Sesquiterpene lactones form a large group belonging to natural terpenoids series, generally found in plants of Asteraceae family and exhibiting anti-tumor, antiviral, immunostimulant, antifungal, antimicrobial, anti-inflammatory, antimutagenic, growth stimulating, antifeedant effects. Therefore, search for new compounds with a broad spectrum of pharmacological activity in this series provides the opportunities for effective and conceptually new drug design. The basis of the technology for the isolation of sesquiterpene lactones is the extraction of raw materials with various organic solvents, followed by chromatographic purification. Sesquiterpene lactones have no common properties that can be used in their isolation. Some of them are well soluble in non – polar solvents, others-only in polar, in this regard, the methods of isolation of sesquiterpene lactones are diverse. The greatest number of sesquiterpene lactones is isolated from leaves and flowers, slightly less – from roots and bark. Therefore, the development of methods for their isolation is associated with the selection of solvents and optimization of the extraction mode. Unfortunately, very few medicines based on sesquiterpene lactones are produced by the pharmaceutical companies today. Complexity of introduction of pharmacologically active sesquiterpene lactones technology into pharmaceutical production is in imperfection of their isolation methods from plant raw material, their purification and separation from obtained extracts. Production technologies of the patented medicines "Santonin", "Alanton" on the basis of sesquiterpene lactones are multiphase, labor-intensive, implying the use of many toxic organic solvents which is against the international GMP standards.
BACKGROUND: Chartolepis intermedia Boiss. and Centaurea ruthenica Lam. are new medicinal plants containing pharmacologically active sesquiterpene lactones grossheimin and cynaropicrin. The article discusses the methods for the isolation of grossheimin and cynaropicrin and presents the results of studying the pharmacological activity of the isolated sesquiterpene lactones. AIM: The aim of this work was chemical, morphological, and anatomical study of Ch. intermedia Boiss. and C. ruthenica Lam., determination of pharmacological activity to substantiate the possibility of using these plants as medicinal raw materials. METHODS: The antitumor activity of grossheimin was studied in white outbred rats and mice in 12 strains of transplanted tumors. The antiparasitic activity of grossheimin and cynaropicrin was studied during replication of models of experimental opisthorchiasis on male golden hamsters (Mesocricetus auratus) of the SPF category. Experiments in vivo were carried out on pastoral dogs infested with various types of helminths. The hypolipidemic activity of grossheimin was studied in experimental rats with a single intragastric administration of ethanol, causing acute hyperlipidemia. The antimicrobial activity of cynarpicrin was determined in relation to test strains of Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis and Gram-negative strains of Escherichia coli and Pseudomonas aeruginosa by the method of diffusion in agar. RESULTS: Characteristic diagnostic features for Ch. intermedia Boiss. and C. ruthenica Lam. were revealed, which make it possible to diagnose and standardize the medicinal plants under study. Pharmacological studies have shown that grossheimin and cynaropicrin have antitumor, antiparasitic, hypolipidemic, and antimicrobial activity. Grossheimin significantly inhibits the growth of sarcoma 180, Pliss lymphosarcoma, and Ehrlich’s solid tumor. On the model of acute hyperlipidemia caused by the introduction of ethanol, grossheimin had a hypolipidemic effect, reducing the serum levels of triacylglycerides, total cholesterol, and low-density lipoprotein cholesterol. Under in vitro conditions, grossheimin and cynaropicrin exhibited anthelmintic action against Opisthorchis felineus worms, and under in vivo conditions, cynaropicrin was up to 100% effective against tapeworm infections (Taenia sp.). CONCLUSION: It was determined that the quantitative yield of sesquiterpene lactones is provided by extraction of plant raw materials with an ethanol: water (1:1) mixture under the action of ultrasound. Characteristic diagnostic features for C. intermedia Boiss. and C. ruthenica Lam. were revealed, which make it possible to diagnose and standardize the medicinal plants under study.
The review summarizes data on biologically active compounds of Achillea nobilis L. and methods of their isolation. From Achillea nobilis L., collected in different places of growth, the following have been isolated: essential oil, the main components of which are monoterpene compounds; sesquiterpene lactones estafiatin, hanphyllin, anobin, chrysartemine A, canin, anolide and tanapartin-β-peroxide; the steroid acetyleucanbin; flavonoids: 3,5-dihydroxy-6,7,8-trimethoxyflavone, 5-hydroxy-3,6,7,4’-tetramethoxyflavone and 5,3’-di-hydroxy-3,6,7,4’-tetramethoxyflavone. It has been determined that the component composition of the essen-tial oil of Achillea nobilis L. largely depends on the soil and climatic factors in the places of its growth, the phase of the growing season and the method of its extraction from plant raw materials, and the extractant used (chloroform, ethanol, hot water, diethyl ether). Antibacterial, antimicrobial, antioxidant, antiparasitic activi-ties are characteristic both for the sums of extractive substances from Achillea nobilis L. and for individual compounds isolated from them. Methods for the isolation of biologically active substances from Achillea nobilis L. for the development of new drug substances are described. The main aim of this work was a com-parative analysis of the available research results on the phytochemical study of Achillea nobilis L.
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