Table 5.

Effects of artemisinins and its derivatives on other features.

Feature	Disease model	Cell line(s)/ stimulus/ allergen/ animal type	Derivative	Effective conc./ dose; route of administration	Outcomes	in vitro/ in vivo	Ref.
Lung function	Asthma	Mouse/ human ASM cells	Artesunate	0.75−2 mM	↓ traction force; ↑ [Ca2+]i	in vitro	[78]
	Asthma (airway inflammation)	CSE or OVA; BALB/c mice	Artesunate	30 mg/kg; i.p.	↓ AHR	in vivo	[50]
	Allergic asthma	OVA; BALB/c mice	Artesunate	3−30 mg/kg; i.p.	↓ AHR		[74]
	Allergic asthma	OVA; BALB/c mice	DHA	30 mg/kg/day; i.g.	↓ AHR		[75]
	Asthma	OVA; BALB/c mice	DHA	50 mg/kg/day; i.p.	↓ AHR		[76]
	Asthma	OVA; BALB/c mice	Artesunate	30−120 μg	↓ AHR		[78]
	Allergic rhinitis	OVA; BALB/c mice	Artemisinin	10−100 mg/kg/day; nasally	↓ sneezing, nasal rubbing		[77]
Angiogenesis	Tumour lymphangiogenesis	LLC	Artemisinin	5−20 μM	↓ VEGF-C	in vitro	[57]
	Lung cancer	A549; BALB/c nude mice	DHA	10 mg/kg; i.p.	↓ VEGF, microvessel density	in vivo	[29]
	Lung cancer	A549 and A549/DDP; BALB/c athymic mice	DHA	50, 100, 200 mg/kg/day; i.g.	↓ HIP-1α, VEGF, tumour microvessel density		[56]
			Cisplatin	2 mg/kg/3 days, 12 (A549) or 28 (A54/DDP) days; i.p.
	Lung cancer	LLC; C57BL/6 mice	Artemisinin	50 mg/kg/day; orally	↓ LMVD, VEGF-C, p-p38		[57]
Fibrosis/ remodelling	Lung cancer	H460, H1299, Calu3, LXF289, A549, H1398	Artesunate	2.5 μM	↓ u-PA, MMP2, MMP7 and NF-κB activities	in vitro	[54]
	EMT	TGFβ1-induced EMT RLE-6TN	Artesunate	n.d.	↓ p-Smad3, Smad3; ↑ Smad7		[82]
	Pulmonary fibrosis	AEC	DHA	5−7 mol/L	↓ sm-α actin		[65]
	Allergic asthma	OVA; C57BL/6 mice	Artesunate	30 mg/kg; i.p.	↓ sm-α actin, cyclin D1	in vivo	[31]
	Allergic asthma	OVA; BALB/c mice	Artesunate	3−30 mg/kg; i.p.	↓ muc5ac, mucus hypersecretion		[74]
	Allergic asthma	OVA; BALB/c mice	DHA	30 mg/kg/day; i.g.	↓ muc5ac		[75]
	Asthma	OVA; BALB/c mice	DHA	50 mg/kg/day; i.p.	↓ mucus		[76]
	Pulmonary fibrosis	Bleomycin; Sprague Dawley rats	DHA	50 mg/kg/day; i.p.	↓ alveolitis, fibrosis, sm-α actin, MDA; ↑ E-cadherin		[65]
	Pulmonary fibrosis	Bleomycin; Sprague Dawley rats	DHA	25−100 mg/kg/day; i.p.	↓ hydroxyproline, TGFβ1, TNF-α, sm-α actin, NF-κB		[79]
	Pulmonary fibrosis	Bleomycin; Sprague Dawley rats	Artesunate	100 mg/kg/day; i.p.	↓ hydroxyproline, TGFβ1, Smad3, hsp47, sm-α actin, collagen I		[80]
	Pulmonary fibrosis	Bleomycin; Sprague Dawley rats	Artesunate	100 mg/kg/day; i.p.	↓ collagen-IV, TIMP1, TIMP2; ↑ MMP2, MMP9		[81]
	Lung cancer	A549; BALB/c nude mice	Artesunate	10−40 mg/kg/day; i.p.	↓ ICAM-1, MMP9		[30]
	Lung cancer	A549; BALB/c mice and ovariectomized mice	ARTD	10−20 mg/kg; oral gavage	↓ RANKL, MMP9, cathepsin K		[58]
	Metastasis assay	H460; chicken embryo	Artesunate	i.v.	↓ u-PA, MMP2, MMP7		[54]
Oxidative stress	Lung cancer	A549, H1975	DHA	7.5−30 μM	↓ Warburg effect, NF-κB, c-myc, GLUT1	in vitro	[55]
	Pulmonary fibrosis	Bleomycin; Sprague Dawley rats	DHA	50 mg/kg/day; i.p.	↑ Nrf2, HO-1, SOD, GSH	in vivo	[65]
Others	Asthma	CSE/ OVA-induced airway inflammation in BEAS-2B	Artesunate	10 μM	Reversed glucocorticoid (Dex 10−11-10-6 M) insensitivity	in vitro	[50]
	Lung cancer	A549	DHA	10−60 μM	↓ glucose uptake, glycolysis (ATP and lactate), glycolytic metabolism (p-mTOR, GLUT1)		[21]
		PC-9		8−64 μM
	Lung cancer	A549, ASTC-a-1	DHA	20 μg/mL	↑		[46]
	Lung cancer	A549	ARTD	2.5−7.5 μM	↓ HNF4A; ↑ ATF3		[58]
	ALI	LPS; BALB/c mice	Artesunate	10−40 mg/kg; i.v.	↓ lung wet-to-dry ratio	in vivo	[52]
	ALI	RIR; Sprague Dawley rats	Artesunate	15 mg/kg; i.p.	↓ lung wet-to-dry ratio		[53]
	Pulmonary fibrosis	Bleomycin; Sprague Dawley rats	Artesunate	100 mg/kg/day; i.p.	↓ mortality		[80]

n.d.: no data.