A Traditional Medicine Plant, Onopordum acanthium L. (Asteraceae): Chemical Composition and Pharmacological Research

For many years, plants have been used in the traditional medicine of different cultures. The biennial plant of the family Asteraceae, Onopordum acanthium L., also known as Scotch thistle, is used in traditional medicine as an anti-inflammatory, antitumor, and cardiotonic agent. The plant is widespread in the world; it grows in Europe and Asia and was introduced to America and Australia. Stems and buds of the first-year plant are used in cooking as an analogue of artichoke in European cuisine. Additionally, inflorescences contain a complex of proteolytic enzymes “onopordosin”, which may be used as a milk-clotting agent in the dairy industry. The chemical composition of the aerial part and roots of O. acanthium is represented by flavonoids, phenylpropanoids, lignans, triterpenoids, sesquiterpene lactones, and sterols. The anti-inflammatory, antiproliferative, and cardiotonic properties of the plant have been confirmed by pharmacological experiments with extracts and individual compounds using in silico, in vitro, and in vivo methods. This work is a review of information on the chemical composition and pharmacological studies of O. acanthium as a promising medicinal plant.

Properties and synthesis of milrinone

Milrinone, 1,6-dihydro-2-methyl-6-oxo-[3,4?-bipyridine]-5-carbonitrile, is a positive inotropic cardiotonic agent with vasodilator properties that acts as selective phosphodiesterase 3 inhibitor in cardiac and vascular smooth muscle. Trade names of milrinone are Primacor, Corotrop, Corotrope, and Milrila. Milrinone, an amrinone derivative, is 20 to 50 times more active than amrinone and possesses reduced propensity to side effects. The use of milrinone has created controversy in the medical as the result of increased mortality rate among patients that received high amounts of milrinone in oral form. Reaserch show that it can be benifitial for patients with severe congestive heart failure when used as short-time intravenous therapy. Milrinone properties, stability, as well as mechanism of action and synthesis under laboratory and industry conditions have been described in this paper. For industrial purposes milrinone is synthesized by condensation of cyanoacetamide with 4-(dimethylamino)-3-(4-pyridinyl)-3-buten-2-one and 4-ethoxy-3-(4-pyridinyl)-3-buten-2-one in presence of a base, or by the reaction of 1-(4-pyridinyl)- 2-propanone with ethoxymethylenmalononitrile or 4-alkoxy-3-(4-pyridinyl)-3-buten-2-one with malononitrile without the use of external base. The starting compound for these syntheses is 4-picoline. Alternative synthesis of milrinone starts from 2-methyl-3-(4-pyridylidiene)-1,1,5-tricyano-1,4-pentadiene-5-carboxamide and 2-methyl-6-oxo-1,6-dihydro-3,4?-bipyridine-5-carboxamide. Lastly, methods for milrinone synthesis in laboratory, injection preparation and purification have been summarized.