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Artemisinin is the
chemical compound obtained from the Artemisia annua plant, a component of
Chinese traditional medicine and herbolary. Its use has been described for over
2000 years, mainly for its antipyretic activity. In the 1970s the compound was
discovered in China and has since been used to treat Malaria. Recently, studies
both in vivo and in vitro have shown that artemisinin is not only
capable of treating Malaria, but other diseases. Most of these studies have
centered on its antineoplastic activity, while others have study it in other
fields of medicine, such as dermatology. Because of its low adverse effect
rate, artemisinin and its synthetic derivatives could change the current
paradigm of chemotherapy against cancer.
Interestingly,
there is only one report of an artemisinin derivative to treat patients
infected with the SARS-CoV-2 virus, responsible for the COVID-19 pandemic.
Keywords:
Artemisinin, Artesunate, COVID-19,
Malaria, Herbolary
REVIEW
Artemisia
annua is plant commonly used in Chinese traditional medicine and herbolary. It
has been described for over two thousand years, mainly for its antipyretic
effects. However, it was not until the 1970s that the active compound,
artemisinin, was found by Dr. Youyou Tu while performing research to find
alternative treatments for Malaria, because at the time there was an outbreak
that proved to be resistant to chloroquine and quinolones, the standard
treatment for the disease in the past [1]. She would eventually be awarded the
Nobel prize in Medicine or Physiology for those findings in 2015.
Later
on, synthetic derivatives such as artesunate, artemether, arteether,
dihydroartemisinin among others, were developed and have proved to be more
effective against the Plasmodium parasite than the original compound [2]. The
artemisinin compound is a sesquiterpene with an endoperoxide group, which is
the main source of its cell toxicity capacities.
Artemisinin
is only approved for the treatment of Malaria; however, it has also been used
to treat other diseases and is now a prospect drug for cancer treatment. The
main breakthrough with these findings is not the anticancer capabilities of the
compounds, but rather its minimal adverse effect rates [3,4].
Currently
approved chemotherapy schemes include specific medications that partake in
stopping the cell cycle or inhibiting proteins and enzymes necessary for cell
replication. Although effective and powerful, those medications tend to cause
severe adverse effects to the patient, many times causing to stop treatment.
The
way that artemisinin acts to stop the growth of neoplastic cells is vast and
still not clearly defined, however, many mechanisms of action have been shown
to be a part of this spectrum and include endoperoxide bridges interacting with
heme groups in cancer cells, therefore producing cytotoxic radicals, induction
of apoptosis via cyclin dependent kinases (CDK) and procaspases, inhibition of
cellular replication pathways, assembling of lysosomes, and have also been proved
to inhibit metastasis [5-9].
Studies
have reported artemisinin and its compounds as synergistic drugs for currently
approved cancer medications, as well as sensitizing agents for multidrug
resistant cancer cells [4].
Artemisinin or
other derivatives have been widely studied as a possible alternative cancer
therapy, but recent evidence has shown that it could also be possibly used for
other diseases.
In
the field of dermatology, it has been noted as a drug prospect for common
pathologies. For example, it has been studied for its ability to modulate scar
formation and its beneficial effect on seborrheic keratoses [10,11].
Artesunate
was shown to be effective against other parasitic infections such as
schistosomiasis and could also be effective against viral pathogens such as
Cytomegalovirus, and other members of the Herpesviridae family [12,13]. With
this antiviral effect studied, it is noteworthy to mention the possibility of
artemisinin and its derivative as a treatment prospect for SARS-CoV-2 virus, which
causes the COVID-19 disease, currently a pandemic that has reached all
continents and infected over 8 million people as of mid-June 2020 (https://coronavirus.jhu.edu/map.html).
Because
of its interaction and inhibition of cell signalling pathways involving NF-kB (Nuclear Factor kappa B) and
other interleukins, it is believed that these drugs could be effective and
should be considered and studied to treat COVID-19 patients in the setting of a
clinical trial [14].
As of mid-June 2020, there is only one article
in which artesunate was used to treat COVID-19 patients.
In a study
published in April 2020 in the Nanning region of China, artesunate was studied
for its possible antiviral effect. The control group of the study consisted of
25 patients and were treated with lopinavir-ritonavir and aerosolized
interferon, which they designate as their “standard” treatment, while 18
patients in the experimental group were treated with 60 mg of artesunate twice
daily plus the “standard” treatment. At the cut off of 10 days, the
experimental group showed a reduced time of symptom improvement, negative
SARS-CoV-2 PCR, lung lesion absorption and length of hospital stay, compared
with the control group. All data was statistically significant (p < 0.05)
[15].
With
this brief report in mind, it is quintessential to think of artemisinin and its
derivatives as prospects for many diseases. Because of the minimal adverse
effect rates, scientists should expand clinical trials both in-vitro and
in-vivo to study its benefits and interactions in other morbidities besides
Malaria.
1. Tu
Y (2016) Artemisinin-A gift from Traditional Chinese medicine to the world
(Nobel Lecture) Angew. Chem Int 55: 10210-10226.
2. Li
Y (2012) Qinghaosu (artemisinin): Chemistry and pharmacology. Acta Pharmacol
Sin 33: 1141-1146.
3. Ribeiro
IR, Olliaro PL (1998) Safety of artemisinin and its derivatives: A review of
published and unpublished clinical trials. Med Trop (Mars) 58: 50-53.
4. Konstat-Korzenny
E, Ascencio-Aragón JA, Niezen-Lugo S, Vázquez-López R (2018) Artemisinin and
its synthetic derivatives as a possible therapy for cancer. Med Sci (Basel) 6:
19.
5. Yoon
MK, Mitrea DM, Ou L, Kriwacki RW (2012) Cell cycle regulation by the
intrinsically disordered proteins p21 and p27. Biochem Soc Trans 40: 981-988.
6. Olliaro
PL, Haynes RK, Meunier B, Yuthavong Y (2001) Possible modes of action of the
artemisinin-type compounds. Trends Parasitol 17: 122–126.
7. Crespo-Ortiz
MP, Wei MQ (2012) Antitumor activity of artemisinin and its derivatives: From a
well-known antimalarial agent to a potential anticancer drug. J Biomed
Biotechnol 247597.
8. Willoughby
JA, Sundar SN, Cheung M, Tin AS, Modiano J, et al. (2009) Artemisinin blocks
prostate cancer growth and cell cycle progression by disrupting Sp1
interactions with the cyclin-dependent kinase-4 (CDK4) promoter and inhibiting
CDK4 gene expression. J Biol Chem 284: 2203-2213.
9. Weifeng
T, Feng S, Xiangji L, Changging S, Zhiquian Q, et al. (2011) Artemisinin
inhibits in vitro and in vivo invasion and metastasis of human hepatocellular
carcinoma cells. Phytomedicine 18: 158–162.
10. Nong
X, Rajbanshi G, Chen L, Li J, Li Z, et al. (2019) Effect of artesunate and
relation with TGF-β1 and SMAD3 signaling on experimental hypertrophic scar
model in rabbit ear. Arch Dermatol Res 311: 761-772.
11. Härtel
A, Jung T, Carter SR (2018) Artemether for topical use in patients with
seborrhoeic keratosis. Br J Dermatol 179: 1225-1226.
12. Raffetin
A, Bruneel F, Roussel C (2018) Use of artesunate in non-malarial indications.
Med Mal Infect 48: 238-249.
13. Efferth
T, Romero MR, Wolf DG, Stamminger T, Marin JJ, et al. (2008) The antiviral
activities of artemisinin and artesunate. Clin Infect Dis 47: 804-811.
14. Uzun
T, Toptas O (2020) Artesunate: Could be an alternative drug to chloroquine in
COVID-19 treatment? Chin Med 15: 54.
15. Lin
Y, Wu F, Xie Z (2020) Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 32: 417-420.
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