Investigation of genotoxic effects of the anti-asthmatic and anti-inflammatory drugs Apocynin and Acetosyringenin in the Salmonella typhimurium mutagenicity assay and the SCE-test with human lymphocytes

Pfuhler, Stefan; Stehrer-Schmid, Paula; Dorsch, Walter; Wagner, Hildebert; Wolf, H. U.

doi:10.1016/s0944-7113(11)80010-3

Cited by 8 publications

(5 citation statements)

References 12 publications

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“…Even when treated with apocynin for a 3-month period, rabbits do not show any signs of ill-health and other parameters compared to control-treated animals [19]. Furthermore, when tested in the Salmonella typhimurium mutagenicity assay (Ames test) and the sister chromatid exchange (SCE) test, which tests for DNA damaging properties, apocynin showed no genotoxic effects at concentrations up to 600 uM [171]. This safety profile may be due to the relative inertness of the compound in the absence of metabolism.…”

Section: Toxicitymentioning

confidence: 99%

The Role of the Methoxyphenol Apocynin, a Vascular NADPH Oxidase Inhibitor, as a Chemopreventative Agent in the Potential Treatment of Cardiovascular Diseases

Yu¹,

Weïwer²,

Linhardt³

et al. 2008

CVP

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Abstract:Oxidative stress has been linked to the origin and progression of cardiovascular diseases. Nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase is a multi-component, NADPH-dependent enzyme that generates superoxide anion in the presence of molecular oxygen. The enzyme has been identified and characterized in all 3 vascular wall cell types and represents the major source of reactive oxygen species (ROS) production in the vascular wall. Inhibition of NADPH oxidase activation appears to suppress the sequence of cellular events that leads to a variety of cardiovascular diseases, including atherosclerosis. The naturally occurring methoxyphenol apocynin has been found to inhibit NADPH oxidase upon activation by peroxidases (e.g. soybean peroxidase, myeloperoxidase) or ROS under mild reaction conditions. Upon peroxidase-catalyzed activation, the apocynin oxidation products act to block the assembly and activation of NADPH oxidase. Although the mechanism of inhibition of NADPH oxidase remains largely unknown, apocynin's high effectiveness and low toxicity makes it a promising lead compound in the development of new therapeutic agents for cardiovascular diseases.

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Section: Toxicitymentioning

confidence: 99%

The Role of the Methoxyphenol Apocynin, a Vascular NADPH Oxidase Inhibitor, as a Chemopreventative Agent in the Potential Treatment of Cardiovascular Diseases

Yu¹,

Weïwer²,

Linhardt³

et al. 2008

CVP

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“…2 Some very recent findings include the improvement in the renal glutathione status in Zucker diabetic fatty rats 3 , inhibition of haemodynamic changes in cisplatin-induced cardiotoxicity in rats 4 and a protective effect in a mouse model of chemically-induced colitis. Actually, we believe that without the ancient pharmacological applications of the herb Picrorhiza kurroa in the folk medicine and the posterior isolation of apocynin as one of its active principles [6][7][8] , this molecule would never have been tested as a potential drug. Actually, we believe that without the ancient pharmacological applications of the herb Picrorhiza kurroa in the folk medicine and the posterior isolation of apocynin as one of its active principles [6][7][8] , this molecule would never have been tested as a potential drug.…”

Section: Introductionmentioning

confidence: 99%

“…5 Structurally, apocynin is a very simple molecule. Actually, we believe that without the ancient pharmacological applications of the herb Picrorhiza kurroa in the folk medicine and the posterior isolation of apocynin as one of its active principles, [6][7][8] this molecule would never have been tested as a potential drug. Indeed, apocynin could be considered a simple precursor for the synthesis of more complex molecules.…”

Section: Introductionmentioning

confidence: 99%

Experimental, DFT and docking simulations of the binding of diapocynin to human serum albumin: induced circular dichroism

et al. 2015

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Diapocynin has been regarded as the active principle of apocynin, which is the most used inhibitor of NADPH oxidase. Here we performed a comprehensive study of the interaction of diapocynin with human serum albumin (HSA). We found that diapocynin binds with higher efficacy to site I of HSA and its binding constant (8.5x10 5 mol -1 L) was almost 100-fold higher compared to apocynin. By interacting with this chiral cavity of the protein, diapocynin became a chiral molecule, which was evidenced by its induced circular dichroism spectrum.The axial chirality was theoretically confirmed by searching the most stable conformations adopted by diapocynin using the Density Function Theory (DFT). The four minimum energy conformers, which presented dihedral angles of 58.00° and 302.00° (syn-aS and syn-aR enantiomers pair bearing 2,2'-dihydroxyl groups at the same side) and 132.86° and 227.14° (anti-aS and anti-aR enantiomers pair bearing 2,2'-dihydroxyl groups at opposite sides) were used as initial conformations for the docking simulations. The highest scored docking pose was obtained for site 1 and the dihedral angle resulted in 106.44°, i.e., an anti-aS chiral conformer. In conclusion, diapocynin is a strong ligand of HSA. An unprecedented combination of DFT calculation and docking simulation was used to explain the acquired chirality of diapocynin when bound to HSA.

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“…Three medicinal plants, namely Picrorhizakurroa(Kutki), Azadirachta indica (Neem) andCyperusrotundus(Mustak), were selected based on their Ayurvedic indications against respiratory illness, and antipyretic properties. 17 Candidature of these plants as antiviral, 14,18,19 anti-inflammatory, 20,21 antioxidant, 16,22 and immunomodulatory 23 agents is also supported by research evidence. Moreover, it is anticipated that medicinal plant based ligands can fulfil the two fold criteria for potential anti SARS-CoV-2 pharmacological agents, ie inhibiting viral entry, and enhancing the host immunity to combat the virus.…”

Section: Introductionmentioning

confidence: 94%

Ayurvedic Medicinal Plants Against COVID-19: An In Silico Analysis

Khuntia

Sharma

Qazi

et al. 2021

Natural Product Communications

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Even after one and a half years since the outbreak of COVID-19, its complete and effective control is still far from being achieved despite vaccination drives, symptomatic management with available drugs, and wider lockdowns. This has inspired researchers to screen potential phytochemicals from medicinal plants against SARS-CoV-2, adopting a bio-informatics approach. The current study aimed to assess anti-viral activity of the phytochemicals derived from Ayurvedic medicinal plants against SARS-CoV-2 drug targets [3-chymotrypsin-like protease (3CLpro) and RNA dependent RNA polymerase (RdRp)] using validated in silico methods.3D Structures of 196 phytochemicals from three Ayurvedic plants were retrieved from PubChem and KNApSAcK databases and screened for Absorption Distribution Metabolism Excretion and Toxicity(ADMET) to predict drug-likeness. The phytochemicals were subjected to molecular docking and only three showed promise: Acetovanillonewith a binding affinity of −4.7Kcal/mol with RdRp and −4.1 Kcal/mol with 3CL pro; myrtenol with equivalent values of −4.3 Kcal/mol with RdRP and −3.2 Kcal/mol with 3CLpro; and nimbochalcin with equivalent values of −5.0Kcal/mol with RdRp and −4.9 Kcal/mol with 3CLpro. Molecular dynamics simulation (50ns) analysis was made of 3CLpro and RdRp using Autodock Vina 1.1.2 software and VMD software. After ADMET analysis, 78 phytochemicals were found suitable for molecular docking. Three, namely acetovanillone, myrtenol and nimbochalcin from Picrorhiza kurroa, Azadirachta indica and Cyperus rotundus,respectively,exhibited good binding affinity with 3CLproand RdRp of SARS-CoV-2. Interaction analysis, molecular dynamics simulations and MM-PBSA calculations were executed for two complexes, acetovanillone_RdRp and myrtenol_3CL pro.Acetovanillone_RdRpcomplex did not display any structural change after MD simulation as compared to myrtenol_3CL pro. The overall stability of acetovanillone_6NUR was 154.7 kJ/mol, and for myrtenol_1UJ1 90.5 kJ/mol. In silico analysis revealed that acetovanillone ( Picrorhiza kurroa) and myrtenol ( Cyperus rotundus) possess anti SARS-CoV-2 activity. Further studies are needed to validate their efficacy in biological models.

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Investigation of genotoxic effects of the anti-asthmatic and anti-inflammatory drugs Apocynin and Acetosyringenin in the Salmonella typhimurium mutagenicity assay and the SCE-test with human lymphocytes

Cited by 8 publications

References 12 publications

The Role of the Methoxyphenol Apocynin, a Vascular NADPH Oxidase Inhibitor, as a Chemopreventative Agent in the Potential Treatment of Cardiovascular Diseases

The Role of the Methoxyphenol Apocynin, a Vascular NADPH Oxidase Inhibitor, as a Chemopreventative Agent in the Potential Treatment of Cardiovascular Diseases

Experimental, DFT and docking simulations of the binding of diapocynin to human serum albumin: induced circular dichroism

Ayurvedic Medicinal Plants Against COVID-19: An In Silico Analysis

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