Elsevier

Phytomedicine

Volume 104, September 2022, 154259
Phytomedicine

Review
Artesunate: A review of its therapeutic insights in respiratory diseases

https://doi.org/10.1016/j.phymed.2022.154259Get rights and content
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Abstract

Background

Artesunate, as a semi-synthetic artemisinin derivative of sesquiterpene lactone, is widely used in clinical antimalarial treatment due to its endoperoxide group. Recent studies have found that artesunate may have multiple pharmacological effects, indicating its significant therapeutic potential in multiple respiratory diseases.

Purpose

This review aims to summarize proven and potential therapeutic effects of artesunate in common respiratory disorders.

Study design

This review summarizes the pharmacological properties of artesunate and then interprets the function of artesunate in various respiratory diseases in detail, such as bronchial asthma, chronic obstructive pulmonary disease, lung injury, lung cancer, pulmonary fibrosis, coronavirus disease 2019, etc., on different target cells and receptors according to completed and ongoing in silico, in vitro, and in vivo studies (including clinical trials).

Methods

Literature was searched in electronic databases, including Pubmed, Web of Science and CNKI with the primary keywords of ‘artesunate’, ‘pharmacology’, ‘pharmacokinetics’, ‘respiratory disorders’, ‘lung’, ‘pulmonary’, and secondary search terms of ‘Artemisia annua L.’, ‘artemisinin’, ‘asthma’, ‘chronic obstructive lung disease’, ‘lung injury’, ‘lung cancer’, ‘pulmonary fibrosis’, ‘COVID-19′ and ‘virus’ in English and Chinese. All experiments were included. Reviews and irrelevant studies to the therapeutic effects of artesunate on respiratory diseases were excluded. Information was sort out according to study design, subject, intervention, and outcome.

Results

Artesunate is promising to treat multiple common respiratory disorders via various mechanisms, such as anti-inflammation, anti-oxidative stress, anti-hyperresponsiveness, anti-proliferation, airway remodeling reverse, induction of cell death, cell cycle arrest, etc.

Conclusion

Artesunate has great potential to treat various respiratory diseases.

Graphical abstract

Artesunate: A Review of Its Therapeutic Insights in Respiratory Diseases.

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Keywords

Artesunate
Respiratory disease
Bronchial asthma
Chronic obstructive lung disease
Lung cancer
COVID-19

Abbreviations

3-NT
3-nitrotyrosine
8−OhdG
8-hydroxy-2′-deoxyguanosine
α-SMA
α-smooth muscle actin
ACE2
angiotensin-converting enzyme 2
AHR
airway hyperresponsiveness
AIF
apoptosis-inducing factor
AJ
adherence junction
ALI
acute lung injury
AP-1
activator protein 1
ARDS
acute respiratory distress syndrome
ASAS
artesunate
ASM
airway smooth muscle
ASMC
airway smooth muscle cell
ATP
adenosine triphosphate
BALF
bronchoalveolar lavage fluid
CAM
chicken embryo metastasis
Cdc2
cell division cycle 2
CLC
Charcot-Leyden crystal protein
COPD
chronic obstructive pulmonary disease
COVID-19
coronavirus disease-19
COX-2
cyclooxygenase-2
CS
cigarette smoke
CSE
cigarette smoke extract
DAMP
danger-associated molecular pattern
DC
dendritic cell
DCR
disease controlled rate
DHA
dihydroartemisinin
E protein
envelope protein
EC
epithelial cell
ECM
extracellular matrix
EGFR
epidermal growth factor receptor
GCM
goblet cell metaplasia
GM-CSF
granulocyte-macrophage colony-stimulating factor
GSH
glutathione
HDAC2
histone deacetylase 2
HMGB1
High Mobility Group Box 1
HO-1
heme oxygenase 1
HSP47
heat shock protein 47
ICAM-1
intercellular adhesion molecule-1
IL
interleukin
ILC
innate lymphoid cell
iNOS
inducible nitric oxide synthase
IP-10
IFNγ-induced protein 10
IP3
inositol (1, 4, 5)-triphosphate
IPF
Idiopathic pulmonary fibrosis
KC
keratinocyte chemoattractant
Keap1
Kelch-like ECH-associated protein 1
LPS
lipopolysaccharide
M protein
membrane protein
MAPK
mitogen-activated protein kinases
MBP
major basic protein
MCP-1
monocyte chemoattractant protein 1
MDA
malondialdehyde
MPO
myeloperoxidase
MPT
mitochondrial permeability transition
MST
mean survival time
NF- κB
nuclear factor kappa B
NLRP3
nucleotide-binding domains and leucine-rich repeat pyrin domains containing 3
NO
nitric oxide
NOX
NAPDH oxidase
Nrf2
nuclear factor erythroid-2-related factor 2
NSCLC
non-small cell lung cancer
OVA
ovalbumin
PCD
programmed cell death
PF
pulmonary fibrosis
PI3K
phosphoinositide 3-kinase
PLCc
phospholipase Cc
RBD
receptor-binding domain
RIR
renal ischemia-reperfusion
ROS
reactive oxygen species
S protein
spike protein
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SD
Sprague Dawley
SLI
septic lung injury
Smac
second mitochondrial activator of caspases
TAS2R
bitter taste receptors
TFRC
transferrin receptor
TGF-β1
transforming growth factor β1
TIMP-1
tissue inhibitor of matrix metalloproteinases 1
TJ
tight junction
TLR4
Toll-like receptor 4
TNF-α
tumor necrosis factor α
TTP
time to progression
u-PA
urokinase-type plasminogen activator
W/D
wet/dry ratio
WHO
World Health Organization
xCT
cystine/glutamate transporter

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