The anticancer potential of the dietary polyphenol rutin: Current status, challenges, and perspectives.

Rutin is one of the most common dietary polyphenols found in vegetables, fruits, and other plants. It is metabolized by the mammalian gut microbiota and absorbed from the intestines, and becomes bioavailable in the form of conjugated metabolites. Rutin exhibits a plethora of bioactive properties, making it an extremely promising phytochemical. Numerous studies demonstrate that rutin can act as a chemotherapeutic and chemopreventive agent, and its anticancer effects can be mediated through the suppression of cell proliferation, the induction of apoptosis or autophagy, and the hindering of angiogenesis and metastasis. Rutin has been found to modulate multiple molecular targets involved in carcinogenesis, such as cell cycle mediators, cellular kinases, inflammatory cytokines, transcription factors, drug transporters, and reactive oxygen species. This review summarizes the natural sources of rutin, its bioavailability, and in particular its potential use as an anticancer agent, with highlighting its anticancer mechanisms as well as molecular targets. Additionally, this review updates the anticancer potential of its analogs, nanoformulations, and metabolites, and discusses relevant safety issues. Overall, rutin is a promising natural dietary compound with promising anticancer potential and can be widely used in functional foods, dietary supplements, and pharmaceuticals for the prevention and management of cancer.

Antivirulence properties and related mechanisms of spice essential oils: A comprehensive review.

In recent decades, reduced antimicrobial effectiveness, increased bacterial infection, and newly emerged microbial resistance have become global public issues, leading to an urgent need to find effective strategies to counteract these problems. Strategies targeting bacterial virulence factors rather than bacterial survival have attracted increasing interest, since the modulation of virulence factors may prevent the development of drug resistance in bacteria. Spices are promising natural sources of antivirulence compounds owing to their wide availability, diverse antivirulence phytochemical constituents, and generally favorable safety profiles. Essential oils are the predominant and most important antivirulence components of spices. This review addresses the recent efforts of using spice essential oils to inhibit main bacterial virulence traits, including the quorum sensing system, biofilm formation, motility, and toxin production, with an intensive discussion of related mechanisms. We hope that this review can provide a better understanding of the antivirulence properties of spice essential oils, which have the potential to be used as antibiotic alternatives by targeting bacterial virulence.

Deoxyelephantopin impairs growth of cervical carcinoma SiHa cells and induces apoptosis by targeting multiple molecular signaling pathways.

Deoxyelephantopin, a sesquiterpene lactone extracted and purified from Elephantopus scaber, has been shown to exhibit antitumor and hepatoprotective activities. The purpose of this study was to investigate the antiproliferative and apoptosis-inducing properties of deoxyelephantopin in SiHa cells and to elucidate the underlying molecular mechanisms. Deoxyelephantopin inhibited growth of SiHa cells and triggered apoptosis. Apoptosis was accompanied by sequential activation of caspases (8, 9, 3, and 7) and reactive oxygen species (ROS) production. Downregulation of antiapoptotic proteins (Bcl2 and Bcl-xL) and upregulation of apoptotic protein (bax) were also detected. Our results demonstrated that deoxyelephantopin-induced G2/M phase arrest was associated with a marked increase in the levels of p53 and p21 and a decrease in phospho-signal transducer and activator of transcription 3 (pSTAT3-Tyr705), cyclin-dependent kinase 1 (cdc2), and cyclin B1. The expression of p-Akt and p-mTOR was downregulated. p-ERK was inhibited while p-JNK and p-p38 was activated on deoxyelephantopin treatment. Our findings provided the first evidence that STAT3/p53/p21 signaling, MAPK pathway, PI3k/Akt/mTOR pathway, caspase cascades, and ROS play critical roles in deoxyelephantopin-induced G2/M phase arrest and apoptosis of SiHa cells.

Raspberry Ketone-Mediated Inhibition of Biofilm Formation in Salmonella enterica Typhimurium-An Assessment of the Mechanisms of Action.

Salmonella enterica is an important foodborne pathogen that causes gastroenteritis and systemic infection in humans and livestock. Salmonella biofilms consist of two major components-amyloid curli and cellulose-which contribute to the prolonged persistence of Salmonella inside the host. Effective agents for inhibiting the formation of biofilms are urgently needed. We investigated the antibiofilm effect of Raspberry Ketone (RK) and its mechanism of action against Salmonella Typhimurium 14028 using the Congo red agar method, Calcofluor staining, crystal violet method, pellicle assay, and the TMT-labeled quantitative proteomic approach. RK suppressed the formation of different types of Salmonella biofilms, including pellicle formation, even at low concentrations (200 µg/mL). Furthermore, at higher concentrations (2 mg/mL), RK exhibited bacteriostatic effects. RK repressed cellulose deposition in Salmonella biofilm through an unknown mechanism. Swimming and swarming motility analyses demonstrated reduced motility in RK-treated S. typhimurium. Proteomics analysis revealed that pathways involved in amyloid curli production, bacterial invasion, flagellar motility, arginine biosynthesis, and carbohydrate metabolism, were targeted by RK to facilitate biofilm inhibition. Consistent with the proteomics data, the expressions of csgB and csgD genes were strongly down-regulated in RK-treated S. typhimurium. These findings clearly demonstrated the Salmonella biofilm inhibition capability of RK, justifying its further study for its efficacy assessment in clinical and industrial settings.

Anti-quorum sensing effects of batatasin III: in vitro and in silico studies.

The spread of multidrug resistant bacteria has fueled the development of new antibiotics to combat bacterial infections. Disrupting the quorum sensing (QS) mechanism with biomolecules is a promising approach against bacterial infections. Plants used in Traditional Chinese Medicine (TCM) represent a valuable resource for the identification of QS inhibitors. In this study, the in vitro anti-QS activity of 50 TCM-derived phytochemicals against the biosensor Chromobacterium violaceum CV026 was tested. Among the 50 phytochemicals, 7-methoxycoumarin, flavone, batatasin III, resveratrol, psoralen, isopsoralen, and rhein inhibited violacein production and showed good QS inhibitory effects. Batatasin III was selected as the best QS inhibitor based on drug-likeness, physicochemical properties, toxicity, and bioactivity score prediction analyses using SwissADME, PreADMET, ProtoxII, and Molinspiration. At 30 µg/ mL, Batatasin III inhibited violacein production and biofilm formation in C. violaceum CV026 by more than 69% and 54% respectively without affecting bacterial growth. The in vitro cytotoxicity evaluation by MTT assay demonstrated that batatasin III reduced the viability of 3T3 mouse fibroblast cells to 60% at 100 µg/mL. Furthermore, molecular docking studies showed that batatasin III has strong binding interactions with the QS-associated proteins CViR, LasR, RhlR, PqsE, and PqsR. Molecular dynamic simulation studies showed that batatasin III has strong binding interactions with 3QP1, a structural variant of CViR protein. The binding free energy value of batatasin III-3QP1 complex was -146.295 ± 10.800 KJ/mol. Overall results suggested that batatasin III could serve as a lead molecule that could be developed into a potent QS inhibitor.Communicated by Ramaswamy H. Sarma.

Large-Scale Screening of 239 Traditional Chinese Medicinal Plant Extracts for Their Antibacterial Activities against Multidrug-Resistant Staphylococcus aureus and Cytotoxic Activities.

Novel alternative antibacterial compounds have been persistently explored from plants as natural sources to overcome antibiotic resistance leading to serious foodborne bacterial illnesses. In this study, the ethanolic extracts from 239 traditional Chinese medicinal plants (TCMP)' materials were screened to discover promising candidates that have strong antibacterial properties against multidrug-resistant Staphylococcus (S.) aureus and low cytotoxicity. The results revealed that 74 extracts exhibited good antibacterial activities (diameter of inhibition zone (DIZ) ≥ 15 mm). Furthermore, 18 extracts (DIZ ≥ 20 mm) were determined their minimum inhibitory concentrations (MIC) and minimum bactericide concentrations (MBC), ranging from 0.1 to 12.5 mg/mL and 0.78 to 25 mg/mL, respectively. In addition, most of the 18 extracts showed relatively low cytotoxicity (a median lethal concentration (LC50) >100 µg/mL). The 18 extracts were further determined to estimate possible correlation of their phenolic contents with antibacterial activity, and the results did not show any significant correlation. In conclusion, this study selected out some promising antibacterial TCMP extracts with low cytotoxicity, including Rhus chinensis Mill., Ilex rotunda Thunb., Leontice kiangnanensis P.L.Chiu, Oroxylum indicum Vent., Isatis tinctorial L., Terminalia chebula Retz., Acacia catechu (L.f.) Willd., Spatholobus suberectus Dunn, Rabdosia rubescens (Hemsl.) H.Hara, Salvia miltiorrhiza Bunge, Fraxinus fallax Lingelsh, Coptis chinensis Franch., Agrimonia Pilosa Ledeb., and Phellodendron chinense C.K.Schneid.

Bioprospecting potential and secondary metabolite profile of a novel sediment-derived fungus Penicillium sp. ArCSPf from continental slope of Eastern Arabian Sea.

Marine fungi, one of the major decomposers of marine environment, is found to produce potential enzymes and novel biomolecules. The present study explored bioprospecting potentials such as antimicrobial, anticancer and enzymatic activities of marine sediment-derived fungi isolated from continental slope of Eastern Arabian Sea. Morphology and ITS sequencing identified the fungus as Penicillium sp. ArCSPf. The fungal strain exhibited amylase, gelatinase, phytase, lipase and pectinase activity. The active fraction obtained from the ethyl acetate extract column fractionation (F2) of fungus showed antibacterial activity against both methicillin-resistant Staphylococcus aureus (MRSA) and Bacillus cereus. Minimum inhibitory concentrations of F2 were 125 µg/mL for MRSA and 62.5 µg/mL for B. cereus. The active fraction showed a significant anticancer activity (IC50 = 22.79 µg/mL) against MCF-7 breast cancer cells. The secondary metabolite (Z)-Octadec-9-enamide (oleamide, m/z 282.27 (M + H+)] was identified in the LC-MS/MS analysis of active fraction F2 in positive ionisation mode. To the best of our knowledge, this is the first report on exploring the bioprospecting potential of a sediment-derived fungus from continental slope of eastern Arabian Sea for the production of therapeutically active compounds.

Discovery of Antibacterial Dietary Spices That Target Antibiotic-Resistant Bacteria.

Although spice extracts are well known to exhibit antibacterial properties, there is lack of a comprehensive evaluation of the antibacterial effect of spices against antibiotic-resistant bacteria. In the present study, ethanolic extracts from a total of 67 spices were comprehensively investigated for their in vitro antibacterial activities by agar well diffusion against two common food-borne bacteria, Staphylococcus aureus and Salmonella enteritidis, with multi-drug resistance. Results showed that S. aureus was generally more sensitive to spice extracts than S. enteritidis. Of the 67 spice extracts, 38 exhibited antibacterial activity against drug-resistant S. aureus, while only four samples were effective on drug-resistant S. enteritidis. In addition, 11 spice extracts with inhibition zones greater than 15 mm were further verified for their broad-spectrum antibacterial properties using another 10 drug-resistant S. aureus strains. It was found that five spice extracts, including galangal, fructus galangae, cinnamon, yellow mustard seed, and rosemary, exhibited the highest antibacterial capacity. Further cytotoxicity of these 11 spices was determined and LC50 values were found to be more than 100 µg/mL except for galangal, rosemary, and sage, whose LC50 values were 9.32 ± 0.83, 19.77 ± 2.17, and 50.54 ± 2.57, respectively. Moreover, the antioxidant activities (ferric-reducing antioxidant power (FRAP) and trolox equivalent antioxidant capacity (TEAC) values) and total phenolic content (TPC) of spice extracts were determined to establish possible correlations with the antibacterial activity. Although the antibacterial effect was positively correlated with the antioxidant activities and TPC, the correlation was weak (r < 0.5), indicating that the antibacterial activity could also be attributed to other components besides antioxidant polyphenols in the tested spice extracts. In conclusion, dietary spices are good natural sources of antibacterial agents to fight against antibiotic-resistant bacteria, with potential applications as natural food preservatives and natural alternatives to antibiotics in animal feeding.

Phylogenetic diversity and biotechnological potentials of marine bacteria from continental slope of eastern Arabian Sea.

Marine environments are substantially untapped source for the isolation of bacteria with the capacity to produce various extracellular hydrolytic enzymes, which have important ecological roles and promising biotechnological applications. Hydrolases constitute a class of enzymes widely distributed in nature from bacteria to higher eukaryotes. Marine microbial communities are highly diverse and have evolved during extended evolutionary processes of physiological adaptations under the influence of a variety of ecological conditions and selection pressures. A number of marine hydrolases have been described, including amylases, lipases and proteases, which are being used extensively for biotechnological applications. The present study was carried out to isolate marine bacteria from continental slope sediments of the eastern Arabian Sea and explore their biotechnological potential. Among the 119 isolates screened, producers of amylases (15%), caseinases (40%), cellulases (40%), gelatinases (60%), lipases (26%), ligninases (33%), phytase (11%) and Malachite Green dye degraders (16%) were detected. Phylogenetic analysis based on 16S rRNA gene sequencing showed that predominant marine sediment bacteria possessing more than four enzymatic activities belonged to the phyla Firmicutes and Proteobacteria, was assigned to the genera Bacillus, Planococcus, Staphylococcus, Chryseomicrobium, Exiguobacterium and Halomonas. Biodegradation of the dye Malachite Green using the liquid decolorization assay showed that both the individual cultures (Bacillus vietnamensis, Planococcus maritimus and Bacillus pumilus) and their consortium were able to decolorize more than 70% of dye within 24 h of incubation. This is the first report on diversity and extracellular hydrolytic enzymatic activities and bioremediation properties of bacteria from continental slope sediment of eastern Arabian Sea.