Abstract
Increasing antimicrobial resistance, together with the occurrence of side effects of NSAIDs or glucocorticoids represents certain motivation to search for new natural dual antimicrobial and anti-inflammatory drugs. We here present selected natural compounds, possessing both antimicrobial and anti-inflammatory activity. The review contains also the information about structure–activity relationships with respect to natural or semisynthetic origin of compounds and synergy effects between natural dual inhibitors and commercially available antibiotics. Data published from 2000 to 2018 were obtained using databases Google Scholar, Science Direct and Web of Science, and searching keywords such as alkaloids, anti-inflammatory activity, antimicrobial activity, chalcones, coumarins, flavonoids, IC50, lignans, MIC, natural compounds, synergistic effect and terpenoids, alone or in a combination. The primary criteria for the selection of appropriate compounds were the MICs and IC50s used for a quantification of effects. The natural compounds with activity close to the reference substances or showing MIC up to 32 µg ml−1, and IC50 of anti-inflammatory effect up to 15 µM were considered as promising. When available, information about in vivo testing was included. Reviewed dual inhibitors can represent modern therapeutic approach, especially when the process of inflammation is followed by a secondary bacterial infection. Benefits of dual inhibitors are based on better compliance of patients, decreased number of side effects and extended spectrum of action.
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Abbreviations
- AA:
-
Arachidonic acid
- AMPK:
-
AMP-activated protein kinase
- Arg1:
-
Arginase 1
- BMMC:
-
Bone marrow-derived mast cells
- CAPE:
-
Caffeic acid phenethylester
- CAT:
-
Catalase
- CLSI:
-
Clinical and Laboratory Standards Institute
- COX:
-
Cyclooxygenase
- DAI:
-
Disease activity index
- DSS:
-
Dextran sulphate sodium
- EDTA:
-
Ethylenediaminetetraacetic acid
- ERK:
-
Extracellular signal-regulated kinase
- ESBL:
-
Extended-spectrum β-lactamases
- EUCAST:
-
European Committee on Antimicrobial Susceptibility Testing
- FIC:
-
Fractional inhibitory concentration
- FICI:
-
Fractional inhibitory concentration index
- fMLP:
-
Formyl-met-leu-phe
- GPX:
-
Glutathione peroxidase
- HETE:
-
Hydroxyeicosatetraenoic acid
- ICAM-1:
-
Intercellular adhesion molecule 1
- IDH:
-
Isocitrate dehydrogenase
- Ig:
-
Immunoglobulin
- IKK-β-CA:
-
Constitutively active form of the IKK catalytic subunit IKK-β
- IKK:
-
IκB kinase
- IL:
-
Interleukin
- INF-γ:
-
Interferon gamma
- iNOS:
-
Inducible nitric oxide synthase
- JNK:
-
c-Jun N-terminal kinase
- KAS III:
-
β-Acetoacetyl-ACP synthase
- LDH:
-
Lactate dehydrogenase
- l-NA:
-
l-Nitroarginine
- LOX:
-
Lipoxygenase
- LPS:
-
Lipopolysaccharide
- LT:
-
Leukotriene
- MBC:
-
Minimum bactericidal concentration
- MCP:
-
Monocyte chemoattractant protein
- MDA:
-
Malondialdehyde
- MDR:
-
Multidrug resistant
- MDR-TB:
-
Multidrug-resistant tuberculosis
- MFC:
-
Minimum fungicidal concentration
- MIC:
-
Minimal inhibitory concentration
- MIP:
-
Macrophage inflammatory protein
- MMPs:
-
Matrix metalloproteinases
- mPGES-1:
-
Microsomal prostaglandin E synthase-1
- MPO:
-
Myeloperoxidase
- MRCNS:
-
Methicillin-resistant coagulase-negative Staphylococcus
- MRSA:
-
Methicillin-resistant Staphylococcus aureus
- MSCNS:
-
Methicillin-susceptible coagulase-negative Staphylococci
- MSSA:
-
Methicillin-susceptible Staphylococcus aureus
- NF-κB:
-
Nuclear factor kappaB
- NO:
-
Nitric oxide
- NOX:
-
NADPH oxidase
- OPG:
-
Osteoprotegerin
- PAMP:
-
Pathogen-associated molecular patterns
- PKC:
-
Protein kinase C
- PRRs:
-
Pathogen-recognition receptors
- PG:
-
Prostaglandin
- PMA:
-
Phorbol 12-myristate-13-acetate
- PMNL:
-
Polymorphonuclear leukocyte
- PPARγ:
-
Peroxisome proliferator-activated receptor gamma
- RANKL:
-
Receptor activator of nuclear factor kappa-Β ligand
- ROR-γt:
-
RAR-related orphan receptor gamma
- ROS:
-
Reactive oxygen species
- SOD:
-
Superoxide dismutase
- sPLA2s:
-
Recombinant human secretory phospholipase A2s
- STAT:
-
Signal transducer and activator of transcription
- TLR:
-
Toll-like receptor
- TNF-α:
-
Tumor necrosis factor
- TPA:
-
12-O-Tetradecanoylphorbol-13-acetate
- Treg:
-
Regulatory T cells
- TRSA:
-
Tetracycline-resistant Staphylococcus aureus
- TX:
-
Thromboxane
- VCAM-1:
-
Vascular cell adhesion molecule 1
- VEGF:
-
Vascular endothelial growth factor
- VRE:
-
Vancomycin-resistant enterococci
- VRSA:
-
Vancomycin-resistant Staphylococcus aureus
- VSE:
-
Vancomycin-sensitive enterococci
- XDR-TB:
-
Extensively drug-resistant tuberculosis
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Funding
This work was supported by the Internal Grant Agency of the University of Veterinary and Pharmaceutical Sciences Brno (Project No. 313/2018/FaF to A.S.) and The Slovak Research and Development Agency (Project No. APVV-15-0377 Synergistic effect of secondary metabolites of plants and products of probiotic bacteria on inhibition of biofilm-producing pathogens to M.Ž.)
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Sychrová, A., Koláriková, I., Žemlička, M. et al. Natural compounds with dual antimicrobial and anti-inflammatory effects. Phytochem Rev 19, 1471–1502 (2020). https://doi.org/10.1007/s11101-020-09694-5
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DOI: https://doi.org/10.1007/s11101-020-09694-5