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Direct rooting from leaf explants of Withania somnifera was achieved on half strength Murashige and Skoog's medium supplemented with 15 g l )1 sucrose, and different concentrations of growth regulators. Basal medium supplemented with 2.85 lM indoleacetic acid and 9.85 lM indolebutyric acid achieved maximum number of roots with 100% response. The roots were cultured on MS liquid medium for the establishment of root-organ culture with the same plant growth regulators and incubated on an orbital shaker at 80 rpm at 25 ± 2°C. A root biomass of 6.15 ± 0.17 g was obtained after 5 weeks. When 1 g roots were inoculated to 2.5 l bubble column reactor, 47 g roots were obtained after 6 weeks. The concentration of alkaloids was increased as compared to field grown roots. The maximum concentration of withanolides (10 mg g )1 dry weight) was obtained in the bioreactor.

Bioflavonoids are plant compounds touted for their potential to treat or prevent several diseases including cancer caused by various stress conditions. Galangin (4H-1-Benzopyran-4-one, 3, 5, 7-trihydroxy-2-phenyl-), a flavonoid, is a polyphenolic compound found primarily in medicinal herb, Alpinia galanga. This study aims to demonstrate the galangin as a pharmacological lead compound using in vitro, in vivo, and in silico model targeting specific cancer condition and proteins. The proliferation of MCF-7 and Ehrlich ascites carcinoma (EAC) cells was significantly inhibited with an IC₅₀ of 34.11 and 22.29 μg/ml, respectively. In an animal model system, galangin has inhibited the tumor growth by 73.51% ± 4.742 in EAC-induced Swiss Albino mice with no evidences of mortality as compared to standard drug, 5-fluorouracil. The effectiveness of galangin is proven in an animal system suggesting its pharmacokinetics behavior in an animal model which is also complemented by outcome of in silico analysis with more than 88 % of human intestinal absorption and significant Caco-2 cell, MDCK cell, and skin permeability as predicted by in silico methods. Galangin was docked against 19 different proteins involved in tumorogenesis and apoptosis; the energetic analysis indicates that it exhibits higher predicted binding free energy of -12.7 kcal/mol with Bcl-xL protein.

The crude extracts from stem bark of Crataeva nurvala Buch.-Ham containing naturally occurring antioxidants were screened for their most abundant phytosecondary metabolite, antiproteolytic and cytotoxic properties. The antioxidant activity of the extracts was determined by DPPH radical scavenging activity, Ferric reducing power and β Carotene linoleic acid assay. The antiproteolytic activity of crude extracts was determined by inhibition of trypsin-induced hydrolysis of BSA. The IC50 of cytotoxic effect on HepG2 and B16F0 cell line was investigated using MTT assay. Preliminary phytochemical analysis exhibited the presence of terpenoids as a major phytochemical reflecting higher antioxidant activity in a dose dependent manner. The PEECN extract showed good antiproteolytic activity with 26.04% inhibition on BSA. The IC50 values of PEECN against HepG2 and B16F0 cells using MTT assay were determined to be 34.67 ± 1.10 μg/ml and 49.43 ± 4.778 μg/ml after 48 h, respectively. These results demonstrate that the petroleum ether extract containing most terpenoid fraction exhibited potential antiproteolytic and cytotoxic activity against hepatocellular carcinoma and mouse melanoma in vitro through inhibition of proliferating cancerous cells.

Signaling through c-Raf downstream pathways is the crucial subject of extensive studies because over expressed or mutated genes in this pathway lead to a variety of human cancers. On the basis of cellular localization, this pathway has been sub-divided into two cascades. The first RAF1-MEK1-ERK2 cascade which remains in the cytosol, whereas the second MEK1-ERK2-RSKs transduces into the nucleus and regulates the transactivation function. But how a few amino acids critically regulate the transcriptional function remains unclear. In this paper, we have performed in silico studies to unravel how atomic complexities at the MEK1-ERK2-RSKs pathways intercedes different functional responses. The secondary structure of the ERK, RSKs have been modeled using Jpred3, PSI-PHRED, protein modeler, and Integrated sequence analyzer from Discovery Studio software. Peptides of RSKs isozymes (RSK1/2/3/4) were built and docked on ERK2 structure using ZDOCK module. The hydropathy index for the RSKs molecules was determined using the KYTE-DOOLITTLE plot. The simulations of complex molecules were carried out using a CHARMM force field. The protein-protein interactions (PPIs) in different cascade of MAP kinase (MAPK) have been shown to be similar to those predicted in vivo. PPIs elucidate that the amino acids located at the conserved domains of MAPK pathways are responsible for transactivation functions.