽

Dependent Manner ◽

Protective Effects ◽

Group I

Aim: Moringa oleifera commonly known as “miracle plant” possesses enormous nutritional and medicinal properties. It is used in traditional medicine in treating many ailments, including liver disorders. Though some works on hepatoprotective effects have been done (Mishra et al., 2011), the present study aims at evaluating the methanolic leaf extract (MLE) of Moringa oleifera harvested in Ewet Housing Estate in Uyo; AkwaIbom State in South-South Nigeria.Materials and Methods: The Carbon tetrachloride (CCl₄) model was employed throughout this investigation (Dongare et al., 2013). Briefly, thirty animals were randomly divided into six groups of five animals in each group. Group I served as normal control and was administered 10ml/kg normal saline. Group II was the toxic control and received 3 ml/kg of CCl₄. Group III served as the reference control and received 100mg/kg silymarin while groups IV, V and VI received 9, 18 and 27 mg/kg of MLE respectively. Phytochemical screening, acute toxicity tests as well as free radical scavenging effects using DPPH (in vitro) were also carried out.Results: Preliminary phytochemical tests revealed the presence of tannins, flavonoids, alkaloids, anthraquinones, saponins, terpenes, phlobatanins and cardiac glycosides. The acute toxicity investigations showed that MLE LD₅₀ was 90 mg/kg. In the hepatoprotective studies, liver function tests (LFT) revealed a significant (p<0.05) protective effect when compared with silymarin. The histopathological studies also provided supportive evidence for the protective effects of MLE. The DPPH studies showed that MLE has antioxidant property.Conclusion: It can be concluded based on findings from this study that the MLE of Moringa oleifera possesses antioxidant and hepatoprotective activities in a dose-dependent manner and safe for oral administration.

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Potential Anticancer Properties of Grape Antioxidants

Journal of Oncology ◽

10.1155/2012/803294 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 64

Author(s):

Kequan Zhou ◽

Julian J. Raffoul

Keyword(s):

Antioxidant Properties ◽

Radical Scavenging ◽

Grape Juice ◽

Phenolic Antioxidants ◽

Protective Effects ◽

Exciting Field ◽

Grape Skin ◽

Seed Extracts

Dietary intake of foods rich in antioxidant properties is suggested to be cancer protective. Foods rich in antioxidant properties include grape (Vitis vinifera), one of the world’s largest fruit crops and most commonly consumed fruits in the world. The composition and cancer-protective effects of major phenolic antioxidants in grape skin and seed extracts are discussed in this review. Grape skin and seed extracts exert strong free radical scavenging and chelating activities and inhibit lipid oxidation in various food and cell modelsin vitro. The use of grape antioxidants are promising against a broad range of cancer cells by targeting epidermal growth factor receptor (EGFR) and its downstream pathways, inhibiting over-expression of COX-2 and prostaglandin E2 receptors, or modifying estrogen receptor pathways, resulting in cell cycle arrest and apoptosis. Interestingly, some of these activities were also demonstrated in animal models. However,in vivostudies have demonstrated inconsistent antioxidant efficacy. Nonetheless, a growing body of evidence from human clinical trials has demonstrated that consumption of grape, wine and grape juice exerts many health-promoting and possible anti-cancer effects. Thus, grape skin and seed extracts have great potential in cancer prevention and further investigation into this exciting field is warranted.

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Inhibition of Fe2+ Induced Lipid Peroxidation in Rats Brain by Extract of Euphorbia heterophylla in vitro

European Journal of Medicinal Plants ◽

10.9734/ejmp/2019/v27i130103 ◽

2019 ◽

pp. 1-8

Author(s):

Leye Jonathan Babatola ◽

Oluwakemisola B. Oshanimi ◽

Olanrewaju M. Oluba ◽

Lawrence Okoror ◽

Adewale Agboola Odutuga

Keyword(s):

Lipid Peroxidation ◽

Antioxidant Activity ◽

Methanol Extract ◽

Antioxidant Properties ◽

Radical Scavenging ◽

Reducing Power ◽

Total Phenol ◽

Dependent Manner ◽

Significant Difference

This study is sought to determine the antioxidant activity and protective ability of aqueous and methanol extractible phytochemicals from Euphorbia heterophylla leaves on lipid peroxidation induced in rat brain by pro-oxidant, in vitro. The extracts of the leaves were prepared, and the ability of the extracts is to inhibit 25 µM FeSO4 induced lipid peroxidation in isolated rats’ brain, were determined. Thereafter, total phenol content, reducing power (FRAP), Fe (II) chelating, and DPPH* free radical scavenging ability of the extracts was determined and considered as an index of antioxidant activity. The results revealed that the extracts inhibit malondialdehyde (MDA) production in the basal and pro-oxidant induced lipid peroxidised rats in a dose-dependent manner, [methanol 80.11%, aqueous 70.3%] with the methanol extract (MEE) significantly (P< 0.05) than that of aqueous extract (AEE). The methanol extract (0.74 ± 0.6 mg/g) had higher total phenol contents than the aqueous (0.57 ± 1.2 mg/g); likewise the methanol extract had higher reducing power (0.08 ± 0.2, 0.03 ± 0.1 mg/g), but had no significant difference in Fe (II) chelating ability (EC50= 0.34, 0.36) with DPPH* scavenging ability (EC50=0.075, 0.075). This antioxidant properties and the protective effect of this leaf could be harnessed in the management and prevention of degenerative diseases in association with oxidative stress.

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