Molecular mechanisms of anti-inflammatory activity mediated by flavonoids
Abstract
Flavonoids (or bioflavonoids) are naturally occurring compounds, ubiquitous in all vascular plants. These compounds have been considered to possess anti-inflammatory properties, both in vitro and in vivo. Although not fully understood, these health-promoting effects have been mainly related to their interactions with several key enzymes, signaling cascades involving cytokines and regulatory transcription factors, and antioxidant systems. The biological effects of flavonoids will depend not only on these pharmacodynamic features but also on their pharmacokinetics, which are dependent on their chemical structure, administered dose schedule and route of administration. Thus, the therapeutic outcome mediated by flavonoids will result from a complex and interactive network of effects, whose prediction require a deep and integrated knowledge of those pharmacokinetic and pharmacodynamic factors. The aim of the present review is thus to provide an integrated update on the bioavailability and biotransformation of flavonoids and the mechanisms of activity at the molecular, cellular, organ and organism levels that may contribute to their anti-inflammatory effects.
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Nitric oxide is produced in large quantities by inducible nitric oxide synthase in activated macrophages and neutrophils during defence and immunological reactions.
“Nitric oxide is produced in large quantities by the inducible nitric oxide synthases (iNOS) in activated macrophages and neutrophils during defence and immunological reactions.”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [22]
ROS and RNS play important roles in inflammation as trigger elements or signalling messenger molecules.
“In addition these reactive species play important roles in inflammation by being trigger elements or by being signalling messenger molecules.”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [22]
Overproduction of ROS and RNS may be responsible for damage at inflammatory sites.
“Nevertheless, their overproduction may be responsible for damage at inflammatory sites.”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [22]
Hydrogen peroxide can oxidise halide ions to hypochlorous acid, which can react with amines to produce chloramines, some of which are very toxic.
“Peroxide hydrogen can also oxidise halide ions (Cl-) to hypochlorous acid (HOCl), which is a strong oxidant that can react with amines producing chloramines, some of them being very toxic [18,19,20,21,22].”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [22]
Essential oils may possess anti-inflammatory activities of interest in food, cosmetic, and human health.
“Essential oils are complex mixtures isolated from aromatic plants which may possess antioxidant and anti-inflammatory activities of interest in thye food and cosmetic industries as well as in the human health field.”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [22]
Nitric oxide can exert toxicity by generating peroxynitrite anion after reacting with superoxide anion radical.
“However this reactive species can also exerts its toxicity by generating the peroxynitrite anion after reacting with the superoxide anion radical [22,23,24,25].”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [22]
Hydrogen peroxide can be reduced by transition metal ions to generate hydroxyl radical, which can react with polyunsaturated fatty acids to produce peroxyl radicals.
“Hydrogen peroxide can then also be reduced by transition metal ions generating the hydroxyl radical (HO°), one of the strongest oxidizing agents that can rapidly react with polyunsaturated fatty acids, resulting the production of peroxyl radicals (ROO•).”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [22]
During an inflammatory process, reactive nitrogen species such as nitric oxide and peroxynitrite anion are generated.
“Nevertheless and during an inflammatory process, there is also the generation of other free radicals named RNS (reactive nitrogen species). Nitric oxide (•NO) and peroxynitrite anion (ONOO-) are two examples of this sort of radicals.”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [22]
ROS and RNS act as modulators of protein and lipid kinases and phosphatases, membrane receptors, ion channels, and transcription factors including NF-κB, which regulate expression of key cytokines.
“ROS and RNS act as modulators of protein and lipid kinases and phosphatases, membrane receptors, ion channels, and transcription factors, including nuclear factor-κB (NF-κB), which regulate the expression of key cytokines [22].”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [22]
Phagocytosis of bacteria during inflammation is accompanied by increased oxygen consumption resulting in formation of superoxide anion radical.
“Phagocytosis of bacteria, which occurs during inflammation, is accompanied by a dramatic increase in oxygen consumption resulting in the formation of superoxide anion radical (O2•-) which is quickly converted to hydrogen peroxide (H2O2), spontaneously, or by the enzyme superoxide dismutase.”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [22]
ROS and RNS are generated in phagocytes to neutralise invading organisms and have an important role in host defence.
“ROS and RNS are generated in phagocytes in order to neutralise the invading organisms, having therefore an important role in the host defence mechanism.”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [22]
Arachidonic acid is released from cell membranes by phospholipase A2 under inflammatory stimuli and is metabolised by cyclooxygenase and lipoxygenase pathways into eicosanoids including prostaglandins, leukotrienes, and thromboxane A2.
“Arachidonic acid is a polyunsaturated fatty acid that is released from cell membranes by phospholipase A2 under the stimulus of several factors associated with inflammation. The same fatty acid is metabolised by cyclooxygenase (COX) and lipoxygenase (LOX) pathways in different eicosanoids such as prostaglandins (PGs) and leukotrienes (LTs) in diverse cells and thromboxane A2 in platlets [22].”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [22]
Inhibition of COX-2 activity or expression by some anti-inflammatory agents is due to interference with signalling mechanisms regulating the COX-2 gene; NF-κB, C/EBP, AP-1, and CREB have been identified as regulators of COX-2 transcription.
“The inhibition of activity or expression of COX-2 by some anti-inflammatory is due to the interference with the signalling mechanisms that regulate the COX-2 gene. In this gene, four transcription factors including NF-κB, CCAAT/enhancer-binding protein (C/EBP), activator protein 1 (AP-1) and CRE-binding protein (CREB) have been identified as regulators of COX-2 transcription [22,126].”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [22]
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- Authors
- Gomes, A., Fernandes, E., Lima, J., Mira, L., & Corvo, M.
- Affiliations
- Universidade do Porto (PT)
- Venue
- Current Medicinal Chemistry
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2008-07-01
- Volume
- 15
- Issue
- 16
- Pages
- 1586-1605
- ISSN
- 0929-8673 (ISSN-L)
- OpenAlex
- W2117790528
- Cited by
- 227
- References
- 2
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 19 · 2023: 16 · 2022: 21 · 2021: 9 · 2020: 10 · 2019: 9 · 2018: 8 · 2017: 19 · 2016: 8 · 2015: 6 · 2014: 21 · 2013: 14 · 2012: 16
- FWCI
- 8.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Health Sciences › Medicine › Pharmacology › Synthesis of Organic Compounds
- Keywords
- flavonoids, anti-inflammatory activity, bioavailability, biotransformation, pharmacokinetics, pharmacodynamics, antioxidant defense, cytokines, transcription factors, enzyme interaction, molecular mechanisms
- MeSH terms
- Animals, Anti-Inflammatory Agents, Antioxidants, Flavonoids, Gene Expression Regulation, Humans, Cell Proliferation
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