Targeting NF-κB signaling cascades of glioblastoma by a natural benzophenone, garcinol, via in vitro and molecular docking approaches.

Glioblastoma multiforme (GBM) is regarded as the most aggressive form of brain tumor delineated by high cellular heterogeneity; it is resistant to conventional therapeutic regimens. In this study, the anti-cancer potential of garcinol, a naturally derived benzophenone, was assessed against GBM. During the analysis, we observed a reduction in the viability of rat glioblastoma C6 cells at a concentration of 30 µM of the extract (p < 0.001). Exposure to garcinol also induced nuclear fragmentation and condensation, as evidenced by DAPI-stained photomicrographs of C6 cells. The dissipation of mitochondrial membrane potential in a dose-dependent fashion was linked to the activation of caspases. Furthermore, it was observed that garcinol mediated the inhibition of NF-κB (p < 0.001) and decreased the expression of genes associated with cell survival (Bcl-XL, Bcl-2, and survivin) and proliferation (cyclin D1). Moreover, garcinol showed interaction with NF-κB through some important amino acid residues, such as Pro275, Trp258, Glu225, and Gly259 during molecular docking analysis. Comparative analysis with positive control (temozolomide) was also performed. We found that garcinol induced apoptotic cell death via inhibiting NF-κB activity in C6 cells, thus implicating it as a plausible therapeutic agent for GBM.

Structure-Based Multi-Targeted Molecular Docking and Dynamic Simulation of Soybean-Derived Isoflavone Genistin as a Potential Breast Cancer Signaling Proteins Inhibitor.

Globally, breast cancer (BC), the second-biggest cause of cancer death, occurs due to unregulated cell proliferation leading to metastasis to other parts of the human organ. Recently, the exploration of naturally derived anticancer agents has become popular due to their fewer adverse effects. Among the natural products, soybean is a very well-known legume that contains important bioactive compounds such as diadazine, glycetin, genistein, and genistin. Therefore, keeping its therapeutic potential in mind, multi-targeted molecular docking and simulation studies were conducted to explore the potential role of soybean-derived isoflavone genistin against several breast cancer-signaling proteins (ER-alpha, ER-Beta, collapsin response mediator protein 2, CA 15-3, human epidermal growth factor receptor 2). A comparative study of the genistin-protein docked complex was explored to investigate its potential role in BC. The molecular binding energy (∆G) of the docked complex was calculated along with ADMET properties. The molecular docking score of genistin with ubiquitin-like protein activation complex-a type of Cancer Antigen (CA) 15.3 (PDB ID-2NVU, 5T6P, and 1YX8) showed the highest binding energy, ranging from -9.5 to -7.0 Kcal/mol, respectively. Furthermore, the highest docking scores of the complex were additionally put through molecular dynamics (MD) simulation analysis. MD simulations of the selected complex were performed at 100 ns to study the stability of the genistin-ubiquitin-like protein CA 15.3 complex, which appeared to be quite stable. Additionally, the ADMET study demonstrated that genistin complies with all drug-likeness standards, including Lipinski, Egan, Veber, Ghose, and Muegge. Therefore, based on the results, genistin can be considered as one of the potential drugs for the management and treatment of BC. In addition, the obtained results suggest that genistin could pave the way for new drug discovery to manage breast cancer and has potential in the development of nutraceuticals.

Biosurfactant derived from probiotic Lactobacillus acidophilus exhibits broad-spectrum antibiofilm activity and inhibits the quorum sensing-regulated virulence.

Antimicrobial resistance by pathogenic bacteria has become a global risk to human health in recent years. The most promising approach to combating antimicrobial resistance is to target virulent traits of bacteria. In the present study, a biosurfactant derived from the probiotic strain Lactobacillus acidophilus was tested against three Gram-negative bacteria to evaluate its inhibitory potential on their biofilms, and whether it affected the virulence factors controlled by quorum sensing (QS). A reduction in the virulence factors of Chromobacterium violaceum (violacein production), Serratia marcescens (prodigiosin production) and Pseudomonas aeruginosa (pyocyanin, total protease, LasB elastase and LasA protease production) was observed at different sub-MIC concentrations in a dose-dependent manner. Biofilm development was reduced by 65.76%, 70.64% and 58.12% at the highest sub-MIC levels for C. violaceum, P. aeruginosa and S. marcescens, respectively. Biofilm formation on glass surfaces exhibited significant reduction, with less bacterial aggregation and reduced formation of extracellular polymeric materials. Additionally, swimming motility and exopolysaccharides (EPS) production were shown to be reduced in the presence of the L. acidophilus-derived biosurfactant. Furthermore, molecular docking analysis performed on compounds identified through gas chromatography-mass spectrometry (GC-MS) analysis of QS and biofilm proteins yielded further insights into the mechanism underlying the anti-QS activity. Therefore, the present study has clearly demonstrated that a biosurfactant derived from L. acidophilus can significantly inhibit virulence factors of Gram-negative pathogenic bacteria. This could provide an effective method to inhibit the formation of biofilms and QS in Gram-negative bacteria.

Biosynthesized Silver Nanoparticles Derived from Probiotic Lactobacillus rhamnosus (AgNPs-LR) Targeting Biofilm Formation and Quorum Sensing-Mediated Virulence Factors.

In recent years, bacterial pathogens have developed resistance to antimicrobial agents that have created a global threat to human health and environment. As a novel approach to combating antimicrobial resistance (AMR), targeting bacteria's virulent traits that can be explained by quorum sensing (QS) is considered to be one of the most promising approaches. In the present study, biologically synthesized silver nanoparticles derived from Lactobacillus rhamnosus (AgNPs-LR) were tested against three Gram-negative bacteria to determine whether they inhibited the formation of biofilms and triggered the virulence factors controlled by QS. In C. violaceum and S. marcescens, a remarkable inhibition (>70%) of QS-mediated violacein and prodigiosin production was recorded, respectively. A dose-dependent decrease in virulence factors of P. aeruginosa (pyocyanin, pyoverdine, LasA protease, LasB elastase and rhamnolipid production) was also observed with AgNPs-LR. The biofilm development was reduced by 72.56%, 61.70%, and 64.66% at highest sub-MIC for C. violaceum, S. marcescens and P. aeruginosa, respectively. Observations on glass surfaces have shown remarkable reductions in biofilm formation, with less aggregation of bacteria and a reduced amount of extra polymeric materials being formed from the bacteria. Moreover, swimming motility and exopolysaccharides (EPS) was also found to reduce in the presence of AgNPs-LR. Therefore, these results clearly demonstrate that AgNPs-LR is highly effective in inhibiting the development of biofilms and the QS-mediated virulent traits of Gram-negative bacteria. In the future, AgNPs-LR may be used as an alternative to conventional antibiotics for the treatment of bacterial infections after careful evaluation in animal models, especially for the development of topical antimicrobial agents.

Aloe-emodin exhibits growth-suppressive effects on androgen-independent human prostate cancer DU145 cells via inhibiting the Wnt/ß-catenin signaling pathway: an in vitro and in silico study.

At the molecular level, several developmental signaling pathways, such as Wnt/ß-catenin, have been associated with the initiation and subsequent progression of prostate carcinomas. The present report elucidated the anti-cancerous attributes of an anthraquinone, aloe-emodin (AE), against androgen-independent human prostate cancer DU145 cells. The cytotoxicity profiling of AE showed that it exerted significant cytotoxic effects and increased lactose dehydrogenase levels in DU145 cells (p < 0.01 and p < 0.001). AE also induced considerable reactive oxygen species (ROS)-mediated oxidative stress, which escalated at higher AE concentrations of 20 and 25 µM. AE also efficiently instigated nuclear fragmentation and condensation concomitantly, followed by the activation of caspase-3 and -9 within DU145 cells. AE further reduced the viability of mitochondria with increased cytosolic cytochrome-c levels (p < 0.01 and p < 0.001) in DU145 cells. Importantly, AE exposure was also correlated with reduced Wnt2 and ß-catenin mRNA levels along with their target genes, including cyclin D1 and c-myc. Furthermore, the molecular mechanism of AE was evaluated by performing molecular docking studies with Wnt2 and ß-catenin. Evidently, AE exhibited good binding energy scores toward Wnt2 and ß-catenin comparable with their respective standards, CCT036477 (Wnt2 inhibitor) and FH535 (ß-catenin inhibitor). Thus, it may be considered that AE was competent in exerting anti-growth effects against DU145 androgen-independent prostate cancer cells plausibly by modulating the expression of Wnt/ß-catenin signaling.

3-Methoxy Carbazole Impedes the Growth of Human Breast Cancer Cells by Suppressing NF-κB Signaling Pathway.

Breast cancer represents the most frequently occurring cancer globally among women. As per the recent report of the World Health Organization (WHO), it was documented that by the end of the year 2020, approximately 7.8 million females were positively diagnosed with breast cancer and in 2020 alone, 685,000 casualties were documented due to breast cancer. The use of standard chemotherapeutics includes the frontline treatment option for patients; however, the concomitant side effects represent a major obstacle for their usage. Carbazole alkaloids are one such group of naturally-occurring bioactive compounds belonging to the Rutaceae family. Among the various carbazole alkaloids, 3-Methoxy carbazole or C13H11NO (MHC) is obtained from Clausena heptaphylla as well as from Clausena indica. In this study, MHC was investigated for its anti-breast cancer activity based on molecular interactions with specific proteins related to breast cancer, where the MHC had predicted binding affinities for NF-κB with −8.3 kcal/mol. Furthermore, to evaluate the biological activity of MHC, we studied its in vitro cytotoxic effects on MCF-7 cells. This alkaloid showed significant inhibitory effects and induced apoptosis, as evidenced by enhanced caspase activities and the cellular generation of ROS. It was observed that a treatment with MHC inhibited the gene expression of NF-kB in MCF-7 breast cancer cells. These results suggest that MHC could be a promising medical plant for breast cancer treatment. Further studies are needed to understand the molecular mechanisms behind the anticancer action of MHC.

Development and Characterization of PEGDA Microneedles for Localized Drug Delivery of Gemcitabine to Treat Inflammatory Breast Cancer.

Inflammatory breast cancer (IBC) is one of the most belligerent types of breast cancer. While various modalities exist in managing/treating IBC, drug delivery using microneedles (MNs) is considered to be the most innovative method of localized delivery of anti-cancer agents. Localized drug delivery helps to treat IBC could limit their adverse reactions. MNs are nothing but small needle like structures that cause little or no pain at the site of administration for drug delivery via layers of the skin. The polyethylene glycol diacrylate (PEGDA) based MNs were fabricated by using three dimensional (3D) technology called Projection Micro-Stereo Lithography (PµSL). The fabricated microneedle patches (MNPs) were characterized and coated with a coating formulation comprising of gemcitabine and sodium carboxymethyl cellulose by a novel and inventive screen plate method. The drug coated MNPs were characterized by various instrumental methods of analysis and release profile studies were carried out using Franz diffusion cell. Coat-and-poke strategy was employed in administering the drug coated MNPs. Overall, the methods employed in the present study not only help in obtaining MNPs with accurate dimensions but also help in obtaining uniformly drug coated MNPs of gemcitabine for treatment of IBC. Most importantly, 100% drug release was achieved within the first one hour only.

Biosynthesized Silver Nanoparticles from Eruca sativa Miller Leaf Extract Exhibits Antibacterial, Antioxidant, Anti-Quorum-Sensing, Antibiofilm, and Anti-Metastatic Activities.

Worldwide, the primary problem today is the proliferation of cancer and secondary bacterial infections caused by biofilms, as they are the principal causes of death due to the lack of effective drugs. A great deal of biological activities of silver nanoparticles (AgNPs) have made them a brilliant choice for the development of new drugs in recent years. The present study was conducted to evaluate the anticancer, antibacterial, anti-QS, and antibiofilm effects of AgNPs synthesized from Eruca sativa (E. sativa) leaf extract. The ultraviolet-visible (UV-Vis) spectra showed a peak of surface plasmon resonance at 424 nm λmax, which corresponded to AgNP formation. The Fourier transform infrared spectroscopy (FT-IR) confirmed that biological moieties are involved for the development of AgNPs. Moreover, transmission electron microscopy (TEM) analyses confirmed the spherical shape and uniform size (8.11 to 15 nm) of the AgNPs. In human lung cancer cells (A549), the anticancer potential of AgNPs was examined by the MTT [3-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, scratch assay, and invasion assay. The results indicated that AgNPs inhibit the migration of A549 cells. The synthesized AgNPs showed MIC values of 12.5 µg/mL against Chromobacterium violaceum (C. violaceum) and 25 µg/mL against Pseudomonas aeruginosa (P. aeruginosa), which demonstrated their antibacterial abilities. Biological compounds that disable the QS system are being investigated as potential strategies for preventing bacterial infections. Thus, we analyzed the potential effectiveness of synthesized AgNPs in inhibiting QS-regulated virulence factors and biofilm formation in both strains of bacteria. In C. violaceum, the synthesized AgNPs significantly inhibited both violacein (85.18% at 1/2 × MIC) and acyl homoserine lactone (78.76% at 1/2 × MIC). QS inhibitory activity was also demonstrated in P. aeruginosa at a sub-MIC concentration (1/2 × MIC) by a reduction in pyocyanin activity (68.83%), total protease (68.50%), LasA activity (63.91%), and LasB activity (56.40%). Additionally, the exopolysaccharide production was significantly reduced in both C. violaceum (65.79% at 1/2 × MIC) and P. aeruginosa (57.65% at 1/2 × MIC). The formation of biofilm was also significantly inhibited at 1/2 × MIC in C. violaceum (76.49%) and in P. aeruginosa (65.31%). Moreover, a GC-MS analysis confirmed the presence of different classes of bioactive phytochemical constituents present in the leaf extract of E. sativa. On the basis of our results, we conclude that biologically synthesized AgNPs showed numerous multifunctional properties and have the potential to be used against human cancer and bacterial biofilm-related infections.

Lactiplantibacillus plantarum-Derived Biosurfactant Attenuates Quorum Sensing-Mediated Virulence and Biofilm Formation in Pseudomonas aeruginosa and Chromobacterium violaceum.

Quorum sensing (QS) controls the expression of diverse biological traits in bacteria, including virulence factors. Any natural bioactive compound that disables the QS system is being considered as a potential strategy to prevent bacterial infection. Various biological activities of biosurfactants have been observed, including anti-QS effects. In the present study, we investigated the effectiveness of a biosurfactant derived from Lactiplantibacillus plantarum on QS-regulated virulence factors and biofilm formation in Pseudomonas aeruginosa and Chromobacterium violaceum. The structural analogues of the crude biosurfactant were identified using gas chromatography-mass spectrometry (GC-MS). Moreover, the inhibitory prospects of identified structural analogues were assessed with QS-associated CviR, LasA, and LasI ligands via in silico molecular docking analysis. An L. plantarum-derived biosurfactant showed a promising dose-dependent interference with the production of both violacein and acyl homoserine lactone (AHL) in C. violaceum. In P. aeruginosa, at a sub-MIC concentration (2.5 mg/mL), QS inhibitory activity was also demonstrated by reduction in pyocyanin (66.63%), total protease (60.95%), LasA (56.62%), and LasB elastase (51.33%) activity. The swarming motility and exopolysaccharide production were also significantly reduced in both C. violaceum (61.13%) and P. aeruginosa (53.11%). When compared with control, biofilm formation was also considerably reduced in C. violaceum (68.12%) and P. aeruginosa (59.80%). A GC-MS analysis confirmed that the crude biosurfactant derived from L. plantarum was a glycolipid type. Among all, n-hexadecanoic acid, oleic acid, and 1H-indene,1-hexadecyl-2,3-dihydro had a high affinity for CviR, LasI, and LasA, respectively. Thus, our findings suggest that the crude biosurfactant of L. plantarum can be used as a new anti-QS/antibiofilm agent against biofilm-associated pathogenesis, which warrants further investigation to uncover its therapeutic efficacy.

Anti-Adhesion and Antibiofilm Activity of Eruca sativa Miller Extract Targeting Cell Adhesion Proteins of Food-Borne Bacteria as a Potential Mechanism: Combined In Vitro-In Silico Approach.

Bacterial cells have the ability to form biofilm onto the surfaces of food matrixes and on food processing equipment, leading to a source of food contamination posing serious health implications. Therefore, our study aimed to determine the effect of Eruca sativa Miller (E. sativa) crude extract against biofilms of food-borne bacteria along with in silico approaches to investigate adhesion proteins responsible for biofilm activity against the identified phytochemicals. The antibacterial potential of crude extract was evaluated using agar well diffusion technique and combinations of light and scanning electron microscopy to assess the efficacy of crude extract against the developed biofilms. Our results showed that crude extract of E. sativa was active against all tested food-borne bacteria, exhibiting a rapid kinetics of killing bacteria in a time-dependent manner. MIC and MBC values of E. sativa crude extract were found to be ranging from 125 to 500 µg/mL and 250 to 1000 µg/mL respectively. Furthermore, inhibition of developed biofilm by E sativa was found to be ranging from 58.68% to 73.45% for all the tested strains. The crude extract also reduced the viability of bacterial cells within biofilms and amount of EPS (ranging 59.73-82.77%) in the biofilm matrix. Additionally, the microscopic images also revealed significant disruption in the structure of biofilms. A molecular docking analysis of E. sativa phytochemicals showed interaction with active site of adhesion proteins Sortase A, EspA, OprD, and type IV b pilin of S. aureus, E. coli, P. aeruginosa, and S. enterica ser. typhi, respectively. Thus, our findings represent the first demonstration of E. sativa crude extract's bioactivity and potency against food-borne bacteria in their planktonic forms, as well as against the developed biofilms. Therefore, a possible mechanistic approach for inhibition of biofilm via targeting adhesion proteins can be explored further to target biofilm producing food-borne bacterial pathogens.

Phytochemical and In Silico ADME/Tox Analysis of Eruca sativa Extract with Antioxidant, Antibacterial and Anticancer Potential against Caco-2 and HCT-116 Colorectal Carcinoma Cell Lines.

Eruca sativa Mill. (E. sativa) leaves recently grabbed the attention of scientific communities around the world due to its potent bioactivity. Therefore, the present study investigates the metabolite profiling of the ethanolic crude extract of E. sativa leaves using high resolution-liquid chromatography-mass spectrometry (HR-LC/MS), including antibacterial, antioxidant and anticancer potential against human colorectal carcinoma cell lines. In addition, computer-aided analysis was performed for determining the pharmacokinetic properties and toxicity prediction of the identified compounds. Our results show that E. sativa contains several bioactive compounds, such as vitamins, fatty acids, alkaloids, flavonoids, terpenoids and phenols. Furthermore, the antibacterial assay of E. sativa extract showed inhibitory effects of the tested pathogenic bacterial strains. Moreover, the antioxidant activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H2O2) were found to be IC50 = 66.16 µg/mL and 76.05 µg/mL, respectively. E. sativa also showed promising anticancer activity against both the colorectal cancer cells HCT-116 (IC50 = 64.91 µg/mL) and Caco-2 (IC50 = 83.98 µg/mL) in a dose/time dependent manner. The phytoconstituents identified showed promising pharmacokinetics properties, representing a valuable source for drug or nutraceutical development. These investigations will lead to the further exploration as well as development of E. sativa-based nutraceutical products.

Integrating Network Pharmacology Approaches to Decipher the Multi-Target Pharmacological Mechanism of Microbial Biosurfactants as Novel Green Antimicrobials against Listeriosis.

Listeria monocytogenes (L. monocytogenes) is a serious food-borne pathogen that can cause listeriosis, an illness caused by eating food contaminated with this pathogen. Currently, the treatment or prevention of listeriosis is a global challenge due to the resistance of bacteria against multiple commonly used antibiotics, thus necessitating the development of novel green antimicrobials. Scientists are increasingly interested in microbial surfactants, commonly known as "biosurfactants", due to their antimicrobial properties and eco-friendly nature, which make them an ideal candidate to combat a variety of bacterial infections. Therefore, the present study was designed to use a network pharmacology approach to uncover the active biosurfactants and their potential targets, as well as the signaling pathway(s) involved in listeriosis treatment. In the framework of this study, 15 biosurfactants were screened out for subsequent studies. Among 546 putative targets of biosurfactants and 244 targets of disease, 37 targets were identified as potential targets for treatment of L. monocytogenes infection, and these 37 targets were significantly enriched in a Gene Ontology (GO) analysis, which aims to identify those biological processes, cellular locations, and molecular functions that are impacted in the condition studied. The obtained results revealed several important biological processes, such as positive regulation of MAP kinase activity, protein kinase B signaling, ERK1 and ERK2 cascade, ERBB signaling pathway, positive regulation of protein serine/threonine kinase activity, and regulation of caveolin-mediated endocytosis. Several important KEGG pathways, such as the ERBBB signaling pathway, TH17 cell differentiation, HIF-1 signaling pathway, Yersinia infection, Shigellosis, and C-type lectin receptor signaling pathways, were identified. The protein-protein interaction analysis yielded 10 core targets (IL2, MAPK1, EGFR, PTPRC, TNF, ITGB1, IL1B, ERBB2, SRC, and mTOR). Molecular docking was used in the latter part of the study to verify the effectiveness of the active biosurfactants against the potential targets. Lastly, we found that a few highly active biosurfactants, namely lichenysin, iturin, surfactin, rhamnolipid, subtilisin, and polymyxin, had high binding affinities towards IL2, MAPK1, EGFR, PTPRC, TNF, ITGB1, IL1B, ERBB2, SRC, and mTOR, which may act as potential therapeutic targets for listeriosis. Overall, based on the integrated network pharmacology and docking analysis, we found that biosurfactants possess promising anti-listeriosis properties and explored the pharmacological mechanisms behind their effect, laying the groundwork for further research and development.

Inhibition of Bacterial Adhesion and Antibiofilm Activities of a Glycolipid Biosurfactant from Lactobacillus rhamnosus with Its Physicochemical and Functional Properties.

Biosurfactants derived from different microbes are an alternative to chemical surfactants, which have broad applications in food, oil, biodegradation, cosmetic, agriculture, pesticide and medicine/pharmaceutical industries. This is due to their environmentally friendly, biocompatible, biodegradable, effectiveness to work under various environmental conditions and non-toxic nature. Lactic acid bacteria (LAB)-derived glycolipid biosurfactants can play a major role in preventing bacterial attachment, biofilm eradication and related infections in various clinical settings and industries. Hence, it is important to explore and identify the novel molecule/method for the treatment of biofilms of pathogenic bacteria. In the present study, a probiotic Lactobacillus rhamnosus (L. rhamnosus) strain was isolated from human breast milk. Firstly, its ability to produce biosurfactants, and its physicochemical and functional properties (critical micelle concentration (CMC), reduction in surface tension, emulsification index (% EI24), etc.) were evaluated. Secondly, inhibition of bacterial adhesion and biofilm eradication by cell-bound biosurfactants from L. rhamnosus was performed against various biofilm-forming pathogens (B. subtilis, P. aeruginosa, S. aureus and E. coli). Finally, bacterial cell damage, viability of cells within the biofilm, exopolysaccharide (EPS) production and identification of the structural analogues of the crude biosurfactant via gas chromatography-mass spectrometry (GC-MS) analysis were also evaluated. As a result, L. rhamnosus was found to produce 4.32 ± 0.19 g/L biosurfactant that displayed a CMC of 3.0 g/L and reduced the surface tension from 71.12 ± 0.73 mN/m to 41.76 ± 0.60 mN/m. L. rhamnosus cell-bound crude biosurfactant was found to be effective against all the tested bacterial pathogens. It displayed potent anti-adhesion and antibiofilm ability by inhibiting the bacterial attachment to surfaces, leading to the disruption of biofilm formation by altering the integrity and viability of bacterial cells within biofilms. Our results also confirm the ability of the L. rhamnosus cell-bound-derived biosurfactant to damage the architecture of the biofilm matrix, as a result of the reduced total EPS content. Our findings may be further explored as a green alternative/approach to chemically synthesized toxic antibiofilm agents for controlling bacterial adhesion and biofilm eradication.

Functional and Structural Characterization of Pediococcus pentosaceus-Derived Biosurfactant and Its Biomedical Potential against Bacterial Adhesion, Quorum Sensing, and Biofilm Formation.

Biosurfactants are surface-active molecules of microbial origin and alternatives to synthetic surfactants with various applications. Due to their environmental-friendliness, biocompatibility, biodegradability, effectiveness to work under various environmental conditions, and non-toxic nature, they have been recently recognized as potential agents with therapeutic and commercial importance. The biosurfactant produced by various probiotic lactic acid bacteria (LAB) has enormous applications in different fields. Thus, in vitro assessment of biofilm development prevention or disruption by natural biosurfactants derived from probiotic LAB is a plausible approach that can lead to the discovery of novel antimicrobials. Primarily, this study aims to isolate, screen, and characterize the functional and biomedical potential of biosurfactant synthesized by probiotic LAB Pediococcus pentosaceus (P. pentosaceus). Characterization consists of the assessment of critical micelle concentration (CMC), reduction in surface tension, and emulsification index (% EI24). Evaluation of antibacterial, antibiofilm, anti-QS, and anti-adhesive activities of cell-bound biosurfactants were carried out against different human pathogenic bacteria (B. subtilis, P. aeruginosa, S. aureus, and E. coli). Moreover, bacterial cell damage, viability of cells within the biofilm, and exopolysaccharide (EPS) production were also evaluated. As a result, P. pentosaceus was found to produce 4.75 ± 0.17 g/L biosurfactant, which displayed a CMC of 2.4 ± 0.68 g/L and reduced the surface tension from 71.11 ± 1.12 mN/m to 38.18 ± 0.58 mN/m. P. pentosaceus cells bound to the crude biosurfactant were found to be effective against all tested bacterial pathogens. It exhibited an anti-adhesion ability and impeded the architecture of the biofilm matrix by affecting the viability and integrity of bacterial cells within biofilms and reducing the total EPS content. Furthermore, the crude biosurfactant derived from P. pentosaceus was structurally characterized as a lipoprotein by GC-MS analysis, which confirms the presence of lipids and proteins. Thus, our findings represent the potent anti-adhesion and antibiofilm potential of P. pentosaceus crude biosurfactant for the first time, which may be explored further as an alternative to antibiotics or chemically synthesized toxic antibiofilm agents.

Development and Characterization of Novel Biopolymer Derived from Abelmoschus esculentus L. Extract and Its Antidiabetic Potential.

Abelmoschus esculentus (Okra) is an important vegetable crop, widely cultivated around the world due to its high nutritional significance along with several health benefits. Different parts of okra including its mucilage have been currently studied for its role in various therapeutic applications. Therefore, we aimed to develop and characterize the okra mucilage biopolymer (OMB) for its physicochemical properties as well as to evaluate its in vitro antidiabetic activity. The characterization of OMB using Fourier-transform infrared spectroscopy (FT-IR) revealed that okra mucilage containing polysaccharides lies in the bandwidth of 3279 and 1030 cm-1, which constitutes the fingerprint region of the spectrum. In addition, physicochemical parameters such as percentage yield, percentage solubility, and swelling index were found to be 2.66%, 96.9%, and 5, respectively. A mineral analysis of newly developed biopolymers showed a substantial amount of calcium (412 mg/100 g), potassium (418 mg/100 g), phosphorus (60 mg/100 g), iron (47 mg/100 g), zinc (16 mg/100 g), and sodium (9 mg/100 g). The significant antidiabetic potential of OMB was demonstrated using α-amylase and α-glucosidase enzyme inhibitory assay. Further investigations are required to explore the newly developed biopolymer for its toxicity, efficacy, and its possible utilization in food, nutraceutical, as well as pharmaceutical industries.

Deciphering the Molecular Mechanism Responsible for Efficiently Inhibiting Metastasis of Human Non-Small Cell Lung and Colorectal Cancer Cells Targeting the Matrix Metalloproteinases by Selaginella repanda.

Selaginella species are known to have antimicrobial, antioxidant, anti-inflammatory, anti-diabetic as well as anticancer effects. However, no study has examined the cytotoxic and anti-metastatic efficacy of Selaginella repanda (S. repanda) to date. Therefore, this study aimed to evaluate the potential anti-metastatic properties of ethanol crude extract of S. repanda in human non-small-cell lung (A-549) and colorectal cancer (HCT-116) cells with possible mechanisms. Effect of S. repanda crude extract on the growth, adhesion, migration and invasion of the A-549 and HCT-116 were investigated. We demonstrated that S. repanda crude extract inhibited cell growth of metastatic cells in a dose and time dependent manner. Incubation of A-549 and HCT-116 cells with 100-500 µg/mL of S. repanda crude extract significantly inhibited cell adhesion to gelatin coated surface. In the migration and invasion assay, S. repanda crude extract also significantly inhibited cellular migration and invasion in both A-549 and HCT-116 cells. Moreover, reverse transcription-polymerase chain reaction, and real-time PCR (RT-PCR) analysis revealed that the activity and mRNA level of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2) and membrane type 1-matrix metalloproteinase (MT1-MMP) were inhibited. While the activity of tissue inhibitor matrix metalloproteinase 1 (TIMP-1); an inhibitor of MMPs was stimulated by S. repanda crude extract in a concentration-dependent manner. Therefore, the present study not only indicated the inhibition of motility and invasion of malignant cells by S. repanda, but also revealed that such effects were likely associated with the decrease in MMP-2/-9 expression of both A-549 and HCT-116 cells. This further suggests that S. repanda could be used as a potential source of anti-metastasis agent in pharmaceutical development for cancer therapy.

Okra (Abelmoschus Esculentus) as a Potential Dietary Medicine with Nutraceutical Importance for Sustainable Health Applications.

Recently, there has been a paradigm shift from conventional therapies to relatively safer phytotherapies. This divergence is crucial for the management of various chronic diseases. Okra (Abelmoschus esculentus L.) is a popular vegetable crop with good nutritional significance, along with certain therapeutic values, which makes it a potential candidate in the use of a variety of nutraceuticals. Different parts of the okra fruit (mucilage, seed, and pods) contain certain important bioactive components, which confer its medicinal properties. The phytochemicals of okra have been studied for their potential therapeutic activities on various chronic diseases, such as type-2 diabetes, cardiovascular, and digestive diseases, as well as the antifatigue effect, liver detoxification, antibacterial, and chemo-preventive activities. Moreover, okra mucilage has been widely used in medicinal applications such as a plasma replacement or blood volume expanders. Overall, okra is considered to be an easily available, low-cost vegetable crop with various nutritional values and potential health benefits. Despite several reports about its therapeutic benefits and potential nutraceutical significance, there is a dearth of research on the pharmacokinetics and bioavailability of okra, which has hampered its widespread use in the nutraceutical industry. This review summarizes the available literature on the bioactive composition of okra and its potential nutraceutical significance. It will also provide a platform for further research on the pharmacokinetics and bioavailability of okra for its possible commercial production as a therapeutic agent against various chronic diseases.

Phytochemistry, Bioactivities, Pharmacokinetics and Toxicity Prediction of Selaginella repanda with Its Anticancer Potential against Human Lung, Breast and Colorectal Carcinoma Cell Lines.

In this study, we investigated the bioactive potential (antibacterial and antioxidant), anticancer activity and detailed phytochemical analysis of Selaginellarepanda (S. repanda) ethanolic crude extract for the very first time using different in vitro approaches. Furthermore, computer-aided prediction of pharmacokinetic properties and safety profile of the identified phytoconstituents were also employed in order to provide some useful insights for drug discovery. S. repanda, which is a rich source of potent natural bioactive compounds, showed promising antibacterial activity against the tested pathogenic bacteria (S. aureus, P. aeruginosa, E. coli and S. flexneri). The crude extract displayed favorable antioxidant activity against both 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC50 = 231.6 µg/mL) and H2O2 (IC50 = 288.3 µg/mL) molecules. S. repanda also showed favorable and effective anticancer activity against all three malignant cancer cells in a dose/time dependent manner. Higher activity was found against lung (A549) (IC50 = 341.1 µg/mL), followed by colon (HCT-116) (IC50 = 378.8 µg/mL) and breast (MCF-7) (IC50 = 428.3 µg/mL) cancer cells. High resolution-liquid chromatography-mass spectrometry (HR-LC-MS) data of S. repanda crude extract revealed the presence of diverse bioactive/chemical components, including fatty acids, alcohol, sugar, flavonoids, alkaloids, terpenoids, coumarins and phenolics, which can be the basis and major cause for its bioactive potential. Therefore, achieved results from this study confirmed the efficacy of S. repanda and a prospective source of naturally active biomolecules with antibacterial, antioxidant and anticancer potential. These phytocompounds alone with their favorable pharmacokinetics profile suggests good lead and efficiency of S. repanda with no toxicity risks. Finally, further in vivo experimental investigations can be promoted as probable candidates for various therapeutic functions, drug discovery and development.

Cordycepin for Health and Wellbeing: A Potent Bioactive Metabolite of an Entomopathogenic Cordyceps Medicinal Fungus and Its Nutraceutical and Therapeutic Potential.

Cordyceps is a rare naturally occurring entomopathogenic fungus usually found at high altitudes on the Himalayan plateau and a well-known medicinal mushroom in traditional Chinese medicine. Cordyceps contains various bioactive components, out of which, cordycepin is considered most vital, due to its utmost therapeutic as well as nutraceutical potential. Moreover, the structure similarity of cordycepin with adenosine makes it an important bioactive component, with difference of only hydroxyl group, lacking in the 3' position of its ribose moiety. Cordycepin is known for various nutraceutical and therapeutic potential, such as anti-diabetic, anti-hyperlipidemia, anti-fungal, anti-inflammatory, immunomodulatory, antioxidant, anti-aging, anticancer, antiviral, hepato-protective, hypo-sexuality, cardiovascular diseases, antimalarial, anti-osteoporotic, anti-arthritic, cosmeceutical etc. which makes it a most valuable medicinal mushroom for helping in maintaining good health. In this review, effort has been made to bring altogether the possible wide range of cordycepin's nutraceutical potential along with its pharmacological actions and possible mechanism. Additionally, it also summarizes the details of cordycepin based nutraceuticals predominantly available in the market with expected global value. Moreover, this review will attract the attention of food scientists, nutritionists, pharmaceutical and food industries to improve the use of bioactive molecule cordycepin for nutraceutical purposes with commercialization to aid and promote healthy lifestyle, wellness and wellbeing.