Astragalin (kaempferol-3-glucoside), a flavonoid from leaves of persimmon and green tea seeds | CS exposure: BALB/c mice CSE treatment: A549 cells | Astragalin may interrupt the smoking-induced oxidative stress–MAPK signalling–inflammation axis via disconnection between alveolar PAR activation and pulmonary thromboembolism. | [164] |
Curcumin | CS exposure: male SD rats CSE treatment: BEAS-2B cells | Curcumin attenuated CS-induced inflammation in vivoand in vitro, by modulating the PPARγ–NF-κB pathway. | [106] |
Fisetin, a flavone from apples strawberries and onion | CS exposure: male Wistar rats | Fisetin blunted CS-induced oxidative stress and inflammation in the lungs and prevented tissue damage via the Nrf2-mediated upregulation of antioxidant gene expression. | [165] |
Hesperidin, a flavanone glycoside | CSE injection: C57BL/6 mice male and female mixed | Hesperidin alleviated inflammation and oxidative stress responses in CSE-induced COPD mice, associated with SIRT1/PGC-1α/NF-κB signalling axis. | [166] |
Icariin, a flavonoid from Epimedium brevicornum Maxim (Berberidaceae) | CSE treatment: BEAS-2B cells | Decreased CSE-induced inflammation, airway remodelling and ROS production by mitigating GC resistance. Icariin combination with GC can potentially increase therapeutic efficacy and reduce GC resistance in COPD. | [167] |
ISOF, a flavonoid from Coleus forskohlii | CS exposure: mice and infected with influenza virus A/Puerto Rico/8/34 (H1N1), Th17 cells | The levels of inflammatory mediators (TNF-α, IL-1β, IL-6, IL-17A, MCP-1, MIG, IP-10 and CRP) in the lung homogenate were reduced after ISOF treatment. ISOF alleviated AECOPD by improving pulmonary function and attenuating inflammation via the downregulation of pro-inflammatory cytokines, Th17–IL-17A and NF-κB–NLRP3 pathways. | [149] |
Isoliquiritigenin, a polyphenol from Glycyrrhizae radix | CS exposure: male C57BL/6N mice | Isoliquiritigenin protected against CS-induced COPD by inhibiting inflammatory and oxidative stress via the regulation of the Nrf2 and NF-κB signalling pathways. | [168] |
Isorhapontigenin, a polyphenol from Belamcanda chinensis | CS exposure: SD rats CSE treatment: primary HAECs (healthy and COPD), A549 cells | Isorhapontigenin reduced the activation of NF-κB and AP-1 and notably the PI3 K–Akt–FoxO3A pathway was insensitive to dexamethasone. | [101] |
Liquiritin apioside, a flavonoid from Glycyrrhiza uralensis | CS exposure: ICR mice CSE treatment: A549 cells | The protective role of liquiritin apioside on CS-induced the lung epithelial cell injury and are mediated by inhibiting TGF-β and TNF-α expression and increasing anti-oxidative levels of GSH. | [129] |
MgIG | CS exposure: male Wistar rats with endotracheal-atomized LPS | MgIG might be an alternative for COPD treatment, and the suppression of NLRP3 inflammasome. | [80] |
Oroxylin A, a flavonoid from Scutellaria baicalensis Georgi | CS exposure: male C57BL/6 mice CSE treatment: BEAS-2B, RAW264.7 cells | Oroxylin A attenuated oxidative stress and lung inflammation by CS-induced via activating the Nrf2 signalling pathway. | [169] |
Phloretin, a polyphenol from Prunus mandshurica | CS exposure: male BALB/c mice CSE treatment: NCI-H292 cells | The protective effect of phloretin on CS-related airway mucus hypersecretion and inflammation, where EGFR, ERK and P38 might be involved. | [170] |
Sal-B, a polyphenol of danshen | PPE endotracheal treatment: male SD rats CSE intraperitoneal treatment: male SD rats | Sal-B as one of the first anti-emphysema agents enabling reversal of alveolar structural destruction and loss via local lung treatment by STAT3 activation and VEGF stimulation. | [98] |
EGCG | CSE treatment: NHBE cells | EGCG sequestered 4-hydroxynonenal and inhibited NF-κB activation, antioxidative and anti-inflammatory effects of EGCG in CSE-treatment AECs. | [73] |
EC, flavonoid | CS exposure: male Wistar rats CSE treatment: BEAS-2B cells | The protective effect of EC on experimental COPD rats and elucidated the mechanism of EC promoting Nrf2 activity. | [171] |
Baicalin, a polyphenol of Scutellaria baicalensis | CS exposure: male SD rats, CSE treatment: HBEpCs | Baicalin ameliorated CS-induced airway inflammation in rats, and these effects were partially attributed to the modulation of HDAC2–NF-κB–PAI-1 signalling. | [81] |
CS exposure: male BALB/c mice CSE treatment: A549 cells | Anti-inflammatory effects in CS-induced inflammatory models in mice and A549 cells, achieved by modulating HDAC2. | [172] |
Casticin, a flavonoid from Vitex species (Vitex rotundifolia, Vitex agnus-castus) | CS exposure: male Wistar rats | Casticin protected lungs against COPD via improving lung function and inhibition of oxidative stress and inflammation via the reduction of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6). | [173] |
CS exposure: female C57BL/6 mice | Casticin had significant effects on the lung inflammation induced by CS in a COPD mouse model. | [174] |
Naringenin, a flavanone from grapefruit | CS exposure: male BALB/c mice CSE treatment: A549 cells | Naringenin inhibited the production of pro-inflammatory cytokines such as IL-8, TNF-α, and MMP9 in the BALF and serum of CS-induced animals. | [175] |
Naringin, a flavonoid glycoside from grapefruit and citrus fruits | CS exposure: male and female guinea pigs | Naringin exhibited antitussive, anti-AHR and anti-inflammation effects on chronic CS exposure-induced chronic bronchitis of guinea pigs. | [125] |
CS exposure: male and female SD rats | Naringin prevented CS-induced infiltration of neutrophils and activation of MPO and MMP-9, in parallel with suppression of the release of cytokines, TNF-α, IL-8 and IL-10. | [128] |
Quercetin, a flavonoid | CSE treatment: J774A.1 cells CSE injection: male C57BL/6 mice | An effective adjuvant effects from quercetin for treating CS exposure. | [176] |
CSE treatment: U937 cells, COPD patient PBMC | Quercetin restored corticosteroid sensitivity, to be a novel treatment in combination with corticosteroids in COPD. | [85] |
Resveratrol | CS exposure: male Wistar rats | Resveratrol inhibited oxidative stress and inflammatory response via the activation and upgrading of the SIRT1/PGC-1α signalling pathways. | [120] |
CS exposure: male Kunming mice with LPS | Resveratrol has a therapeutic effect on mouse CS-induced COPD and reduced the production of the beclin1 protein. | [124] |
CSE treatment: HBEpC | A protective effect against CSE-induced apoptosis, and a molecular pathway involving SIRT1 and ORP150 may be associated with the anti-apoptotic functions, caspase-3 and caspase-4 of resveratrol in HBEpC. | [122] |
PPE endotracheal treatment: female C57BL/6JNarl mice CSE treatment: MSC cells | cis-Resveratrol-regulated VEGFA expression in HSP–VEGFA–MSC significantly improved the therapeutic effects in the treatment of a COPD mouse, avoiding side effects associated with constitutive VEGFA expression. | [123] |
CS exposure: male SD rats with LPS | Co-administered with sirtinol, a SIRT1 inhibitor. The combination therapy may serve as a potential approach for treating lung inflammatory conditions like COPD. | [119] |
Silibinin, a flavonoid from the milk thistle Silybum marianum | CSE treatment: NCI-H292 cells CS exposure: male C57BL/6 N mice with LPS | Silibinin effectively suppressed the neutrophilic airway inflammation provoked by treatment with LPS and CS, which was associated with downregulation of ERK phosphorylation. | [177] |
CS exposure: male C57BL/6N mice with LPS | Silibinin effectively inhibited the fibrotic response induced by CS+LPS exposure, via suppression of TGF-β1/Smad 2/3 signalling, resulting in reduced collagen deposition. | [178] |
Silymarin, a flavonoid from the seeds and fruits of milk thistle | CS exposure: male BALB/c mice | Silymarin attenuated inflammation and oxidative stress induced by CS. The anti-inflammatory effect might partly act through the MAPK pathway. | [103] |
CSE treatment: BEAS-2B cells | Silymarin could attenuate inflammatory responses through intervening in the crosstalk between autophagy and the ERK–MAPK pathway. | [102] |
HSYA, a polyphenol from edible plant safflower | CS exposure: male Wistar rats with LPS | HSYA inhibited the phosphorylation of p38 MAPK in the lung tissue of rat. HSYA can attenuate experimentally induced airway remodelling and was attributed to suppression of TGF-β1 expression. | [179] |
CS exposure: male Wistar rats | HSYA alleviated inflammatory cell infiltration and inhibited inflammatory cytokine expression and increased phosphorylation of p38 MAPK and p65 NF-κB in the lungs of COPD rats. | [180] |
Jaboticabin and related polyphenols from jaboticaba (Myrciaria cauliflora) | CSE treatment: SAE cells, Caco-2 cells | The polyphenols, jaboticabin and 3,3'-dimethyellagic acid-4-O-sulphate from jaboticaba both exhibited anti-inflammatory activities. | [88] |
Apple polyphenol | CS exposure: female ICR mice | Apple polyphenol may be a potential dietary nutrient supplement agent to improve quality of life of COPD patients by inhibiting CS-induced ALI via the p38 MAPK signalling pathway. | [115] |
DRIAs | CS exposure: male C57BL/6 mice | DRIAs significantly attenuated the pathological changes of COPD via suppression of neutrophilic inflammation. | [104] |
Anthocyanins delphinidin and cyanidin from the edible fruits of Eugenia brasiliensis | CSE treatment: SAE cells | Delphinidin inhibited IL-8 in the CSE-treated cells in a dose-dependent manner. | [181] |
Flower buds of Tussilago farfara L. | CS exposure: mice | FTF-EtOH effectively attenuated lung inflammation in vitroand in vivo. The protection of FTF-EtOH against inflammation was produced by activation of Nrf2 and inhibitions of NF-κB and NLRP3 inflammasome. | [90] |
Glycyrrhiza glabra, Agastache rugosa | Coal fly ash, diesel-exhaust particle exposure: male BALB/c mice | Herbal combinational mixture more effectively inhibited neutrophilic airway inflammation by regulating the expression of inflammatory cytokines and CXCL-2 by blocking the IL-17/STAT3 pathway. | [182] |
Pomegranate juice | CS exposure: male C57BL/6J mice CSE treatment: A549 cells | The expression of inflammatory mediators and the emphysematous changes noted with chronic CS exposure were reduced with pomegranate juice supplementation. In vitro, pomegranate juice attenuated the damaging effects of CSE on cultured human alveolar cells. | [97] |
Total flavonoids from sea buckthorn | CSE/LPS treatment: HBE16 cells CS exposure: male ICR mice with LPS | Total flavonoids from sea buckthorn including quercetin and isorhamnetin showed potent binding affinities to MAPK1 and PIK3CG, two upstream kinases of ERK and Akt, respectively. Against LPS/CS-induced airway inflammation through inhibition of ERK, PI3 K/Akt and PKCα pathways. | [183] |
Extracts of Ximenia americana L. | CS exposure: male and female rats | The aqueous extract of X. americana presents itself as a new option for CS-COPD treatment. | [184] |
Melatonin | CS exposure: male Swiss albino mice CSE treatment: L-132 cells | Activated the intracellular antioxidant thioredoxin-1 (thereby suppressing the TXNIP–NLRP3 pathway) and inhibited the impaired the mitophagy mediated inflammasome activation (upregulating PINK-1, Parkin, LC3B-II expression). Also improved the overall antioxidant status of the COPD lung via Nrf2–HO-1 axis restoration. | [142] |
| CSE treatment: HAECs | Melatonin effectively protected against smoking-induced vascular injury and atherosclerosis through the Nrf2–ROS–NLRP3 signalling pathway. | [185] |
CS exposure: male Wistar rats with LPS | Melatonin attenuated airway inflammation via SIRT1-dependent inhibition of NLRP3 inflammasome and IL-1β in COPD rats. | [143] |
TFEB | CSE treatment: RAW 264.7 cells | TFEB acted as autophagy-inducing drugs in restoring of CS-impaired phagocytosis. | [186] |