Artemisia, Wormwood (Artemisia annua)
Artemisia annua is a medicinal plant that originated in Southeast Asia but is now cultivated all around the world. It has been used in traditional Chinese medicine for more than 2000 years as a treatment for fevers, inflammation, headaches, bleeding, and malaria, but its medicinal properties were rediscovered by modern science in the 1970’s when research revealed that the plant contains more than 10 active substances. Currently, Artemisia annua is the source for the production of artemisinin and semi-synthetic artemisinin derivatives (including dihydroartemisinin, artesunate, artemether, and arteether) that are used for the production of combination therapies for the treatment of malaria Today, one of those substances – artemisinin – is the foundation of all anti-malarial medicine, the discovery of which won Prof. Tu Youyou the Nobel Prize in 2015.
A. annua, may be effective for protozoal infections including leishmaniasis, Chagas’ disease, and African sleeping sickness. Cytotoxic effects of A. annua compounds have also been evaluated in tumor cell lines.
Artemisinin-based combination therapies are part of the standard treatment arsenal for malaria. Systematic reviews suggest it is as effective as quinine, but an increased risk of relapse may limit its uses. It is also unclear whether it is effective against quinine-resistant malaria strains. Other reports of artemisinin-based therapy resistance are also emerging, prompting additional drug development.
The plants contained numerous chemical constituents including 3′,4′-dihydroxybonanzin, apigenin, betulinic acid, bonanzin, dehydroleucodine, dihydroluteolin, dracunculin and bis-dracunculin, helenalin, nepetin, scoparol, scopoletin, stigmasterol, (Z)-p-hydroxy cinnamic acid, β-sitosterol and others. In addition to artemisinin from A. annua, artemether and artesunate, further novel artemisinin derivatives and nanotechnological preparations may also be useful to combat Trypanosoma infections.
Animal studies have suggested that artemisinin and related compounds inhibit tumor growth and metastasis. A few safety studies in advanced cancer patients suggest oral add-on artesunate, a semisynthetic artemisinin derivative, is well tolerated, although monitoring for ototoxicity is needed. In other studies, oral or intravenous artesunate did not produce a response, although modest clinical activity was observed with intravenous administration. In one study a low dose artemisia formulation produced clinically relevant pain reductions in patients with hip or knee osteoarthritis.
Artemisinin, the active constituent of A. annua, exerts antimalarial effects by free radicals formed via cleavage of the endoperoxide bond in its structure, which are responsible for eradicating the Plasmodium species.
Artemisinin induces apoptosis and cell cycle arrest of Leishmani donovani promastigotes, an intercellular parasite. It has antiproliferative effects on medullary thyroid carcinoma cells and induces apoptosis in a lung cancer cell line by modulating p38 and calcium signaling. In another study, it significantly inhibited cell growth and proliferation and caused G1 cell-cycle arrest in neuroblastoma cell lines. Dihydroartemisinin, a semi-synthetic derivative of artemisinin, demonstrates anti-inflammatory activity by attenuating COX-2 production via downregulation of serine/threonine kinase and MAPK pathways. Recent findings suggest that dihydroartemisinin-triggered apoptosis in colorectal cells occurs through the ROS-mediated mitochondria-dependent pathway.
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