Table 2.

The biological activities of verticine in references.

Activities	Models	Biological activities	Action mechanism	Ref.
Anti-breast cancer	MCF-7	Inhibit proliferation, reversing multidrug resistance	-	[4, 5]
	MCF -7/TAM	Inhibit proliferation (at 48 h IC50=191.16 g/mL; at 72 h, IC50=138.10 g/mL), induce apoptosis	Decrease expression of Bcl-2	[6]
	4T1	Inhibit proliferation (at 48h, IC50=14.7 μmol/L)	(1) Down-regulate TGF-β, VEGF and MCP-1 secretion, decrease TGF-β and VEGF mRNA expression, regulating its tumor inflammatory microenvironment. (2) Regulate blood viscosity, improve blood flow state, reduce the expression of u-PA, VEGF, PAI-1 protein and the secretion of IL-8, reduce the infiltration of neutrophils, improve TFPI-2 protein expression	[7, 8]
Anti-human leukemia	HL60, HL-60/ADR, K562 K562/A02	Inhibit proliferation (IC50=288.27±34.23, 256.52±26.15, 320.80±36.52, 300.06±33.18, μg/mL), reverse multidrug resistance	Increase intracellular drug concentration and inhibit P-gp protein expression	[5, 9]
	K562 /A02	Inhibit the cell viability and induce apoptosis, different concentrations of verticine (100, 200, 400 mol/L); the cell viabilities were 0.392±0.040, 0.314±0.022, 0.161±0.033	Induce the ROS outbreak and increase the GSH content, redox imbalance	[10, 11]
	K562	Inhibit proliferation (IC50=238 mol/L)
Anti-lung cancer	A549/DDP	Inhibit proliferation, induce apoptosis, reversing multidrug resistance	Down-regulate expression of LRP and ERCC1 mRNA	[12, 13]
Anti-gastric cancer	SGC-7901 and SGC-7901/VCR	Inhibit proliferation	-	[14]
Anti-inflammatory effect	4T1	Regulate inflammatory microenvironment	Control release of inflammatory factors, such as TGF-β, VEGF, MMP-9, and MCP-1, decreasing the expression of TGF-β and VEGF mRNA	[6]
	Confluent NCI-H292 cells	Remedy for inflammatory pulmonary diseases	Inhibit gene and protein expression of MUC5AC mucin induced by EGF, PMA or TNF-α by directly acting on airway epithelial cells	[15]
	LPS-induced RAW264.7 macrophages	Inhibit production of inflammatory cytokines induced by LPS	Block MAPKs and NF-kB signaling pathways	[16]
	HMC-1 Cells	Inhibit production of inflammatory cytokines	Regulate the Phosphorylation of NF-κB and MAPKs	[17]
	HEK 293	anti-inflammatory	Inhibit Kv1.3 channels	[18]
Protection against acute lung injury	Mice	Protective effect on acute lung injury	Inhibit expression of TNF-α, IL-2, IL-6 and IL-8 and COX-2, promote the synthesis and release of SP-A, decrease the levels of PGE2 and NO. And, in addition, down-regulate phosphorylation level of MAPKs in the inflammatory response signaling pathway, and reduce NF-κB gene transcriptional intensity	[19–23]
Tracheobronchial Relaxation	Isolated tracheal strips of guinea pigs	Inhibit contraction	M receptor	[24]
	rat isolated tracheal and bronchial	Inhibit carbachol-induced contraction	Inhibit influx of calcium ions	[25]
Antitussive effect	Mice	Antitussive effect for ammonium hydroxide induced cough (4 mg/kg)	-	[26]
	Guinea pig trachea	Antitussive effect for mechanical stimulation induced cough(4 mg/kg)	-	[26]
	Cat superior laryngeal nerve	Antitussive effect electrical stimulation induced cough (4 mg/kg)	-	[26]
	Mice	Inhibit cough frequency and increase latent period of cough induced by ammonia	-	[27]
Expectorant effect	Mice's tracheal	Enhance mice's tracheal phenol red output in expectorant evaluation	Increase tracheobronchial mucus secretion and decrease the viscosity of mucus	[27, 28]
Sedative effect	Mice	Reduce spontaneous activity, prolong pentobarbital sleep time and increase sleep rate	-	[29]
Analgesic effect	Mice	Inhibit writhing reaction induced by acetic acid	Block Nav1.7 ion channel (IC50=47.2±3.3 μM)	[17, 26]
Inhibit proliferation of cultured Orbital fibroblast	Thyroid-associated ophthalmopathy (TAO)-patients	Different concentrations (5, 25,50, 75, 100 mg/L) inhibit the proliferation of orbital fibroblasts in vitro in a dose-dependent manner.	-	[30]
Inhibit angiotensin converting enzyme (ACE) activity	Rat plasma	Inhibit ACE I activity in a dose-dependent manner (IC50=312.8 μM)	-	[31]
Inhibit acetylcholine (AChE) inhibitory activity		At 100 μg/mL, inhibition rate was only 25%	-	[32]
Inhibit hERG potassium channels	HEK293 cell line	Inhibit hERG peak tail currents with IC50 value of 43.7 mM	channel inactivation, Mutation of Y652 to Alanine reduced sensitivity	[33]