JNK signaling-dependent regulation of histone acetylation are involved in anacardic acid alleviates cardiomyocyte hypertrophy induced by phenylephrine

Cardiac hypertrophy is a complex process induced by the activation of multiple signaling pathways. We previously reported that anacardic acid (AA), a histone acetyltransferase (HAT) inhibitor, attenuates phenylephrine (PE)-induced cardiac hypertrophy by downregulating histone H3 acetylation at lysine 9 (H3K9ac). Unfortunately, the related upstream signaling events remained unknown. The mitogen-activated protein kinase (MAPK) pathway is an important regulator of cardiac hypertrophy. In this study, we explored the role of JNK/MAPK signaling pathway in cardiac hypertrophy induced by PE. The mice cardiomyocyte hypertrophy model was successfully established by treating cells with PE in vitro. This study showed that p-JNK directly interacts with HATs (P300 and P300/CBP-associated factor, PCAF) and alters H3K9ac. In addition, both the JNK inhibitor SP600125 and the HAT inhibitor AA attenuated p-JNK overexpression and H3K9ac hyperacetylation by inhibiting P300 and PCAF during PE-induced cardiomyocyte hypertrophy. Moreover, we demonstrated that both SP600125 and AA attenuate the overexpression of cardiac hypertrophy-related genes (MEF2A, ANP, BNP, and β-MHC), preventing cardiomyocyte hypertrophy and dysfunction. These results revealed a novel mechanism through which AA might protect mice from PE-induced cardiomyocyte hypertrophy. In particular, AA inhibits the effects of JNK signaling on HATs-mediated histone acetylation, and could therefore be used to prevent and treat pathological cardiac hypertrophy.

Determine the Effectiveness of Anacardic Acid and Stannous Fluoride as an Anti-erosive Agent

Background: The key goal of the study is to find out the effectiveness of anacardic acid and the stannous fluoride as an anti erosive agent. Objectives: To evaluate the erosive effect of Bio vinegar and antierosive effect of Anacardic acid and Stannous Fluoride. Methodology: The extracted teeth were collected for in vitro study. Three solutions were selected Bio vinegar, Anacardic acid, Fluoride to treat the extracted teeth to study and compare the anti-erosive effect. The sets of extracted teeth of ten each were grouped to be treated with different solutions. The set was immersed in Bio vinegar for 8 hours for erosive action. The second set of ten extracted teeth were immersed in anacardic acid for four days. The same set of teeth were treated with vinegar for 8 hours. The cross sectional view of stained teeth was viewed under Scanning Electron Microscope. The third set of teeth was immersed in stannous fluoride for four days and then treated with Bio vinegar for 8 hours. The cross sectional view of stained teeth was viewed under Scanning Electron Microscope. A comparison of anti-erosive effect of anacardic acid and stannous fluoride were studied under Scanning Electron Microscope. Expected Results: Determining a better effectiveness of Anacardic acid antierosive agent than stannous fluoride. Conclusion: Reduction in the level of erosion by the application of anacardic acid and stannous fluoride on extracted teeth exposed to carbonated drinks and assessment of erosive effect of carbonated drink on tooth.

Comparative Transcriptomic Response Of Pancreatic And Breast Cancer Cells To Anacardic Acid Ans Olaparib

The study seeks to compare the transcriptomic response of pancreatic and breast cancer cells to Anarcadic Acid and Olaparib via the preparation of Pancreatic Cancer Cell Culture which involves the seeding of PANC-1 cells in 6-well plates (5× 105 cells per well). 24hours later, cells will be untreated or treated by 5mM anacardic acid, 2mM olaparib or a combination of anacardic acid (5mM) and olaparib (2mM) for 48hours; after which Pancreatic Cancer Cell’s mRNA Library will be Prepared and Sequenced using the Illumina TruSeq™ RNA Sample Prep Kit v2. Samples will be sequenced on the Illumina HiSeq 2500, 2× 100bp paired-end reads, to a minimum depth of 30 million reads per sample. Thereafter, the Computational Analyses of Pancreatic Cancer RNA-seq Data will be done by obtaining a total of 240 million obtained reads of high quality clean tags which will then be mapped and annotated via human reference genome using Bioconductor package biomaRt (http://www.bioconductor.org) (Durinck et al 2009). Mapped reads with mapping quality 10 or more will be defined as uniquely mapped reads and used in the downstream analyses. Biological networks and pathways related to anachardic acid, olaparib and the combination will be analyzed with Ingenuity Pathway Analysis (IPA) software (Qiagen, CA, USA). The lists of all genes identified in gene expression analysis will be uploaded into the IPA software. For the analysis of networks and pathways, the cutoff values will be set at P≤ 1× 10−5 and FC≥ |2| respectively.Validation of RNA-seq Results by qRT-PCR via the expression of mRNA which will be determined in all 4 samples using Power SYBR® Green RNA-to-CT™ 1-Step Kit (Life Technologies, CA, USA). The Western blotting for the selected proteins will be performed, as described by Yue (Yue et al 2015). Thereafter, the Breast Cancer Cell Culture will be prepared and treated. Breast Cancer Cell’s mRNA RNA-seq will be prepared. The Truseq Stranded mRNA kit (Illumina) will be used to prepare mRNA libraries from 1 µg total RNA. Libraries will be confirmed on the Agilent 2100 Bioanalyzer and quantitated using the Illumina Library Quantification Kit, ABI Prism qPCR Mix from Kapa Biosystems and the ABI7900HT real-time PCR instrument. The differential Gene Expression will be analysed RNA-seq reads will be assembled according to the hg19.gtf annotation file (downloaded from ENSEMBL) (Flicek et al 2014) using Cufflinks (version 2.2.1) (Trapnell et al 2012). For each comparison, both cufflinks assemblies shall be merged, and the resulting merged gtf file serves as the transcript input for differential gene expression analysis in Gene Ontology and KEGG pathways. For three of the comparisons, a p-value cutoff ≤0.05 shall be used to determine differential expression. In-silico pathway and network analysis of differentially expressed genes shall be performed in MetaCore version 6.27 (GeneGO, Thomson Reuters, New York, N.Y.) (Bolser et al 2012). The results obtained will be statistically analysed. The results of RT-PCR shall be normalized to expression of GAPDH using the formula 2∆ CT. One-way ANOVA shall be used for comparing treatment with the combination of anacardic acid and olaparib to the untreated control. A P value less than 0.05 will be considered statistically significant.

Acid-Base Extraction of Anacardic Acid from Cashew Seed Shell

Research on the isolation of anacardic acid compounds from cashew nut shells has been carried out. This study aims to develop a method of isolating anacardic acid compounds from cashew nut shells in an easier way but still produces compounds that remain pure. In this study isolation and identification of anacardic acid compounds contained in CNSL was carried out. The results of anacardic acid isolation contained in CNSL in the form of a thick brown extract that has a characteristic dark odor. Anacardic acid was isolated using a maceration method using methanol as a solvent. The results of the isolation of anacardic acid compounds were then tested for purity using a thin layer chromatography test (TLC) using an eluent or a mobile phase of methanol: chloroform. Furthermore anacardic acid compounds were identified using IR spectroscopy and UV-vis spectroscopy. This identification was carried out to prove that the compound obtained was indeed an anacardic acid compound. From the identification results it was found that the compound isolated in this study was indeed an anacardic acid compound. This can be compared with the structure of existing anacardic acid compounds.

Quantification of anacardic acid, the toxic component in raw and purified samples of Semecarpus anacardium L. by Siddha purification processes

Objectives The knowledge of purification process is unique since it deals with various physical and chemical changes in the inherent toxic properties during the process and it renders a strong support in the art of medicine preparation in Siddha system of medicine. Semecarpus anacardium L. is listed under Schedule e (1) drugs and purification is mandatory before its administration in medicine preparation. The bioactive compounds present in the plant like alkaloids, terpenoids, flavonoids, saponins, glycosides, steroids enhance the medical efficacy and defense mechanisms of the plant. Hence an attempt has been made to reveal the chemical change, occurring during the purification process in Siddha system of medicine by evaluating the phytochemicals and anacardic acid which is responsible for forming blisters and dermatitis. Methods Five common methods were used to purify the Semecarpus anacardium nuts as per the Siddha classical texts. The quantification of phytochemicals and anacardic acid has been done in unpurified, intermediate and purified samples. Results Significant changes were observed in phytochemicals and anacardic acid quantity in unpurified and purified samples. The major reduction of anacardic acid from 5.62 % in S1 to below detectable limit (BDL) in S2, S3, S4, 0.24% in S5 and 3.32% in S6. There is mild to moderate change in the phytochemicals which will support the efficacy of the drug. Conclusions With the results of phytochemicals, though all the purification methods have been evidenced to reduce the toxic nature, among the above five, the process II may be recommended for further research and medicine preparation.