Could essential oils enhance biopolymers performance for wound healing? A systematic review.

BACKGROUND: Millions of people in the world suffer from chronic wounds of different etiologies such as diabetic foot and leg ulcers, without solutions nowadays. Molecules obtained from plants offer an alternative to aid wound healing. Strong evidence about essential oils (EO) anti-inflammatory and antimicrobial properties is thoroughly described in literature and their chemical compositions are well characterized. More recently, EO effects in experimental wounds have begun to be analyzed. AIM: We aim to summarize the evidence of EO in experimental wounds, and the possibility of combining them with biopolymers commonly used in skin regeneration. METHODS: Electronic databases such as ScienceDirect, PubMed and Scopus were used to search scientific contributions until March 2017, using relevant keywords. In a first step, literature focusing on EO and/or mono- or sesqui-terpenoids effects in rodent wounds was identified and summarized. In all cases, chemical structures and EO composition were detailed, as well as references to in vitro activities previously determined, e.g. antibacterial, antioxidant or anti-inflammatory. In a second step, scientific literature devoted to combine EO and biopolymers with the focus set on wound healing innovations, was collected and analyzed. RESULTS: Treatments with EO from species of genders Lavandula, Croton, Blumea, Eucalyptus, Pinus, Cymbopogon, Eucalyptus, Cedrus, Abies, Rosmarinus, Origanum, Salvia and Plectranthus, have shown positive results in rodent wounds. All of these EO were mainly composed by monoterpenoids-thymol, 1,8-cineole, linalool-or monoterpenes, as limonene or pinenes. Experimental wounds in rodents have shown faster closure rate, better collagen deposition and/or enhanced fibroblasts proliferation. In blends with biopolymers, several EO combined with chitosan, alginate, gelatin or collagen, were processed to give active films or nanofibers, with antioxidant, anti-inflammatory or antimicrobial activities. Curiously, all of these works were carried out since 2010. CONCLUSIONS: There is significant evidence about the effectivity of EO as wound healers. The incorporation of EO into a polymer matrix that contributes to wound healing is still incipient. However, scientific based evidence of the EO incorporation in resorbable polymeric scaffolds was found and analyzed herein. In summary, EO-biopolymer dressings or scaffolds have become promising artifacts regarding wound treatments, especially in chronic wounds, where treating infection and inflammation are still important issues.

Carrageenan and agaran structures from the red seaweed Gymnogongrus tenuis.

The galactan system biosynthesized by the red seaweed Gymnogongrus tenuis (Phyllophoraceae) is constituted by major amounts of κ/ι-carrageenans, with predominance of ι-structures, which were isolated by extraction with hot water in high yield (∼ 45%). A small amount of non-cyclized carrageenans mostly of the ν-type was also obtained. Besides, 12% of these galactans are agaran structures, which were present in major quantities in the room temperature water extracts, but they were also found in the hot water extract. They are constituted by 3-linked ß-D-galactose units partially substituted on C-6 with sulfate or single stubs of ß-D-xylose and 4-linked residues that comprise α-L-galactose units partially sulfated or methoxylated on C-3 or sulfated on C-3 and C-6 and 3,6-anhydro-α-L-galactose. Related structural patterns were previously found for agarans synthesized by other carrageenophytes. Results presented here show that these agarans are low molecular weight molecules independent of the carrageenan structures, with strong interactions between them.

In vitro and in vivo immunomodulatory activity of sulfated polysaccharides from red seaweed Nemalion helminthoides.

Water-soluble sulfated polysaccharides from the red seaweed Nemalion helminthoides: two xylomannan fractions (N3 and N4) and a mannan fraction (N6) were investigated to determine their in vitro and in vivo immunomodulatory activities. N3 and N4 induced in vitro proliferation of macrophages of the murine cell line RAW 264.7 and significantly stimulated the production of nitric oxide (NO) and cytokines (IL-6 and TNF-α) in the same cells, whereas this response was not observed with the mannan N6. The cytokine production was also stimulated by sulfated xylomannans in vivo in BALB/c mice inoculated intravenously with these polysaccharides. Remarkably, when mice were treated with N3 and N4 for 1 h before being infected with Herpes simplex virus type 2, they remained asymptomatic with no signs of disease. The in vitro and in vivo results suggest that sulfated xylomannans could be strong immunomodulators.

Chemical modifications of algal mannans and xylomannans: effects on antiviral activity.

The structures of two sulfated xylomannans extracted from the red alga Nemalion helminthoides were determined. These two fractions plus a sulfated mannan, isolated from the same alga and whose structure was previously reported, were subjected to chemical modification. The mannan was oversulfated with SO(3)-pyridine in dimethyl sulfoxide at 60 °C during two and three hours and the xylomannans were subjected to Smith degradation in order to eliminate xylose side-chains. Structural analysis of all derivatives was carried out by methylation analysis and (13)C NMR spectroscopy. Antiviral activity against herpes simplex virus type 1 and 2, and dengue virus type 2 of native and modified mannans and xylomannans was estimated. Anticoagulant effect of the active fractions was also determined.

Sulfated mannans from the red seaweed Nemalion helminthoides of the South Atlantic.

Nemalion helminthoides, collected in the Argentine South Atlantic coast, was extracted with hot water and the crude product fractionated using cetrimide. The complexed material was subjected to fractional solubilization in solutions of increasing sodium chloride concentration and seven fractions were separated and analyzed. Structural analysis of the main fractions, those soluble in 3.0 and 4.0 M NaCl (yields 21.0% and 13.8%, respectively) and those insoluble in 4.0 M NaCl (yield 20.0%), indicated that this seaweed biosynthesizes (1-->3)-linked alpha-D-mannans that are sulfated at positions 4 and 6. Three mannan fractions comprising considerable amounts of xylose were also isolated in very low total yield (2.0%). The fractions that were soluble in 3.0 and 4.0 M NaCl showed low antiherpetic activity whereas this activity was considerable for the fraction solubilized in 2.0 M NaCl (yield 0.5%) which contained single stubs of beta-D-xylose. A xylan, soluble in cetrimide solution, containing (1-->3, 1-->4)-linked beta-D-xylose residues, was also isolated in minor amount.