TABLE 1.

Summary of the in vitro researches about pharmacological activities of RSV in IDD

Type of model	Dose	Findings	Molecular mechanism	Reference
Human NP cells	10, 20, 50 μM	HSP90↑, N‐cadherin↑, aggrecan↑, collagen II↑, collagen X↓, IL‐6↓, p‐JAK1↓, p‐STAT3↓	Promoted ECM synthesis and inhibited NP cells apoptosis by blocking IL‐6/JAK/STAT3 pathway	54
SD rats NP cells	100 μM RSV	caspase‐3↓, Bcl‐2↑, Bax↓, cleaved PARP↓, p‐Akt/Akt↑	Inhibited IL‐1β‐induced NP cells apoptosis through activation of PI3K/Akt pathway	21
SD rats NP cells	100 μM RSV	ROS↓, SA‐β‐Gal activity↓, telomerase activity↑, p16↓, p53↓, MMP‐3↓, MMP‐13↓, ADAMTS4↓, collagen II↑, aggrecan↑	Inhibited NP cells senescence in inflammatory environment	55
Pig NP tissues	50 and 100 μM	GAG↑, HYP↑, aggrecan↑, collagen II↑, p‐Akt/Akt↑, SOX‐9↑	Promoted ECM biosynthesis through activating the PI3K/Akt signaling pathway under mechanical compression	69
Human NP Cells	50 μM RSV	SIRT1↑, aggrecan↑, collagen II ↑, MMP‐1↑	Promoted ECM biosynthesis by activating the SIRT1 expression	73
Human NP Cells	25 μM	SIRT1↑, collagen II ↑, MMP‐13↓, ADAMTS‐5↓, p21↓, p16↓	Promoted ECM biosynthesis, suppressed cellular senescence, increased cell proliferation, and restrained the apoptosis by activating the SIRT1 expression	72
Human NP Cells	100 μM	aggrecan↑, collagen II↑, SIRT1↑, β‐catenin↓	Promoted ECM biosynthesis by activating the SIRT1 expression via Wnt/β‐catenin signaling pathway	22
SD rats NP cells	1 μM E2, 10 μM, 100 μM and 200 μM RSV	collagen II↑, aggrecan↑, MMP‐3↓, MMP‐13↓, p‐Akt/Akt↑, caspase‐3↓	Combined with E2 inhibited NP cells apoptosis and ECM degradation by activating PI3k/Akt pathway	74
Bovine NP cells	10, 50, 200 μM RSV	MMP‐13↓, ADAMTS4↓, PG↑, CREB↓	Slowed the progression of IDD by inhibiting catabolism and promoting PG synthesis in NP cells	75
SD rats NP cells	100 μM RSV	caspase‐3↓, caspase‐9↓, mitochondrial membrane potential↑, ROS↓	Inhibited SNP induced NP cells apoptosis by scavenging ROS	20
Pig NP tissues	50 μM, 100 μM RSV	Caspase‐9 activity↓, Caspase‐3 activity↓, Bcl‐2↑, Bax↓, caspase‐3↓, p‐ERK1/2↓	Inhibited mechanical compression induced NP cells apoptosis through the inhibition of ERK1/2 pathway	79
SD rats NP cells	100 μM	Bcl‐2↑, Bax↓, caspase‐3↓, p16↓, p53↓, p‐Akt/Akt↑	Inhibited high glucose induced NP cells apoptosis and senescence by activating the PI3K/Akt pathway	82
Human NP cells	100 μM RSV 1 mM E2	caspase‐3↓, p‐mTOR/mTOR↑, P‐GSK‐3b/GSK‐3b↑, NF‐κB↓	Combined with E2 prevented IL‐1β induced NP cells apoptosis via the PI3K/AKT/mTOR and PI3K/AKT/ GSK‐3β Pathway	84
Human NP cells	50 μM	mitochondrial membrane potential↑, ROS↓, LC3II/LC3 I↑, p62↓	Attenuated oxidative stress induced mitochondrial dysfunction by activation of autophagy	87
SD rats NP cells	50 μM	aggrecan↑, collagen II↑, LC3II/LC3 I↑, beclin‐1↑, GAG↑, p‐Akt/Akt↑	Promoted ECM biosynthesis through activating autophagy via the PI3K/Akt pathway under oxidative damage	23
Human NP cells	24 μM RSV	MMP‐3↓, SIRT1↑, p‐AMPK↑, beclin‐1↑, LC3II/LC3 I↑	Inhibited TNF‐a–induced MMP‐3 expression by activating autophagy via SIRT1/AMPK pathway	88
Human NP cells	8 μM RSV	LC3II/LC3 I↑, Nampt↑, NAD + ↑, SIRT1↑	Promoted autophagy of NP cells by activating Nampt/NAD+/SIRT1 signaling pathway	89
SD rats NP cells	30 μM, 60 μM RSV	SA‐β‐Gal activity↓, ROS↓, telomerase activity↑, p16↓, p53↓	Inhibited NP cells senescence induced by mechanical overload through inhibition of ROS/NF‐κB pathway	19
SD rats CEP cells	10 μM, 20 μM, 30 μM, 40 μM RSV	TNF‐α↓, IL‐10↑, HMGB1↓, p‐ERK↓, Bax ↓, Bcl‐2↑	Inhibited CEP cells apoptosis by suppressing HMGB1/ERK signaling pathway	95