Identifying druggable targets from active constituents of Azadirachta indica A. Juss. for non-small cell lung cancer using network pharmacology and validation through molecular docking.

INTRODUCTION: Azadirachta indica A. Juss. is a well-known medicinal plant that has been used traditionally to cure various ailments in every corner of the globe. There are many in vitro and in vivo experimental evidences in connection with the bioactivity of the extracts of this plant. Lung cancer is the deadliest form of cancer and contributes to the most cancer related deaths. The mode of action of anticancer components of this plant is still to be established explicitly. OBJECTIVE: The objective of this study is to identify druggable targets of active constituents of A. indica A. Juss. for non-small cell lung cancer (NSCLC) using network pharmacology and validation of activity through molecular docking analysis. METHODOLOGY: Targets of all the active phytochemicals from A. indica were predicted and genes related to NSCLC were retrieved. A protein-protein interaction (PPI) network of the overlapping genes were prepared. Various databases and servers were employed to analyse the disease pathway enrichment analysis of the clustered genes. Validation of the gene/protein activity was achieved by performing molecular docking, and ADMET profiling of selected phytocompounds was performed. RESULT: Gene networking revealed three key target genes as EGFR, BRAF and PIK3CA against NSCLC by the active components of A. indica. Molecular docking and ADMET analysis further validated that desacetylnimbin, nimbandiol, nimbin, nimbinene, nimbolide, salannin and vepinin are the best suited anti- NSCLC among all the phytocompounds present in this plant. CONCLUSION: The present study has provided a better understanding of the pharmacological effects of active components from A. indica and its potential therapeutic effect on NSCLC.

Ethnomedicinal, Phytochemical and Nutra-pharmaceutical Potentials of Indian Arrowroot (Curcuma angustifolia Roxb).

Indian Arrowroot (Curcuma angustifolia Roxb) belonging to the Zingiberaceae family is widely distributed in India and some parts of Nepal, Thailand, Bangladesh and Pakistan. It is traditionally used as medicine for treating various diseases and also used as food. Few data are available about its application in pharmacology and therapeutics. Literature search for related contents, keywords such as "Curcuma angustifolia Roxb", "traditional food", "ethnomedicine", "pharmacology", "phytochemicals", "pharmacological activities" were used in search engines including PubMed, Google Scholar, Scopus, ScienceDirect, and Semantic Scholar. Secondary metabolites found in Indian Arrowroot include essential oils, alkaloids, flavonoids, terpenoids, phytosterols, terpenes, phenols, and others. Pharmacological activities such as antioxidant, antiinflammatory, anti-proliferative, anti-ulcerogenic, hepatoprotective, and anti-cancerous activities have been shown by Indian Arrowroot (Curcuma angustifolia Roxb). The presence of nutritional value and pharmaceutical potential gained demand in the various food production industries and pharmacology research. It may play a vital role in future studies of Curcuma angustifolia Roxb as ethnomedicine and further exploitation in pharmacological studies.

Effect of acetone fraction of Ottelia alismoides on the G2/M cell cycle arrest and apoptosis in the human carcinoma cell lines.

ETHNOPHARMACOLOGICAL RELEVANCE: The North-eastern parts of India have immense therapeutic floras, Ottelia alismoides is an aquatic plant that has been in use for a long time in traditional medicine for treating diseases like cancer, tuberculosis, diabetes, febrifuge, hemorrhoids, and rubefacient. In lung and skin carcinoma cells with a high rate of proliferation and metastasis including drug resistance and non-specific target activity, generates important challenges towards their treatment strategy. Thus, finding novel therapeutic targets to treat lung and skin cancer progression is essential to enhance the patients' survival with treatment. AIM OF THE STUDY: The purpose of this study was to evaluate the apoptotic potential of acetone extract of O. alismoides (L.) Pers. (OA-AC) and to identify the compounds responsible for this effect, HRLC-MS-QTOF analysis of the extract has been undertaken along with in-silico molecular docking analysis of the identified compounds. MATERIALS AND METHODS: A549 and A431 cells were treated with acetone extract of O. alismoides (OA-AC) at 24 h and 48 h exposure and cell cycle phase distribution was evaluated and also apoptosis induction activity was evaluated by OA-EtBr staining and Mitochondrial outer membrane potential assay. Western blotting was performed for the evaluation of apoptotic protein expression. At last, the HR-LCMS of OA-AC was analyzed to identify the compounds responsible for the apoptotic activity of the extract. RESULTS: The cell cycle phase distribution analysis in A549 and A431 cells at 24hrs exposure with 10 µg/mL and 25 µg/mL of OA-AC showed a potent arrest or blockage at the G2/M phase of the cell cycle with reduced expression of cyclin B and p-Cdc2. At 48 h exposure, apoptosis was observed in these cancer cells with elevated expression of Bax, p21 and cleaved caspase 3 and reduced expression of the Bcl2. CONCLUSION: AO-EtBr staining of these cancer cells reveals that the death induced by OA-AC was apoptotic in nature with depolarization of mitochondrial membrane due to loss or damage of the mitochondrial membrane. The HRLC-MS-QTOF analysis of OA-AC depicted 14 major isolable compounds and molecular docking analysis displayed 4 compounds that might act as an inhibitor of cyclin B for G2/M phase arrest that leads to apoptotic induction in the cells.

Acteoside (Verbascoside): A Prospective Therapeutic Alternative against Hepatocellular Carcinoma by Inhibiting the Expression of AXL, FGFR, BRAF, TIE2 and RAF1 Targets.

AIM: Hepatocellular carcinoma (HCC) is the world's second leading cause of cancerrelated mortality and the fifth most prevalent cancer overall. Several synthetic and plant-based remedies are in practice to treat diverse liver disorders. Because of their minimal side effects and protective characteristics, plant phenolics have the potential to become alternative therapeutics, replacing currently existing HCC medications. The present study identifies the plant phenolics as having the capacity to inhibit HCC with low side effects and cost efficiency. BACKGROUND: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality, despite the proven effectiveness of screening programs for at-risk individuals, the majority of patients have disease progression or tumor characteristics that preclude curative therapies at the time of diagnosis. Acteoside (Verbascoside) is a naturally occurring phenylethanoid glycoside found throughout the plant kingdom. Acteoside is a physiologically active chemical with the number of pharmacological and protective effects against various liver illnesses. OBJECTIVES: Currently used HCC medications have a variety of side effects. Plant-based chemicals offer the possibility of treating HCC with minimal side effects. The work is targeted to find the best phytochemical (plant phenolic) lead molecule for future drug development research against Hepatocellular carcinoma. METHODS: The targets were selected based on an analysis of relevant literature, and the 3D structures of the selected receptors were obtained in. pdb format from the RCSB-Protein data bank (PDB, http://www.rscb.org/pdb). Based on a review of the literature, sixty plant secondary metabolites, or plant phenolics, were selected. The ligand structures were obtained and downloaded in.sdf format from the NCBI PubChem chemicals database (https://pubchem.ncbi.nlm.nih.gov/). Molecular docking between the receptor and ligands was accomplished using the Molegro Virtual Docker 6.0 (MVD) software. RESULTS: The target RAF1, BRAF chain 1, TIE2 chain 2 FGFR1, FGFR2, AXL, and FGFR4 showed the best binding effectiveness with acteoside compared to their respective positive control. RET chain 1 and BRAF chain 2 acteoside showed prominent binding efficacy after Curcumin, and Epigallocatechingallate, respectively, against positive control. Present findings clearly point towards the potentiality of acteoside in inhibiting various HCC targets. CONCLUSION: Acteoside may be used as a prominent lead molecule in the future treatment of hepatic cancer with its multifaceted binding efficiencies against various target proteins.