Disruption of mitochondrial membrane potential by ferulenol and restoration by propolis extract: Antiapoptotic role of propolis

Abstract

This paper reports an investigation of the ability of propolis extract (a resinous substance collected by honeybees from various plant sources) to restore the collapse of mitochondrial membrane potential induced by ferulenol, a sesquiterpene prenylated coumarin derivative isolated from the plant Ferula vesceritensis . We show that ferulenol was able to induce the permeability transition pore (PTP) opening. This effect is caused by the interaction of the compound with the mitochondrial respiratory chain, more particularly by the fall of membrane potential and the inhibition of complex II. We have previously demonstrated that this inhibition results from a limitation of electron transfers involved in the respiratory chain and initiated by the reduction of ubiquinone. We hypothesized that the protective effect of propolis could be due to a direct action on mitochondrial functions. So we have investigated in vitro the mitochondrial effects of Algerian propolis using rat liver mitochondria, by analysing their effects on membrane potential, mitochondrial respiration and mitochondrial swelling. We show that propolis extract was able to restore the fall of mitochondrial membrane potential. Taken together these data reveal that propolis extract may be an interesting inhibitor of PTP and provide an additional mechanism by which the natural product propolis extract may restore the mitochondrial membrane potential and to prevent apoptotic process.

The anticancer activity of propolis

“…Despite the results on the proapoptotic activity of propolis, the study by Nadia et al [38] demonstrates the antiapoptotic effect of propolis. Induced permeability transition pore (PTP) opening in the rat liver mitochondria after exposure to ferulenol, a sesquiterpene prenylated coumarin derivative isolated from the plant Ferula vesceritensis [38], was restored by propolis and in this way the apoptotic process was prevented.…”

“…Induced permeability transition pore (PTP) opening in the rat liver mitochondria after exposure to ferulenol, a sesquiterpene prenylated coumarin derivative isolated from the plant Ferula vesceritensis [38], was restored by propolis and in this way the apoptotic process was prevented. Since opposite effects of propolis on apoptosis have been published, further studies are necessary to understand the exact influence of propolis on the apoptotic pathways in cancer cells.…”

Cytotoxicity of sesquiterpenes ferulenol and coladin on liver FAO and B16F1 melanoma cells

“…[30] As far as the anticancer activity is concerned, lapiferin isolated from F. vesceritensis has reflected this anticancer activity against human breast cancer cells (MCF-7). [21] Considering all the previously mentioned elements, we speculated that the antitumor activity of sesquiterpenes could be due to their ability to alter many signaling pathways including stimulation of necrosis and induction of apoptosis. As a consequence, ferulenol was able to induce mitochondrial swelling, which may have contributed to the induction of apoptotic process.…”

“…On our continued investigation carried out for the chemical and pharmacological studies on the roots of F. vesceritensis, [19], [20], [21], [22] we have reported the specific anticancer activity of the isolated compounds. A sesquiterpene coumarins; Ferulenol, coladin and carotene sesquiterpene designed lapiferin (10_-acetoxy-6_-angeloyloxy-8_, 9_-epoxy-trans-caxotan-4_-ol) for the first time from F. vesceritensis as a new natural source against human cancer cells [ Figure 1].…”

Chemical composition and antibacterial activity of the essential oils of Ferula vesceritensis Coss et Dur. leaves, endemic in Algeria

“…Our continuation of investigation carried out on F. vesceritensis [15-17]. The essential oils of the leaves of F. vesceritensis led to the identification of 23 compounds.…”