Subramaniyam Sathiyamoorthy

Molecular docking studies of anti-apoptotic BCL-2, BCL-XL, and MCL-1 proteins with ginsenosides from Panax ginseng

Anti-apoptotic proteins such as BCL-2, BCL-XL and MCL-1 bind with pro-apoptotic proteins to induce apoptosis mechanism. BCL-2 family proteins are key regulators of apoptosis process. Over expression of these anti-apoptotic proteins lead to several cancers by preventing apoptosis. A number of studies revealed that ginseng derivatives reduce tumor growth. Ginseng, the most valuable medicinal herb found in eastern Asia belongs to Araliaceae family. In this study, docking simulations were performed for anti-apoptotic proteins with several ginsenosides from Panax ginseng. Our finding shows ginsenosides Rf, Rg1, Rg3 and Rh2 have more binding affinity with BCL-2, BCL-XL and MCL-1 and other ginsenosides also interact with each anti-apoptotic proteins. Therefore, ginseng derivatives represent a novel class of potent inhibitors and could be used for cancer chemotherapy.

Identification of BACE1 inhibitors from Panax ginseng saponins-An Insilco approach

BACE1, a β secretase candidate enzyme, initiates the Alzheimers disease (AD) pathogenesis via amyloid β (Aβ) peptide production serving as a potential therapeutic target. Previous experimental evidence suggested that ginsenosides, a key component of Panax ginseng, are effective against AD. In this study, we implemented a molecular modeling method to reveal the inhibitory action of ginsenosides on BACE1 activity. We selected 12 ginsenosides and performed molecular docking studies to evaluate its interaction with the BACE1 active site, which is essential for inhibition. Further ADMET filtration was applied to find drug-like molecules with a specific ability to cross blood brain barrier (BBB), and to determine toxicity. The BACE1-ginsenosides complex was further subjected to a molecular dynamics simulation to study the stability of the complex and its hydrogen bond interactions. In summary, our findings show ginsenosides CK, F1, Rh1 and Rh2 are potential BACE1 inhibitors from Panax ginseng.

Computer-aided identification of EGFR tyrosine kinase inhibitors using ginsenosides from Panax ginseng

Natural products have served as structural resources in the history of drug discovery for cancer therapy. Among these natural products, Korean Panax ginseng serves as a potential anti-cancer medicinal plant. To determine the anti-cancer activities of Korean P. ginseng active compounds, we performed pharmacophore-based virtual screening and molecular docking studies on EGFR (epidermal growth factor receptor) tyrosine kinase domain. The EGFR family tyrosine kinase receptor is a cell surface receptor that regulates diverse biological processes including cell proliferation, differentiation, survival, and apoptosis. Over expression of EGFR tyrosine kinase domain associated with the development and progression of numerous human cancers. In our study, we developed the best pharmacophore model (Hypo1) using a diverse training set and validated by Fischers randomization, a test set, and a decoy set. The best validated model was employed in the virtual screening of P. ginseng compound database. Further, chosen molecules were evaluated by applying ADMET screening and molecular docking studies. Finally, 14 compounds were obtained based on binding affinity scores and interactions with protein active site residues. These final lead compounds from P. ginseng can be used in the designing of new EGFR tyrosine kinase inhibitors.

Gene ontology study of methyl jasmonate-treated and non-treated hairy roots of Panax ginseng to identify genes involved in secondary metabolic pathway

The roots of Panax ginseng C.A. Meyer, known as Korean ginseng have been a valuable and important folk medicine in East Asian countries. It mainly used to maintain the homeostasis of the human body, with the presence of ginsenosides and non-saponin compounds like phenol compounds, acidic polysaccharides and polyethylene compounds. Functional genomics aid to annotate EST sequences based on gene ontology. In this study, we focused, genes which involve in secondary metabolic pathways and to visualize temporal changes of gene expression in ginseng hairy roots with methyl ester methyl jasmonate (MeJA) along with non-treated hairy roots. A 5.774 EST clones were clustered and assembled into 501 contigs and 2.955 singletons. Annotations categorized with molecular functions, biological processes, cellular compounds of gene ontological terms and biochemical functions, enzyme commission number, and metabolic pathways are assigned through Kyoto Encyclopedia of Genes and Genomes database. Comparatively, EST sequences are assigned to cellular process, metabolic process, biotic and abiotic stress stimuli, developmental and biological regulations and transports are up-regulated 2–3 fold in MeJA treated hairy roots. 46 different sub groups of enzymes found in the MeJA treated plants. These annotated ESTs represents a significant proportion of the P. ginseng and provides molecular resource for develop microarray to study genes expressions to development, metabolism and reproduction.

In silico gene expression analysis in Codonopsis lanceolata root

Expressed sequence tags (ESTs) provide valuable tools that can be used to predict the genes involved in primary and secondary metabolite synthesis. To the best of our knowledge, ESTs have not yet been developed for Codonopsis.lanceolata, and therefore, the EST referenced in this report is the first transcript for C.lanceolata. A cDNA library was constructed using the roots of C. lanceolata plants that were grown in a field. The selected 881 cDNA clones were sequenced and processed with an EST pipeline, resulting in 636 unique sequences, including 517 singletons and 119 contig sequences. Using bioinformatics tools, 81% of the EST sequence was putatively annotated. Data for unique transcripts were mined from biological databases and functionally classified using gene ontology (GO), the Kyoto Encyclopedia of Genes and Genomes Orthology, KEGG pathway maps, and protein family. The GO-based analyses were examined in terms of biotic and abiotic stress response, transport, cellular component organization, biogenesis, and secondary metabolic processes. The KEGG-based analyses of most transcripts were sorted by carbohydrate metabolism, energy metabolism, and biosynthesis of secondary metabolites. Five randomly-selected putative genes were used for an expression study using various stresses such as salt, H2O2, salicylic acid, and methyl jasmonic acid. Mined data were organized in “The Codonopsis EST Database” (www.bioherbs.khu.ac.kr/Codonopsis).

Development of a multiplex amplification refractory mutation system for simultaneous authentication of Korean ginseng cultivars “Gumpoong” and “Chungsun”

Background and aims. Molecular authentication of Korean ginseng cultivars was investigated using the mitochondrial nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 7 (nad7) intron 3 region. Materials and methods. A mutation site specific to Panax ginseng “Gumpoong” and “Chungsun” cultivars was detected within the sequence data. Based on this mutation site and the “Gumpoong”-specific single nucleotide polymorphism site reported in 26S rDNA, two modified allele-specific primer pairs were designed and a multiplex amplification refractory mutation system (MARMS) was applied to identify “Gumpoong” and “Chungsun.” Results. The results showed that “Gumpoong” and “Chungsun” can be clearly discriminated from the other Korean ginseng cultivars by simultaneously identifying the haplotype of “Gumpoong” and the specific allele of “Chungsun” by applying the MARMS. Conclusion. This study, therefore, provides a simple and reliable method for simultaneous authentication of “Gumpoong” and “Chungsun” cultivars.