Norway spruce galactoglucomannans exhibiting immunomodulating and radical-scavenging activities.

Wood-derived naturally acetylated galactoglucomannans (AcGGM) can be recovered even in ton-scale at mechanical pulp mills using spruce as raw material. These cell wall polysaccharides have a great potential as hydrocolloids and bioactive polymers in food and pharmaceutical applications, or as starting material for production of functional polymers. The immunostimulatory activity of both AcGGM and its deacetylated form (GGM) was now in vitro tested. The biological response of both AcGGM and GGM in the lymphocyte transformation test was dose-dependent. The direct mitogenic as well as comitogenic activities of the AcGGM were comparable to those of the immunogenic corn cob xylan used as control, and GGM showed significantly higher biological responses also at lower doses. In contrast to GGM, AcGGM possessed also DPPH radical-scavenging activity. The results suggested that the spruce AcGGM and GGM are potentially important as additives with immuno-potentiating and antioxidant properties in food products and pharmaceutical formulations.

Almond shell xylo-oligosaccharides exhibiting immunostimulatory activity.

Partially O-acetylated xylo-oligosaccharides (DXO) isolated from almond shells by autohydrolysis as well as their de-acetylated form (DeXO) were subjected to chemical, molecular, and structural analyses. They represent a mixture of neutral and acidic oligomers and low-molecular weight polymers related to (4-O-methyl-D-glucurono)-D-xylan. DXO and DeXO showed direct mitogenic activity and enhancement of the T-mitogen-induced proliferation of rat thymocytes, indicating the immunostimulatory potential of the almond shell xylo-oligosaccharides.

Water-soluble polysaccharides from Salvia officinalis L. possessing immunomodulatory activity.

A water-soluble polysaccharide complex (A) composed of galactose (17.9%), 3-O-methyl-galactose (3.0%), glucose (15.5%), mannose (8.3%), arabinose (30.4%), xylose (7.6%), fucose (2.6%), rhamnose (6.7%), and uronic acids (8.0%) has been isolated from the aerial parts of sage (Salvia officinalis L.) by cold water extraction. It showed a broad molecular-mass distribution pattern (Mw approximately 2000-93,000) with a predominance of polymers with Mw< 10,000. Ion-exchange chromatography of A afforded six polymeric fractions (A1-A6) in which arabinogalactans associated with galacturonan and/or rhamnogalacturonan backbones prevail. Sage polysaccharides were examined for their immunomodulatory activity in the comitogenic thymocyte test which is interpreted as being an in vitro correlate of adjuvant activity. The acidic polysaccharide fractions A2, A3 and A4 exhibited the highest mitogenic and comitogenic activities of all fractions tested, and relatively high SI(comit)/SI(mit) ratios approximately 3 indicate potential adjuvant properties of these polysaccharides.

Liposomal preparations of muramyl glycopeptides as immunomodulators and adjuvants.

The need for safe and structurally defined immunomodulators and adjuvants is increasing in connection with the recently observed marked increase in the prevalence of pathological conditions characterized by immunodeficiency. Important groups of such compounds are muramyl glycopeptides, analogs of muramyl dipeptide (MDP), glucosaminyl-muramyl dipeptide (GMDP), and desmuramylpeptides. We have designed and synthesized new types of analogs with changes in both the sugar and the peptide parts of the molecule that show a high immunostimulating and adjuvant activity and suppressed adverse side effects. The introduction of lipophilic residues has also improved their incorporation into liposomes, which represent a suitable drug carrier. The proliposome-liposome method is based on the conversion of the initial proliposome preparation into liposome dispersion by dilution with the aqueous phase. The description of a home-made stirred thermostated cell and its link-up with a liquid delivery system for a rapid and automated preparation of multilamellar liposomes at strictly controlled conditions (sterility, temperature, dilution rate and schedule) is presented. The cell has been designed for laboratory-scale preparation of liposomes (300-1000 mg of phospholipid per run) in a procedure taking less than 90 min. The method can be readily scaled up. Examples of adjuvant and immunostimulatory effect of liposomal preparation in mice model will be presented.