Integrated omics profiling and network pharmacology uncovers the prognostic genes and multi-targeted therapeutic bioactives to combat lung cancer.

Non-small cell lung cancer (NSCLC) is the frequent subtype of lung cancer and the currently used treatment methods, diagnosis, and chemoresistance are relatively ineffective. Determining the pharmacological targets from active biomolecules of medicinal plants has become a frontiers era for biomedical research to develop novel therapies. In view of these scenarios, this pilot study, network pharmacology, cheminformatics, integrative omics, molecular docking and in vitro anti-cancer analysis were performed to unveil the multi-targeted treatment mechanisms of novel plant bioactives to treat lung cancer. Bioactive molecules from medicinal plants were compiled from PubChem. Network pharmacology approach revealed that 29 compounds efficiently target the 390 human and lung cancer associated genes. In addition, comparative analysis was performed and identified the 7 bioactive molecules significantly targeting 8 lung cancer genes. The integrative omics analysis discovered unique genes between the lung cancer and normal lung tissues. These genes were further validated through protein-protein interaction, gene ontology, gene functional and pathway enrichment, boxplot and overall survival analyses to understand the function of unique genes and their involvement in cancer signaling pathways. Survival heatmap analyses identified the significant prognostic genes. Docking results revealed that, lupeol and p-coumaric acid displayed high binding affinities with MIF, CCNB1, FABP4. Hence, we selected these two bioactives for in vitro analysis. Furthermore, these selected bioactives were showed concentration dependent cytotoxicity against the lung adenocarcinoma cells (A549). This holistic study has opened up novel avenues and unravels the cancer prognostic genes which could serve as druggable target and bioactives with anti-cancerous efficacy. Further functional validations are prerequisites to deciphering these bioactives as commercial drug candidates.

Recent Updates on Source, Biosynthesis, and Therapeutic Potential of Natural Flavonoid Luteolin: A Review.

Nature gives immense resources that are beneficial to humankind. The natural compounds present in plants provide primary nutritional values to our diet. Apart from food, plants also provide chemical compounds with therapeutic values. The importance of these plant secondary metabolites is increasing due to more studies revealing their beneficial properties in treating and managing various diseases and their symptoms. Among them, flavonoids are crucial secondary metabolite compounds present in most plants. Of the reported 8000 flavonoid compounds, luteolin is an essential dietary compound. This review discusses the source of the essential flavonoid luteolin in various plants and its biosynthesis. Furthermore, the potential health benefits of luteolins such as anti-cancer, anti-microbial, anti-inflammatory, antioxidant, and anti-diabetic effects and their mechanisms are discussed in detail. The activity of luteolin and its derivatives are diverse, as they help to prevent and control many diseases and their life-threatening effects. This review will enhance the knowledge and recent findings regarding luteolin and its therapeutic effects, which are certainly useful in potentially utilizing this natural metabolite.

Bioactive Components and Health Potential of Endophytic Micro-Fungal Diversity in Medicinal Plants.

The endophytic fungi that reside inside medicinal plants have the potential to produce various pharmaco-potential bioactive compounds. The endophytic fungi Graminicolous helminthosporium, Bipolaris australiensis and Cladosporium cladosporioides were isolated from different medicinal plants. The GC-MS analysis of intra- and extracellular products of endophytic fungi revealed the presence of various bioactive metabolites, such as Anthracene, Brallobarbital, Benzo [h] quinolone, Ethylacridine, 2-Ethylacridine, Cyclotrisiloxane, 5 methyl 2 phenylindolizine, and 1,4-Cyclohexadien-1-one, etc. The phytochemical composition analysis of endophytic fungus extracts also revealed the presence of flavonoids, phenols, saponins, carbohydrates, glycosides, and proteins. The intra- and extracellular endophytic extracts exhibited strong antibacterial and antioxidant activity, which was screened with the agar-well diffusion method and DPPH, H2O2, and nitric oxide scavenging activity, respectively. The bioactive compounds identified in the endophytic extracts from GC-MS profiling served as ligands for molecular-docking analysis to investigate the anticancer potential against non-small cell lung carcinoma receptor EGFR. Molecular docking results showed that compounds, such as Brallobarbital, and 5 methyl 2 phenylindolizine had the lowest E- min values, which suggests that these compounds could be used in anticancer drug development. Thus, the isolated endophytic fungal species can be used to produce various bioactive compounds that could be used in novel drug development from natural sources and reduce the environmental burden of synthetic chemical drugs.

Biosynthesis of ZnONP Using Chamaecostus cuspidatus and Their Evolution of Anticancer Property in MCF-7 and A549 Cell Lines.

The ZnO nanoparticle synthesis using the leaf part of Chamaecostus cuspidatus was characterized using UV-Vis spectrophotometry, IR, XRD, DLS, FESEM, EDX, TEM, AFM and XPS. The MTT assay was used to examine the cytotoxicity activity against lung epithelial and breast cell lines, and the IC50 value was determined. The presence of ZnO nanoparticles, which range in size from 200 to 800 nm, was confirmed by the absorption peak at 350 nm. The median particle size was 145.1 nm, and the ζ -the potential was -19.45 mV, showing that ZnONP is stable. Zinc, carbon, and oxygen contribute to the elemental composition of ZnONP, as determined by EDX analysis. MTT assay was used to investigate in vitro cytotoxicity in MCF-7 and A549 cell lines. The cytotoxicity activity IC50 value was determined to be 30 µg/mL for the A549 cell line and 37 µg/mL for the MCF-7 cell line.

Subcritical water extraction of withanosides and withanolides from ashwagandha (Withania somnifera L) and their biological activities.

Subcritical water extraction (SWE) applied to analyses the bioactives from ashwagandha (W. somnifera) at varying temperature (100-200 °C) and extraction time (10-30 min). The effect of temperature and time has been investigated in terms of extraction yield (EY), total phenolic content (TPC), cytotoxicity, antioxidant, and enzyme inhibitory activities. The withanosides and withanolides responsible for various biological effects were quantified using high performance liquid chromatography (HPLC). The HPLC analysis revealed Withanoside V, Withanoside IV, 12-Deoxywithastramonolide, Withanolide A, and Withaferin A as a principle bioactive compounds in SWE, with high in concentration compared to microwave-assisted extraction (MAE), Soxhlet extraction (SE) and maceration (MC). For SWE the highest EY (65.6%; 200 °C for 30 min), TPC (82.5 mg GAE/g DE), antioxidant activity (DPPH: 80.3%, FRAP: 60.5% and ABTS: 78.9), and potent enzyme inhibitory effects were observed. The SWE and Withaferin A showed significant reduction in cell viability of cervical cancer (HeLa) cells, with IC50 values 10 mg/ml and 8.5 µM/ml, respectively but no cytotoxic effect for normal cells (MDCK). Thus, SWE can provide effective extraction for ashwagandha withanosides and withanolides compared MAE, SE and MC to conventional methods, which could be used for extraction of pharmacologically active fractions with therapeutic applications.

Enhanced Tolerance of Transgenic Potato Plants Over-Expressing Non-specific Lipid Transfer Protein-1 (StnsLTP1) against Multiple Abiotic Stresses.

Abiotic stresses such as heat, drought, and salinity are major environmental constraints that limit potato (Solanum tuberosum L.) production worldwide. Previously, we found a potential thermo-tolerance gene, named StnsLTP1 from potato using yeast functional screening. Here, we report the functional characterization of StnsLTP1 and its role in multiple abiotic stresses in potato plants. Computational analysis of StnsLTP1 with other plant LTPs showed eight conserved cysteine residues, and four α-helices stabilized by four disulfide bridges. Expression analysis of StnsLTP1 gene showed differential expression under heat, water-deficit and salt stresses. Transgenic potato lines over-expressing StnsLTP1 gene displayed enhanced cell membrane integrity under stress conditions, as indicated by reduced membrane lipid per-oxidation, and hydrogen peroxide content relative to untransformed (UT) control plants. In addition, transgenic lines over-expressing StLTP1 also exhibited increased antioxidant enzyme activity with enhanced accumulation of ascorbates, and up-regulation of stress-related genes including StAPX, StCAT, StSOD, StHsfA3, StHSP70, and StsHSP20 compared with the UT plants. These results suggests that StnsLTP1 transgenic plants acquired improved tolerance to multiple abiotic stresses through enhanced activation of antioxidative defense mechanisms via cyclic scavenging of reactive oxygen species and regulated expression of stress-related genes.

An Update on Potential Perspectives of Glucosinolates on Protection against Microbial Pathogens and Endocrine Dysfunctions in Humans.

Glucosinolates are the major bioactive secondary metabolites found in the Brassicaceae family and studied extensively in biosynthetic and application perspectives. Because of their potential applications in the welfare of plants (protection against plant pathogens) and human life (prevention of cancer and other diseases), these compounds attracted much interest in the scientific community. In this review, we presented updates on glucosinolate derivatives in protection against microbial pathogens and endocrine related diseases in human. Further, the mechanism of action of glucosinolate derivatives and the strategies to improve their efficiency through modern approaches were discussed. Finally, the genetic enrichment of their contents in plant systems has also been discussed.