Biomedical Properties and Origins of Sesquiterpene Lactones, with a Focus on Dehydroleucodine

Abstract

Dehydroleucodine, a sesquiterpene lactone, belongs to the terpenoid class of secondary metabolites. Dehydroleucodine and other Artemisia-derived phytochemicals evolved numerous biodefenses that were first co-opted for human pharmacological use by traditional cultures in the Middle East, Asia, Europe and the Americas. Later, these phytochemicals were modified through the use of medicinal chemical techniques to increase their potency. All sesquiterpene lactones contain an α-methylene-γ-lactone group, which confers thiol reactivity, which is responsible, in part, for their therapeutic effects. A wide range of therapeutic uses of sequiterpene lactones has been found, including anti-adipogenic, cytoprotective, anti-microbial, anti-viral, anti-fungal, anti-malarial and, anti-migraine effects. Dehydroleucodine significantly inhibits differentiation of murine preadipocytes and also significantly decreases the accumulation of lipid content by a dramatic down regulation of adipogenic-specific transcriptional factors PPARγ and C-EBPα. Dehydroleucodine also inhibits secretion of matrix metalloprotease-2 (MMP-2), which is a known protease involved in migration and invasion of B16 cells. In addition to these anti-adipogenic and anticancer effects, dehydroleucodine effectively neutralizes several bacterial species, including Bacillus cereus, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Helicobacter pylori, methicillin resistant Staphylococcus aueus (MRSA) and S. epidermis (MRSE). The compound also inhibits the growth and secretion of several toxins of Pseudomonas aeruginosa, possesses gastro-protective qualities and possesses anti-parasitic properties against Trypanosoma cruzi, responsible for Chagas disease. Other sesquiterpene lactones, such as parthenolide, costunolide, and helanin, also possess significant therapeutic utility.

Challenges and Considerations in the Preparation of Novel Antibiotic Phytochemicals

“…Over the last century, natural products (also known as phytochemicals or plant secondary metabolites) have served as the most successful source of drug leads for medications pertaining to a variety of diseases [4]. It is postulated that these compounds are selected for over time to fortify opportunistic vulnerabilities to various abiotic threats such as nutrient deficiency, drought, lack of oxygen, excessive temperature, ultraviolet radiation, or pollution, and as a co-evolutionary biodefense to biotic agents, which include vertebrates, insects, protists, fungi, and bacteria [5][6][7][8]. A causal relationship between microbial trespass and phytochemical synthesis is supported by the discovered synthesis of some of these compounds post-infection [9,10].…”

“…The essential oils of Origanum syriacum showed antibacterial activity against 16 tetracycline-resistant Brucella melitensis isolates at a minimal inhibitory concentration of 3.125 µl/ml [13]. The Old Testament continues its antibiotic references when it mentions a botanical called wormwood, which possibly refers to either Artemisia judaica L. or Artemisia herba-alba, species present in Middle Eastern regions where the books of the Bible were written and compiled [5]. Isolated compounds from Artemisia judaica L. have exhibited antibacterial effects [5].…”

“…The Old Testament continues its antibiotic references when it mentions a botanical called wormwood, which possibly refers to either Artemisia judaica L. or Artemisia herba-alba, species present in Middle Eastern regions where the books of the Bible were written and compiled [5]. Isolated compounds from Artemisia judaica L. have exhibited antibacterial effects [5]. Likewise, the essential oils from four Artemisia herbaalba populations showed antibacterial activity in the concentration range of 1-2 mg/ml [14].…”

In-vitro Evaluation of Anti-microbial and Cytotoxic Activity of Artemisia judaica Leaves and Stem Extracts via Induction of Caspase Dependent Apoptosis

“…Sesqui-terpene lactones were used for their therapeutic and other properties, 10 recently, monoterpenes, sesqui-terpenes, sesqui-terpene lactones, flavonoids, coumarins, sterols, poly-acetylenes have been isolated from Artemisia species. 11 Isolated compounds from Artemisia judaica have exhibited antiviral, antibacterial, antifungal, and cytoprotective effects, [12][13][14] and used for the treatment of hepatitis, cancer and menstrual-related disorders, 15 Artemisia judaica showed a promising cytotoxic activity against some cancer cell lines, 16 which may be due to its essential oil content of thujone. 17 The present study is designed to evaluate the antimicrobial and cytotoxic effect of methanolic extract of Artemisia judaica leaves and stem with mechanistic determination of its cytotoxic effect on different cell lines.…”

Phenolic Composition, Antioxidant Capacity and Antibacterial Activity of White Wormwood (Artemisia herba-alba)

“…In recent decades, many researchers have conducted phytochemical analysis of A. Herba-alba in several countries [ 23 , 24 , 25 ]. The terpenoid sesquiterpene lactone dehydroleucodine, mainly found in the aerial parts of A. herba-alba , is responsible for its medicinal properties [ 26 ]. Various volatile compounds, such as chrysanthenyl acetate, chrysanthenol, acetophenone xanthocyclin, 1,8-cineole, α- and β-thujone, terpinen-4-ol, camphor, and borneol, were observed in different collected populations of A. Herba-alba plants in Eilat and Judian desert region of Israel [ 27 ] and also in Morocco [ 28 ].…”