Clinical application and extraction method of artemisinin

Artemisinin is a colorless needle-like crystal extracted from the compound inflorescence plant Artemisia annua L., which is chemically named (3R, 5aS, 6R, 8aS, 9R, 12S, 12aR). )-octahydro-3,6,9-trimethyl-3,12-oxooxy-12H-pyrano[4,3-j]-1,2-benzodioxan-10(3H)-one.

The 2015 Nobel Prize in Physiology or Medicine, Tu Yu, used artemisinin to develop a new antimalarial drug, artemisinin and dihydroartemisinin, which has a 100% inhibition rate against malaria parasites. The extremely high medicinal value of artemisinin is reflected in more clinical applications.

Anti-malaria

Artemisinin has the characteristics of quick-acting and low-toxicity, and has been called by the World Health Organization as "the only effective malaria treatment drug in the world". Its anti-malarial mechanism mainly consists in the activation of artemisinin to produce free radicals during the treatment of malaria. Free radicals bind to malaria protein and act on the membrane structure of Plasmodium, causing its membrane, nuclear membrane and plasma membrane to be damaged. Upon destruction, the mitochondria swell and the inner and outer membranes fall off, thereby destroying the cell structure and function of the malaria parasite, and the chromatin in the nucleus is also affected. Artemisinin also significantly reduces the intake of isoleucine by the malaria parasite, thereby inhibiting the synthesis of protein in the body.

Antitumor

The anti-tumor effect of artemisinin and its derivatives is mainly achieved by inducing apoptosis of cells, and has a significant inhibitory effect on the growth of cancer cells. Dihydroartemisinin can inhibit the activation of hypoxia-induced related factors by increasing reactive oxygen species, and exerts selective cytotoxicity. Mitochondria are amplifiers and receptors for apoptosis, which regulate the metabolic activities of cells, and the membrane potential of mitochondria induces apoptosis. Artemisinin acts on the cell membrane of leukemia cells, changes the permeability of the cell membrane, and increases the concentration of calcium ions in the cells, which not only activates calpain, causes it to swell and die, but also promotes the release of apoptotic substances. Apoptosis is accelerated.

Immunomodulatory

Studies have found that the use of artemisinin and its derivatives can inhibit T lymphocyte mitogens and induce the proliferation of mouse spleen lymphocytes without causing cytotoxicity. This finding has good reference value for the treatment of autoimmune diseases mediated by T lymphocytes. Artemisia sinensis vinegar has the effect of enhancing non-specific immunity and can increase the total complement activity of mouse serum. Dihydroartemisinin can directly inhibit the proliferation of B lymphocytes, thereby reducing the secretion of autoantibodies by B lymphocytes, reducing the humoral immune response, inhibiting humoral immunity, and reducing immune complexes. Formation. Shanghai Chuangsai provides artemisinin, 63968-64-9, UV≥99%v standard, C84-6836-20mg, price 135 yuan

Antifungal

The antifungal action of artemisinin also makes artemisinin exhibit certain antibacterial activity. Studies have confirmed that artemisinin slag powder and decoction have strong antibacterial activity against Bacillus anthracis, Staphylococcus epidermidis, Kleococcus, and Diphtheria, for Mycobacterium tuberculosis, Pseudomonas aeruginosa, Staphylococcus aureus, Shigella Etc. also has a certain antibacterial effect. Shanghai Chuangsai provides dihydroartemisinin, 71939-50-9vUV≥98%, standard product, C84-6911-20mg, price 135 yuan

other

Artemisinin is also clinically used in combination with Cordyceps sinensis to inhibit the recurrence of lupus nephritis to protect the kidneys. Its anti-fibrotic effect can significantly reduce the degree of fibrosis in lung tissue, and has a good practical prospect for the prevention and treatment of scar.

method of extraction

The method for extracting artemisinin from Artemisia annua L. is based on the extraction principle, mainly including diethyl ether extraction and solvent gasoline extraction. The volatile oil is mainly extracted by steam distillation and separated by vacuum distillation. The process is as follows: feeding---adding water---distilling---cooling---oil-water separation---essential oil; non-volatile components are mainly extracted by organic solvent. Column chromatography and recrystallization separation, the basic process is: drying - crushing - soaking, extraction (repeated) - concentrated extract - crude - refined.

Semi-synthetic route

Starting from artemisinic acid as a raw material, artemisinin was obtained through a five-step reaction.

The first step: artemisinic acid is reacted with methanol under diazomethane/iodomethane/acid catalysis, and then selectively reduced by sodium borohydride in the presence of nickel chloride to obtain methyl dihydroartemisinate;

The second step: the methyl dihydroartemisinic acid is reduced to the artenimol with lithium aluminum hydride in a tetrahydrofuran or diethyl ether solution;

The third step: artemisinol is oxidized by ozone in methanol/dichloromethane/chloroform/carbon tetrachloride solution to obtain a peroxide, which is then dried and treated with p-toluenesulfonic acid in xylene to obtain a cyclic enolate. ;

The fourth step: the cyclic olefin ether is dissolved in a solvent, photooxidized in the presence of a photosensitizer rose red / methylene blue / hypocrellin to form a dioxetane intermediate, and then treated with an acid to obtain decarboxylated artemisinin;

The fifth step: decarboxylation of artemisinin is oxidized by an osmium tetroxide oxidation system or a chromic acid oxidant to obtain artemisinin.

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