Delicato, Antonella (2023) Bioactive metabolites from natural sources for the pharmaceutical, nutraceutical and cosmeceutical industry. [Tesi di dottorato]

Anteprima

Testo Delicato_Antonella_35.pdf Download (29MB) | Anteprima

Abstract

One goal of modern biotechnology is the continuous research and development of innovative products derived from natural sources with potential applications in diverse industrial sectors, such as the cosmeceutical, pharmaceutical and nutraceutical industries. Historically, natural metabolites have been used in folk medicine for the treatment of several diseases and injuries since ancient times until the renewed interest of the current scientific community. Living terrestrial and marine organisms, such as plants, algae and fungi, are an excellent source of structurally different natural compounds which are significant for their biological activities and potential therapeutic applications as well as for agricultural applications such as pesticides and insecticides. In addition to their great structural diversity, secondary metabolites from natural sources can be subjected to chemical modifications to improve their biological properties both in terms of bioavailability and degree of activity. Some bioactive compounds can help to maintain cellular homeostasis while fighting degenerative factors. This is the reason why these compounds continued to be considered interesting drug candidates. Plants have been well-documented for their traditional medicinal uses against illness and infectious diseases. Plants have evolved and adapted over millions of years to withstand bacteria, insects, fungi, and aging producing unique and structurally diverse bioactive secondary metabolites. These include pheromones that act as social signaling molecules among individuals of the same species, communication molecules that attract and activate symbiotic organisms, agents that solubilize and carry nutrients, and competitive weapons (repellents, poisons, toxins, etc.) that are used against competitors, preys, and predators. For many other secondary metabolites, the function remains unknown. One hypothesis is that they give a competitive advantage to the organism that produces them or in analogy to the immune system they can fight a multitude of deleterious factors thanks to their different chemical structures and properties. In my thesis, I chose to deal mainly with two plant species, Crinum biflorum Rottb. (sin. Crinum distichum) and Cistanche phelypaea belonging to the Amaryllidaceae and Orobanchaceae families, respectively. Both species grow in a tropical or desert climate. C. biflorum is widely used in traditional African medicine, although very few studies have been carried out from a chemical point of view and possible practical applications. I have isolated four homoisoflavanoids and an alkylamide, never reported before in this species. Remarkably, some of these flavonoids have shown promising anticancer properties being cytotoxic at low micromolar concentrations to Hela and A 431 human cancer cell lines. The N-p-coumaroyltyramine (alkylamide) was cytotoxic in A431 and Hela cancer cells but not in not transformed HaCaT cells. Il also showed acetylcholinesterase inhibitory activity and interesting antiamylase and anti-glucosidase activity. The obtained results indicate that C. biflorum produces compounds of nutraceutical and pharmacological interest with potential applications as food supplements having important anti-diabetic properties and supplements in the therapy against cancer and neurodegenerative diseases. C. phelypaea belongs to the genus Cistanche including more than 20 species typically growing in deserts or coastal dunes. They are considered parasitic plants of shrub roots. Cistanche species have long been a source of traditional herbal medicine or food, C. deserticola and C. tubulosa are the most used in China. I have isolated and identified some of the most abundant phenylethanoid glycosides and iridoids, obtained from the hydroalcoholic extract of C. phelypaea collected in Spain. Besides their antioxidant property, I have explored the potential of novel bioactivities never investigated so far in Cistanche metabolites such as the effect on keratinocytes and pluripotent stem cells proliferation and differentiation in light of their potential application in regenerative medicine and the cosmeceutical industry. In particular, I have explored the effect of acetoside which is the most abundant metabolite in C. phelypaea extract. I have shown that acetoside, in addition to its strong antioxidant potential, can sustain the proliferative potential of human basal keratinocytes and the pluripotent status of mesenchymal progenitors needed for tissue morphogenesis and renewal. Although obtained in vitro my results strongly suggest that acetoside may be of practical relevance for the application of human stem cell culture protocols in tissue engineering and regeneration. Finally, in the last period of my PhD project, I focused on the sustainable exploitation of pomace extract to produce edible particles based on pectin and divalent metal ions, loaded with antioxidant compounds in a circular economy perspective. After the optimization of the grape pomace extraction process and its characterization, the mixture of polyphenolic compounds was loaded into edible particles for nutraceutical applications. The release capacity of the polyphenols encapsulated in the beads and the conservation of their antioxidant activity in the gastrointestinal environment were tested in vitro.

Downloads

Actions (login required)

Modifica documento