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Artemisia integrifolia, A. capillaris Components, and Sesquiterpene Lactones
Published in Abu Zahrim Yaser, Poonam Khullar, A. K. Haghi, Green Materials and Environmental Chemistry, 2021
Francisco Torrens, Gloria Castellano
As a result of the Vietnam War, as the North Vietnamese forces were suffering heavily from malaria, they appealed to their ally, China, for help [11]. Many Chinese herbs were tested and attention was drawn to an ancient herbal remedy based on the plant Artemisia annua, which was used by Chinese herbalists for over 1000 years. Peasants in rural areas made a tea from it (via hot, not boiling, H2O) or chewed fresh plants mixed with brown sugar, as a way of treating fevers. A team led by Professor Tu Youyou obtained ART, the active ingredient, by low-temperature (LT) ether extraction; they found the formula C15H22O5 of the white crystals in 1972 and its structure was determined in 1976. The ART (cf. Figure 7.1a) presents relatively short-term potency; because of this, it is not a suitable prophylactic. It also suffers from a lack of H2O solubility. Semisynthetic ARTDs developed to improve its potency were soon in use as antimalarial drugs (e.g., artesunate, Figure 7.1b, artemether, Figure 7.1c). When Plasmodium parasites ingest hemoglobin (Hb) to extract protein for growth, heme groups are freed. Either Haem groups or free Fe2+ attack the peroxide group in ART, resulting in the generation of free radicals (FRs) that attack and kill Plasmodium deoxyribonucleic acid (DNA). The ART was suggested to inhibit enzyme Plasmodium falciparum PfATP6 that is involved in pumping Ca2+ into membrane organelles, which may be a means of its action. Concerns exist about the possible emergence of ART-resistant parasites, which is compounded by the widespread availability of fake ART medications, especially in Southeast Asia, and by people not completing their course of treatment. The ART combination therapy (ACT, via artemether-lumefantrine, artesunate-mefloquine, artesunate-amodiaquine, artesunate-sulphadoxine/pyrimethamine) was endorsed by the World Health Organization (WHO) as a frontline treatment for severe P. falciparum malaria.
Pharmacokinetics of α-amanitin in mice using liquid chromatography-high resolution mass spectrometry and in vitro drug–drug interaction potentials
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Ria Park, Won-Gu Choi, Min Seo Lee, Yong-Yeon Cho, Joo Young Lee, Han Chang Kang, Chang Hwan Sohn, Im-Sook Song, Hye Suk Lee
The inhibition potential of α-amanitin against the eight major CYP and six major UGT enzymes was evaluated in HLMs. α-Amanitin weakly inhibited CYP2A6-catalyzed coumarin 7′-hydroxylation (IC50, 49.3 μM), CYP2B6-catalyzed bupropion hydroxylation (IC50, 52.7 μM), CYP2C19-catalyzed [S]-mephenytoin 4′-hydroxylation (IC50, 68.8 μM), CYP2D6-catalyzed bufuralol 1′-hydroxylation (IC50, 56.9 μM), and CYP3A4-catalyzed midazolam 1′-hydroxylation (IC50, 91.1 μM) in HLMs. α-Amanitin showed negligible inhibition of CYP1A2-catalyzed phenacetin O-deethylation, CYP2C8-catalyzed amodiaquine N-deethylation, and CYP2C9-catalyzed diclofenac 4′-hydroxylation upto100 μM α-amanitin in HLMs (Figure 4). There was no time-dependent inhibition of α-amanitin on 8 CYPs after 30-min preincubation (Figure 4, Table 8).