Table 2.

Natural flavonoids with pharmacological potential.

Name	Source	Antioxidant stress	Anti-inflammatory	Antiapoptosis	Promote matrix anabolism	Promote proliferation	Signal path	Type of study	References
Icariin	Epidemic	ROS↓		Caspase-3, Bax↓, Bcl-2↑, TUNEL↓		CCK-8↑	Nrf2	B	[93]
			COX-2, iNOS, PGE2↓		Collagen II, aggrecan↑, MMP3, ADAMTS-4↓	CCK-8↑	MAPK and NF-κB	B	[94]
		ROS↓		Caspase-3, Bax↓, Bcl-2↑		CCK-8↑	PI3K/AKT	A	[95]
Naringin	Citrus fruits		TNF-α↓		Collagen II, aggrecan↑, MMP3↓	MTT↑		B	[100]
				Caspase-3, Bax↓, Bcl-2↑	Collagen II↑, MMP13↓	CCK-8↑	AMPK	A	[101]
			TNF-α, IL-6↓		Collagen II, aggrecan↑, MMP3/13, ADAMTS-4/5↓		NF-κB	B	[102]
		ROS↓		Caspase-3, Bax↓, Bcl-2↑		CCK-8↑	PI3K/Akt	A	[103]
Genistein	Soybeans	ROS↓		Caspase-3, Bax↓, Bcl-2↑	Collagen II↑, ADAMTS-5, MMP13↓	CCK-8↑	Nrf2	A	[107]
			TNF-α, IL-1β↓		Collagen II, aggrecan↑, MMP3↓	CCK-8↑	p38 MAPK	A	[108]
Wogonin	Scutellaria baicalensis Georgi		COX-2, iNOS↓		Collagen II↑, MMP3/13, ADAMTS-4↓	CCK-8/EdU↑	Nrf2/ARE	A	[111]
Luteoloside	Honeysuckle, lettuce, silver flower		TNF-α, COX-2, iNOS, PGE2↓	Caspase-3, Bax↓, Bcl-2↑	Collagen II, aggrecan↑, MMP13, ADAMTS-5↓		NF-κB	A	[114]
Quercetin	Vegetables, fruits, and teas	ROS↓		Caspase-3↓	Aggrecan↑, MMP13↓	CCK-8↑	SIRT1-autophagy	C	[117]
			IL-6, IL-8↓		MMP13, MMP3↓	EDU↑	Nrf2/NF-κB	C	[118]
Baicalein	Scutellaria baicalensis and Scutellaria lateriflora		iNOS, COX-2, TNF-α, IL-6, PGE2, NO↓		Collagen II, aggrecan↑, MMP13, ADAMTS-5↓	CCK-8↑	NF-κB and MAPK	A	[120]
Apigenin	Asteraceae		COX-2, IL-2, IL-6, IL-8, IL-17, IFN-γ, IL-1β↓		Aggrecan↑, MMP1/3/9, ADAMTS-4/5↓	CCK-8↑		A	[122]
Kaempferol	Ginkgo and Moringa		IL-6↓		Collagen II, aggrecan, SOX-9↑, MMP3/13↓	CCK-8↑	NF-κB	D	[124]

A: rat model of NP in vitro, in vivo. B: human model of NP in vitro. C: human model of NP in vitro and rat model of IDD in vivo. D: rat model of BMSCs in vitro.