1
Examining the Effectiveness of the Artemisinin.
Super-Herb Artemisinin (Antimalarial Drugs) Kills Parasites (Plasmodium), Cancer Cells,
Viruses and Other Pathogens and Mammalian Diseases
Student’s Name
Department
Institution Affiliation
Word Count: 1120
2
Abstract
Artemisinin is extracted from a Chinese herb known as Artemisia annual and is firmly
established as an effective treatment of malaria. Nevertheless, its effectiveness extends to the
treatment of parasitic infections such as schistosomiasis. Artemisinin is composed of
dihydroartemisinin (DHA), artemether, artesunate, and arteether. In this vein, they have shown
immense potential in sidelining cancerous properties in animal models and cell lines.in this regard,
this paper examines various roles of artemisinin in medicine more so on their contentious
mechanism of action.
Key words: Schistosoma, Artemisinin, Artesunate, Plasmodium
Introduction
Discovery of the artemisinin drug is a remarkable achievement in the field of medicine in
21st century. Moreover, it’s safe and affordable as compared to other forms of malaria treatment
such as administration of the classical quinolone antimalarial and has a great potential in oncology.
According to the world health organization (WHO), more than 500 million cases of malaria
infections are treated on annual basis. Artemisinins assists in combating parasites species such as
protozoa which are unrelated to apicomplexan parasites such as Plasmodium species which is an
active agent of malaria. On the other hand, artemisinins counters against metazoan parasites such
as Schistosoma spp.In addition, they exhibit anti-disease properties such as potent anticancer
activities in both in vitro and in vivo model of colorectal cancer. The duo focuses on advancing
the field of arteminism science and usage that indicates the potential role of the arteminism to
combat acetylsalicylic acid through anti-disease mechanisms. The artemisinin has proven to be
effective in treating malaria and diverse types of cancer such as colorectal cancer
3
Plasmodium Vs Schistosoma
There are similarities and differences as far as Plasmodium and Schistosoma parasites are
concerned. There are similarities in the mechanisms behind the formation of pigments Plasmodium
berghei and schisto-soma mansoni respectively. The fundamental principle underlying this process
is that both pigments emanate from digestion of these parasites of the hemoglobin of erythrocytes.
Arthemeter is used to treat Schistosoma infection although it has limitation especially when the
patient is suffering from severe liver, early pregnancy, renal or hematologic diseases and allergy
to artemether. 2
Artemisinin and Its Derivatives as a Treatment for Cancer
In recent years, artemisinin has been reported to contain anti-cancer activities where the
anti-cancer mechanisms resemble its mechanism towards malaria parasites.4 In this case, the anticancer mechanism is catalyzed by Heme, an iron-containing compound that is a crucial component
of many biologically essential proteins such as metabolic pathway enzymes and hemoglobin.5-7 In
addition, malaria parasites heavily rely on the hemoglobin as a source of the food when residing
in red blood cells. A large amount of home is released when the parasites digest hemoglobin
consequently leading to the activation of the artemisinin in the parasites, destroying multiple
proteins that are a necessity for survival thus killing them.8
Arteminism in Cancer Treatment
Cancer cells have higher amount of Heme and an elevated Heme biosynthesis pathways as
compared to the non-cancer cell.1 Essentially, cancer cells have high rates of metabolism and
various metabolic pathway enzymes require Heme for their activities. This makes it possible for
artemisinin to combat and destroy cancer cells. Artesunate a derivative of artemisinin can be
4
administered by oral, rectal and parenteral routes. In this case, artemisinin via in vitro and animal
models have justified their remarkable ability to exert a wide array of anti-cancer effects, 3, 9
additionally, they reduce cell proliferation and angiogenesis subsequently triggering apoptosis.
There have been isolated cases of anti-cancer effects of artemisinin such as cases of laryngeal
squamous carcinoma, metastatic uveal melanoma, and pituitary macroadenoma.
The Antiviral Activities of Artemisinin and Its Derivatives
Artemisinin and its derivatives have a huge potential in combating viruses such as herpes
simplex virus type 1(HSV-1), Human Cytomegalovirus (HCMV AD169) and Hepatitis B and C
virus among others. Artesunate has a potential in inhibiting HCMV and other different types of a
virus with a variety of phenotype11. These include low passage clinical isolates, drug-resistant
mutants, recombinant virus clones and laboratory strains all are highly responsive to artesunate.in
this case, artesunate inhibits central regulatory processes of the infected cells thus interfering with
the critical cell host type and metabolism requirement for virus replication.10
Advantages of Artemisinin
Artemisinin and its structural components are not toxic hence are safe and well tolerated.
Several reports of artemisinin toxicities have been reported in cell lines and laboratory species
which are due to prolonged exposure to artemisinin at high doses12. Most animals are affected by
high doses of arteninism especially in neuro brainstem center but these findings have not been
established in humans. Therefore, it remains one of the most used treatments for cancer and
malaria.14
Limitations of the Arteminisins
5
There has been a huge debate concerning the potential of the artemisinin in the treatment
of malaria since the chemical interactions of both artemisinin and parasite is not well known.15In
addition, the role of the ferrous species in the antimalarial actions of the Arteminisisns is also
questioned since cations can act as a catalyst in vitro reactions in artemisinin such as their
decomposition in aqueous solutions.13 Further, fully synthetic trioxolanes contains endoperoxide
but lacks other essential properties of artemisinins consequently increasing complexity of the
debate regarding mechanism action of arteminisins.in essence, clarifying the mechanisms of action
of the artemisinins is crucial for understanding how fully synthetic trioxolanes might function and
the principles of the development of the resistance by parasites particularly to this class of the
antimalarial. However, various models such as rodent malarial have been formulated to assist in
comprehension of resistance mechanisms of distinct categories of the antimalarial.19 For example,
genetic analyses permitted by Plasmodium chabaudi carried out in mice established a locus
interconnected to artemisinin resistance that is stable after mosquito passage. In this case, this
resistance is attributed to a de-ubiquitination enzyme that often functions in the endoplasmic
reticulum of parasites and encompassed in stress response.16, 17, and 18
In conclusion, Arteminisins are strongly are administered together with combination
therapies to combat drug-resistant malaria. In addition, this drug acts as anti-schistomasal agents
which have great potential to treat a broad range of diseases such as advanced cancers that have
presented an immense challenge for decades. Artemisias coupled with existing therapies have also
been proven to treat tumors although there is a need for further investigations of drugs such as
artesunate for specialized oncological treatments. Further, artemisinin derivatives have immensely
revolutionized the management and treatment of malaria. The treatment is safe and efficient
thereby reducing malaria-related morbidity and mortality. However, its aspect of resistance may
6
be a threat hence compromise the milestone achieved so far. In this vein, there is an urgent need
to combat artemisinin resistance by all means possible to ease the burden of the malaria epidemic
in the continent, especially in sub-Saharan Africa
7
References
1. Chen Q, Espey MG, Sun AY, et.al. Pharmacologic doses of ascorbate act as a prooxidant
and decrease growth of aggressive tumor xenografts in mice. Proceedings of the National
Academy of Sciences. 2008 Aug 12; 105(32):11105-9.
2. Ariey F, Witkowski B, Amaratunga C, et al. A molecular marker of artemisinin-resistant
Plasmodium falciparum malaria. Nature. 2014 Jan 2; 505(7481):50-5.
3. Ashley EA, Dhorda M, Fairhurst RM, et al. Spread of artemisinin resistance in Plasmodium
falciparum malaria. New England Journal of Medicine. 2014 Jul 31; 371(5):411-23.
4. Tun KM, Imwong M, Lwin KM, et al. Spread of artemisinin-resistant Plasmodium
falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker. The Lancet
infectious diseases. 2015 Apr 30; 15(4):415-21.
5. Miotto O, Amato R, Ashley EA, MacInnis B, Almagro-Garcia J, Amaratunga C, Lim P,
Mead D, Oyola SO, Dhorda M, Imwong M. Genetic architecture of artemisinin-resistant
Plasmodium falciparum. Nature genetics. 2015 Mar 1; 47(3):226-34.
6. Mok S, Ashley EA, Ferreira PE, Zhu L, Lin Z, Yeo T, Chotivanich K, Imwong M,
Pukrittayakamee S, Dhorda M, Nguon C. Population transcriptomics of human malaria
parasites reveals the mechanism of artemisinin resistance. Science. 2014 Dec 11:1260403.
7. Bastiaens GJ, Bousema T, Leslie T. Scale-up of malaria rapid diagnostic tests and
artemisinin-based combination therapy: challenges and perspectives in sub-Saharan
Africa. PLoS medicine. 2014 Jan 21;11(1):e1001590.
8. Steely AM, Willoughby Sr JA, Sundar SN, Aivaliotis VI, Firestone GL. Artemisinin
disrupts androgen responsiveness of human prostate cancer cells by stimulating the 26S
8
proteasome-mediated degradation of the androgen receptor protein. Anti-cancer drugs.
2017 Oct 1; 28(9):1018-31.
9. Ho WE, Peh HY, Chan TK, Wong WF. Artemisinins: pharmacological actions beyond
anti-malarial. Pharmacology & therapeutics. 2014 Apr 30; 142(1):126-39.
10. Kumari K, Keshari S, Sengupta D, Sabat SC, Mishra SK. Transcriptome analysis of genes
associated with breast cancer cell motility in response to Artemisinin treatment. BMC
cancer. 2017 Dec; 17(1):858.
11. Efferth T. From ancient herb to modern drug: Artemisia annua and artemisinin for cancer
therapy. InSeminars in cancer biology 2017 Oct (Vol. 46, pp. 65-83).
12. Das AK. Anticancer effect of antimalarial artemisinin compounds. Annals of medical and
health sciences research. 2015; 5(2):93-102.
13. Gerhardt T, Jones R, Park J, Lu R, Chan HW, Fang Q, Singh N, Lai H. Effects of
antioxidants and pro-oxidants on cytotoxicity of dihydroartemisinin to Molt-4 human
leukemia cells. Anticancer research. 2015 Apr 1; 35(4):1867-71.
14. Krishna S, Ganapathi S, Ster IC, Saeed ME, Cowan M, Finlayson C, Kovacsevics H,
Jansen H, Kremsner PG, Efferth T, Kumar D. A randomised, double blind, placebocontrolled pilot study of oral artesunate therapy for colorectal cancer. EBioMedicine. 2015
Jan 31; 2(1):82-90.
9
15. Mesa LE, Lutgen P, Velez ID, Segura AM, Robledo SM. Artemisia annua L., Potential
Source of Molecules with Pharmacological Activity in Human Diseases. International
Journal of Medical Research and Review. 2015 May 31; 3(5):436-50.
16. Liu YX, Wu W, Liang YJ, Jie ZL, Wang H, Wang W, Huang YX. New uses for old drugs:
the tale of artemisinin derivatives in the elimination of schistosomiasis japonica in China.
Molecules. 2014 Sep 19; 19(9):15058-74.
17. Shi C, Li H, Yang Y, Hou L. Anti-inflammatory and immunoregulatory functions of
artemisinin and its derivatives. Mediators of inflammation. 2015 Apr 16; 2015.
18. Picot S. The Other Face of Artesunate: Southern Drug to Treat Northern Diseases.
EBioMedicine. 2015 Jan 1; 2(1):17-8.
19. Sun J, Li C, Wang S. Organism-like formation of Schistosoma hemozoin and its function
suggest a mechanism for anti-malarial action of artemisinin. Scientific reports. 2016; 6.