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Since its first isolation in 1934, hyaluronic acid (HA) has been studied across a variety of research areas. This unbranched glycosaminoglycan consisting of repeating disaccharide units of N-acetyl-D-glucosamine and D-glucuronic acid is almost ubiquitary in humans and in other vertebrates. HA is involved in many key processes -including cell signaling, wound reparation, tissue regeneration, morphogenesis, matrix organization and pathobiology-, and has unique physico-chemical properties -such as biocompatibility, biodegradability, mucoadhesivity, hygroscopicity and viscoelasticity. For these reasons, exogenous HA has been investigated as drug delivery system and treatment in cancer, ophthalmology, arthrology, pneumology, rhinology, urology, aesthetic medicine and cosmetic. To improve and customize its properties and applications, HA can be subjected to chemical modifications: conjugation and crosslinking. The present review gives an overview regarding HA, describing its history, physico-chemical, structural and hydrodynamic properties, and biology –occurrence, biosynthesis (by hyaluronan synthases), degradation (by hyaluronidases and oxidative stress), roles, mechanisms of action and receptors. Furthermore, both conventional and recently emerging methods developed for the industrial production of HA and its chemical derivatization are presented. Finally, the medical, pharmaceutical and cosmetic applications of HA and its derivatives are reviewed, reporting examples of HA-based products which currently are on the market or are undergoing further investigations.

Piper pubinervulum C. DC., es una planta medicinal utilizada por los indígenas amazónicos del sur del Ecuador, las hojas poseen características aromáticas. El objetivo de la presente investigación es la de extraer y analizar las propiedades químicas y de actividad biológica del aceite esencial proveniente de las hojas.El estudio de composición química a través de GC-EM y RMN 1H arrojó la detección de 44 constituyentes dentro de los cuales b cariofileno, isoeugenol-metil éter, asarona y el nerolidol fueron los mayoritarios. La Actividad antioxidante del aceite fue evaluada por los métodos DPPH (1,1-diphenyl-2-picrylhydrazyl), ABTS (2,2’-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) y la fotoquimioluminiscencia (PCL). Adicionalmente se realizaron estudios de actividad empleando (HP)TLC-DPPH bioautográficos. La actividad antimicrobiana fue evaluada por el método de difusión de disco en dos bacterias Gram+, dos bacterias Gram- y dos levaduras. Los resultados más interesantes se producen con las dos levaduras Candida tropicalis (MIC 0,77mg/ml) y Candida albicans (MIC0,33mg/ml) donde la actividad fue similar al aceite esencial de Thymus vulgaris el estándar natural de referencia. Los buenos resultados con respecto a la actividad antifúngica nos llevan a concluir que el aceite esencial podría ser usado con esta finalidad. // Piper puvinervulum C. DC. is a medicinal plant used by Amazon Indians in southern Ecuador, the leaves possess aromatic characteristics. The objective of this research is to extract and analyze the chemical properties and biological activity of the essential oil from the leaves. The study of the chemical composition based on analysis GC-MS and 1H RMN data resulted in the identification of 44 compounds including the main components: b-caryophyllene (1), isoeugenol methyl ether (2), asarona (3), and nerolidol (4). The antioxidant potential of the oils was assessed with the DPPH (1,1-diphenyl-2-picrylhydrazyl), ABTS (2,2’-Azinobis(3- ethylbenzothiazoline-6-sulfonic acid) diammonium salt), Photochemiluminescence and bioautographic HPTLC-DPPH methods. The antimicrobial activity was evaluated by means of disc diffusion method while the antimicrobial effect was evaluated in two Gram+ bacteria, two Gram- bacteria, and two yeasts. The essential oil was found effective against Candida tropicalis (MIC0,77 mg/ml) and Candida albicans (MIC0,33mg/ml) yeasts in a manner similar to the reference essential oil of Thymus vulgaris. The positive results in terms of antifungal activity suggest that the essential oil could be used for this purpose.

In this work, we investigated white blood cell gene expression of SOD-1, SOD-2, catalase, GPX-1, GSR and GSTM-1; plasma content of GSH and GSSG; plasma Oxygen Radical Absorbance Capacity; amount of plasma carbonylated proteins; urinary levels of Hexanoyl-Lysine adduct; lipid composition of erythrocyte membranes. Oxidative stress is always associated with Friedreich’s Ataxia (FRDA) also accompained by impaired mitochondrial functions. Patients are currently treated with idebenone, a CoQ10 analogue, believed effective in view of its ability to counteract free radical damages. Vit. E is known to be effective on oxidative stress related pathologies, taking into account our esperience in the field of the class of natural vitamin E “tocotrienol” we have started the present investigation in order to develop a model useful to investigate the efficacy of a tocotrienol based approaches on oxidative stress damage protection. A mixture (OXI-3 internal reference name) of enantiomerically pure tocotrienols (alpha, beta, gamma and delta) has been selected and tested in patients monitoring the above reported different biochemical parameters. The pilot investigation was conducted on five young FRDA patients who assumed OXI-3 (equivalent to 5 mg/kg/day), for two months. The wide array of different markers consistently pointed to the presence of oxidative stress in FRDA patients, despite the fact that the idebenone therapy had not been discontinued. However, even a two month low-dose tocotrienol supplementation led to the decrease of oxidative stress indexes and to parameter values that approached those of healthy controls. Moreover, there are evidences that a longer tocotrienol treatment may be more effective in reducing oxidative stress.