Preparazione e valutazione dell'attività biologica di nuovi polifenoli semisintetici.

During recent years a return to the study of medicinal plants is evident with aim to discover new molecules with pharmacological activity, with particular interest to the antioxidants, for example, those that have been proposed as functional ingredients for anti-aging formulations, with the aim to prevent and modulate oxidative damage to the skin. The research group of Prof. Manfredini, studies and acknowledges the active ingredients of natural origin that are already known in the literature to possess healing abilities, in order to chemically modify and evaluate their activities. My PhD project is a part of NTF (Non Timber Forest), which aims to develop supply chain for sustainable raw materials for support of the local economy, moreover, the natural compounds studied, in collaboration with external companies, have been isolated from waste products of different strains.The molecules studied are Verbascoside ( Buddleja davidii cell cultures ), phloridzin, rutin and salicin which are described in the literature for the many benefits of the human health (antioxidant, anti-inflammatory, antimicrobial, etc. . ). Despite the different activities demonstrated, being very hydrophilic substances, are difficult to be used in vivo because of the reduced cellular uptake as well as for insertion into different pharmaceutical formulations. For this reason we have decided to increase the lipophilicity, by protecting from esterification the multiple hydroxyl groups present in these structures, but leaving free the phenolic component (pharmacophore). For the obtained semisynthetic derivatives, we investigated the relationship structure-activity between the natural compound and its semisynthetic derivative, in particular we evaluated the antioxidant capacity, antimycotic and stability in a formulation. Furthermore, in collaboration with the research group of Prof. Gambari we decided to assess the anti-inflammatory ability of florizina and the semi-synthetic derivative (F2). In addition, in collaboration with Prof. Valacchi we studied the activity of the Verbascoside florizina and their respective derivatives of semi-synthesis, in the process of cutaneous wound healing

Frataxin mRNA isoforms in FRDA patients and normal subjects: effect of tocotrienol supplementation.

Friedreich's ataxia (FRDA) is caused by deficient expression of the mitochondrial protein frataxin involved in the formation of iron-sulphur complexes, and by consequent oxidative stress. We analysed low-dose tocotrienol supplementation effects on the expression of the three splice variant isoforms (FXN-1, FXN-2 and FXN-3) in mononuclear blood cells of FRDA patients and healthy subjects. In FRDA patients, tocotrienol leads to a specific and significant increase of FXN-3 expression, while not affecting FXN-1 and FXN-2 expression. Since no structural and functional details were available for FNX-2 and FXN-3, 3D-models were built. FXN-1, the canonical isoform, was then docked on the human iron-sulphur complex and functional interactions were computed; when FXN-1 was replaced by FXN-2 or FNX-3, we found that the interactions were maintained, thus suggesting a possible biological role for both isoforms in human cells. Finally, in order to evaluate whether tocotrienol enhancement of FXN-3 was mediated by an increase in peroxisome proliferator-activated receptor-\uf067 (PPARG), PPARG expression was evaluated. At low dose of tocotrienol, the increase of FXN-3 expression appeared to be independent of PPARG expression. Our data show that it is possible to modulate the mRNA expression of the minor frataxin isoforms, and that they may have a functional role

Activity and stability studies of verbascoside, a novel antioxidant, in dermo-cosmetic and pharmaceutical topical formulations.

We here report the results of our investigations carried out on Verbascoside, a phenylpropanoid glycoside known for its antioxidant, anti-inflammatory and photoprotective actions. Verbascoside was obtained from Buddleia davidii meristematic cells in turn obtained using a sustainable biotechnology platform which employs an in vitro plant cell culture technology. Verbascoside was firstly investigated to assess the behaviour of the active ingredient in solution or in finished preparations in view of its potential topical use, especially in skin protection. Stability studies were performed by HPLC, and PCL assay was adopted to determine the radical scavenging activity toward superoxide anion. The high hydrophilic character of Verbascoside, resulted somewhat in a limitation of possible applications, inducing to explore the derivatization, to obtain by semi-synthetic derivative VPP, an acyl derivative of Verbascoside, that can increase with its lower hydrophilic profile the range of applications. Completely unattended, the VPP revealed increased antioxidant activity both as active ingredient and in dermocosmetic preparations. Stability studies showed a greater stability of VPP in lipophilic vehicle, whereas the parent Verbascoside resulted more stable in an O/W emulsions. Verbascoside was also stable in suppositories, an interesting pharmaceutical form for possible applications to the inflammation of the intestinal mucosa

A Multi-Target Approach toward the Development of Novel Candidates for Antidermatophytic Activity: Ultrastructural Evidence on α-Bisabolol-Treated Microsporum gypseum

Multi-target strategies are directed toward targets that are unrelated (or distantly related) and can create opportunities to address different pathologies. The antidermatophytic activities of nine natural skin lighteners: α-bisabolol, kojic acid, β-arbutin, azelaic acid, hydroquinone, nicotinamide, glycine, glutathione and ascorbyl tetraisopalmitate, were evaluated, in comparison with the known antifungal drug fluconazole, on nine dermatophytes responsible for the most common dermatomycoses: Microsporum gypseum, Microsporum canis, Trichophyton violaceum, Nannizzia cajetani, Trichophyton mentagrophytes, Epidermophyton floccosum, Arthroderma gypseum, Trichophyton rubrum and Trichophyton tonsurans. α-Bisabolol showed the best antifungal activity against all fungi and in particular; against M. gypseum. Further investigations were conducted on this fungus to evaluate the inhibition of spore germination and morphological changes induced by α-bisabolol by TEM

Activity and Stability Studies of Verbascoside, a Novel Antioxidant, in Dermo-Cosmetic and Pharmaceutical Topical Formulations

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Synthesis, Antioxidant and Antimicrobial Activity of a New Phloridzin Derivative for Dermo-Cosmetic Applications

The phenolic compound phloridzin (phloretin 2′-O-glucoside, variously named phlorizin, phlorrhizin, phlorhizin or phlorizoside) is a prominent member of the chemical class of dihydrochalcones, which are phenylpropanoids. Phloridzin is specifically found in apple and apple juice and known for its biological properties. In particular we were attracted by potential dermo-cosmetic applications. Here we report the synthesis, stability studies and antimicrobial activity of compound F2, a new semi-synthetic derivative of phloridzin. The new derivative was also included in finished formulations to evaluate its stability with a view to a potential topical use. Stability studies were performed by HPLC; PCL assay and ORAC tests were used to determine the antioxidant activity. F2 presented an antioxidant activity very close to that of the parent phloridzin, but, unlike the latter, was more stable in formulations. To further explore potential health claims, antifungal activity of phloridzin and its derivative F2 were determined; the results, however, were rather low; the highest value was 31,6% of inhibition reached by F2 on Microsporum canis at the highest dose