The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Francisco Fabio Oliveira De Sousa - One of the best experts on this subject based on the ideXlab platform.
-
development of Anacardic Acid loaded zein nanoparticles physical chemical characterization stability and antimicrobial improvement
Journal of Molecular Liquids, 2021Co-Authors: Jennifer Thayanne Cavalcante De Araujo, Manuel Martinpastor, Loures Perez, Aurora Pinazo, Francisco Fabio Oliveira De SousaAbstract:Abstract Anacardic Acid (AA) has gained interest regarding its extraordinary antimicrobial activity. Nanotechnology based delivery systems are a modern approach to improve both pharmacological and functional properties of therapeutic agents. In this paper we aimed to design and characterize AA loaded-zein nanoparticles and evaluate its antimicrobial efficiency in vitro using microdilution and antibiofilm assays. AA nanoparticles were spherical, stable, with an average size of 381.6 nm and negative ζ potential. The saturation transfer difference-NMR analysis demonstrated the association of zein and AA in two different conformations, enlightening its enhanced pharmacological activity. Bacteriostatic concentrations were 0.05 and 3.12 μg/ml for Staphylococcus aureus and Pseudomonas aeruginosa, while bactericide activity was observed only for S. aureus at 0.2 μg/ml. Fungistatic/fungicide concentrations for Candida rugosa were 1.17/2.34 μg/ml, for Candida albicans and Candida parapsilosis 2.34/4.69 μg/ml and for Candida tropicalis, Candida jardinii, Candida glabratta and Candida auris 4.69/4.69 μg/ml. Furthermore, nanoencapsulated AA was more efficient in reducing S. aureus and C. albicans biofilms viability than AA solution, while they presented a similar inhibition against P. aeruginosa biofilm. Therefore, AA loaded-zein nanoparticles could represent an alternative for potential applications where the low concentrations of this phytochemical are useful to prevent or treat bacterial and fungical infections.
-
larvicidal activity aquatic and in vivo toxicity of Anacardic Acid loaded zein nanoparticles
Journal of Drug Delivery Science and Technology, 2021Co-Authors: Eduardo Junior Serrao Pinto, Jennifer Thayanne Cavalcante De Araujo, Ricardo Ferreira, Raimundo Nonato Picanco Souto, Lais Aragao Lima, Paulo Goberlânio De Barros Silva, M T Garcia, Ana De La Fuente, Francisco Fabio Oliveira De SousaAbstract:Abstract The present study aimed to evaluate the larvicidal activity, the aquatic and subacute toxicity of Anacardic Acid in solution and encapsulated in zein nanoparticles. For the larvicidal potential, different Anacardic Acid concentrations were tested against young A. aegypti larvae, determining the mortality rates at 24, 48 h and the residual effect between 1 and 4 weeks. For the acute ecotoxicology test, Daphnia magna was selected as the untargeted environmental organism. To evaluate the subacute toxicity, blank and Anacardic Acid loaded-zein nanoparticles were administered orally to Swiss mice in the dose of 2.25 μg/kg for 7 days. Anacardic Acid loaded-zein nanoparticles showed remarkable larvicidal activity up to 48 h at very low concentrations. Moreover, under the larvicide concentrations mortality was limited in aquatic toxicity assay, while no signs of toxicity were found in the mice treated with blank or Anacardic Acid nanoparticles. Accordingly, the Anacardic Acid nanoformulations were found to be very potent and efficient on eliminating A. aegypt larvae, and also unhazardous to non-target species, representing a new larvicide candidate against arboviruses diseases’ vectors.
-
Toxicological and genotoxic evaluation of Anacardic Acid loaded-zein nanoparticles in mice.
Toxicology reports, 2020Co-Authors: Jennifer Thayanne Cavalcante De Araujo, Lais Aragao Lima, Paulo Goberlânio De Barros Silva, Everton Pantoja Vale, Manuel Martín-pastor, Ramille Araújo Lima, Francisco Fabio Oliveira De SousaAbstract:Abstract Anacardic Acid extracted from cashew nut shells of Anacardium occidentale L has demonstrated important biological activities, such as antibacterial activity against the cariogenic specie Streptococcus mutans. Zein nanoparticles containing Anacardic Acid (9.375 μg/mL) were evaluated in terms of toxicity and genotoxicity in vivo. The subacute toxicity assay was used to evaluate the cumulative effects of the oral administration of nanoencapsulated Anacardic Acid at 2.25 and 112.5 μg/kg for 7 days in mice, simulating a mouth rinse short-term clinical course treatment. Blank zein nanoparticles and saline solution 0.9 % were used as negative controls. Peripheral blood samples were collected to evaluate the genotoxicity in polychromatic erythrocytes using the micronucleus test. The animals were anesthetized, euthanized and the target organs collected, weighed and submitted to histopathological analysis. Liver, kidney and spleen relative weights did not change. Nevertheless, stomach, lung and heart increased the relative weights in the group receiving the highest dose, in which occasional histopathological findings were also identified. Both doses maintained the micronucleus frequency within the normal range and the animals treated with the highest dose presented a discrete weight lost, which could explain the organs’ relative weight reductions. Blank and Anacardic Acid loaded zein nanoparticles were nontoxic when administered repeatedly for 7 days, as no relevant histopathological changes neither genotoxicity were observed. These preparations demonstrated limited toxicity under the conditions used in this study and could become an antibacterial alternative for preventing/treating oral infections in short-term treatments.
-
antimicrobial effect of Anacardic Acid loaded zein nanoparticles loaded on streptococcus mutans biofilms
Brazilian Journal of Microbiology, 2020Co-Authors: Ramille Araújo Lima, Jennifer Thayanne Cavalcante De Araujo, Lais Aragao Lima, Francisco Fabio Oliveira De Sousa, Smyrna Luiza Ximenes De Souza, Ana Larissa Ximenes Batista, Juliana Paiva Marques Lima Rolim, Tereza De Jesus Pinheiro Gomes BandeiraAbstract:Bacterial biofilms play a key role in the pathogenesis of major oral diseases. Nanoparticles open new paths for drug delivery in complex structures such as biofilms. This study evaluated the antimicrobial effect of zein nanoparticles containing Anacardic Acid (AA) extracted from cashew shells of Anacardium occidentale on in vitro Streptococcus mutans biofilm formation and mature biofilms. The minimum inhibitory concentration (MIC), minimum bacterial concentration (MBC), and antibiofilm assays were performed. Streptococcus mutans UA159 biofilms were formed on saliva-coated hydroxyapatite disk for 5 days. To evaluate the preventive effect on biofilm formation, before contact with the inoculum, the disks were immersed once for 2 min in (1) hydroethanolic solution; (2) blank zein nanoparticles; (3) zein nanoparticles containing AA; and (4) 0.12% chlorhexidine gluconate. To determine the effect against mature biofilms, the disks containing 5-day preformed biofilms were further treated using the same procedure. The bacterial viability and dry weight were determined for both assays and used to compare the groups using ANOVA followed by Tukey’s test (p < 0.05). Both MIC and MBC for AA-loaded zein nanoparticles were 0.36 μg/mL. Groups 3 and 4 were very effective in inhibiting S. mutans biofilm formation, as no colony-forming units were detected. In contrast, for mature biofilms, no difference in bacterial viability (p = 0.28) or dry weight (p = 0.09) was found between the treatments. Therefore, the AA-based nanoformulation presented very high inhibitory and bactericidal activities against planktonic S. mutans, and the results indicate a strong antiplaque effect. However, the formulation showed no antimicrobial effect on the established biofilm.
Isao Kubo - One of the best experts on this subject based on the ideXlab platform.
-
Molecular design of anti-MRSA agents based on the Anacardic Acid scaffold.
Bioorganic & medicinal chemistry, 2007Co-Authors: Ivan R. Green, Felismino E. Tocoli, Sang Hwa Lee, Ken-ichi Nihei, Isao KuboAbstract:A series of Anacardic Acid analogues possessing different side chains viz. phenolic, branched, and alicyclic were synthesized and their antibacterial activity tested against methicillin-resistant Staphylococcus aureus (MRSA). The maximum activity against this bacterium occurred with the branched side-chain analogue, 6-(4',8'-dimethylnonyl)salicylic Acid, and the alicyclic side-chain analogue, 6-cyclododecylmethyl salicylic Acid, with the minimum inhibitory concentration (MIC) of 0.39 microg/mL, respectively. This activity was superior to that of the most potent antibacterial Anacardic Acid isolated from the cashew Anacardium occidentale (Anacardiaceae), apple and nut, that is, the 6-[8'(Z),11'(Z),14'-pentadecatrienyl]salicylic Acid.
-
Antibacterial activity of Anacardic Acid and totarol, alone and in combination with methicillin, against methicillin-resistant Staphylococcus aureus
The Journal of applied bacteriology, 1996Co-Authors: Hisae Muroi, Isao KuboAbstract:The inhibitory and bactericidal activities of Anacardic Acid and totarol, alone and in combination with methicillin, were investigated against methicillin-resistant Staphylococcus aureus (MRSA). The growth of two MRSA strains was inhibited by 6 x 25 microg ml-1 of Anacardic Acid and 0 x 78 microg ml-1 of totarol. The time-kill curve study showed that these two compounds were bactericidal against MRSA. Anacardic Acid killed MRSA cells more rapidly than totarol, and no viable cells were detected after being exposed to 6 x 25 microg ml-1 of Anacardic Acid for 6 h. Anacardic Acid showed bactericidal activity against MRSA at any stage of growth, and also even when cell division was inhibited by chloramphenicol. In the combination studies, the minimal inhibitory concentration (MIC) of methicillin was lowered from 800 to 1 x 56 microg ml-1 for MRSA ATCC 33591, and from 800 to 6 x 25 microg ml-1 for MRSA ATCC 33592, by combining with 1/2 x MIC of Anacardic Acid. The time-kill curves demonstrated synergistic bactericidal activities for these combinations.
-
bactericidal effects of Anacardic Acid and totarol on methicillin resistant staphylococcus aureus mrsa
Bioscience Biotechnology and Biochemistry, 1994Co-Authors: Hisae Muroi, Isao KuboAbstract:Growth of two strains of methicillin-resistant Staphylococcus aureus (MRSA) was inhibited by 6.25 μg/ml of Anacardic Acid and 0.78 μg/ml of totarol, and these two compounds were found to be bactericidal. Anacardic Acid was bactericidal against MRSA at any stage of growth.
Jennifer Thayanne Cavalcante De Araujo - One of the best experts on this subject based on the ideXlab platform.
-
development of Anacardic Acid loaded zein nanoparticles physical chemical characterization stability and antimicrobial improvement
Journal of Molecular Liquids, 2021Co-Authors: Jennifer Thayanne Cavalcante De Araujo, Manuel Martinpastor, Loures Perez, Aurora Pinazo, Francisco Fabio Oliveira De SousaAbstract:Abstract Anacardic Acid (AA) has gained interest regarding its extraordinary antimicrobial activity. Nanotechnology based delivery systems are a modern approach to improve both pharmacological and functional properties of therapeutic agents. In this paper we aimed to design and characterize AA loaded-zein nanoparticles and evaluate its antimicrobial efficiency in vitro using microdilution and antibiofilm assays. AA nanoparticles were spherical, stable, with an average size of 381.6 nm and negative ζ potential. The saturation transfer difference-NMR analysis demonstrated the association of zein and AA in two different conformations, enlightening its enhanced pharmacological activity. Bacteriostatic concentrations were 0.05 and 3.12 μg/ml for Staphylococcus aureus and Pseudomonas aeruginosa, while bactericide activity was observed only for S. aureus at 0.2 μg/ml. Fungistatic/fungicide concentrations for Candida rugosa were 1.17/2.34 μg/ml, for Candida albicans and Candida parapsilosis 2.34/4.69 μg/ml and for Candida tropicalis, Candida jardinii, Candida glabratta and Candida auris 4.69/4.69 μg/ml. Furthermore, nanoencapsulated AA was more efficient in reducing S. aureus and C. albicans biofilms viability than AA solution, while they presented a similar inhibition against P. aeruginosa biofilm. Therefore, AA loaded-zein nanoparticles could represent an alternative for potential applications where the low concentrations of this phytochemical are useful to prevent or treat bacterial and fungical infections.
-
larvicidal activity aquatic and in vivo toxicity of Anacardic Acid loaded zein nanoparticles
Journal of Drug Delivery Science and Technology, 2021Co-Authors: Eduardo Junior Serrao Pinto, Jennifer Thayanne Cavalcante De Araujo, Ricardo Ferreira, Raimundo Nonato Picanco Souto, Lais Aragao Lima, Paulo Goberlânio De Barros Silva, M T Garcia, Ana De La Fuente, Francisco Fabio Oliveira De SousaAbstract:Abstract The present study aimed to evaluate the larvicidal activity, the aquatic and subacute toxicity of Anacardic Acid in solution and encapsulated in zein nanoparticles. For the larvicidal potential, different Anacardic Acid concentrations were tested against young A. aegypti larvae, determining the mortality rates at 24, 48 h and the residual effect between 1 and 4 weeks. For the acute ecotoxicology test, Daphnia magna was selected as the untargeted environmental organism. To evaluate the subacute toxicity, blank and Anacardic Acid loaded-zein nanoparticles were administered orally to Swiss mice in the dose of 2.25 μg/kg for 7 days. Anacardic Acid loaded-zein nanoparticles showed remarkable larvicidal activity up to 48 h at very low concentrations. Moreover, under the larvicide concentrations mortality was limited in aquatic toxicity assay, while no signs of toxicity were found in the mice treated with blank or Anacardic Acid nanoparticles. Accordingly, the Anacardic Acid nanoformulations were found to be very potent and efficient on eliminating A. aegypt larvae, and also unhazardous to non-target species, representing a new larvicide candidate against arboviruses diseases’ vectors.
-
Toxicological and genotoxic evaluation of Anacardic Acid loaded-zein nanoparticles in mice.
Toxicology reports, 2020Co-Authors: Jennifer Thayanne Cavalcante De Araujo, Lais Aragao Lima, Paulo Goberlânio De Barros Silva, Everton Pantoja Vale, Manuel Martín-pastor, Ramille Araújo Lima, Francisco Fabio Oliveira De SousaAbstract:Abstract Anacardic Acid extracted from cashew nut shells of Anacardium occidentale L has demonstrated important biological activities, such as antibacterial activity against the cariogenic specie Streptococcus mutans. Zein nanoparticles containing Anacardic Acid (9.375 μg/mL) were evaluated in terms of toxicity and genotoxicity in vivo. The subacute toxicity assay was used to evaluate the cumulative effects of the oral administration of nanoencapsulated Anacardic Acid at 2.25 and 112.5 μg/kg for 7 days in mice, simulating a mouth rinse short-term clinical course treatment. Blank zein nanoparticles and saline solution 0.9 % were used as negative controls. Peripheral blood samples were collected to evaluate the genotoxicity in polychromatic erythrocytes using the micronucleus test. The animals were anesthetized, euthanized and the target organs collected, weighed and submitted to histopathological analysis. Liver, kidney and spleen relative weights did not change. Nevertheless, stomach, lung and heart increased the relative weights in the group receiving the highest dose, in which occasional histopathological findings were also identified. Both doses maintained the micronucleus frequency within the normal range and the animals treated with the highest dose presented a discrete weight lost, which could explain the organs’ relative weight reductions. Blank and Anacardic Acid loaded zein nanoparticles were nontoxic when administered repeatedly for 7 days, as no relevant histopathological changes neither genotoxicity were observed. These preparations demonstrated limited toxicity under the conditions used in this study and could become an antibacterial alternative for preventing/treating oral infections in short-term treatments.
-
antimicrobial effect of Anacardic Acid loaded zein nanoparticles loaded on streptococcus mutans biofilms
Brazilian Journal of Microbiology, 2020Co-Authors: Ramille Araújo Lima, Jennifer Thayanne Cavalcante De Araujo, Lais Aragao Lima, Francisco Fabio Oliveira De Sousa, Smyrna Luiza Ximenes De Souza, Ana Larissa Ximenes Batista, Juliana Paiva Marques Lima Rolim, Tereza De Jesus Pinheiro Gomes BandeiraAbstract:Bacterial biofilms play a key role in the pathogenesis of major oral diseases. Nanoparticles open new paths for drug delivery in complex structures such as biofilms. This study evaluated the antimicrobial effect of zein nanoparticles containing Anacardic Acid (AA) extracted from cashew shells of Anacardium occidentale on in vitro Streptococcus mutans biofilm formation and mature biofilms. The minimum inhibitory concentration (MIC), minimum bacterial concentration (MBC), and antibiofilm assays were performed. Streptococcus mutans UA159 biofilms were formed on saliva-coated hydroxyapatite disk for 5 days. To evaluate the preventive effect on biofilm formation, before contact with the inoculum, the disks were immersed once for 2 min in (1) hydroethanolic solution; (2) blank zein nanoparticles; (3) zein nanoparticles containing AA; and (4) 0.12% chlorhexidine gluconate. To determine the effect against mature biofilms, the disks containing 5-day preformed biofilms were further treated using the same procedure. The bacterial viability and dry weight were determined for both assays and used to compare the groups using ANOVA followed by Tukey’s test (p < 0.05). Both MIC and MBC for AA-loaded zein nanoparticles were 0.36 μg/mL. Groups 3 and 4 were very effective in inhibiting S. mutans biofilm formation, as no colony-forming units were detected. In contrast, for mature biofilms, no difference in bacterial viability (p = 0.28) or dry weight (p = 0.09) was found between the treatments. Therefore, the AA-based nanoformulation presented very high inhibitory and bactericidal activities against planktonic S. mutans, and the results indicate a strong antiplaque effect. However, the formulation showed no antimicrobial effect on the established biofilm.
Lupituko L. Mkayula - One of the best experts on this subject based on the ideXlab platform.
-
Isolation of Anacardic Acid from Natural Cashew Nut Shell Liquid (CNSL) Using Supercritical Carbon Dioxide.
Journal of agricultural and food chemistry, 2008Co-Authors: Joseph Yoeza Naimani Philip, José Da Cruz Francisco, Estera Szwajcer Dey, Joseph Buchweishaija, Lupituko L. MkayulaAbstract:Solvent extracted cashew nut shell liquid (CNSL), conventionally known as natural CNSL, is a mixture of several alkenyl phenols. One of these alkenyl phenols is Anacardic Acid, which is present at the highest concentration. In view of anticipated industrial applications of Anacardic Acid, the objective of this work was to isolate Anacardic Acid from natural CNSL by supercritical carbon dioxide (scCO 2). In this study, the solubility data for natural CNSL in scCO 2 under a range of operating conditions of pressure (100, 200, and 300 bar), temperature (40 and 50 degrees C), and CO 2 flow rate (5, 10, and 15 g min (-1)) were established. The best scCO 2 working conditions were found to be 50 degrees C and 300 bar at a flow rate of 5 g min (-1) CO 2. Using 3 g of sample (CNSL/solid adsorbent = 1/2) under these scCO 2 conditions, it was possible to quantitatively isolate high purity Anacardic Acid from crude natural CNSL (82% of total Anacardic Acid) within 150 min. The Anacardic Acid isolated by scCO 2 was analyzed by different spectroscopic techniques (UV-vis, FT-IR, and (1)H NMR) and HPLC analysis, indicating that the Anacardic Acid isolated by scCO 2 has better quality than that obtained through a conventional method involving several chemical conversion steps.
-
preparation of molecularly imprinted polymers using Anacardic Acid monomers derived from cashew nut shell liquid
Journal of Agricultural and Food Chemistry, 2007Co-Authors: Joseph Yoeza Naimani Philip, Joseph Buchweishaija, Lupituko L. MkayulaAbstract:The objective of this work was to use monomers from cashew (Anacardium occidentale L.) nut shells to develop molecularly imprinted polymers. Cashew nut shell liquid (CNSL) is a cheap and renewable agro byproduct consisting of versatile monomers. Solvent-extracted CNSL contains over 80% Anacardic Acid (AnAc) with more than 90% degree of unsaturation in its C15 side chain. From AnAc monomer, anacardanyl acrylate (AnAcr) and anacardanyl methacrylate (AnMcr) monomers were synthesized and their chemical structures were characterized by Fourier transform IR and NMR. Different imprinted bulk polymers based on AnAc, AnAcr, and AnMcr functional monomers have been prepared. In the present study, each functional monomer was separately copolymerized in toluene with ethylene glycol dimethacrylate and divinylbenzene as cross-linkers, using racemic propranolol as a model template. While the AnAc based polymer revealed a meager rebinding ability, the imprinted polymers made from AnAcr and AnMcr displayed highly specific ...
Chinchu Bose - One of the best experts on this subject based on the ideXlab platform.
-
impregnation of catheters with Anacardic Acid from cashew nut shell prevents staphylococcus aureus biofilm development
Journal of Applied Microbiology, 2018Co-Authors: S E Sajeevan, Chinchu Bose, Bipin G. Nair, Maitrayee Chatterjee, V Paul, Gaurav Baranwal, V A Kumar, Asoke Banerji, B P Prasanth, Raja BiswasAbstract:Aim The effect of Anacardic Acid impregnation on catheter surfaces for the prevention of Staphylococcus aureus attachments and biofilm formations were evaluated. Methods and results Silicon catheter tubes were impregnated using different concentrations of Anacardic Acids (0·002-0·25%). Anacardic Acids are antibacterial phenolic lipids from cashew nut (Anacardium occidentale) shell oil. Anacardic Acid-impregnated silicon catheters revealed no significant haemolytic activity and were cytocompatible against fibroblast cell line (L929). Sustained release of Anacardic Acids was observed for 4 days. Anacardic Acid-impregnated silicon catheters efficiently inhibited S. aureus colonization and the biofilm formation on its surface. The in vivo antibiofilm activity of Anacardic Acid-impregnated catheters was tested in an intraperitoneal catheter-associated medaka fish infection model. Significant reduction in S. aureus colonization on Anacardic Acid-impregnated catheter tubes was observed. Conclusions Our data suggest that Anacardic Acid-impregnated silicon catheters may help in preventing catheter-related staphylococcal infections. Significance and impact of the study This study opens new directions for designing antimicrobial phytochemical-coated surfaces with ideal antibiofilm properties and could be of great interest for biomedical research scientists.
-
Anacardic Acid inhibits gelatinases through the regulation of Spry2, MMP-14, EMMPRIN and RECK.
Experimental cell research, 2016Co-Authors: Jyotsna Nambiar, Chinchu Bose, Asoke Banerji, Geetha B. Kumar, Meera Venugopal, Tarun B. Patel, Bipin G. NairAbstract:Earlier studies from our laboratory have identified Anacardic Acid (AA) as a potent inhibitor of gelatinases (MMP-2 and 9), which are over-expressed in a wide variety of cancers (Omanakuttan et al., 2012). Disruption of the finely tuned matrix metalloproteinase (MMP) activator/inhibitor balance plays a decisive role in determining the fate of the cell. The present study demonstrates for the first time, that in addition to regulating the expression as well as activity of gelatinases, AA also inhibits the expression of its endogenous activators like MMP-14 and Extracellular Matrix MetalloProteinase Inducer (EMMPRIN) and induces the expression of its endogenous inhibitor, REversion-inducing Cysteine-rich protein with Kazal motifs (RECK). In addition to modulating gelatinases, AA also inhibits the expression of various components of the Epidermal Growth Factor (EGF) pathway like EGF, Protein Kinase B (Akt) and Mitogen-activated protein kinases (MAPK). Furthermore, AA also activates the expression of Sprouty 2 (Spry2), a negative regulator of EGF pathway, and silencing Spry2 results in up-regulation of expression of gelatinases as well as MMP-14. The present study thus elucidates a novel mechanism of action of AA and provides a strong basis for utilizing this molecule as a template for cancer therapeutics.
-
Anacardic Acid induces apoptosis-like cell death in the rice blast fungus Magnaporthe oryzae.
Applied microbiology and biotechnology, 2015Co-Authors: Suhail Muzaffar, Chinchu Bose, Ashok Banerji, Bipin G. Nair, Bharat B. ChattooAbstract:Anacardic Acid (6-pentadecylsalicylic Acid), extracted from cashew nut shell liquid, is a natural phenolic lipid well known for its strong antibacterial, antioxidant, and anticancer activities. Its effect has been well studied in bacterial and mammalian systems but remains largely unexplored in fungi. The present study identifies antifungal, cytotoxic, and antioxidant activities of Anacardic Acid in the rice blast fungus Magnaporthe oryzae. It was found that Anacardic Acid causes inhibition of conidial germination and mycelial growth in this ascomycetous fungus. Phosphatidylserine externalization, chromatin condensation, DNA degradation, and loss of mitochondrial membrane potential suggest that growth inhibition of fungus is mainly caused by apoptosis-like cell death. Broad-spectrum caspase inhibitor Z-VAD-FMK treatment indicated that Anacardic Acid induces caspase-independent apoptosis in M. oryzae. Expression of a predicted ortholog of apoptosis-inducing factor (AIF) was upregulated during the process of apoptosis, suggesting the possibility of mitochondria dependent apoptosis via activation of apoptosis-inducing factor. Anacardic Acid treatment leads to decrease in reactive oxygen species rather than increase in reactive oxygen species (ROS) accumulation normally observed during apoptosis, confirming the antioxidant properties of Anacardic Acid as suggested by earlier reports. Our study also shows that Anacardic Acid renders the fungus highly sensitive to DNA damaging agents like ethyl methanesulfonate (EMS). Treatment of rice leaves with Anacardic Acid prevents M. oryzae from infecting the plant without affecting the leaf, suggesting that Anacardic Acid can be an effective antifungal agent.
-
Anacardic Acid inhibits the catalytic activity of matrix metalloproteinase-2 and matrix metalloproteinase-9
Molecular pharmacology, 2012Co-Authors: Athira Omanakuttan, Chinchu Bose, Asoke Banerji, Jyotsna Nambiar, Rodney Harris, Nanjan Pandurangan, Rebu K. Varghese, Geetha B. Kumar, John A. Tainer, J. Jefferson P. PerryAbstract:Cashew nut shell liquid (CNSL) has been used in traditional medicine for the treatment of a wide variety of pathophysiological conditions. To further define the mechanism of CNSL action, we investigated the effect of cashew nut shell extract (CNSE) on two matrix metalloproteinases, MMP-2/gelatinase A and MMP-9/gelatinase B, which are known to have critical roles in several disease states. We observed that the major constituent of CNSE, Anacardic Acid, markedly inhibited the gelatinase activity of 3T3-L1 cells. Our gelatin zymography studies on these two secreted gelatinases, present in the conditioned media from 3T3-L1 cells, established that Anacardic Acid directly inhibited the catalytic activities of both MMP-2 and MMP-9. Our docking studies suggested that Anacardic Acid binds into the MMP-2/9 active site, with the carboxylate group of Anacardic Acid chelating the catalytic zinc ion and forming a hydrogen bond to a key catalytic glutamate side chain and the C15 aliphatic group being accommodated within the relatively large S1' pocket of these gelatinases. In agreement with the docking results, our fluorescence-based studies on the recombinant MMP-2 catalytic core domain demonstrated that Anacardic Acid directly inhibits substrate peptide cleavage in a dose-dependent manner, with an IC₅₀ of 11.11 μM. In addition, our gelatinase zymography and fluorescence data confirmed that the cardol-cardanol mixture, salicylic Acid, and aspirin, all of which lack key functional groups present in Anacardic Acid, are much weaker MMP-2/MMP-9 inhibitors. Our results provide the first evidence for inhibition of gelatinase catalytic activity by Anacardic Acid, providing a novel template for drug discovery and a molecular mechanism potentially involved in CNSL therapeutic action.