TABLE 1.

The effects of flavonoid on COPD.

Flavonoids	Sources	Models	Effects	Dose	Application	Ref
Baicalin	Scutellaria baicalensis Georgi	In vivo: COPD mice model was established by cigarette smoke (CS) exposure	Inhibition of the NF-kB pathway	20–80 mg/kg	In vivo	Lixuan et al. (2010)
		In vitro: cell model was established by using cigarette smoke extract (CSE) to stimulate type-II pneumocytes		5–20 μM	In vitro
		CS-induced inflammatory models in mice; CSE-induced inflammatory models in A549 cells	Modulating HDAC2/anti-inflammatory	25–100 mg/kg	In vivo	Li et al. (2012)
				10–100 μM	In vitro
		CS-induced rat model of COPD	Anti-infammatory/anti-airway remodeling/antioxidant	40–160 mg/kg	In vivo	Wang et al. (2018a)
		CS/CSE-induced airway inflammation in mice or human bronchial epithelial (HBE) cells	Anti-infammatory	40–160 mg/kg	In vivo	Zhang et al. (2021)
				10–40 μM	In vitro
		CSE-induced MLE-12 cells; CS-induced COPD mice model	Regulation of HSP72-mediated JNK pathway	25–100 mg/kg	In vivo	Hao et al. (2021)
				5–20 μmol/L	In vitro
Quercetin	Polygoni avicularis herba	CSE-induced muman monocytic U937 cells and peripheral blood mononuclear cells (PBMC) collected from patients with COPD	Increased AMPK activation and Nrf2 expression, and restored corticosteroid resistance	10 μM	In vitro	Mitani et al. (2017)
		CSE-induced mice model/human airway epithelial NCI-H292 cells	Inhibiting the NF-κB pathway and EGFR phosphorylation	25–50 mg/kg	In vivo	Yang et al. (2012)
				5–20 μM	In vitro
		Primary human osteoblasts exposed to cigarette smoke medium (CSM)	Activation of the anti-oxidative enzymes HO-1 and SOD-1	25–100 μM	In vitro	Braun et al. (2011)
		Elastase/lipopolysaccharide (LPS)-exposed mice	Negatively regulating MMP expression	10 mg/kg	In vivo	Ganesan et al., 2010
		Rhinovirus-infected mice with COPD phenotype	Preventing progression of lung disease in COPD	0.1% quercetin containing diet	In vivo	Farazuddin et al. (2018)
Silymarin	Silybum marianum	CS-induced mice mode	Suppression of inflammation and oxidative stress by inhibiting the ERK/p38 MAPK pathway	25–50 mg/kg	In vivo	Li et al. (2015)
		CSE-induced human bronchial epithelial cell line (BEAS-2B) model	Inhibition of autophagy and the ERK/p38 MAPK pathway	10–40 μM	In vitro	Li et al. (2016a)
Silibinin	Silybum marianum	CS and LPS exposure-induced mice model	Inhibited the pulmonary fibrosis induced by CS via suppression of TGF-β1/Smad 2/3 signaling	10–20 mg/kg	In vivo	Ko et al. (2017)
		CS-/LPS-induced COPD model mice; CS condensate-stimulated H292 cells	Inhibition in ERK phosphorylation	20–40 mg/kg	In vivo	Park et al. (2016)
				6.25–50 μg/ml	In vitro
Icariin	Epimedium	CSE-exposed BEAS-2B cells model	Reversing Glucocorticoids (GC)resistance	20–80 µM	In vitro	Hu et al. (2020)
		CS-induced lung inflammation using BALB/c mice; CSE-exposed A549 epithelial cells	Ameliorated inflammation by suppressing NF-kB activation and modulating glucocorticoid receptor (GR) protein expression	25–100 mg/kg	In vivo	Li et al. (2014)
				10–100 µM	In vitro
Casticin	Vitex rotundifolia and Vitex agnus-castus	CS-induced C57BL/6 mice model	Inhibition of inflammatory cytokines and chemokines	1–10 mg/kg	In vivo	Lee et al. (2015)
		CS-exposed mice	Attenuated oxidative Stress and inflammation via inhibition of NF-ĸB	10–30 mg/kg	In vivo	Li et al. (2020)
Fisetin	Gleditsiae spina	Human airway epithelial cells	Inhibiting the TNF-α/NF-κB signaling pathway	2.5–10 μM	In vitro	Lee et al. (2018a)
		CS-exposed mice	Up-regulation of Nrf2 expression	50 mg/kg	In vivo	Hussain et al. (2019)
Phloretin	Crotonis fructus; Rubi fructus	CS-induced mice model; CSE-induced NCI-H292 cells model	Inhibition of epidermal growth factor receptor (EGFR)/MAPK signaling pathways	10–20 mg/kg	In vivo	Wang et al. (2018b)
				1–10 μM	In vitro
Morin	Cudrania tricuspidata	CS-induced mice model	Anti-inflammation via inhibiting the P13K/ATK/NF-κB signaling pathway	10–40 mg/kg	In vivo	Cai et al. (2018)
Oroxylin A	Scutellaria baicalensis Georgi	CS-stimulated BEAS-2B cells and RAW264.7 cells; CS-induced mice	Activating the Nrf2 signaling pathway	15–60 mg/kg	In vivo	Li et al. (2016b)
				50–150 μM	In vitro
Hesperetin	Citrus reticulata	CSE-induced mice model	Regulation of SIRT1/PGC-1α/NFκ-B signaling axis	25–50 mg/kg	In vivo	Wang et al. (2020)
		CS- and urethane-induced lung cancer with COPD in mice	Preventing COPD progression to lung cancer	25–100 mg/kg	In vivo	Zhou et al. (2021)
Liquiritin apioside	Glycyrrhiza uralensis	CSE-induced cell injury in the A549 lung epithelial cell; CS-induced mice inflammation model	Inhibiting TGF-β and TNF-α expression and increasing levels of GSH	3–30 mg/kg	In vivo	Guan et al. (2012)
				108–106 M	In vitro
Isoliquiriti-genin	liquorice	CS-induced mice model	Regulating the Nrf2 and NF-κB signaling pathways	10–30 mg/kg	In vivo	Yu et al. (2018a)
Chrysin	Flowers	CS-induced airway inflammation in mice	Inhibition of ERK and p38 phosphorylation	10–20 mg/kg	In vivo	Shen et al. (2015)
Naringenin	Amacardi-um occidentale L	CS-induced mice model; CSE-exposed A549 cells	Suppression of NF-κB	20–80 mg/kg	In vivo	Liu et al. (2018)
					In vitro