5.Discovery and repurposing of artemisinin.
Qiaoli SHI ; Fei XIA ; Qixin WANG ; Fulong LIAO ; Qiuyan GUO ; Chengchao XU ; Jigang WANG
Frontiers of Medicine 2022;16(1):1-9
Malaria is an ancient infectious disease that threatens millions of lives globally even today. The discovery of artemisinin, inspired by traditional Chinese medicine (TCM), has brought in a paradigm shift and been recognized as the "best hope for the treatment of malaria" by World Health Organization. With its high potency and low toxicity, the wide use of artemisinin effectively treats the otherwise drug-resistant parasites and helps many countries, including China, to eventually eradicate malaria. Here, we will first review the initial discovery of artemisinin, an extraordinary journey that was in stark contrast with many drugs in western medicine. We will then discuss how artemisinin and its derivatives could be repurposed to treat cancer, inflammation, immunoregulation-related diseases, and COVID-19. Finally, we will discuss the implications of the "artemisinin story" and how that can better guide the development of TCM today. We believe that artemisinin is just a starting point and TCM will play an even bigger role in healthcare in the 21st century.
Artemisinins/therapeutic use*
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COVID-19/drug therapy*
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Drug Repositioning
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Humans
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Medicine, Chinese Traditional
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Neoplasms/drug therapy*
6.Reasearch on lipid metabolism of Plasmodium and antimalarial mechanism of artemisinin.
Shuo LI ; Cang-Hai LI ; Ting-Liang JIANG
China Journal of Chinese Materia Medica 2021;46(18):4849-4864
As a unicellular organism, Plasmodium displays a panoply of lipid metabolism pathways that are seldom found together in a unicellular organism. These pathways mostly involve the Plasmodium-encoded enzymatic machinery and meet the requirements of membrane synthesis during the rapid cell growth and division throughout the life cycle. Different lipids have varied synthesis and meta-bolism pathways. For example, the major phospholipids are synthesized via CDP-diacylglycerol-dependent pathway in prokaryotes and de novo pathway in eukaryotes, and fatty acids are synthesized mainly via type Ⅱ fatty acid synthesis pathway. The available studies have demonstrated the impacts of artemisinin and its derivatives, the front-line compounds against malaria, on the lipid metabolism of Plasmodium. Therefore, this article reviewed the known lipid metabolism pathways and the effects of artemisinin and its derivatives on these pathways, aiming to deepen the understanding of lipid synthesis and metabolism in Plasmodium and provide a theoretical basis for the research on the mechanisms and drug resistance of artemisinin and other anti-malarial drugs.
Antimalarials/pharmacology*
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Artemisinins/therapeutic use*
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Humans
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Lipid Metabolism
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Malaria/drug therapy*
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Plasmodium
7.Effect of dihydroartemisinin supplementation on inflammation and lipid metabolism induced by lipopolysaccharide in liver of weaned piglets.
Yong-Wei ZHAO ; Yu NIU ; Jin-Tian HE ; Shu-Li JI ; Li-Li ZHANG ; Chao WANG ; Tian WANG
China Journal of Chinese Materia Medica 2020;45(1):202-208
To study the effect of dihydroartemisinin(DHA) on hepatic inflammation and lipid metabolism in weaned piglets, a liver injury model of weaned piglets was established by lipopolysaccharide(LPS)-induced method. In this study, 30 healthy weaned piglets were selected and randomly divided into control group(CON), model group(LPS) and treatment group(LD, LPS+DHA), with 10 in each group. The CON group and the LPS group were fed with a basal diet, and the LD group was fed with a basal diet+80 mg·kg~(-1) DHA. The test period was 21 days. The LPS group and the LD group were intraperitoneally injected with 100 μg·kg~(-1) LPS at 4 hours before slaughter, and the CON group was injected with the same dose of sterile physiological saline. The results showed that compared with the CON group, contents of TC, AST activity and AST/ALT ratio were significantly increased in the serum of LPS piglets(P<0.05), content of HDL-c was significantly decreased(P<0.05). In addition, in the liver, the levels of TG, NEFA, IL-1β, IL-6 and TNF-α were increased significantly(P<0.05), and activities of LPL, HL and TL were decreased significantly(P<0.05). Compared with LPS group, content of TC, activities of AST and ALT and the AST/ALT ratio were decreased significantly(P<0.05), and HDL-c content increased significantly in the serum of LD piglets(P<0.05). The contents of TG, NEFA, IL-1β, IL-6 and TNF-α and activity of FAS in the liver were decreased significantly(P<0.05), and the activities of LPL, HL and TL were increased significantly(P<0.05). Compared with the CON group, the mRNA expressions of IL-1β, IL-6, TNF-α, ACCβ and SREBP-1 c in the LPS group were significantly increased(P<0.05), the mRNA expressions of AMPKα, SIRT1, CPT-1 and SCD were decreased significantly(P<0.05). The above indicators were improved in the LD group compared with the LPS group. These results indicated that DHA had a certain effect in recovering LPS-induced liver inflammation and abnormal lipid metabolism.
Animals
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Artemisinins/therapeutic use*
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Dietary Supplements
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Inflammation/drug therapy*
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Lipid Metabolism
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Lipopolysaccharides
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Liver/physiopathology*
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Swine
8.Drug Resistance and in Vitro Susceptibility of Plasmodium falciparum in Thailand during 1988-2003.
Nantana SUWANDITTAKUL ; Wanna CHAIJAROENKUL ; Pongchai HARNYUTTANAKORN ; Mathirut MUNGTHIN ; Kesara NA BANGCHANG
The Korean Journal of Parasitology 2009;47(2):139-144
The aim of the present study was to investigate antimalarial drug pressure resulting from the clinical use of different antimalarials in Thailand. The phenotypic diversity of the susceptibility profiles of antimalarials, i.e., chloroquine (CQ), quinine (QN), mefloquine (MQ), and artesunate (ARS) in Plasmodium falciparum isolates collected during the period from 1988 to 2003 were studied. P. falciparum isolates from infected patients were collected from the Thai-Cambodian border area at different time periods (1988-1989, 1991-1992, and 2003), during which 3 different patterns of drug use had been implemented: MQ + sulphadoxine (S) + pyrimethamine (P), MQ alone and MQ + ARS, respectively. The in vitro drug susceptibilities were investigated using a method based on the incorporation of [3H] hypoxanthine. A total of 50 isolates were tested for susceptibilities to CQ, QN, MQ, and ARS. Of these isolates, 19, 16, and 15 were adapted during the periods 1988-1989, 1991-1993, and 2003, respectively. P. falciparum isolates collected during the 3 periods were resistant to CQ. Sensitivities to MQ declined from 1988 to 2003. In contrast, the parasite was sensitive to QN, and similar sensitivity profile patterns were observed during the 3 time periods. There was a significantly positive but weak correlation between the IC50 values of CQ and QN, as well as between the IC50 values of QN and MQ. Drug pressure has impact on sensitivity of P. falciparum to MQ. A combination therapy of MQ and ARS is being applied to reduce the parasite resistance, and also increasing the efficacy of the drug.
Animals
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Antimalarials/*pharmacology/therapeutic use
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Artemisinins/pharmacology/therapeutic use
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Chloroquine/pharmacology/therapeutic use
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*Drug Resistance
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Humans
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Malaria/drug therapy/*parasitology
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Mefloquine/pharmacology/therapeutic use
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Parasitic Sensitivity Tests/methods
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Plasmodium falciparum/*drug effects/isolation & purification
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Quinine/pharmacology/therapeutic use
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Thailand
10.Research advance in antitumor activities of artemisinin and its derivatives.
Acta Academiae Medicinae Sinicae 2013;35(4):466-471
Artemisinin and its derivatives are highly effective in fighting against malaria. Notably, these drugs have shown potent anti-timor activities by arresting cellular growth, enhancing apoptosis, inhibiting angiogenesis, and regulating the expression of tumor-associated genes, although the underlying mechanisms remain unclear.
Antineoplastic Agents
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pharmacology
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therapeutic use
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Apoptosis
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drug effects
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Artemisinins
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pharmacology
;
therapeutic use
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Cell Cycle
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drug effects
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Humans
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Neoplasms
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drug therapy
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Neovascularization, Pathologic
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drug therapy