scholarly journals Oxidative Stress Modulation and ROS-Mediated Toxicity in Cancer: A Review on In Vitro Models for Plant-Derived Compounds

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
María José Vallejo ◽  
Lizeth Salazar ◽  
Marcelo Grijalva

Medicinal and aromatic plants (MAPs) are known and have been long in use for a variety of health and cosmetics applications. Potential pharmacological usages that take advantage of bioactive plant-derived compounds’ antimicrobial, antifungal, anti-inflammatory, and antioxidant properties are being developed and many new ones explored. Some phytochemicals could trigger ROS-mediated cytotoxicity and apoptosis in cancer cells. A lot of effort has been put into investigating novel active constituents for cancer therapeutics. While other plant-derived compounds might enhance antioxidant defenses by either radical scavenging or stimulation of intracellular antioxidant enzymes, the generation of reactive oxygen species (ROS) leading to oxidative stress is one of the strategies that may show effective in damaging cancer cells. The biochemical pathways involved in plant-derived bioactive compounds’ properties are complex, and in vitro platforms have been useful for a comprehensive understanding of the mechanism of action of these potential anticancer drugs. The present review aims at compiling the findings of particularly interesting studies that use cancer cell line models for assessment of antioxidant and oxidative stress modulation properties of plant-derived bioactive compounds.

2012 ◽  
Vol 67 (5-6) ◽  
pp. 297-307 ◽  
Author(s):  
Osama M. Ashour ◽  
Ashraf B. Abdel-Naim ◽  
Hossam M. Abdallah ◽  
Ayman A. Nagy ◽  
Ahmed M. Mohamadin ◽  
...  

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


2021 ◽  
Vol 10 (5) ◽  
pp. 1
Author(s):  
Eric Beyegue ◽  
Boris G. K. Azantsa ◽  
Angie M-A Mbong ◽  
Julius E. Oben

Prolonged hyperglycemia enhances oxidative stress. Bioactive compounds extracted possess antioxidant, anti-free radical potentials or the ability to reduce blood sugar levels. The objective of this study was to evaluate the antioxidant properties of extracts of stem bark of Coula edulis Baill., their abilities to trap free radicals and glucose, as well as their ability to inhibit α-amylase and invertase activities. In vitro assays were used to test the trapping capacity of extracts on DPPH, ABTS, NO, and OH radicals; to evaluate the antioxidant capacity, the activity of glycosylation and the capacity of inhibition of the activities of α-amylase and invertase were conducted. Also, phenolic, flavonoid and alkaloid contents of extracts were determined. Results showed that extracts of the stem bark of C. edulis have anti-radical properties. The extracts chelate DPPH, hydroxyl (OH), nitrite oxide (NO), ABTS radicals, and even glucose. The IC50 values varied depending on the nature of the extraction solvent. Ethanolic extract has the highest polyphenolic content (289.12 ± 30.31 µg catechin equivalent/g), flavonoids (1.12 ± 0.09 µg quercetin equivalent/g) and alkaloids (5.54 ± 0.59 µg quinin equivalent/g). The extracts also reduce invertase and α-amylase activities. C. edulis extracts present strong antioxidant potentials and can be used as a source of natural antioxidants for the prevention of oxidative stress and hyperglycemia.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Beatrice Muthoni Guchu ◽  
Alex King’ori Machocho ◽  
Stephen Kiruthi Mwihia ◽  
Mathew Piero Ngugi

Oxidative stress is the result of the disparity between pro-oxidants and antioxidants in an organism, and it is important in the pathogenesis of several degenerative disorders, such as arthritis, Alzheimer’s, cancer, and cardiovascular diseases. Free radicals can damage biomolecules, such as nucleic acids, lipids, proteins, polyunsaturated fatty acids, and carbohydrates, and the DNA leading to mutations. The use of antioxidants is effective in delaying the oxidation of biomolecules. Antioxidants are complexes found in the food that can retard or deter oxidation by preventing the initiation and propagation of oxidizing chain reactions. Medicinal plants have been used for centuries by man to manage diseases and have a host of antioxidant complexes. Traditionally, Caesalpinia volkensii, Vernonia lasiopus, and Acacia hockii have folkloric remedies against associated oxidative stress-mediated complications. However, the upsurge in its use has not been accompanied by scientific validations to support these claims. In this study, in vitro antioxidant activity of Caesalpinia volkensii, Vernonia lasiopus, and Acacia hockii collected from Embu County (Kenya) were determined by radical scavenging activities of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical in addition to ferric reducing antioxidant power analyzed against that of L-ascorbic acid as the standard. The obtained results revealed remarkable antioxidant activities of the studied plant extracts as evidenced by the low IC50 and EC50 values. These antioxidant activities could be due to the presence of antioxidants phytochemicals such as flavonoids, phenols, terpenoids, and saponins among others. Therefore, the therapeutic potential of this plant could be due to their antioxidant properties. This study recommends bioassay of the extracts against oxidative stress-related disorders for development of phytomedicine with antioxidant properties.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tahereh Jamali ◽  
Gholamreza Kavoosi ◽  
Yousef Jamali ◽  
Saeed Mortezazadeh ◽  
Susan K. Ardestani

AbstractWe aimed to explore and compare new insights on the pharmacological potential of Oliveria decumbence essential oil (OEO) and its main components highlighting their antioxidant activity in-vitro, in-vivo, and in-silico and also cytotoxic effects of OEO against A549 lung cancer cells. At first, based on GC–MS analysis, thymol, carvacrol, p-cymene, and γ-terpinene were introduced as basic ingredients of OEO and their in-vitro antioxidant capacity was considered by standard methods. Collectively, OEO exhibited strong antioxidant properties even more than its components. In LPS-stimulated macrophages treated with OEO, the reduction of ROS (Reactive-oxygen-species) and NO (nitric-oxide) and down-regulation of iNOS (inducible nitric-oxide-synthase) and NOX (NADPH-oxidase) mRNA expression was observed and compared with that of OEO components. According to the results, OEO, thymol, and carvacrol exhibited the highest radical scavenging potency compared to p-cymene, and γ-terpinene. In-silico Molecular-Docking and Molecular-Dynamics simulation indicated that thymol and carvacrol but no p-cymene and γ-terpinene may establish coordinative bonds in iNOS active site and thereby inhibit iNOS. However, they did not show any evidence for NOX inhibition. In the following, MTT assay showed that OEO induces cytotoxicity in A549 cancer cells despite having a limited effect on L929 normal cells. Apoptotic death and its dependence on caspase-3 activity and Bax/Bcl2 ratio in OEO-treated cells were established by fluorescence microscopy, flow cytometry, colorimetric assay, and western blot analysis. Additionally, flow cytometry studies demonstrated increased levels of ROS in OEO-treated cells. Therefore, OEO, despite showing antioxidant properties, induces apoptosis in cancer cells by increasing ROS levels. Collectively, our results provided new insight into the usage of OEO and main components, thymol, and carvacrol, into the development of novel antioxidant and anti-cancer agents.


Molecules ◽  
2019 ◽  
Vol 24 (13) ◽  
pp. 2489 ◽  
Author(s):  
Leon M. Larcher ◽  
Tao Wang ◽  
Rakesh N. Veedu

MicroRNAs (miRNAs) are short non-coding RNAs that are involved in the regulation of gene expression. Previous reports showed an over-expression of miRNA-21 (miR-21) in various cancer cells, and its up-regulation is closely related to cancer initiation, proliferation and metastasis. In this work, we envisioned the development of novel antimiRzymes (anti-miRNA-DNAzyme) that are capable of selectively targeting and cleaving miR-21 and inhibit its expression in cancer cells using the DNAzyme technique. For this purpose, we have designed different antimiRzyme candidates by systematically targeting different regions of miR-21. Our results demonstrated that RNV541, a potential arm-loop-arm type antimiRzyme, was very efficient (90%) to suppress miR-21 expression in U87MG malignant glioblastoma cell line at 200 nM concentration. In addition, RNV541 also inhibited miR-21 expression (50%) in MDA-MB-231 breast cancer cell line. For targeted delivery, we conjugated RNV541 with a transferrin receptor (TfR) targeting aptamer for TfR-mediated cancer cell delivery. As expected, the developed chimeric structure efficiently delivered the antimiRzyme RNV541 into TfR positive glioblastoma cells. TfR aptamer-RNV541 chimeric construct showed 52% inhibition of miR-21 expression in U87MG glioblastoma cells at 2000 nM concentration, without using any transfection reagents, making it a highly desirable strategy to tackle miR-21 over-expressed malignant cancers. Although these are in vitro based observations, based on our results, we firmly believe that our findings could be beneficial towards the development of targeted cancer therapeutics where conventional therapies face several challenges.


Author(s):  
SATYAPRAKASH BERAIYA ◽  
PIR MOHAMMAD ISHFAQ ◽  
ZAVED AHMAD ◽  
SWATI TRIPATHI ◽  
SIDDHARTHA KUMAR MISHRA

Oxidative stress has emerged as one of the targets in several medical conditions and in several types of clinical researches. Growing evidences from research on diverse diseases show that oxidative stress is conjoined with the pathogenesis of diabetes and its complications. This review has examined the role of oxidative stress in the pathogenesis of insulin resistance and beta-cell dysfunction. A vast variety of medicinal plants and products have been utilized for the prevention of diabetes and its related complications. Natural products such as phenolic acids and flavonoids construct one of the most ubiquitous groups of plant phenolics. At present, the effect of dietary phenolics is of extreme concern due to their antioxidant, free radical scavenging, and as quenchers of singlet oxygen formation. Reactive oxygen species (ROS) as well as reactive nitrogen species play either harmful or beneficial roles in biological systems depending on pathophysiological conditions. This review extends on the fundamental aspect of ROS in biological processes and diseases and how natural bioactive compounds of fruits and vegetables regulate their health improving properties. Flavonoids and phenolics acids are the most important groups of secondary metabolites and bioactive compounds in plants. Diverse phytochemical agents have become the backbone in pharmacotherapy of diabetes by virtue of their antioxidant properties along with their other pharmacological actions. Consequently, accession to obstruction the generation of reactive free radicals or abduct the reactive free radical may yield direct and casual approach for the medication of diabetes and its complications.


Author(s):  
Festus O. Taiwo ◽  
Olaoluwa Oyedeji ◽  
Moyosore T. Osundahunsi

Aim: To evaluate the antimicrobial and antioxidant activities of bioactive compounds isolated from Annona muricata (Linn.) leaf extract. Study Design: In vitro antimicrobial assay of bioactive compounds isolated from solvent fractions of plant leaf extract against selected clinical bacterial and fungal isolates. Antioxidant assay of plant leaf extract. Place and Duration of Study: All the work was carried out in the Departments of Chemistry and Microbiology, Obafemi Awolowo University, Ile-Ife, Nigeria between March, 2015 and January, 2016. Methodology: Isolation of bioactive compounds was by column and thin layer chromatographic techniques. Isolated compounds were characterized by nuclear magnetic resonance spectroscopic analysis. Antimicrobial activities were evaluated by disc diffusion and broth microdilution methods while antioxidant activity was investigated using the 2,2-dipheny-1-picrylhydrazyl (DPPH) radical-scavenging assay. Results: Two compounds kaempferol-3-O-glucoside (1) and 1-(4-Hydroxyphenyl)-3-Phenylpropan-1-one (2) were isolated from the ethyl acetate fraction of leaf extract of A. muricata. The two compounds showed broad spectrum antimicrobial activities with zones of inhibition ranging from 26.00 ± 1.73 to 31 ± 1.00 mm and 17.33 ± 1.15 to 31.33 ± 1.15 mm respectively, for compounds 1 and 2 for the test bacteria species and 15.33 ± 1.15 to 31.33 ± 1.15 mm and 17.67 ± 0.58 to 29.67 ±1.53 mm respectively, for compounds 1 and 2 for the test fungi. Minimum inhibitory concentrations ranged between 0.625-5.00 µg/mL and 1.25-5.00 µg/ml respectively, for compounds 1 and 2. Minimum bactericidal concentrations ranged between 2.5-10.00 µg/mL for both compounds which compared favourably with the reference drugs used. DPPH radical-scavenging activities were IC50 = 13.41 ± 0.64 µg/mL and 7.42 ± 0.90 µg/mL for compounds 1 and 2 respectively, compared with IC50 = 51.99 ± 1.44 µg/ml obtained for the standard ascorbic acid. The results show that both isolated compounds from A. muricata leaf possess in vitro antimicrobial and antioxidant properties and they may be useful as active ingredients in antimicrobial drug formulations and as agents for the control of free radical-related pathological disorders.


2010 ◽  
Vol 299 (5) ◽  
pp. F1120-F1133 ◽  
Author(s):  
Imari Mimura ◽  
Masaomi Nangaku ◽  
Hiroshi Nishi ◽  
Reiko Inagi ◽  
Tetsuhiro Tanaka ◽  
...  

Cytoglobin (Cygb), a novel member of the globin superfamily, is expressed by fibroblasts in various organs. However, its function remains unknown. Because of its localization, we speculated that a biological role of Cygb may be related to fibrogenesis. To clarify the role of Cygb in kidney fibrosis, we employed the remnant kidney model in rats. Immunohistochemical analysis showed an increase in Cygb expression in parallel with disease progression. To investigate the functional consequence of Cygb upregulation, we established transgenic rats overexpressing rat Cygb. Overexpression of Cygb improved histological injury, preserved renal function, and ameliorated fibrosis, as estimated by the accumulation of collagen I and IV as well as Masson trichrome staining. These protective effects of Cygb were associated with a decrease in nitrotyrosine deposition in the kidney and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) excretion as a marker of oxidative stress. We also performed in vitro studies utilizing a rat kidney fibroblast cell line transiently overexpressing Cygb, an inducible kidney cell transfected with Cygb, and primary cultured fibroblasts isolated from the kidneys of the transgenic rats. These different experimental systems consistently showed that Cygb inhibited collagen synthesis. Furthermore, mutant disruption of heme in Cygb that impaired its antioxidant properties led to the loss of antifibrotic effects, suggesting that Cygb reduces fibrosis via a radical scavenging function. In conclusion, we showed that Cygb plays an important role in protection of the kidney against fibrosis via the amelioration of oxidative stress both in vitro and in vivo. Cygb might represent a good therapeutic target in chronic kidney disease.


Author(s):  
Amrutha Koottasseri ◽  
Amal Babu ◽  
Anna Augustin ◽  
Joice Tom Job ◽  
Arunaksharan Narayanankutty

Background: Oxidative stress and inflammation are the predominant cause of chronic diseases including multiple forms of cancers. Due to the prominent roles, prevention of these oxidative stress and inflammation is considered to be a target for preventing these disorders. Various natural products and plant extracts prevent the process of free radical-induced damages. Objectives: The present study evaluated the biological properties of Thottea siliquosa, belonging to the family Aristolochiaceae, which is a traditionally used Ayurvedic plant. Methods: Antioxidant assays carried out were DPPH, FRAP, hydrogen peroxide scavenging, and hemolysis inhibition assay; nitric oxide and lipoxygenase inhibition assays were used for anti-inflammatory studies. Anticancer activity was done using human endometrial and breast cancer cells by MTT assay. Bioactive compounds present in T. siliquosa were identified by LCMS and each was docked with various cancer targets including EGFR, VEGFR, GST, COX2, and Lipooxygenase. Results: The results of the present study showed antioxidant properties for the methanolic crude extract of T. siliquosa as DPPH radical scavenging (110.40 ± 4.5µg/mL), FRAP capacity (41.1 ± 6.2), peroxide scavenging (233.4 ± 14.2µg/mL). Besides, anti-inflammatory properties are also evident in terms of nitric oxide radical scavenging (28.76± 3.9 µg/mL) and lipoxygenase inhibition (39.2 ± 3.2µg/mL) assays. In silico analysis confirmed the inhibitory potential of the bioactive compounds of T. siliquosa against cancer drug targets such as EGFR, VEGFR, and inflammatory enzymes cyclooxygenase as well as lipooxygenase. Further, the anticancer activity of the extract has been identified against human endometrial and breast cancer cells. The possible mechanism of anticancer action of the extract is mediated through the apoptosis induction mediated through increased caspase and APAF-1 expression. Conclusion: The study thus concludes that T. siliquosa showed significant antioxidant, anti-inflammatory and anticancer properties. Further studies together with a bioassay-guided fractionation may identify possible bioactive compounds.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Tongyu Gu ◽  
Nianmin Wang ◽  
Tong Wu ◽  
Qi Ge ◽  
Liang Chen

Over the past decade, oxidative stress was shown to be a key factor for various diseases. The term “antioxidant” also rapidly gained attention worldwide, viewed as beneficial in disease prevention. Resveratrol (RSV), a natural polyphenol, is a plant antitoxin formed in response to harmful environmental factors such as infection and injury. This antitoxin is found in grapes, strawberries, peanuts, or herbal medicines and exhibits many pharmacological effects involved in antitumor, anti-inflammatory, antiaging, and antioxidation stress mechanisms. Recently, numerous in vitro and in vivo experiments have shown that RSV harbors antioxidative stress properties and can be used as an antioxidant. Here, we review the free radical scavenging ability, antioxidant properties, signaling pathways, expression and regulation of antioxidant enzymes, and oxidative stress-related diseases associated with RSV.


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