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 anti-cancer 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 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
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 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Steely AM, Willoughby Sr JA, Sundar SN, Aivaliotis VI, Firestone GL. Artemisinin disrupts androgen responsiveness of human prostate cancer cells by stimulating the 26S proteasome-mediated degradation of the androgen receptor protein. Anti-cancer drugs. 2017 Oct 1; 28(9):1018-31.
- Ho WE, Peh HY, Chan TK, Wong WF. Artemisinins: pharmacological actions beyond anti-malarial. Pharmacology & therapeutics. 2014 Apr 30; 142(1):126-39.
- 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.
- 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).
- Das AK. Anticancer effect of antimalarial artemisinin compounds. Annals of medical and health sciences research. 2015; 5(2):93-102.
- 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.
- 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, placebo-controlled pilot study of oral artesunate therapy for colorectal cancer. EBioMedicine. 2015 Jan 31; 2(1):82-90.