Table 2.
Multiple beneficial activities of natural compounds involved in wound healing.
| Compound | Cytotoxic Activity | Anti-Inflammatory Activity | Antioxidant Activity | ↓ Bacterial Pathogenicity |
|---|---|---|---|---|
| Alpinumisoflavone | Weak cytotoxicity in PC-3 cells [149] | 5, 10 µg/mL → ↓ TNF-α, IL-6, IL-1β, IL-17, ICAM-1, NO in LPS-stimulated RAW 264.7 cells [150]. | DPPH scavenging activity, IC50 = 54.0 µg/mL [151]. | |
| 1, 5, 10 mg/kg i.p 1 h before → protective effect against pulmonary inflammation in LPS-stimulated acute lung injury in mice [150]. | 5, 10 µg/mL → ↑ the levels of CAT, HO-1, GPx, SOD in LPS-stimulated RAW 264.7 cells [150]. | |||
| 25 and 50 µM → inhibition of TNF-α-induced ↑ in MMP-1, ↓: procollagen I α1, NOS, COX-2, IL-1β, IL-6, IL-8, NF-κB, MAPKs [152]. | ↓ ROS and NO in TNF-α-treated HDFs [152]. | |||
| Artocarpin | IC50 = 45.3 μM in RAW 264.7 cells [153]. | Inhibition of LPS-induced NO production in RAW 264.7 cells, IC50 = 18.7 µM [153]. | TEACABTS = 0.9 mM [154]. | Synergy with norfloxacin against MRSA, P. aeruginosa, and E. coli. Synergy with tetracycline against MRSA and P. aeruginosa. Synergy with ampicillin against MRSA [155]. |
| IC50 = 7.9 µM in PC-3 cells. IC50 = 8.3 µM in NCI-H460 cells [156]. | ||||
| ED50 = 3.3 µg/mL in MCF-7 cells. ED50 = 3.8 µg/mL in MDA-MB-231 cells. ED50 = 3.3 µg/mL in A549 cells. ED50 = 3.4 µg/mL in 1A9 cells. ED50 = 3.8 µg/mL in HCT-8 cells. ED50 = 4.9 µg/mL in CAKI-1 cells. ED50 = 5.4 µg/mL in SK-MEL-2 cells. ED50 = 3.7 µg/mL in U87-MG cells. ED50 = 4.1 µg/mL in PC-3 cells. ED50 = 3.2 µg/mL in KB cells. ED50 = 3.6 µg/mL in KB-VIN cells. [157]. |
Topical dose 0.05–0.1% ↓ TNF-α levels, COX-2 and cPLA2 protein expressions in the skin homogenate. Photoprotective effect on ultraviolet B (UVB)-induced skin damage in hairless mice [158]. | 0.05% artocarpin treatment prevents UVB-induced oxidative stress by affecting antioxidant activity [158]. | ||
| IC50 = 5.1 μmol/L in PC-3 cells. IC50 = 10.2 μmol/L in NCI-H460 cells. IC50 = 8.1 μmol/L in A-549 cells [159]. | ||||
| IC50 = 5.1 µg/mL in KB cells. IC50 = 3.3 µg/mL in BC cells. IC50 = 5.6 µg/mL in Vero cells [160]. | ||||
| Bavachin | CC50 = 20.2 µM in Hep3B cells [161]. | Inhibitory effect on IL-6-induced STAT3 promoter activity in Hep3B cells, IC50 = 4.9 µM [161]. | ||
| Suppression of LPS-induced NO and PGE2 production, and ↓ iNOS and mPGES-1 expression. ↓ of LPS-induced IL-6 and IL-12p40 production and ↓ the activation of MAPKs and NF-κB. Suppression of NLRP3 inflammasome-derived IL-1β secretion, ↓ caspase-1 activation, repression of mature IL-1β expression, and inhibition of inflammasome complex formation [162]. | ||||
| Downregulation of IL-4 in the spleen of T cells from 4get IL-4-GFP mice. ↓ the IL-4 levels by downregulating the level of Gata-3 expression and STAT6 phosphorylation. 50 mg/kg dissolved in the solution by daily lavage administration [163]. | ||||
| Diplacone = propolin C = nymphaeol A | IC50 = 14.3 µM in WB-F344 cells [164]. | 10 µM ↓ the expression of TNF-α and MCP-1 and ↑ the expression of ZFP36 [165]. | DPPH scavenging by SC50 = 3.2 µg/mL) [166]. | Dose-dependent inhibition of S. aureus biofilm formation [107]. |
| Inhibition of IκB-α degradation, ↓ of COX-2 expression [167]. | ||||
| COX-1 inhibitor IC50 = 1.8 μM COX-2 inhibitor IC50 = 4.2 μM 5-LOX inhibitor IC50 = 0.1 μM [168]. | ||||
| Antiproliferative (IC50 = 9.3 μM) and cytotoxic (LC50 = 18.0 µM) effect in THP-1 cells [169]. | 25 mg/kg prior and after induction of colitis ameliorates its symptoms and delays the onset. ↓ of the levels of COX-2 and ↑ the ratio of pro-MMP2/MMP2 activity, ↓ of SOD2 and CAT [170]. | TEACABTS 3.2, TEACDPPH = 1.1, TEACFRAP = 0.5, TEACInhibition of. peroxynitrite induced tyrosine nitration
= 0.8. Superoxide scavenging activity-enzymatic = 45.2%, nonenzymatic = 25.9% at 50 μM [171]. |
||
| EC50 =< 10 µM in MCF-7 cells. EC50 = 3.2 µM in CEM cells. EC50 =< 10 µM in RPMI8226 cells. EC50 = 2.4 µM in U266 cells. EC50 =< 10 µM in HeLa cells. EC50 = 5.9 µM in BJ cells. EC50 =< 10 µM in THP-1 cells [172]. |
Inhibition of LPS-induced NO production in RAW 264.7 cells, IC50 = 5.0 µM [173]. | DPPH quenching activity TEAC 5.2 at 10 µM [164]. | ||
| At tested concentrations did not inhibit cell proliferation; it induced cell proliferation to some extent in RAW 264.7 cells [174]. | Inhibition of albumin denaturation, IC50 = 0.3 µM. Inhibition of nitrite production stimulated by LPS in RAW 264.7 cells, IC50 = 3.2 µM. COX-2 inhibitor = 11.7 µM [174]. |
DPPH radical scavenging activity, IC50 = 6.5 µg/mL [175]. | ||
| Glabrene | Cytotoxic activity for: HepG2 cells (10 μM) = 25.9%. SW480 cells (10 μM) = 30.7%. A549 cells (10 μM) = 0%. MCF7 cells (10 μM) = 17.6% [176]. |
10 μM inhibited LPS-induced NO production in RAW 264.7 cells by 57.5%, IC50 = 9.5 μM. 10 μM inhibited LPS-induced NF-κB activation by 41.7% [176]. |
10 μM treated HepG2 cells transfected with the ARE luciferase reporter gene (HepG2C8 cells) to evaluate Nrf2 activation. 2.7-fold of control for Nrf2 activation activity [176]. | |
| Isobavachalcone | IC50 = 2.90 μM (CCRF-CEM cells) to >123. 46 μM (AML12 cells) [177]. | 20 μg/mL and 50 μg/mL → suppression of iNOS expression induced by TLR agonists in murine macrophages [178]. | Peroxyl radical scavenging activity with an ORAC value of 24.8 μM [179]. |
Antibiofilm activity with MBIC = 0.8 µg/mL against MSSA and MRSA → 75% inhibition of biofilm formation [145]. |
| Cell viability = 98.2% at 50 μM, 64.8% at 100 μM in RAW 264.7 cells [178]. | Inhibition of NO production in LPS-activated RAW 264.7 cells, IC50 = 6.4 µM [153]. | |||
| IC50 = 16.4 µM in RAW 264.7 cells [153]. | ||||
| IC50 =< 20 µM in NB4, U937, K562s, K562r cells. IC50 = >20 µM in HL60, THP-1, U937, MOLM-13 cells. IC50 = 75.5 µM in HCT116 cells. IC50 = 44.1 µM in SW480 cells. IC50 = 128.3 µM in Tca8113 cells. IC50 = 16.5 µM in HepG2 cells. IC50 = 13.2 µM in Hep3B cells. IC50 =< 40 µM in MCF-7, ZR-75–1, MDA-MB-231 cells. IC50 = 26.2 µM in PC-3 cells. IC50 = >50 µM in LNCaP cells. IC50 = 15.1 µM in PC-3 cells. IC50 = >50 µM in HeLa cells [180]. |
Inhibition of NO production in LPS-activated RAW 264.7 cells, IC50 = 17 µM [181]. | Inhibition of NADPH-, ascorbate-, t-BuOOH-, and CCl4-induced lipid peroxidation in microsomes, IC50 = 57.3, 20.8, 61.7, 17.6 μM, respectively [182]. | ||
| 3.12 µg/mL inhibited NO production by 79.57% in LPS-activated RAW 264.7 cells. 15-LOX inhibitor, IC50 = 25.9 µg/mL [183]. | ||||
| Attenuated Sephadex-induced lung injury in rats, inhibition of NF-κB-mediated upregulation of A20 and activation of NRF2/HO-1 signalling pathway [184]. | ||||
| IC50 = 31.6 µM in L-02 IC50 = 31.3 µM in HUVEC [185]. |
||||
| IC50 = >100 µM in cerebellar granule cells [186]. | ||||
| ↓ of the cell viability of HaCaT cells at 25 µg/mL after 24 h [145]. | Inhibitory effect on IL-6-induced STAT3 promoter activity in Hep3B cells, IC50 = 2.5 µM [161]. | |||
| Isosophoranone | CC50 in the range of 25–62 µM in human tumour cells (HSC-2, HSG) and human normal cells (HGF, HPC, HPLF) [187]. | Inhibition of NO production in LPS-activated RAW 264.7 cells, (IC50 = 17 µM) [187]. | ||
| Kazinol B |
(2S)-Kazinol B IC50 = >100 µM in Bcap37, MCF-7, U251, A549 cells. IC50 = 58.4 µM in HepG2 cells. IC50 = 38.9 µM in Hep3B cells. (2R)-Kazinol B IC50 = >100 µM in Bcap37, MCF-7, U251, A549 cells. IC50 = 64.2 µM in HepG2 cells. IC50 = 30.3 µM in Hep3B cells [188]. |
Inhibition of NO production in LPS-activated RAW 264.7 cells (IC50 = 21.6 µM) via inhibition of iNOS activity [189]. | Protection of mitochondria from injury through direct Fyn inhibition [190]. | |
| Kuraridin | Noncytotoxic when compared with the drug-free control in the range of 0.3–64 µg/mL in PBMC cells [123]. | COX-1 inhibitor IC50 = 0.6–1 µM. 5-LOX inhibitor IC50 = 5.4–6.9 µM [191]. |
Additive effect with ciprofloxacin, erythromycin, gentamicin, kanamycin, oxacillin [123]. | |
| IC50 = 37.8 μg/mL in HepG2 cells [114]. | ||||
| Kurarinone | Inhibition of fatty acid β-oxidation through the reduction of l-carnitine and the inhibition of the PPAR-α pathway → lipid accumulation and liver injury (hepatotoxicity) [192]. | COX-1 inhibitor IC50 = 0.6–1 µM. 5-LOX inhibitor IC50 = 22 µM [191]. |
Activation of Nrf2 and ↑ expression of antioxidant enzymes, including HO-1 [193]. | |
| Little toxic effects in BEAS-2B. In vivo apparent signs of toxicity [194]. | Inhibition of the expression of interleukin IL-1β, iNOS in LPS-stimulated RAW 264.7 cells [193]. | |||
| IC50 = 2–62 µM in cervical, lung (non-small and small), hepatic, esophageal, breast, gastric, cervical, and prostate cancer cells 20–500 mg/kg in vivo in lungs (non-small and small) cancer. Higher selectivity toward cancer cells in comparison with respective normal cells [195]. | Psoriasis-like skin disease induced by IL-23 and contact dermatitis induced by TNCB. Repression of disease development by inhibiting the expression of proinflammatory mediators and through the suppression of pathogenic CD4+T-cell differentiation and the overall immune response [196]. | |||
| Inhibition of LPS-induced macrophage activation and expression of proinflammatory genes, while ↑ anti-inflammatory gene expression including IL-10 in an AhR-dependent manner. An immunomodulatory activity in the treatment of IBS [197]. | ||||
| Kuwanon A | Inhibition of NO production stimulated by LPS and IFN-γ in RAW 264.7 cells, IC50 = 10.5 μM [198]. | |||
| COX-2 inhibitor IC50 = 14 μM [199]. | ||||
| Kuwanon C | IC50 = 14.2 µM in B16 melanoma cells [200]. | Inhibition of NO production stimulated by LPS and IFN-γ in RAW 264.7 cells, IC50 = 12.6 μM [198]. | ||
| IC50 = 1.7 µM in THP-1 cells [201]. | 5-LOX inhibitor IC50 = 12 µM. 12-LOX inhibitor IC50 = 19 µM [191]. |
|||
| IC50 = 3.9 μM in MCF-7 cells IC50 = 9.54 μM in HepG2 cells [202]. | Anti-inflammatory effects of kuwanon C are regulated by HO-1 expression [203]. | |||
| Kuwanon E | Noncytotoxic EC50 > 10 µM in MCF-7, CEM, RPMI8226, U266, HeLa, BJ, THP-1 cells [172]. | Inhibition of NO production stimulated by LPS and IFN-γ in RAW 264.7 cells, IC50 = 14.9 μM [198]. | Synergy with amikacin and etimicin [139]. | |
| Inhibition of IL-6 production, IC50 = 47.5 μM without a cytotoxic effect in A549 cells [204]. | ||||
| COX-2 inhibitor IC50 = 34 µM [199]. | ||||
| Kuwanon G | Toxic effect in RAW 264.7 cells ≥ 50 μM. The viability of cells was not affected at concentrations of 2, 5, 10, and 20 μM [205]. | Inhibition of NO production at 100 μM (79.9%) [204]. | ||
| ↓ of the release of RANTES/CCL5, TARC/CCL17, and MDC/CCL22 via downregulation of STAT1 and NF-κB p65 signalling in TNF-α- and IFN-γ-stimulated HaCaT keratinocytes. Inhibition of histamine production and 5-LOX activation in PMA- and A23187-stimulated MC/9 mast cells [206]. | ||||
| 20 µM ↓ the ox-LDL induced inflammatory response by suppressing the NF-κB activation in RAW 264.7 cells [205]. | ||||
| Licochalcone A | Cytotoxic activity for: HepG2 cells (10 μM) = 14%. SW480 cells (10 μM) = 7%. MCF7 cells (10 μM) = 10% [207]. |
Inhibition of NF-κB transcription, IC50 = 13.9 μM [207]. |
Inhibition of peroxyl radical-induced DCFH oxidation without a PBS wash (EC50 = 58.8 μg/mL) and with a PBS wash (EC50 = 46.3 μg/mL) [208]. | Subinhibitory concentrations ↓ the secretion of SEA and SEB by both MSSA and MRSA [209]. |
| IC50 for 24 and 48 h = 6.0 and 13.7 μg/mL, respectively, for the HepG2 cells [208]. | Inhibitor for P. acnes-induced NLRP3 inflammasome activation. Block of C. acnes-induced production of caspase-1 (p10) and IL-1β in macrophages and SZ95. Suppression of C. acnes-induced ASC speck formation and mitochondrial reactive oxygen species [210]. | |||
| IC50 = 4.8 μM in A549 cells. IC50 = 4.6 μM in SK-OV-3 cells. IC50 = 2.7 μM in SK-MEL-2 cells. IC50 = 3.4 μM in HCT-15 cells [211]. |
Suppression of ORAI1, Kv1.3, and KCa3.1 channels, IC50 = 3, 0.8, and 11.2 µM, respectively. Suppressive effects on the IL-2 secretion and proliferation in CD3 and CD28 antibody-induced T-cells [212]. | |||
| IC50 = 36.6 µg/mL in HepG2 cells. IC50 = 26.9 µg/mL in Vero cells [144]. |
Inhibition of LPS-induced phosphorylation at serine 276 and transcriptional activation of NF-κB. Inhibition of LPS-induced activation of PKA [213]. | ↑ protein expression of SOD1, CAT, and GPx1 in a concentration-dependent manner (2–8 μg/mL for 24 h) [208]. | ||
| Attenuation of LPS-induced kidney histopathologic changes, serum BUN, and creatinine levels. Suppression of LPS-induced TNF-α, IL-6, and IL-1β production in both serum and kidney tissues. Inhibition of LPS-induced NF-κB activation [214]. | ||||
| Inhibition of PGE2 and NO production and iNOS and COX-2 expression, induced by IL-1β. Inhibition of MMP-1, MMP-3, and MMP-13 production in IL-1β-stimulated chondrocytes. Inhibition of phosphorylation of NF-κB p65 and IκBα. Upregulation of the expression of Nrf2 and HO-1 [215]. | ||||
| Inhibition of sUV-induced COX-2 expression and PGE2 generation through the inhibition of AP-1 transcriptional activity. Suppression of sUV-induced phosphorylation of Akt/mTOR and ERK1/2/p90 ribosomal protein S6 kinase in HaCaT cells. Suppression of the activity of PI3K, (MEK)1, and B-Raf, but not Raf-1 in cell-free assays [216]. | ||||
| Licochalcone B | Inhibition of LPS-induced phosphorylation at serine 276 and transcriptional activation of NF-kappaB. Inhibition of LPS-induced activation of PKA. Reduction of the LPS-induced production of NO, TNFα, and MCP-1 [217]. | Suppression of the oxidative stress and inflammation, manifesting as the enhancement of SOD, GSH, and IL-4, but the decline of MDA, iNOS, and TNF-α [218]. | ||
| A specific inhibitor of the activation of the NLRP3 inflammasome in macrophages, no effect on the activation of AIM2 or NLRC4 inflammasome. It binds to NEK7 and inhibits the interaction between NLRP3 and NEK7 → suppressing NLRP3 inflammasome activation. Protective effects in mouse models of NLRP3 inflammasome-mediated diseases → LPS-induced septic shock, MSU-induced peritonitis, and nonalcoholic steatohepatitis [219]. | ||||
| Licochalcone C | ↓ NF-κB translocation and several downstream molecules, -iNOS, ICAM-1, and VCAM-1. Upregulation of the PI3K/Akt/eNOS signalling pathway [220]. | 50 µM attenuates inflammatory response by influencing extracellular O2− production and by modulating the antioxidant network activity of SOD, CAT, and GPx activity [221]. | ||
| Attenuation of the LPS-IFN-γ-induced inflammatory response by ↓ the expression and activity of iNOS via NF-κB [221]. | ||||
| Licochalcone E | IC50 = 5.9 μM in A549 cells. IC50 = 5.2 μM in SK-OV-3 cells. IC50 = 2.9 μM in SK-MEL-2 cells. IC50 = 3.4 μM in HCT-15 cells [211]. |
Dose-dependent inhibition of IL-12p40 production from LPS-stimulated RAW 264.7 cells. ↓ binding to the NF-κB site in RAW 264.7. Inhibition of the ↑ IL-12p40 expression and ear thickness induced by oxazolone in chronic allergic contact dermatitis model [222]. | Subinhibitory concentrations → a dose-dependent decrease in α-toxin expression in S. aureus [146]. | |
| Topical application of 0.5–2 mg inhibited TPA-induced ear oedema formation; phosphorylation of SAPK/JNK, c-Jun, and extracellular signal regulated kinase ½, and expression of iNOS and COX-2 in mouse skin. 2.5–7.5 μmol/L → ↓ in LPS-induced release of NO and PGE2; ↓ mRNA expression and secretion of IL-6, IL-1β, and TNF-α; ↓ promoter activity of iNOS and COX-2 and expression of their corresponding mRNAs and proteins; ↓ activation of AKT, MAPK, SAPK/JNK, and c-Jun; ↓ phosphorylation of IκB kinase-αβ and IκBα, degradation of IκBα, translocation of p65 to the nucleus and transcriptional activity of NF-κB; and transcriptional activity of AP-1 in RAW 264.7 cells [223]. | ||||
| Licoflavanone | Inhibition of NO production in LPS-stimulated RAW 264.7 cells, IC50 = 37.7 µM [224]. | IC50 = 59.6 µM in ABTS assay [224]. | ||
| ↓ of NF-kB translocation into the nucleus→ ↓ proinflammatory cytokines and COX-2/iNOS expression levels. ↓ of p38, JNK, and ERK1/2 phosphorylation and activation. Disruption of the NF-kB/MAPKs signal transduction pathway → ↓ in mRNA levels of TNFα, IL 1β, and IL 6 [224]. | ||||
|
Licoflavone C =
8-prenylapigenin |
IC50 = 9 µg/mL in Hep-2 cells [122]. | Inhibition of the LPS-induced gene expression for TNF-α, iNOS, COX-2, and release of TNF-α, NO, and PGE2, through the inhibition of NF-κB activation and reactive oxygen species accumulation in RAW 264.7 cells [225]. | ↓ of increase in the cellular ROS levels at 3 μM in RAW 264.7 cells [225]. | |
| IC50 = 121.4 μM in RAW 264.7 cells [225]. | ||||
| IC50 = 41.6 μM in RAW 264.7 cells [153]. | ||||
| IC50 = 42 μmol/L in H4IIE cells. IC50 = 37 μmol/L in C6 glioma cells [226]. | ||||
| Inhibition of NO production in LPS-activated RAW 264.7 cells, IC50 = 20.4 µM [153]. | ||||
| Lonchocarpol A | COX-1 inhibitor IC50 = 16.9 μM. COX-2 inhibitor IC50 = 9.5 μM [227]. |
|||
| ↓ of NO production, IC50 = 2.5 μM and ↓ NOX activity, IC50 = 24.4 μM in murine microglial cells [228]. | ||||
| Lupalbigenin | IC50 = 11.630–37.712 µM in MCF-7, MDA-MB-231, MDA-MB-468, SW-620, and the mouse fibroblast cell line L-929, [229]. | 1.25 and 2.5 mM effectively inhibited the LPS-induced TNF-α, COX-2, iNOS, and NF-κB [230]. | ||
| Mimulone | Cytotoxicity < 50% of DMSO in WB-F344 [164]. | COX-1 inhibitor IC50 = 3.6 μM. COX-2 inhibitor IC50 = 6.0 μM [168]. |
TEACABTS = 1.7 [171]. | Synergy with oxacillin, additive effect with tetracycline and ciprofloxacin [231]. |
| IC50 = 6.6 µM in THP-1 cells [232]. | 25 mg/kg prior and after induction of colitis ameliorated its symptoms and delayed the onset. ↓ of the levels of COX-2 and ↑ the ratio of pro-MMP2/MMP2 activity, ↓ of SOD2, and CAT [170]. | DPPH quenching activity TEAC 0.4 at 10 µM [164]. | ||
| Morusin | IC50 = 0.6 µM in HeLa. IC50 = 7.9 µM in MCF-7. IC50 = 9.2 µM in Hep3B [233]. |
Inhibition of NO production stimulated by LPS and IFN-γ in RAW 264.7 cells, IC50 = 10.6 μM [198]. | ||
| Inhibition of RANTES/CCL5 and TARC/CCL17 secretion via the suppression of STAT1 and NF-κB p65 phosphorylation in TNF-α- and IFN-γ-stimulated HaCaT keratinocytes, and the release of histamine and LTC4 by suppressing 5-LOX activation in PMA- and A23187-stimulated MC/9 mast cells [206]. | ||||
| Morusinol | IC50 = 4.3 µM in THP-1 cells [201]. | The attenuation of LPS-induced secretion of TNF-α → an effect nearly twice that of prednisone [201]. | Synergy with amikacin, ciprofloxacin, vancomycin, streptomycin [139]. | |
| Papyriflavonol A | IC50 = 20.9 µg/mL in HepG2 cells [114]. | 5-LOX inhibitor IC50 = 7 µM [191]. | ||
| Inhibition of sPLA2s-IIA (IC50 = 3.9 µM) and -V (IC50 = 4.5 µM). Inhibition of LTC4 (IC50 = 0.6 µM) production in mouse bone marrow mast cells. 12.5–50 mg/kg i.p. reduced IgE-dependent PCA [234]. | ||||
|
Propolin D
= nymphaeol B |
12 µM inhibited cell proliferation in RAW 264.7 cells [174]. | Inhibition of albumin denaturation, IC50 = 0.5 µM. Inhibition of nitrite production stimulated by LPS in RAW 264.7 cells, IC50 = 5.4 µM. COX-2 inhibitor = 17.9 µM [174]. |
DPPH radical scavenging activity, IC50 = 7.1 µM. The inhibition of linoleic acid oxidation by β-carotene bleaching systems, IC50 = 5.8 µM [175]. |
Dose-dependent inhibition of S. aureus and C. albicans biofilm formation [107]. |
| At concentrations up to 200 µg/mL, nontoxic in C. elegans model, slightly reduced nematode survival at 500 µg/mL [107]. | ||||
|
Propolin F
= isonymphaeol B |
12 µM inhibited cell proliferation in RAW 264.7 cells [174]. | Inhibition of albumin denaturation, IC50 = 0.4 µM. Inhibition of nitrite production stimulated by LPS in RAW 264.7 cells, IC50 = 6.2 µM. COX-2 inhibitor = 23.8 µM [174]. |
DPPH radical scavenging activity, IC50 = 8.5 µM. The inhibition of linoleic acid oxidation by β-carotene bleaching systems, IC50 = 5.9 µM [175]. | Dose-dependent inhibition of S. aureus biofilm formation. Inhibition of C. albicans biofilm formation [107]. |
|
Propolin G
= nymphaeol C |
At tested concentrations did not inhibit cell proliferation; it induced cell proliferation to some extent in RAW 264.7 cells [174]. | Inhibition of albumin denaturation, IC50 = 0.37 µM. Inhibition of nitrite production stimulated by LPS in RAW 264.7 cells, IC50 = 2.4 µM. COX-2 inhibitor = 15.5 µM [174]. |
DPPH radical scavenging activity IC50 = 9.8 µM. The inhibition of linoleic acid oxidation by β-carotene bleaching systems, IC50 = 10.3 µM [175]. |
Inhibition of C. albicans biofilm formation [107]. |
|
Scandenone
= warangalone |
At 10 µM (86.5 % cell viability) in RAW 264.7 cells [119]. | Inhibition of LPS-stimulated NO production in RAW 264.7 cells, IC50 = 8.5 µM [119]. | ||
| 20 µM inhibited proliferation in MDA-MB-231 cells and 15 µM in MCF-7 cells. Promotion of proliferation in MCF-10A [235]. | Anti-inflammatory and antinociceptive activity in carrageenan-induced hind paw oedema model and TPA-induced mouse ear oedema model at 100 mg/kg dose [236]. | |||
| Sophoraflavanone G | Toxic from 4 to 64 µg/mL in human PBMC with >50% cellular activity inhibition. IC50 = 3.2 µg/mL [123]. | COX-1 inhibitor IC50 = 0.1–0.6 µM. 5-LOX inhibitor IC50 = 0.1–0.3 µM. 12-LOX inhibitor IC50 = 20 µM [191]. |
Additive effect with ciprofloxacin, erythromycin, gentamicin, fusidic acid, oxacillin [123]. | |
| Interruption of the NF-κB and MAPK signalling pathways [237]. | ||||
| Inhibition of cell proliferation in: A549, NCI-H460, SK-OV-3, SK-MEL-2, XF498, HCT-15, HL60, SPC-A-1 cells with IC50 = 2–36 μg/mL [238]. | Inhibition of PGE2 production in LPS-induced RAW cells by COX-2 downregulation at 1–50 μM. 10–250 µg/ear in mouse croton oil-induced ear oedema and 2–250 mg/kg in rat carrageenan paw oedema → effect far less than prednisolone, but higher when applied topically [69]. | Synergy with ampicillin and oxacillin [125]. | ||
| IC50 = 12.5 μM in HL-60 cells [239]. | Inhibition of NO, PGE2, IL-1β, IL-6, TNFα production in Ag I/II-N-stimulated RAW 264.7 cells via the downregulation of iNOS and COX-2 expression. Inhibition of the phosphorylation of IκB-α, nuclear translocation of p65, and subsequent activation of NF- κB. Inhibition of MAPK-mediated pathways [240]. | |||
| IC50 = 12.5 μM in HL-60 cells. IC50 = 13.3 μM in HepG2 cells [241]. | ||||
| CC50 =< 19 μM in HSC-2 cells. CC50 = 19 μM in HSG cells. CC50 = 19 μM in HGF cells [242]. | ||||
| Tomentodiplacone B | IC50 = >20 μM in THP-1 cells, viability at 30 µM [232]. | Reduction of TNF-α secretion as much as or more than the prednisone. IC50 >20 μM [232]. | TEACABTS = 1.0, TEACInhibition of. peroxynitrite-induced tyrosine nitration = 0.8 [171]. | |
| Xanthoangelol | IC50 = 23.6 μM in THP-1. IC50 = 21.7 μM in MRC-5. IC50 = 21.5 μM in HEK293. IC50 = 13.7 μM in HepG2. IC50 = 58.8 μM in CLS-54. IC50 = 1.0 μM in MRSA [109]. |
Inhibition of LPS-stimulated NO production, IC50 = 5 μM. Suppression of AP-1. Reduction of the phosphorylation (at serine 536) level of the p65 subunit of NF-κB [243]. | ||
| IC50 = 25 μM in MRC-5. IC50 = 25 μM in THP-1 [108]. | ||||
| Xanthohumol | IC50 = 5.2 μg/mL in NHLF cells [148]. | NF-κB activity was reduced in vitro as well as in hepatic tissue after ischemia/reperfusion [244]. | TEACABTS = 0.3 μmol/l TEACFRAP = 0.3 μmol/l [245]. | Synergy with oxacillin against S. aureus [147]. |
| IC50 = 11.0 μM in MCF-7. IC50 = 10.7 μM in PC-3. IC50 = 91.3 μM in HT-29 [246]. |
10 μg/mL inhibits 91.7% of the NO production by suppressing iNOS induced by a combination of LPS and IFN-γ [247]. | DPPH radical scavenging activity, IC50 = 2.0 µM [246]. | At MIC reduced biofilm viability by 86.5% [147]. | |
| IC50 = 40.8 μM in HCT116. IC50 = 50.2 μM in HT-29. IC50 = 25.4 μM in HepG2. IC50 = 37.2 μM in Huh7 [248]. |
↓ the expression of the LPS receptor components - TLR4 and MD2 → suppression of NF-κB activation in LPS-activated RAW 264.7 cells. Inhibition of the binding activity of STAT-1alpha and IRF-1 In IFN-γ-stimulated RAW 264.7 cells [249]. | TEACABTS = 0.2, IC50 = 0.7 mg/mL, TEACDPPH = 0.04, IC50 = >1.2 mg/mL [250]. | 15–30 μg/mL → ↓ release of planktonic bacteria from the 24 h old biofilm by more than 90%. BBC = 60–125 μg/mL [148]. |
|
| IC50 = 3.6 μM in HCT-15 [251]. | ↓ the release of MCP-1 and TNF-α in LPS-stimulated RAW 264.7 and U937 human monocytes [252]. | ↓ reactive oxygen species in vitro. Levels of enzymatic and nonenzymatic antioxidants were restored after pretreatment in postischemic hepatic tissue, and lipid peroxidation was attenuated [244]. | ||
| 0.5–10 µM inhibited melanogenesis induced by isobutyl-methylxanthine in B16 melanoma cells [253]. | Inhibition of IL-12 production in stimulated macrophages through the downregulation of NF-κB. In an oxazolone-induced chronic dermatitis model in mouse ear → attenuated dermatitis [254]. | |||
| Stout beer supplemented with 10 mg/L of xanthohumol for 4 weeks decreased serum VEGF levels (18.4%), N-acetylglucosaminidase activity (27.8%), IL1β concentration (9.1%), and NO released (77.1%), accompanied by a reduced redox state as observed by an increased GSH/GSSG ratio (to 198.8%) [255]. | ||||
| 3′-O-methyldiplacol | IC50 = 7.2 μM in THP-1 cells [232]. | Inhibition of LPS-induced NO production in RAW 264.7 cells, IC50 = 5.9 µM [173]. | TEACABTS = 1.6, TEACDPPH = 0.1, TEACFRAP = 0.1, TEACInhibition of. peroxynitrite-induced tyrosine nitration = 0.7 [171]. | Synergy with oxacillin. Additive effect with ciprofloxacin, tetracycline against MRSA [231]. |
| 3′-O-methyldiplacone | IC50 = 30.2 µM in WB 344 [164]. | ↓ the secretion of TNF-α ≥ than the prednisone [164]. | DPPH quenching activity TEAC 0.8 at 10 µM [164]. | |
| IC50 =< 10 μM in THP-1 cells [232]. | TEACABTS = 1.4, TEACDPPH = 0.1, TEACFRAP = 0.1, TEACInhibition of. peroxynitrite induced tyrosine nitration = 0.8 [171]. | |||
| EC50 =< 10 µM in MCF-7 cells, EC50 =< 10 µM in CEM cells, EC50 = 7.3 µM in RPMI8226 cells, EC50 = 5.5 µM in U266 cells, EC50 = 7.4 µM in HeLa cells, EC50 = 4.7 µM in BJ cells, EC50<10 µM in THP-1 cells [172]. | ||||
| 3′-O-methyl-5′-hydroxydiplacone | Antiproliferative (IC50 = 12.6 μM) and cytotoxic (LC50>30 µM) effect [169]. | Inhibition of LPS-induced NO production in RAW 264.7 cells, IC50 = 1.5 µM [173]. | TEACABTS = 1.7, TEACDPPH = 1.0, TEACFRAP = 0.7, TEACInhibition of. peroxynitrite induced tyrosine nitration = 0.8, Superoxide scavenging activity-Enzymatic = 71.2%, Non-Enzymatic = 29.5% at 50 μM [171]. | |
| COX-1 inhibitor IC50 = 3.3 μM COX-2 inhibitor IC50 = 10.6 μM 5-LOX inhibitor IC50 = 0.1 μM [168]. | ||||
| 3′-O-methyl-5′-O-methyldiplacone | IC50 = 7.9 μM in THP-1 cells [232]. | 5-LOX inhibitor IC50 = 0.4 μM [168]. | TEACABTS 1.6, TEAC DPPH = 0.3, TEAC FRAP = 1.2, TEAC Inhibition of. peroxynitrite-induced tyrosine nitration = 0.8 [171]. | |
| 4-hydroxylonchocarpin | IC50 > 100 μM in RAW 264.7 cells [256]. | Inhibition (66.5%) of NO release from LPS-stimulated RAW 264.7 cells. 10 μM inhibited iNOS activity. In the carrageenan-induced paw oedema model, 10 mg/kg showed comparable activity to indomethacin, and 50 mg/kg showed higher activity than indomethacin [256]. |
Abbreviations: reduction/decrease (↓), increase (↑) 5-LOX (5-lipoxygenase), A20 (ubiquitin-editing molecule), A23187 (calcium ionophore), AHR (aryl hydrocarbon receptor), AIM2 (interferon-inducible protein), Akt (protein kinase B), AP-1 (activator protein 1), ARE (antioxidant response element), ASC (caspase recruitment domain), BBC (biofilm bactericidal concentration), BUN (blood urea nitrogen), CAT (catalase), CC50 (50% cytotoxic concentration), CCl4 (tetrachlormethan), CCL5 (chemokine (C-–C motif) ligand 5), CCL17 (CC chemokine ligand 17), CCL22 (CC chemokine ligand 22), CD3 (cluster of differentiation 3), CD4+T-cell (T helper cells), c-Jun (Jun proto-oncogene), COX-1 (cyclooxygenase-1), COX-2 (cyclooxygenase-2), cPLA2 (cytosolic phospholipase A2), DCFH (dichloro-dihydro-fluorescein), DPPH (2,2-difenyl-1-pikrylhydrazyl), E. coli (Escherichia coli), EC50 (half-maximal effective concentration), ED50 (median effective dose), eNOS (endothelial nitric oxide synthase), ERK1/2 (extracellular signal-regulated kinases), ERK1/2/p90 (extracellular signal-regulated kinases), Fyn (proto-oncogene tyrosine-protein kinase), Gata-3 (gene-GATA binding protein 3), GPx (glutathione peroxidase), GPx1 (glutathione peroxidase 1), HO-1 (heme oxygenase-1), IBS (irritable bowel syndrome), ICAM-1 (intercellular adhesion molecule-1), IFN-γ (interferon gamma), IL-10 (interleukin 10), IL-12 (interleukin 12), IL-12p40 (interleukin 12 subunit p40), IL-17 (interleukin 17), IL-1β (interleukin 1β), IL-2 (interleukin 2), IL-23 (interleukin 23), IL-4 (interleukin 4), IL-6 (interleukin 6), iNOS (inducible NO synthase), IRF-1 (interferon regulatory factor 1), IκB (inhibitor of κB), IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cell inhibitor alpha), JNK (Jun N-terminal kinase), KCa3 (1 calcium-activated potassium channel), Kv1.3 (voltage-gated potassium channel), LC50 (lethal concentration 50), LPS (lipopolysaccharide), LTC4 (leukotriene C4), MAPK (mitogen-activated protein kinase), MBIC (minimum inhibitory biofilm concentration), MCP-1 (monocyte chemoattractant protein-1), MD-2 (myeloid differentiation factor 2), MDA (malondialdehyde), MDC (macrophage-derived chemokine), MEK (mitogen-activated protein kinase), MMP-1 (matrix metalloproteinase-1), MMP-13 (matrix metalloproteinase-13), MMP-2 (matrix metalloproteinase-2), MMP-3 (matrix metalloproteinase-3), mPGES-1 (microsomal prostaglandin E synthase-1), mRNA (messenger RNA), MRSA (methicillin-resistant Staphylococcus aureus), MSSA (methicillin-sensitive Staphylococcus aureus), MSU (monosodium urate crystals), mTOR (Akt/mammalian target of rapamycin), NADPH (nicotinamide adenine dinucleotide phosphate), NEK7 (NIMA-related kinase 7), NF-κB (nuclear factor-κB), NF-κB p65 (subunit of NF-kappa-B transcription complex), NLRC4 (NLR family CARD domain containing 4), NLRP3 (NLR family pyrin domain containing 3), NO (nitric oxide), NOS (NO synthase), NOX (NADPH oxidase activity), Nrf2 (nuclear factor erythroid 2-related factor 2), ORAC (oxygen radical absorbance capacity), ORAI1 (calcium release-activated calcium channel protein 1), ox-LDL (oxidized low-density lipoprotein), P. acnes (Propionibacterium acnes), P. aeruginosa (Pseudomonas aeruginosa), PBS (phosphate-buffered saline), PCA (passive cutaneous anaphylaxis), PGE2 (prostaglandin E2), PI3K (phosphoinositide 3-kinase), PKA (protein kinase A), PMA (phorbol-12-myristate-13-acetate), PPAR-α (peroxisome proliferator-activated receptor alpha), pro-MMP-2 (promatrix metalloproteinase-2), RANTES (regulated upon activation, normal T cell expressed and presumably secreted), ROS (reactive oxygen species), SAPK/JNK (stress-activated protein kinase/c-Jun-N-terminal kinase), SC50 (scavenging DPPH free radicals by 50%), SC50 (scavenging DPPH free radicals by 50%), SEA (Staphylococcus aureus enterotoxin), SEB (Staphylococcus aureus enterotoxin B), SOD (superoxide dismutase), SOD1 (superoxide dismutase 1), SOD2 (superoxide dismutase 2), STAT1 (signal transducer and activator of transcription 1), STAT3 (signal transducer and activator of transcription 3), STAT6 (signal transducer and activator of transcription 6), sUV (solar ultraviolet), TARC (thymus- and activation-regulated chemokine), t-BuOOH (tert-butyl hydroperoxide), TEAC (trolox equivalent antioxidant capacity), TEACABTS (trolox equivalent antioxidant capacity 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)), TLR (toll-like receptor), TLR4 (toll-like receptor 4), TNCB (2,4,6-trinitrochlorobenzene), TNF-α (tumour necrosis factor α), TPA (12-O-tetradecanoylphorbol acetate), VCAM-1 (vascular cell adhesion molecule 1), VEGF (vascular endothelial growth factor). Cell lines: 1A9 (endometrioid ovary carcinoma), A549 (adenocarcinomic human alveolar basal epithelial cells), AML12 (murine hepatocyte), Bcap37 (breast cancer), BEAS-2B (bronchial epithelial cells), BJ (fibroblasts), C6 (glioma), CAKI-1 (renal cancer), CCRF-CEM (acute lymphoblastic leukaemia), CEM (acute lymphoblastic leukaemia), CLS-54 (lung adenocarcinoma), H4IIE (hepatoma), HaCaT (aneuploid immortal keratinocyte), HCT116 (colorectal carcinoma), HCT-15 (colorectal carcinoma), HCT-8 (ileocecal carcinoma), HDFs (human dermal fibroblasts), HEK293 (embryonic kidney cells), HeLa (cervical cancer), Hep3B (hepatocellular carcinoma), HepG2 (hepatocellular carcinoma), HGF (primary gingival fibroblast), HL60 (acute promyelocytic leukaemia), HPC (hematopoietic progenitor cell), HPLF (periodontal ligament fibroblasts), HSC-2 (oral squamous cell carcinoma), HSG (submandibular gland), HT-29 (colorectal adenocarcinoma), Huh7 (hepatocellular carcinoma), HUVEC (human umbilical vein endothelial cells), K562r (chronic myeloid leukaemia at blast crisis), K562s (chronic myeloid leukaemia at blast crisis), KB-VIN (epidermoid carcinoma of the nasopharynx and its subclone), L-02 (papillomavirus-related andocervical adenocarcinoma), L-929 (fibroblasts), LNCaP (prostate adenocarcinoma), MC/9 (foetal liver mast cell), MCF-10A (breast epithelial cells), MCF-7 (breast cancer), MDA-MB-231 (breast adenocarcinoma), MDA-MB-468 (breast cancer), MOLM-13 (acute myeloid leukaemia), MRC-5 (fibroblasts), NB4 (acute promyelocytic leukaemia), NCI-H460 (non-small-cell lung cancer), NHLF (lung fibroblasts), PBMC (primary peripheral blood mononuclear cells), PC3 (Caucasian prostate adenocarcinoma), RAW 264.7 (macrophages), RPMI8226 (multiple myeloma), SK-MEL-2 (melanoma), SK-OV-3 (cystadenocarcinoma), SPC-A-1 (lung adenocarcinoma), SW480 (colorectal adenocarcinoma), SW-620 (adenocarcinoma), SZ95 (sebocytes), Tca8113 (squamous cell carcinoma of the tongue), THP-1 (acute monocytic leukaemia), U251 (malignant glioblastoma), U266 (multiple myeloma), U937 (histiocytic lymphoma), Vero (kidney epithelial cells), WB-F344 (epithelial cells), XF498 (glioblastoma), ZR-75-1 (breast cancer).