Cynaroside inhibits Leishmania donovani UDP-galactopyranose mutase and induces reactive oxygen species to exert antileishmanial response

Cynaroside, a flavonoid, has been shown to have antibacterial, antifungal and anticancer activities. Here, we evaluated its antileishmanial properties and its mechanism of action through different in silico and in vitro assays. Cynaroside exhibited antileishmanial activity in time and dose-dependent manner with IC50 value of 49.49 ± 3.515 µM in vitro. It inhibited the growth of parasite significantly at only 20 µM concentration when used in combination with miltefosine, a standard drug which have very high toxicity. It also inhibited the intra-macrophagic parasite significantly at low doses when used in combination with miltefosine. It showed less toxicity than the existing antileishmanial drug, miltefosine at similar doses. Propidium iodide staining showed that cynaroside inhibited the parasites in G0/G1 phase of cell cycle. H2DCFDA staining showed cynaroside induced antileishmanial activity through reactive oxygen species (ROS) generation in parasites. Molecular-docking studies with key drug-targets of Leishmania donovani showed significant inhibition. Out of these targets, cynaroside showed strongest affinity with UDP-galactopyranose mutase with -10.4 Kcal/mol which was further validated by molecular dynamics simulation. The bioactivity, ADMET properties, OECD chemical classification and toxicity risk prediction showed cynaroside as an enzyme inhibitor having sufficient solubility and non-toxic properties. In conclusion, cynaroside may be used alone or in combination with existing drug, miltefosine to control leishmaniasis with less cytotoxicity.

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Protective Effect of a Fucose-Rich Fucoidan Isolated from Saccharina japonica against Ultraviolet B-Induced Photodamage In Vitro in Human Keratinocytes and In Vivo in Zebrafish

Marine Drugs ◽

10.3390/md18060316 ◽

2020 ◽

Vol 18 (6) ◽

pp. 316 ◽

Cited By ~ 2

Author(s):

Wanchun Su ◽

Lei Wang ◽

Xiaoting Fu ◽

Liying Ni ◽

Delin Duan ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Protective Effect ◽

Reactive Oxygen ◽

Saccharina Japonica ◽

Intracellular Reactive Oxygen Species ◽

Dependent Manner ◽

Hacat Cells ◽

Oxygen Species

A fucose-rich fucoidan was purified from brown seaweed Saccharina japonica, of which the UVB protective effect was investigated in vitro in keratinocytes of HaCaT cells and in vivo in zebrafish. The intracellular reactive oxygen species levels and the viability of UVB-irradiated HaCaT cells were determined. The results indicate that the purified fucoidan significantly reduced the intracellular reactive oxygen species levels and improved the viability of UVB-irradiated HaCaT cells. Furthermore, the purified fucoidan remarkably decreased the apoptosis by regulating the expressions of Bax/Bcl-xL and cleaved caspase-3 in UVB-irradiated HaCaT cells in a dose-dependent manner. In addition, the in vivo UV protective effect of the purified fucoidan was investigated using a zebrafish model. It significantly reduced the intracellular reactive oxygen species level, the cell death, the NO production, and the lipid peroxidation in UVB-irradiated zebrafish in a dose-dependent manner. These results suggest that purified fucoidan has a great potential to be developed as a natural anti-UVB agent applied in the cosmetic industry.

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The early embryo response to intracellular reactive oxygen species is developmentally regulated

Reproduction Fertility and Development ◽

10.1071/rd10148 ◽

2011 ◽

Vol 23 (4) ◽

pp. 561 ◽

Cited By ~ 48

Author(s):

Nathan T. Bain ◽

Pavneesh Madan ◽

Dean H. Betts

Keyword(s):

Reactive Oxygen Species ◽

Ex Vivo ◽

Reactive Oxygen ◽

Dependent Manner ◽

Oxygen Species ◽

Blastocyst Development ◽

Developmentally Regulated ◽

H2o2 Treatment ◽

Intracellular Ros

In vitro embryo production (IVP) suffers from excessive developmental failure. Its inefficiency is linked, in part, to reactive oxygen species (ROS) brought on by high ex vivo oxygen (O2) tensions. To further delineate the effects of ROS on IVP, the intracellular ROS levels of early bovine embryos were modulated by: (1) varying O2 tension; (2) exogenous H2O2 treatment; and (3) antioxidant supplementation. Although O2 tension did not significantly affect blastocyst frequencies (P > 0.05), 20% O2 accelerated the rate of first cleavage division and significantly decreased and increased the proportion of permanently arrested 2- to 4-cell embryos and apoptotic 9- to 16-cell embryos, respectively, compared with embryos cultured in 5% O2 tension. Treatment with H2O2, when applied separately to oocytes, zygotes, 2- to 4-cell embryos or 9- to 16-cell embryos, resulted in a significant (P < 0.05) dose-dependent decrease in blastocyst development in conjunction with a corresponding increase in the induction of either permanent embryo arrest or apoptosis in a stage-dependent manner. Polyethylene glycol–catalase supplementation reduced ROS-induced embryo arrest and/or death, resulting in a significant (P < 0.05) increase in blastocyst frequencies under high O2 culture conditions. Together, these results indicate that intracellular ROS may be signalling molecules that, outside an optimal range, result in various developmentally regulated modes of embryo demise.

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Reactive Oxygen Species Mediated Prostaglandin E2 Contributes to Acute Response of Epithelial Injury

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/4123854 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 14

Author(s):

Yi-Ping Hu ◽

Yin-Bo Peng ◽

Yi-Fan Zhang ◽

Ying Wang ◽

Wei-Rong Yu ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Tissue Injury ◽

Reactive Oxygen ◽

Human Keratinocytes ◽

Mechanical Injury ◽

Prostaglandin E ◽

Dependent Manner ◽

Oxygen Species ◽

Cox 2

Reactive oxygen species (ROS) generated after tissue injury play a crucial role during wound healing through initiating acute inflammation, clarifying infection and dead tissue, and mediating various intracellular signal transduction. Prostaglandin E2 (PGE2) has been identified as one of the major factors responsible for inflammation and tissue repair. In this study, we tested our hypothesis that ROS produced by damaged human keratinocytes induces the synthesis of PGE2. In vitro epithelial wounding model was used to observe the production of ROS and secretion of PGE2 as well as the involved signal pathway. The mechanical injury caused the rapid production of ROS in in vitro cultured keratinocytes, which was significantly blocked by an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase. The increased intracellular ROS caused by mechanical injury stimulates PGE2 production in a time-dependent manner via the activation of cyclooxygenase-2 (COX-2), which was stimulated by phosphorylation of extracellular signal-regulated protein kinase (ERK). These results indicate ROS-induced ERK activation leading to the activation of COX-2 and the synthesis of PGE2 in human keratinocytes responding to mechanical injury in the acute phase.

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Candida albicans Induces Arginine Biosynthetic Genes in Response to Host-Derived Reactive Oxygen Species

Eukaryotic Cell ◽

10.1128/ec.00290-12 ◽

2012 ◽

Vol 12 (1) ◽

pp. 91-100 ◽

Cited By ~ 40

Author(s):

Claudia Jiménez-López ◽

John R. Collette ◽

Kimberly M. Brothers ◽

Kelly M. Shepardson ◽

Robert A. Cramer ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Candida Albicans ◽

Amino Acid ◽

Reactive Oxygen ◽

Single Amino Acid ◽

Dependent Manner ◽

Oxygen Species ◽

Biosynthetic Genes ◽

Content Type

ABSTRACTThe interaction ofCandida albicanswith phagocytes of the host's innate immune system is highly dynamic, and its outcome directly impacts the progression of infection. While the switch to hyphal growth within the macrophage is the most obvious physiological response, much of the genetic response reflects nutrient starvation: translational repression and induction of alternative carbon metabolism. Changes in amino acid metabolism are not seen, with the striking exception of arginine biosynthesis, which is upregulated in its entirety during coculture with macrophages. Using single-cell reporters, we showed here that arginine biosynthetic genes are induced specifically in phagocytosed cells. This induction is lower in magnitude than during arginine starvationin vitroand is driven not by an arginine deficiency within the phagocyte but instead by exposure to reactive oxygen species (ROS). Curiously, these genes are induced in a narrow window of sublethal ROS concentrations.C. albicanscells phagocytosed by primary macrophages deficient in thegp91phoxsubunit of the phagocyte oxidase do not express theARGpathway, indicating that the induction is dependent on the phagocyte oxidative burst.C. albicans argpathway mutants are retarded in germ tube and hypha formation within macrophages but are not notably more sensitive to ROS. We also find that theARGpathway is regulated not by the general amino acid control response but by transcriptional regulators similar to theSaccharomyces cerevisiaeArgR complex. In summary, phagocytosis induces this single amino acid biosynthetic pathway in an ROS-dependent manner.

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Acceleration of Phagocytosis in Human Neutrophils Incubated with Gabexate Mesilate

Journal of International Medical Research ◽

10.1177/030006059402200507 ◽

1994 ◽

Vol 22 (5) ◽

pp. 292-295 ◽

Cited By ~ 8

Author(s):

K Mikawa ◽

H Akamatsu ◽

N Maekawa ◽

K Nishina ◽

H Obara ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen Species Production ◽

Reactive Oxygen ◽

Human Neutrophils ◽

Dependent Manner ◽

Oxygen Species ◽

Gabexate Mesilate ◽

Micro Organisms ◽

Species Production

It has recently been shown that gabexate mesilate inhibited human neutrophil functions including chemotaxis and reactive oxygen species production. In the present study, the effects of gabexate mesilate on phagocytosis by human neutrophils in vitro were investigated. Gabexate mesilate significantly enhanced neutrophil phagocytosis in a dose-dependent manner. This characteristic of gabexate mesilate may facilitate protection against infecting micro-organisms, although the inhibition of reactive oxygen species production by neutrophils may be a disadvantage for host-defense against infection.

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High cell density attenuates reactive oxygen species: Implications for in vitro assays

Wound Repair and Regeneration ◽

10.1111/j.1524-475x.2011.00746.x ◽

2011 ◽

Vol 20 (1) ◽

pp. 74-82 ◽

Cited By ~ 2

Author(s):

Dennis P. Kim ◽

Jonathan Yahav ◽

Michael Sperandeo ◽

Lauren Maloney ◽

Monica McTigue ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Cell Density ◽

High Cell Density ◽

Reactive Oxygen ◽

In Vitro Assays ◽

Oxygen Species ◽

High Cell

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Oxyresveratrol Possesses DNA Damaging Activity

Molecules ◽

10.3390/molecules25112577 ◽

2020 ◽

Vol 25 (11) ◽

pp. 2577

Author(s):

Sarayut Radapong ◽

Satyajit D. Sarker ◽

Kenneth J. Ritchie

Keyword(s):

Reactive Oxygen Species ◽

Biological Activities ◽

Reactive Oxygen ◽

Dependent Manner ◽

Oxygen Species ◽

Ability To Act ◽

Phytochemical Profile ◽

Dose Dependent ◽

Anticancer Compound

Artocarpus lakoocha Wall. ex Roxb. (family: Moraceae) has been used as a traditional Thai medicine for the treatment of various parasitic diseases. This species has been reported to be the source of phytochemicals, which show potent biological activities. The objective of this study was to investigate the phytochemical profile of the extracts of the heartwood of A. lakoocha and their pro-oxidant activity in vitro. The heartwood was ground, extracted, and then chromatographic and spectroscopic analyses were carried out; oxyresveratrol was identified as the major component in the extracts. The pro-oxidant activity was investigated using DNA-nick, reactive oxygen species and reducing assays. The results showed that oxyresveratrol induced DNA damage dose-dependently in the presence of copper (II) ions. It was also found to generate reactive oxygen species (ROS) in a dose-dependent manner and reduce copper (II) to copper (I). It is concluded that oxyresveratrol is the most abundant stilbenoid in A. lakoocha heartwood. The compound exhibited pro-oxidant activity in the presence of copper (II) ions, which may be associated with its ability to act as an anticancer compound.

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Modulation of reactive oxygen species by Rac1 or catalase prevents asbestos-induced pulmonary fibrosis

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.90590.2008 ◽

2009 ◽

Vol 297 (5) ◽

pp. L846-L855 ◽

Cited By ~ 51

Author(s):

Shubha Murthy ◽

Andrea Adamcakova-Dodd ◽

Sarah S. Perry ◽

Linda A. Tephly ◽

Richard M. Keller ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Pulmonary Fibrosis ◽

Alveolar Macrophages ◽

Reactive Oxygen ◽

Ros Generation ◽

Dependent Manner ◽

Oxygen Species ◽

Tnf Α

The release of reactive oxygen species (ROS) and cytokines by alveolar macrophages has been demonstrated in asbestos-induced pulmonary fibrosis, but the mechanism linking alveolar macrophages to the pathogenesis is not known. The GTPase Rac1 is a second messenger that plays an important role in host defense. In this study, we demonstrate that Rac1 null mice are protected from asbestos-induced pulmonary fibrosis, as determined by histological and biochemical analysis. We hypothesized that Rac1 induced pulmonary fibrosis via generation of ROS. Asbestos increased TNF-α and ROS in a Rac1-dependent manner. TNF-α was elevated only 1 day after exposure, whereas ROS generation progressively increased in bronchoalveolar lavage cells obtained from wild-type (WT) mice. To determine whether ROS generation contributed to pulmonary fibrosis, we overexpressed catalase in WT monocytes and observed a decrease in ROS generation in vitro . More importantly, administration of catalase to WT mice attenuated the development of fibrosis in vivo. For the first time, these results demonstrate that Rac1 plays a crucial role in asbestos-induced pulmonary fibrosis. Moreover, it suggests that a simple intervention may be useful to prevent progression of the disease.

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