NF-κB Pathway

Studies report arctigenin as the most potent bioactive component of A. lappa; in vitro and preclinical data indicate modulation of NF-κB signalling, suppression of TNF-α and IL-6, and inhibition of COX-2/PGE2 pathways. AMPK activation has also been reported in preclinical models.

Arctiin is the glycosidic precursor to arctigenin; studies report anti-inflammatory activity including inhibition of cytokine induction (IL-6, TNF-α) and downstream NF-κB signalling. In vitro data also suggest collagen-stimulating activity relevant to dermal matrix remodelling.

Phenolic acids identified in A. lappa extracts; preclinical reviews note antioxidant and anti-inflammatory properties including potential modulation of NO pathways.

Flavonoids identified in A. lappa; preclinical data link these compounds to COX-2 and NF-κB modulation.

Preclinical studies report NF-κB pathway and COX-2 modulation; xanthine oxidase inhibitory activity investigated in vitro (Zhang et al. 2018; Annaz et al. 2022)

In vitro evidence suggests AMPK activation and PPAR-γ agonism relevant to metabolic contexts; anti-inflammatory activity via NF-κB and COX pathways reported in preclinical models (Zhang et al. 2018)

Preclinical anti-inflammatory activity reported; contribution to whole-plant effects in human studies unclear (Annaz et al. 2022)

Glucocapparin (methyl glucosinolate) is the primary glucosinolate; hydrolysis products investigated for anti-inflammatory and antioxidant activity in vitro (Chedraoui et al. 2017; Zhang et al. 2018)

Preclinical studies report inhibition of NF-κB pathway activation and downstream pro-inflammatory cytokines (TNF-α, IL-6); also reported to modulate 5-lipoxygenase activity. Ex vivo data suggest pro-apoptotic effects in leukocytes from ALL patients (Orzechowska et al., 2014).

Preclinical reports describe inhibition of COX-2 and 5-LOX, suppression of NF-κB, and AMPK activation relevant to metabolic signalling (Zhao et al., 2019; Wang et al., 2018).

Preclinical data indicate anti-inflammatory activity via NF-κB and COX-2 inhibition (Wang et al., 2018).

Reported as a minor contributor to anti-inflammatory effects in preclinical models; mechanistic human data are lacking.

Preclinical studies propose modulation of NF-κB and TNF-α pathways and PPAR-γ activation as mechanisms underlying reported anti-inflammatory and insulin-sensitising effects; human mechanistic data are limited.

Reviews describe inhibition of COX-2 and NF-κB and activation of AMPK in vitro; clinical relevance at consumed doses is unestablished.

Reported in preclinical models to modulate inflammatory signalling; no dedicated human pharmacokinetic or pharmacodynamic data identified in the verified literature.

Preclinical evidence suggests possible HMG-CoA reductase inhibition contributing to lipid-lowering observations; mechanistic confirmation in humans is lacking.

Primary anti-migraine compound; inhibits platelet serotonin release, mast cell degranulation, and 5-LOX-mediated leukotriene synthesis. Standardization to parthenolide content is the basis of clinically tested products.

Auxiliary lactones contributing to overall anti-inflammatory profile.

Polyphenols with mast-cell-stabilizing and mild GABA-A modulating activity.

Preclinical studies report inhibition of NF-κB signalling and downstream inflammatory mediators; antioxidant activity attributed in part to free-radical scavenging.

Reported in preclinical models to modulate NF-κB pathway and COX-2 expression; mechanism in thyroid tissue under investigation.

In vitro antioxidant and xanthine oxidase inhibitory activity reported; contribution to in vivo effects is uncertain.

Primary bioactive compound in Nigella sativa essential oil. Multi-target — AMPK activation parallels metformin/berberine; NF-κB inhibition is broad anti-inflammatory.

Reduced form of thymoquinone with antioxidant activity.

Saponin contributing to anti-inflammatory and possibly anti-cancer signal in preclinical models.

In vitro studies report inhibition of NF-κB-mediated inflammatory signalling; proposed as a key contributor to astringent and anti-inflammatory activities noted in preclinical models.

In vitro data report antiproliferative activity in cancer cell lines and modulation of inflammatory pathways; TUBULIN interaction remains exploratory.

Standard flavonoid mechanisms investigated in vitro; COX-2 and PGE2 inhibition reported in cell-free and cell-based assays for these compound classes generally; attribution to G. robertianum extracts specifically requires further study.

Polyphenolic constituent investigated for anti-inflammatory signalling modulation in preclinical models; implicated in the anxiolytic and metabolic findings of clinical extracts standardised for phenylpropanoids.

In vitro studies report antiviral activity against yellow fever virus; citral identified as a principal contributor to essential-oil antiviral bioactivity. Anti-inflammatory activity is a class-level mechanistic inference from broader literature, not demonstrated in the cited abstracts.

Combination polyphenolic extract (Lippia citriodora + Hibiscus sabdariffa) investigated in randomised trials for metabolic, appetite, and blood-pressure endpoints; individual plant contribution not fully isolated.

Berberine has been investigated for inhibition of NF-κB-mediated inflammatory signalling and keratinocyte proliferation; in vitro data also suggest PDE4 inhibitory activity. Antimicrobial activity against Plasmodium species is attributed in part to heme polymerization interference.

Studies report antiradical and antioxidant activity; structural analyses suggest modulation of oxidative and inflammatory pathways.

Investigated for anti-proliferative and anti-inflammatory properties in cell-based models; contribution to overall extract activity in psoriasis-model studies is proposed but not fully characterised.

1,4-Naphthoquinones including chimaphilin have been investigated for NF-κB modulation and antimicrobial activity in preclinical models (Widhalm et al., 2016).

Ursolic acid has been investigated for COX-2 and NF-κB inhibition in in-vitro and animal models; clinical translation unestablished.

Quercetin has been studied as a xanthine oxidase inhibitor and NF-κB modulator in preclinical settings; direct extrapolation to Chimaphila umbellata extracts is speculative.

Primary cognitive-enhancement compound; well-characterized neuroprotective antioxidant. Shared with sage.

Oxidized derivative of carnosic acid; anti-inflammatory and anti-cancer signal in preclinical studies.

Same anti-inflammatory polyphenol as in sage, lemon balm, oregano, tulsi.

Preclinical studies report inhibition of platelet aggregation via TXA2 and PAF pathways, modulation of NF-κB signalling, and influences on nitric oxide production; investigated in cardiovascular and cerebrovascular contexts.

Preclinical data report anti-inflammatory activity attributed in part to inhibition of COX-2 and suppression of NF-κB and TNF-α signalling pathways.

Preclinical studies report immunomodulatory and anti-inflammatory activities; RANKL-related effects have been investigated in the context of bone metabolism.

Research has investigated antioxidant and antibacterial activity; studies report free-radical scavenging and reported modulation of inflammatory signalling pathways in preclinical models.

Studies report antioxidant and antibacterial properties in vitro; in vivo anti-inflammatory mechanisms have been investigated in animal models.

Presence reported in fruit; mechanisms investigated in broader flavonoid literature; specific FS-attributed clinical data are limited.

Preclinical data reviewed in Salehi et al. (2019) report aucubin-associated modulation of inflammatory signalling in Veronica genus extracts; no V. officinalis-specific clinical data available.

Safe et al. (2021) describe apigenin's interactions with COX-2 and NF-κB pathways in preclinical models; presence in V. officinalis is reported by Salehi et al. (2019) but clinical relevance for this species is unestablished.

Scutellarin is a flavone with reported preclinical anti-inflammatory activity via COX-2 and NF-κB modulation (Safe et al., 2021); identified in Veronica species by Salehi et al. (2019).

In vitro studies report flavonoid fractions from avocado leaves and pulp may inhibit NF-κB signalling, COX-2 expression, and TNF-α production (Bhuyan et al. 2019; Yasir et al. 2010)

A 2024 systematic review (Collignon et al.) reports that in vitro antineoplastic activity is associated with disruption of microtubule dynamics and NF-κB-mediated apoptotic pathways; one clinical study reported increased free oxygen radical formation in larynx carcinoma tissue following avocado leaf extract administration, though the authors note research has been limited in scope and further clinical investigation is needed

Preclinical studies report gallic acid attenuates LPS-induced NF-κB activation and modulates the Akt/AMPK/Nrf2 pathway; earlier work identified it as the principal hepatoprotective constituent in T. bellirica fruit fractions.

Preclinical data report ellagic acid modulates NF-κB signalling, suppresses COX-2 expression, and reduces TNF-α levels under oxidative and inflammatory challenge conditions.

Rutin is the predominant flavonoid in buckwheat. Cell culture studies reviewed by Borgonovi et al. (2024) report antioxidant, anti-inflammatory, and vascular-related signalling activity. Xanthine oxidase inhibition and modulation of NO/cGMP pathways have been investigated in preclinical models. Clinical translation remains under-characterised.

Characterised in Li et al. (2010) via gene expression studies. Anti-inflammatory and metabolic pathway modulation investigated in cell culture models (Borgonovi et al., 2024); clinical relevance not established from available citations.

In vitro studies report competitive inhibition of casein kinase II (CKII) and suppression of cyclin B/cdc2 kinase activity; casein kinase II is not listed in the allowed target set, so mechanistic detail is described here rather than mapped to a target ID. Also investigated for NF-κB pathway modulation in preclinical models.

Preclinical data suggest modulation of pro-inflammatory cytokine signalling including IL-6 pathways; clinical relevance is not established independently of the whole-extract studies.

Studies report cinnamaldehyde may activate TRPV1, modulate NF-κB signalling, suppress TNF-α production, and inhibit fungal lanosterol 14α-demethylase (CYP51A), investigated as a basis for antifungal and anti-inflammatory activities.

Preclinical data indicate eugenol may inhibit COX-2 expression and NF-κB activation; investigated for anti-inflammatory and antimicrobial properties.

β-caryophyllene is a selective CB2 receptor agonist; preclinical studies report associated modulation of NF-κB signalling and reduction of COX-2-mediated prostaglandin synthesis. Cited mechanistic studies investigate this as a basis for the oleoresin's reported anti-inflammatory activity.

Resinous fraction diterpenic acids have been investigated for inhibition of NF-κB pathway activation and downstream PGE2 production in preclinical models.

Embelin is the principal bioactive constituent. Preclinical studies report it may activate AMPK and PPAR-γ pathways relevant to glucose and lipid homeostasis, sensitise insulin receptor signalling, modulate NF-κB and TNF-α inflammatory pathways, inhibit HMG-CoA reductase contributing to observed lipid-lowering effects, and interact with oestrogen receptors (postulated basis for reported reproductive/contraceptive effects). All mechanistic data are predominantly in vitro or animal-derived.

Broader naphthoquinone fraction investigated for antioxidant and anti-inflammatory activity in preclinical models; specific receptor-level data are limited.

Most studied catechin; broad antioxidant and anti-inflammatory activity. Also investigated in preclinical cancer models for EGFR / receptor-tyrosine-kinase and anti-angiogenic (VEGF) pathway modulation (research only). High-dose extracts can be hepatotoxic.

Auxiliary catechins contributing to overall antioxidant capacity.

Studies report berberine activates AMPK, modulates PPAR-γ and insulin receptor signalling, and suppresses NF-κB-mediated inflammatory cascades; investigated in glycaemic regulation and metabolic contexts.

Review literature describes coptisine as exhibiting anti-inflammatory, anti-cancer, anti-bacterial, and cardioprotective activity in preclinical models, reportedly via NF-κB, COX-2, TNF-α, and IL-6 pathway modulation.

Meghwal et al. (2013) report piperine has demonstrated activity at TRPV1 receptors, inhibition of NF-κB and COX-2-related inflammatory pathways, and monoamine oxidase inhibitory effects in preclinical models. Piperine is also reported to inhibit P-glycoprotein and CYP enzyme systems, with consequent effects on drug bioavailability. Turrini et al. (2020) additionally describe preclinical anticancer pathway modulation, including effects on cell-cycle and apoptotic signalling.

Sesquiterpene constituent; preclinical data reviewed in Takooree et al. (2019) suggest anti-inflammatory activity, with NF-κB pathway implicated.

Piperine is reported in preclinical studies to activate TRPV1, inhibit COX and LOX pathways, suppress NF-κB signalling, and modulate serotonin reuptake. Bioavailability-enhancement properties (inhibition of drug-metabolising enzymes including CYP3A4 and P-gp) are extensively discussed in systematic review data (Takooree et al. 2019).

Preclinical data reviewed in Yadav et al. 2020 report anti-inflammatory and antiproliferative activity ascribed in part to NF-κB and eicosanoid pathway modulation.

Studies report radical-scavenging activity and reduction of oxidative stress biomarkers in human supplementation trials; proposed to modulate NF-κB-linked inflammatory signalling in vitro.

Isolated from OFI stems and fruit; preclinical studies report inhibition of xanthine oxidase-mediated oxidative neuronal injury and modulation of COX-2 and NF-κB pathways at tested concentrations. Clinical translation unestablished.

Broader pharmacological literature proposes inhibition of NF-κB pathway activation and COX-2 expression in vitro; these specific targets are not named in the cited abstracts. Clinical relevance is not established.

Broader review literature proposes antioxidant and anti-inflammatory activity via NF-κB and COX-2 inhibition in vitro; these specific targets are not named in the cited abstracts. Clinical relevance is not established.

Studies report astringent and anti-inflammatory activity via NF-κB pathway modulation and reduction of pro-inflammatory cytokines in preclinical models.

In vitro studies report inhibition of LPS-stimulated macrophage NO production and COX-2-mediated prostaglandin synthesis.

Primary bitter compound; potent NF-κB pathway inhibitor underlying the anti-inflammatory and antiviral activity. Standardization to andrographolide content is used in commercial extracts.

Glycoside variant; contributes to overall anti-inflammatory effect.

Preclinical studies report that bixin and norbixin may modulate NF-κB signalling and COX-2 expression; clinical translation remains under investigation.

Tocotrienols isolated from Bixa orellana seed have been investigated for antioxidant activity and potential modulation of inflammatory pathways in preclinical models.

POAs have been investigated for immunomodulatory activity and NF-κB pathway modulation in preclinical models; chemotype matters — POA-rich extracts are typically selected for clinical study.

Preclinical studies report inhibition of NF-κB activation and differential effects on COX-1 and COX-2 activity; hydroalcoholic extracts show greater anti-inflammatory activity in animal edema models compared to aqueous extracts.

In vitro studies report ROS scavenging and NF-κB modulation; contributes to reported antioxidant and anti-inflammatory activity.

Preclinical data report antioxidant and anti-inflammatory signalling; oral bioavailability is limited.

Preclinical studies report eugenol inhibits COX-1/COX-2 and NF-κB signalling, suppresses PGE2 synthesis, and modulates TRPV1 and voltage-gated sodium channels; proposed as the primary driver of observed analgesic and anti-inflammatory signals.

Preclinical evidence suggests selective CB2 agonism with downstream attenuation of NF-κB and TNF-α; proposed to contribute to anti-inflammatory activity.

In vitro studies report induction of apoptosis in HL-60 leukemia cells and cytotoxic activity; proposed mechanisms include modulation of apoptotic signalling pathways.

Pharmacological review literature reports preclinical investigation of carbazole alkaloids as AChE inhibitors and MAO-B modulators in the context of neurodegeneration research; anti-inflammatory activity via COX-2 and NF-κB modulation also reported in preclinical models.

Marker compound for standardized extracts; primary anti-inflammatory activity through NF-κB and COX-2 modulation.

Secondary iridoid; contributes to overall anti-inflammatory action.

Preclinical literature cited in He et al. 2014 associates chlorogenic acid with anti-inflammatory and antioxidant activity, including NF-κB modulation.

Preclinical data reviewed in He et al. 2014 suggest flavonoid constituents may modulate COX-2 and TNF-α signaling; animal studies (Jiang et al. 2020, Liao et al. 2021) report TNF-α mRNA/protein modulation by leaf extracts.

In vitro studies report HMP inhibits NF-κB activation and MAP kinase (p44/42), reducing LPS-stimulated nitric oxide production and pro-inflammatory cytokine release (IL-1β, TNF-α) in macrophage and PBMC models.

Molecular docking and in vitro studies report binding to COX-2 active site and inhibition of inflammatory mediators; anti-inflammatory activity attributed in part to flavonoid fraction in rhizome extracts.

Studies report guggulsterones modulate bile acid receptor (FXR) antagonism, suppress NF-κB signalling, inhibit 5-lipoxygenase, and have been reported to influence thyroid hormone receptor activity and HMG-CoA reductase pathway — proposed contributors to observed lipid-modulating effects in clinical studies.

Preclinical studies report caspase-dependent apoptosis induction in PC-3 prostate cancer cells via Bax/Bak pathways, and inhibition of angiogenesis in vitro and in vivo, associated with suppression of NF-κB and VEGF signalling. Investigated in cell and animal models only; no clinical cancer data available.

Preclinical studies report tilianin inhibits TNF-α-induced VCAM-1 expression in endothelial cells, with proposed NF-κB pathway involvement; investigated in atherogenesis and neutrophilic lung inflammation models.

Rosmarinic acid biosynthesis in A. rugosa has been characterised metabolomically; the compound class is broadly studied for antioxidant and anti-inflammatory mechanisms in preclinical models.

Preclinical data cited in Shah et al. (2011) describe proposed anti-inflammatory activity via inhibition of NF-κB signalling and downstream mediators; direct clinical translation not established.

Flavonoid fraction reported in preclinical literature to modulate cyclooxygenase and NF-κB pathways; human pharmacokinetic data limited.

Schinella et al. (1998) reported that moderately lipophilic fractions of T. vulgare aerial parts demonstrated anti-inflammatory activity, attributed in part to sesquiterpene lactones that may modulate NF-κB and arachidonic acid cascade enzymes. Parthenolide content in T. vulgare is generally lower than in T. parthenium.

Coté et al. (2017) assessed anti-inflammatory and antioxidant activity of T. vulgare essential oil from a northern Quebec chemotype; biological activities varied with chemical composition. Thujone is neurotoxic at elevated doses; safety implications dominate clinical relevance.

Primary bioactive flavones (S. baicalensis); well-characterized positive allosteric modulators of GABA-A receptors and broad anti-inflammatory activity.

Vasodilatory and anti-inflammatory flavonoid.

Preclinical studies report NF-κB pathway modulation and COX-2 inhibitory activity; proposed to underlie reported anti-inflammatory effects in animal models.

Anticoccidial activity in poultry attributed to coumestan fraction; NF-κB modulation proposed as a mechanistic contributor in preclinical work.

In vitro and in vivo studies report that isothiocyanates (e.g., sulforaphane) may modulate NF-κB signalling, COX-2 expression, and TNF-α levels; indole-3-carbinol has been investigated for aromatase modulation. Evidence is largely preclinical.

Red cabbage anthocyanins demonstrate dose-dependent urinary bioavailability in human volunteers; preclinical studies associate them with anti-inflammatory pathway modulation. Clinical magnitude of effect is not established.

In vitro studies report inhibition of NF-κB signalling and downstream prostaglandin synthesis; clinical relevance in humans has not been established.

Preclinical data report modulation of pro-inflammatory cytokine pathways; human pharmacokinetic data are limited.

Preclinical (avian) studies report PAMK may modulate pro-inflammatory cytokine signalling via NF-κB pathway and reduce TNF-α and IL-6 levels; also investigated in the context of ferroptosis attenuation via antioxidant mechanisms.

Flavonoids present in seed extracts have been investigated for anti-inflammatory pathway modulation in preclinical models

In vitro studies report avenanthramides inhibit COX-1/COX-2 activity and suppress NF-κB signalling; Reynertson et al. 2015 investigated this pathway in the context of colloidal oatmeal's topical anti-inflammatory and anti-itch activity.

In vitro studies, reported in Wang et al. (2022) and Kulinowska et al. (2026), describe cytotoxic, antioxidant, and anti-inflammatory activities. Mechanistic in vivo or clinical translation has not been established.

Preclinical studies report inhibition of NF-κB signalling and cyclooxygenase pathways; also investigated for antimicrobial activity against Gram-positive bacteria and fungi in vitro.

Preclinical studies suggest inhibition of cyclooxygenase isoforms and NF-κB-mediated inflammatory signalling; clinical translation not yet established from provided citations.

Apigenin binds GABA-A at the benzodiazepine site (its anxiolytic mechanism) and has separately been investigated for cyclin-dependent-kinase-mediated cell-cycle arrest in preclinical cancer models. Research only — not a treatment claim.

Preclinical data suggest apigenin may modulate COX-2 expression and NF-κB signalling; reported anti-inflammatory activity in in vitro models. Clinical relevance in Plantago major preparations has not been directly confirmed.

BITC, released from glucotropaeolin by gut bacterial myrosinase-like activity, has been investigated for antimicrobial and anti-inflammatory activity. Studies report modulation of NF-κB and COX-2 pathways in preclinical models; clinical relevance in humans is under investigation.

Apigenin is the principal flavone studied in parsley. In vitro and animal research has investigated inhibition of COX-2 and NF-κB inflammatory signalling, suppression of TNF-α, and aromatase (CYP19A1) inhibition. Human absorption following parsley intake was confirmed in a randomised crossover trial (Nielsen et al., 1999), though downstream target engagement was measured via oxidative-stress biomarkers rather than direct receptor assays.

Beyond mast-cell stabilization and H1 antagonism, quercetin is a broadly characterized protein/receptor tyrosine-kinase modulator (including JAK/STAT) investigated in preclinical models. Research only — not a treatment claim.

Beyond its anti-inflammatory NF-kB/COX/LOX activity, curcumin has been investigated in preclinical cancer models for EGFR-pathway and PI3K–Akt–mTOR signaling inhibition and for anti-angiogenic (VEGF) effects. Research only — not a treatment claim.

Preclinical and review literature reports modulation of NF-κB and COX-2 inflammatory pathways; direct clinical confirmation in humans remains limited.

Preclinical data suggest flavonoid constituents may inhibit NF-κB activation and downstream pro-inflammatory mediators including COX-2 and TNF-α, as reviewed in Malek Mahdavi et al., 2022. Human pharmacokinetic and clinical data are lacking.

Preclinical studies report inhibition of NF-κB activation via suppression of IRAK1, TAK1, IKKβ, and IκBα phosphorylation in LPS-stimulated macrophages; associated with downstream reduction of inflammatory mediators in murine colitis models.

Alongside SIRT1/NF-kB activity, resveratrol has been studied for PI3K–Akt–mTOR pathway modulation and anti-angiogenic (VEGF) effects in preclinical models. Research only — not a treatment claim.