Effect of guaianolides in the meiosis reinitiation of amphibian oocytes

Abstract

Sesquiterpene lactones (STLs) are a large and structurally diverse group of plant metabolites generally found in the Asteraceae family. STLs exhibit a wide spectrum of biological activities and it is generally accepted that their major mechanism of action is the alkylation of the thiol groups of biological molecules. The guaianolides is one of various groups of STLs. Anti-tumour and anti-migraine effects, an allergenic agent, an inhibitor of smooth muscle cells and of meristematic cell proliferation are only a few of the most commonly reported activities of STLs. In amphibians, fully grown ovarian oocytes are arrested at the beginning of meiosis I. Under stimulus with progesterone, this meiotic arrest is released and meiosis progresses to metaphase II, a process known as oocyte maturation. There are previous records of the inhibitory effect of dehydroleucodin (DhL), a guaianolide lactone, on the progression of meiosis. It has been also shown that DhL and its 11,13-dihydroderivative (2H-DhL; a mixture of epimers at C-11) act as blockers of the resumption of meiosis in fully grown ovarian oocytes from the amphibian Rhinella arenarum (formerly classified as Bufo arenarum). The aim of this study was to analyze the effect of four closely related guaianolides, i.e., DhL, achillin, desacetoxymatricarin and estafietin as possible inhibitors of meiosis in oocytes of amphibians in vitro and discuss some structure-activity relationships. It was found that the inhibitory effect on meiosis resumption is greater when the lactone has two potentially reactive centres, either a α,β-α',β'-diunsaturated cyclopentanone moiety or an epoxide group plus an exo-methylene-γ-lactone function.

Trypanocidal Activity of Four Sesquiterpene Lactones Isolated from Asteraceae Species

“…Three main sesquiterpene lactones were isolated from Stevia maimarensis, S. alpina, and S. gilleisi, growing in northern Argentina: eupatoriopicrin, estafietin, and eupahakonenin B, respectively [9][10][11]. These compounds have shown anti-inflammatory, antitumor and antiparasitic activities, among others [12][13][14][15][16].…”

Stevia Genus: Phytochemistry and Biological Activities Update

“…This compound has shown antiallergic effects [ 67 ] and has inhibited melanin pigment synthesis and tyrosinase activity in B16F10 melanoma cells [ 69 ]. This sesquiterpenelactone also inhibited meiosis in oocytes of amphibians [ 70 ].…”

“…Estafietin was also active against promastigotes of L. braziliensis (IC 50 = 1.0 μg/mL). This compound selectively inhibited T cell receptor activation [ 77 ] and showed an in vitro inhibitory effect on the meiosis reinitiation of amphibian oocytes [ 70 ].…”

Research Advances on Health Effects of Edible Artemisia Species and Some Sesquiterpene Lactones Constituents

“…Another highly relevant study with achillin (3) in animal model was its effect as an inhibitor of meiosis in toad (Rhinella arenarum) oocytes was carried out by Zapata-Martínez et al [285], where denuded toad oocytes were exposed to different concentrations of achillin prior to the necessary hormonal stimulus necessary for meiotic resumption. Results showed a marked overall decrease of germinal vesicle breakdown (GVBD) in occytes with exposure to 3.…”

“…It is also worth noting that the response was dose-dependent; a 6 µM concentration of achillin (3) showed a~10% reduction of GVBD compared the control, whereas a 36 µM concentration reduced GVBD by~35% more than control oocytes. So, it appears achillin (3) has meiosis inhibiting potential, which the authors [285] attribute to the covalent bonds formed between achillin's partially electrophilic center and the nucleophilic center of target molecules. The meiotic inhibitors have been shown to improve human embryonic development in in-vitro fertilization procedures by allowing the embryo to have enough time to finish cytoplasmic maturation [286].…”