The crisis of antibiotic resistance necessitates creative and innovative approaches, from chemical identification and analysis to the assessment of bioactivity. Plant natural products (NPs) represent ...a promising source of antibacterial lead compounds that could help fill the drug discovery pipeline in response to the growing antibiotic resistance crisis. The major strength of plant NPs lies in their rich and unique chemodiversity, their worldwide distribution and ease of access, their various antibacterial modes of action, and the proven clinical effectiveness of plant extracts from which they are isolated. While many studies have tried to summarize NPs with antibacterial activities, a comprehensive review with rigorous selection criteria has never been performed. In this work, the literature from 2012 to 2019 was systematically reviewed to highlight plant-derived compounds with antibacterial activity by focusing on their growth inhibitory activity. A total of 459 compounds are included in this Review, of which 50.8% are phenolic derivatives, 26.6% are terpenoids, 5.7% are alkaloids, and 17% are classified as other metabolites. A selection of 183 compounds is further discussed regarding their antibacterial activity, biosynthesis, structure–activity relationship, mechanism of action, and potential as antibiotics. Emerging trends in the field of antibacterial drug discovery from plants are also discussed. This Review brings to the forefront key findings on the antibacterial potential of plant NPs for consideration in future antibiotic discovery and development efforts.
Antimicrobial resistance represents a serious threat to human health across the globe. The cost of bringing a new antibiotic from discovery to market is high and return on investment is low. ...Furthermore, the development of new antibiotics has slowed dramatically since the 1950s' golden age of discovery. Plants produce a variety of bioactive secondary metabolites that could be used to fuel the future discovery pipeline. While many studies have focused on specific aspects of plants and plant natural products with antibacterial properties, a comprehensive review of the antibacterial potential of plants has never before been attempted.
This systematic review aims to evaluate reports on plants with significant antibacterial activities.
Following the PRISMA model, we searched three electronic databases: Web of Science, PubMed and SciFinder by using specific keywords: "plant," "antibacterial," "inhibitory concentration."
We identified a total of 6,083 articles published between 1946 and 2019 and then reviewed 66% of these (4,024) focusing on articles published between 2012 and 2019. A rigorous selection process was implemented using clear inclusion and exclusion criteria, yielding data on 958 plant species derived from 483 scientific articles. Antibacterial activity is found in 51 of 79 vascular plant orders throughout the phylogenetic tree. Most are reported within eudicots, with the bulk of species being asterids. Antibacterial activity is not prominent in monocotyledons. Phylogenetic distribution strongly supports the concept of chemical evolution across plant clades, especially in more derived eudicot families. The Lamiaceae, Fabaceae and Asteraceae were the most represented plant families, while
,
and
were the most studied species. South Africa was the most represented site of plant collection. Crude extraction in methanol was the most represented type of extraction and leaves were the main plant tissue investigated. Finally,
was the most targeted pathogenic bacteria in these studies. We closely examine 70 prominent medicinal plant species from the 15 families most studied in the literature.
This review depicts the current state of knowledge regarding antibacterials from plants and provides powerful recommendations for future research directions.
In the search for new therapeutic solutions to address an increasing number of multidrug-resistant bacterial pathogens, secondary metabolites from plants have proven to be a rich source of ...antimicrobial compounds.
, a tree native to China, has been spread around the world as an ornamental tree. Its seeds have been used as snacks and medical materials in Traditional Chinese Medicine (TCM), while over the last century its leaf extracts emerged as a source of rising pharmaceutical commerce related to brain health in Western medicine. Besides studies on the neuro-protective effects of Ginkgo, its antibacterial activities have gained more attention from researchers in the past decades, though its leaves were the main focus. We reviewed a 16th-century Chinese text, the
by Li Shi-Zhen, to investigate the ancient prescription of Ginkgo seeds for skin infections. We performed antibacterial assays on various Ginkgo seed extracts against pathogens (
,
,
,
) relevant to skin and soft tissue infections (SSTIs). We demonstrate here that Ginkgo seed coats and immature seeds exhibit antibacterial activity against Gram-positive skin pathogens (
, and
), and thus validated its use in TCM. We also identified one compound tied to the antibacterial activity observed, ginkgolic acid C15:1, and examine its toxicity to human keratinocytes. These results highlight the relevance of ancient medical texts as leads for the discovery of natural products with antimicrobial activities.
The Mediterranean is home to a rich history of medical traditions that have developed under the influence of diverse cultures over millennia. Today, many such traditions are still alive in the folk ...medical practices of local people. Investigation of botanical folk medicines used in the treatment of skin and soft tissue infections led us to study Castanea sativa (European Chestnut) for its potential antibacterial activity. Here, we report the quorum sensing inhibitory activity of refined and chemically characterized European Chestnut leaf extracts, rich in oleanene and ursene derivatives (pentacyclic triterpenes), against all Staphylococcus aureus accessory gene regulator (agr) alleles. We present layers of evidence of agr blocking activity (IC50 1.56-25 μg mL-1), as measured in toxin outputs, reporter assays hemolytic activity, cytotoxicity studies, and an in vivo abscess model. We demonstrate the extract's lack of cytotoxicity to human keratinocytes and murine skin, as well as lack of growth inhibitory activity against S. aureus and a panel of skin commensals. Lastly, we demonstrate that serial passaging of the extract does not result in acquisition of resistance to the quorum quenching composition. In conclusion, through disruption of quorum sensing in the absence of growth inhibition, this study provides insight into the role that non-biocide inhibitors of virulence may play in future antibiotic therapies.
Preparative high-performance liquid chromatographic (prep-HPLC) systems are used in many research schemes including purifying products from reaction mixtures, fractionating natural product extracts, ...and isolating compounds. Manual fraction collection from a prep-HPLC is a common method; however, it often lacks the reproducibility of automated fraction collectors due to human error. Automated fraction collectors for prep-HPLC systems can add thousands of dollars to the cost of prep-HPLC and are thus not always available to budgetary constrained research programs. Nevertheless, an automated fraction collector is a tremendous resource for any lab that employs prep-HPLC methods. Using LEGO MINDSTORMS pieces and easily obtained lumber and a steel C-channel, we were able to deploy an automated fraction collector for only a fraction of the cost of a commercial instrument. The programming software allows for a simple interface to create fraction collection programs tailored to individual HPLC methods. This fraction collector can be connected to any LC system and tailored to collect fractions in nearly any size or shaped container. This fraction collector was designed to provide maximum versatility and will make automated fraction collection more accessible to all researchers. The simple interface allows for quickly adapting the fraction collector method to any liquid chromatographic separation, no matter how complex.
Recent investigations have associated white teas with anti-carcinogenic, immune-boosting, and antioxidative properties that may impact human health in a manner comparable to green teas. An in-depth ...chemical analysis of white tea types was conducted to quantify polyphenols and antioxidant potential of 8 commercially available white teas, and compare them to green tea. Extraction and HPLC protocols were optimized and validated for the quantification of 9 phenolic and 3 methylxanthine compounds to examine inter- and intra-variation in white and green tea types and subtypes. A sampling strategy was devised to assess various subtypes procured from different commercial sources. Variation in antioxidant activity and total phenolic content (TPC) of both tea types was further assessed by the 1-1-diphenyl-2-picrylhydrazyl (DPPH) and Folin-Ciocalteau (F-C) assays, respectively. Total catechin content (TCC) for white teas ranged widely from 14.40 to 369.60 mg/g of dry plant material for water extracts and 47.16 to 163.94 mg/g for methanol extracts. TCC for green teas also ranged more than 10-fold, from 21.38 to 228.20 mg/g of dry plant material for water extracts and 32.23 to 141.24 mg/g for methanol extracts. These findings indicate that statements suggesting a hierarchical order of catechin content among tea types are inconclusive and should be made with attention to a sampling strategy that specifies the tea subtype and its source. Certain white teas have comparable quantities of total catechins to some green teas, but lesser antioxidant capacity, suggesting that white teas have fewer non-catechin antioxidants present. In this investigation white and green teas were extracted in ways that mimic common tea preparation practices, and their chemical profiles were determined using validated analytical chemistry methods. The results suggest certain green and white tea types have comparable levels of catechins with potential health promoting qualities. Specifically, the polyphenolic content of green teas was found to be similar to certain white tea varieties, which makes the latter tea type a potential substitute for people interested in consuming polyphenols for health reasons. Moreover, this study is among the first to demonstrate the effect subtype sampling, source of procurement, cultivation, and processing practices have on the final white tea product, as such analysis has previously been mostly carried out on green teas.
Antibiotic resistance poses one of the greatest threats to global health today; conventional drug therapies are becoming increasingly inefficacious and limited. We identified 16 medicinal plant ...species used by traditional healers for the treatment of infectious and inflammatory diseases in the Greater Mpigi region of Uganda. Extracts were evaluated for their ability to inhibit growth of clinical isolates of multidrug-resistant ESKAPE pathogens. Extracts were also screened for quorum quenching activity against S. aureus, including direct protein output assessment (δ-toxin), and cytotoxicity against human keratinocytes (HaCaT). Putative matches of compounds were elucidated via LC-FTMS for the best-performing extracts. These were extracts of Zanthoxylum chalybeum (Staphylococcus aureus: MIC: 16 μg/mL; Enterococcus faecium: MIC: 32 μg/mL) and Harungana madagascariensis (S. aureus: MIC: 32 μg/mL; E. faecium: MIC: 32 μg/mL) stem bark. Extracts of Solanum aculeastrum root bark and Sesamum calycinum subsp. angustifolium leaves exhibited strong quorum sensing inhibition activity against all S. aureus accessory gene regulator (agr) alleles in absence of growth inhibition (IC
values: 1-64 μg/mL). The study provided scientific evidence for the potential therapeutic efficacy of these medicinal plants in the Greater Mpigi region used for infections and wounds, with 13 out of 16 species tested being validated with in vitro studies.
Widespread antibiotic resistance is on the rise and current therapies are becoming increasingly limited in both scope and efficacy. Methicillin-resistant Staphylococcus aureus (MRSA) represents a ...major contributor to this trend. Quorum sensing controlled virulence factors include secreted toxins responsible for extensive damage to host tissues and evasion of the immune system response; they are major contributors to morbidity and mortality. Investigation of botanical folk medicines for wounds and infections led us to study Schinus terebinthifolia (Brazilian Peppertree) as a potential source of virulence inhibitors. Here, we report the inhibitory activity of a flavone rich extract "430D-F5" against all S. aureus accessory gene regulator (agr) alleles in the absence of growth inhibition. Evidence for this activity is supported by its agr-quenching activity (IC
2-32 μg mL
) in transcriptional reporters, direct protein outputs (α-hemolysin and δ-toxin), and an in vivo skin challenge model. Importantly, 430D-F5 was well tolerated by human keratinocytes in cell culture and mouse skin in vivo; it also demonstrated significant reduction in dermonecrosis following skin challenge with a virulent strain of MRSA. This study provides an explanation for the anti-infective activity of peppertree remedies and yields insight into the potential utility of non-biocide virulence inhibitors in treating skin infections.
Local people in the Sudhnoti district of Pakistan share a rich practice of traditional medicine for the treatment of a variety of ailments. We selected nine plants from the Sudhnoti ...ethnopharmacological tradition used for the treatment of infectious and inflammatory disease. Our aim was to evaluate the
anti-infective potential of extracts from these species against multidrug-resistant (MDR) ESKAPE (
, and
species) pathogens. Plant specimens were collected in the Sudhnoti district of Pakistan and vouchers deposited in Pakistan and the USA. Dried bulk specimens were ground into a fine powder and extracted by aqueous decoction and maceration in ethanol. Extracts were assessed for growth inhibitory activity against ESKAPE pathogens and biofilm and quorum sensing activity was assessed in
. Cytotoxicity to human cells was assessed via a lactate dehydrogenase assay of treated human keratinocytes (HaCaTs). Four ethanolic extracts (
, and
) inhibited the growth of MDR strains of ESKAPE pathogens (IC
: 256 μg mL
). All extracts, with the exception of
and
, exhibited significant quorum quenching in a reporter strain for
I. The ethanolic extract of
fruits (Extract 1290) inhibited quorum sensing (IC
32-256 μg mL
) in
reporter strains for
I-III. The quorum quenching activity of extract 1290 was validated by detection of δ-toxin in the bacterial supernatant, with concentrations of 64-256 μg mL
sufficient to yield a significant drop in δ-toxin production. None of the extracts inhibited
biofilm formation at sub-inhibitory concentrations for growth. All extracts were well tolerated by human keratinocytes (LD
≥ 256 μg mL
). Chemical analysis of extract 1290 by liquid chromatography-Fourier transform mass spectrometry (LC-FTMS) revealed the presence of 29 compounds, including eight with putative structural matches. In conclusion, five out of the nine selected anti-infective medicinal plants exhibited growth inhibitory activity against at least one MDR ESKAPE pathogen at concentrations not harmful to human keratinocytes. Furthermore,
was identified as a source of quorum quenching natural products and further bioassay-guided fractionation of this species is merited.
Plants in the genus
(Family: Crassulaceae) are used in traditional medicine throughout the tropics for treating a variety of conditions. Two species,
and
, have established ethnobotanical usage but ...have been neglected in previous research concerning their potential bioactivity. Here, we provide a thorough review of the reported antimicrobial activities of
genus and evaluate the
antibacterial effects of two previously unexplored species against a panel of multidrug-resistant bacteria, the ESKAPE pathogens (
, and
). Plant specimens were collected and voucher specimens deposited in the Emory University Herbarium. Dried plant material was ground into a powder and extracted as ethanolic macerations or as aqueous decoctions. Extracts were tested against the ESKAPE pathogens for growth inhibitory activity. Cytotoxicity to human cells was assessed via a lactate dehydrogenase assay of treated human keratinocytes (HaCaTs).
extracts demonstrated growth inhibitory effects against two Gram-negative species,
(strain CDC-33) and
(AH-71), as well as
(UAMS-1). In these cases, growth inhibition greater than 50% (IC
) was generally observed at concentrations of 256 μg mL
, though one
extract (1465, prepared from stems) exhibited an IC
against
at 128 μg mL
. All extracts were well tolerated by HaCaTs (LD
≥ 256 μg mL
). Chemical characterization using HPLC and chemical standards established the presence of caffeic acid and quercetin in both plant species, as well as kaempferol in
These results reveal
to be a plant of medicinal interest, and future research should aim to characterize the bioactivity of this species and its active constituents through bioassay-guide fractionation. Effects on bacterial biofilm formation and quorum-sensing are also research topics of interest for this genus.
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