Plant-Derived Natural Products for the Treatment of Bacterial Infections.

Bacterial infections are a significant public health concern, and the emergence of antibiotic-resistant bacteria (ARB) has become a major challenge for modern medicine. The overuse and misuse of antibiotics have contributed to the development of ARB, which has led to the need for alternative therapies. Plant-derived natural products (PNPs) have been extensively studied for their potential as alternative therapies for the treatment of bacterial infections. The diverse chemical compounds found in plants have shown significant antibacterial properties, making them a promising source of novel antibacterial agents. The use of PNPs as antibacterial agents is particularly appealing because they offer a relatively safe and cost-effective approach to the treatment of bacterial infections. This chapter aims to provide an overview of the current state of research on PNPs as antibacterial agents. It will cover the mechanisms of action of the main PNPs against bacterial pathogens and discuss their potential to be used as complementary therapies to combat ARB. This chapter will also highlight the most common screening methodologies to discover new PNPs and the challenges and future prospects in the development of these compounds as antibacterial agents.

Analysis of the Arabidopsis venosa4-0 mutant supports the role of VENOSA4 in dNTP metabolism.

Human Sterile alpha motif and histidine-aspartate domain containing protein 1 (SAMHD1) functions as a dNTPase to maintain dNTP pool balance. In eukaryotes, the limiting step in de novo dNTP biosynthesis is catalyzed by RIBONUCLEOTIDE REDUCTASE (RNR). In Arabidopsis, the RNR1 subunit of RNR is encoded by CRINKLED LEAVES 8 (CLS8), and RNR2 by three paralogous genes, including TSO MEANING 'UGLY' IN CHINESE 2 (TSO2). In plants, DIFFERENTIAL DEVELOPMENT OF VASCULAR ASSOCIATED CELLS 1 (DOV1) catalyzes the first step of the de novo biosynthesis of purines. Here, to explore the role of VENOSA4 (VEN4), the most likely Arabidopsis ortholog of human SAMHD1, we studied the ven4-0 point mutation, whose leaf phenotype was stronger than those of its insertional alleles. Structural predictions suggested that the E249L substitution in the mutated VEN4-0 protein rigidifies its 3D structure. The morphological phenotypes of the ven4, cls8, and dov1 single mutants were similar, and those of the ven4 tso2 and ven4 dov1 double mutants were synergistic. The ven4-0 mutant had reduced levels of four amino acids related to dNTP biosynthesis, including glutamine and glycine, which are precursors in the de novo purine biosynthesis. Our results reveal high functional conservation between VEN4 and SAMHD1 in dNTP metabolism.

Phytochemical-Based Nanomaterials against Antibiotic-Resistant Bacteria: An Updated Review.

Antibiotic-resistant bacteria (ARB) is a growing global health threat, leading to the search for alternative strategies to combat bacterial infections. Phytochemicals, which are naturally occurring compounds found in plants, have shown potential as antimicrobial agents; however, therapy with these agents has certain limitations. The use of nanotechnology combined with antibacterial phytochemicals could help achieve greater antibacterial capacity against ARB by providing improved mechanical, physicochemical, biopharmaceutical, bioavailability, morphological or release properties. This review aims to provide an updated overview of the current state of research on the use of phytochemical-based nanomaterials for the treatment against ARB, with a special focus on polymeric nanofibers and nanoparticles. The review discusses the various types of phytochemicals that have been incorporated into different nanomaterials, the methods used to synthesize these materials, and the results of studies evaluating their antimicrobial activity. The challenges and limitations of using phytochemical-based nanomaterials, as well as future directions for research in this field, are also considered here. Overall, this review highlights the potential of phytochemical-based nanomaterials as a promising strategy for the treatment against ARB, but also stresses the need for further studies to fully understand their mechanisms of action and optimize their use in clinical settings.

Hallmarks and Biomarkers of Skin Senescence: An Updated Review of Skin Senotherapeutics.

Aging is a complex process characterized by an ongoing decline in physiological functions, leading to degenerative diseases and an increased probability of death. Cellular senescence has been typically considered as an anti-proliferative process; however, the chronic accumulation of senescent cells contributes to tissue dysfunction and aging. In this review, we discuss some of the most important hallmarks and biomarkers of cellular senescence with a special focus on skin biomarkers, reactive oxygen species (ROS), and senotherapeutic strategies to eliminate or prevent senescence. Although most of them are not exclusive to senescence, the expression of the senescence-associated beta-galactosidase (SA-ß-gal) enzyme seems to be the most reliable biomarker for distinguishing senescent cells from those arrested in the cell cycle. The presence of a stable DNA damage response (DDR) and the accumulation of senescence-associated secretory phenotype (SASP) mediators and ROS are the most representative hallmarks for senescence. Senotherapeutics based on natural compounds such as quercetin, naringenin, and apigenin have shown promising results regarding SASP reduction. These compounds seem to prevent the accumulation of senescent cells, most likely through the inhibition of pro-survival signaling pathways. Although studies are still required to verify their short- and long-term effects, these therapies may be an effective strategy for skin aging.

Artificial Intelligence Applied to Improve Scientific Reviews: The Antibacterial Activity of Cistus Plants as Proof of Concept.

Reviews have traditionally been based on extensive searches of the available bibliography on the topic of interest. However, this approach is frequently influenced by the authors' background, leading to possible selection bias. Artificial intelligence applied to natural language processing (NLP) is a powerful tool that can be used for systematic reviews by speeding up the process and providing more objective results, but its use in scientific literature reviews is still scarce. This manuscript addresses this challenge by developing a reproducible tool that can be used to develop objective reviews on almost every topic. This tool has been used to review the antibacterial activity of Cistus genus plant extracts as proof of concept, providing a comprehensive and objective state of the art on this topic based on the analysis of 1601 research manuscripts and 136 patents. Data were processed using a publicly available Jupyter Notebook in Google Collaboratory here. NLP, when applied to the study of antibacterial activity of Cistus plants, is able to recover the main scientific manuscripts and patents related to the topic, avoiding any biases. The NLP-assisted literature review reveals that C. creticus and C. monspeliensis are the first and second most studied Cistus species respectively. Leaves and fruits are the most commonly used plant parts and methanol, followed by butanol and water, the most widely used solvents to prepare plant extracts. Furthermore, Staphylococcus. aureus followed by Bacillus. cereus are the most studied bacterial species, which are also the most susceptible bacteria in all studied assays. This new tool aims to change the actual paradigm of the review of scientific literature to make the process more efficient, reliable, and reproducible, according to Open Science standards.

The antimicrobial capacity of Cistus salviifolius and Punica granatum plant extracts against clinical pathogens is related to their polyphenolic composition.

Antimicrobial resistance poses a serious threat to human health worldwide. Plant compounds may help to overcome antibiotic resistance due to their potential resistance modifying capacity. Several botanical extracts and pure polyphenolic compounds were screened against a panel of eleven bacterial isolates with clinical relevance. The two best performing agents, Cistus salviifolius (CS) and Punica granatum (GP) extracts, were tested against 100 Staphylococcus aureus clinical isolates, which resulted in average MIC50 values ranging between 50-80 µg/mL. CS extract, containing hydrolyzable tannins and flavonoids such as myricetin and quercetin derivatives, demonstrated higher activity against methicillin-resistant S. aureus isolates. GP extract, which contained mostly hydrolyzable tannins, such as punicalin and punicalagin, was more effective against methicillin-sensitive S. aureus isolates. Generalized linear model regression and multiple correspondence statistical analysis revealed a correlation between a higher susceptibility to CS extract with bacterial resistance to beta-lactam antibiotics and quinolones. On the contrary, susceptibility to GP extract was related with bacteria sensitive to quinolones and oxacillin. Bacterial susceptibility to GP and CS extracts was linked to a resistance profile based on cell wall disruption mechanism. In conclusion, a differential antibacterial activity against S. aureus isolates was observed depending on antibiotic resistance profile of isolates and extract polyphenolic composition, which may lead to development of combinatorial therapies including antibiotics and botanical extracts.

Tackling Antibiotic Resistance with Compounds of Natural Origin: A Comprehensive Review.

Drug-resistant bacteria pose a serious threat to human health worldwide. Current antibiotics are losing efficacy and new antimicrobial agents are urgently needed. Living organisms are an invaluable source of antimicrobial compounds. The antimicrobial activity of the most representative natural products of animal, bacterial, fungal and plant origin are reviewed in this paper. Their activity against drug-resistant bacteria, their mechanisms of action, the possible development of resistance against them, their role in current medicine and their future perspectives are discussed. Electronic databases such as PubMed, Scopus and ScienceDirect were used to search scientific contributions until September 2020, using relevant keywords. Natural compounds of heterogeneous origins have been shown to possess antimicrobial capabilities, including against antibiotic-resistant bacteria. The most commonly found mechanisms of antimicrobial action are related to protein biosynthesis and alteration of cell walls and membranes. Various natural compounds, especially phytochemicals, have shown synergistic capacity with antibiotics. There is little literature on the development of specific resistance mechanisms against natural antimicrobial compounds. New technologies such as -omics, network pharmacology and informatics have the potential to identify and characterize new natural antimicrobial compounds in the future. This knowledge may be useful for the development of future therapeutic strategies.

Antimicrobial Capacity of Plant Polyphenols against Gram-positive Bacteria: A Comprehensive Review.

BACKGROUND: Multi-drug-resistant bacteria such as Methicillin-Resistant Staphylococcus aureus (MRSA) disseminate rapidly amongst patients in healthcare facilities and suppose an increasingly important cause of community-associated infections and associated mortality. The development of effective therapeutic options against resistant bacteria is a public health priority. Plant polyphenols are structurally diverse compounds that have been used for centuries for medicinal purposes, including infections treatment and possess, not only antimicrobial activity, but also antioxidant, anti-inflammatory and anticancer activities among others. Based on the existing evidence on the polyphenols' antibacterial capacity, polyphenols may be postulated as an alternative or complementary therapy for infectious diseases. OBJECTIVE: To review the antimicrobial activity of plant polyphenols against Gram-positive bacteria, especially against S. aureus and its resistant strains. Determine the main bacterial molecular targets of polyphenols and their potential mechanism of action. METHODOLOGY: The most relevant reports on plant polyphenols' antibacterial activity and their putative molecular targets were studied. We also performed virtual screening of thousand different polyphenols against proteins involved in the peptidoglycan biosynthesis to find potential valuable bioactive compounds. The bibliographic information used in this review was obtained from MEDLINE via PubMed. RESULTS: Several polyphenols: phenolic acids, flavonoids (especially flavonols), tannins, lignans, stilbenes and combinations of these in botanical mixtures, have exhibited significant antibacterial activity against resistant and non-resistant Gram-positive bacteria at low µg/mL range MIC values. Their mechanism of action is quite diverse, targeting cell wall, lipid membrane, membrane receptors and ion channels, bacteria metabolites and biofilm formation. Synergic effects were also demonstrated for some combinations of polyphenols and antibiotics. CONCLUSION: Plant polyphenols mean a promising source of antibacterial agents, either alone or in combination with existing antibiotics, for the development of new antibiotic therapies.

Metabolomic analysis of the effects of a commercial complex biostimulant on pepper crops.

Research on plant biostimulants is of interest in their potential benefits for agriculture production and environmental sustainability. These naturally occurring products induce beneficial consequences in plant metabolism and productivity. In most cases their modes of action, and consequences for the whole plant as well as parts, such as the fruit, are well characterized, but the precise mechanisms of action require further attention. This study examined the effects of the commercial biostimulant, Actium®, on Capsicum annuum L. cv Palermo leaves and fruits. The influence of time (characterized by ripening), after 14 and 28 days of treatment, treatment regimen, and their combined impact on the metabolome were studied using HPLC-ESI-QTOF-MS analysis of polar and apolar compounds. The results showed that flavonoids and capsianosides decreased with ripening in leaves, but organic acids, monosaccharides, and carotenoids increased in fruits. The treatment of Capsicum fruits with Actium® increased phenylalanine and total monosaccharides (glucose and fructose) compared to controls, suggesting a further stage in ripening. An increase in carotenoids concomitant with an increase of some digalactosyl diacylglycerols, which are part of the chromoplasts lipid machinery of enzymes involved in the synthesis of carotenoids, was also observed. Our findings suggest that this biostimulant may increase some metabolites related to pepper fruit maturity and coloration in pepper crops.