Conductive hydrogels based on tragacanth and silk fibroin containing dopamine functionalized carboxyl-capped aniline pentamer: Merging hemostasis, antibacterial, and anti-oxidant properties into a multifunctional hydrogel for burn wound healing.

Hydrogels possessing both conductive characteristics and notable antibacterial and antioxidant properties hold considerable significance within the realm of wound healing and recovery. The object of current study is the development of conductive hydrogels with antibacterial and antioxidant properties, emphasizing their potential for effective wound healing, especially in treating third-degree burns. For this purpose, various conductive hydrogels are developed based on tragacanth and silk fibroin, with variable dopamine functionalized carboxyl-capped aniline pentamer (CAP@DA). The FTIR analysis confirms that the CAP powder was successfully synthesized and modified with DA. The results show that the incorporation of CAP@DA into hydrogels can increase the porosity and swellability of the hydrogels. Additionally, the mechanical and viscoelastic properties of the hydrogels are also improved. The release of vancomycin from the hydrogels is sustained over time, and the hydrogels are effective in inhibiting the growth of Methicillin-resistant Staphylococcus aureus (MRSA). In vitro cell studies of the hydrogels show that all hydrogels are biocompatible and support cell attachment. The hydrogels' tissue adhesiveness yielded a satisfactory hemostatic outcome in a rat-liver injury model. The third-degree burn was created on the dorsal back paravertebral region of the rats and then grafted with hydrogels. The burn was monitored for 3, 7, and 14 days to evaluate the efficacy of the hydrogel in promoting wound healing. The hydrogels revealed treatment effect, resulting in enhancements in wound closure, dermal collagen matrix production, new blood formation, and anti-inflammatory properties. Better results were obtained for hydrogel with increasing CAP@DA. In summary, the multifunctional conducive hydrogel, featuring potent antibacterial properties, markedly facilitated the wound regeneration process.

The controlled release, bioactivity and osteogenic gene expression of Quercetin-loaded gelatin/tragacanth/ nano-hydroxyapatite bone tissue engineering scaffold.

In this study, a Gelatin/Tragacanth/Nano-hydroxyapatite scaffold was fabricated via freeze-drying method. A highly porous scaffold with an average pore diameter of 142 µm and porosity of 86% was found by the micro-computed tomography. The mean compressive strength of the scaffold was about 1.5 MPa, a value in the range of the spongy bone. The scaffold lost 10 wt.% of its initial weight after 28 days soaking in PBS that shows a fair degradation rate for a bone tissue engineering scaffold. Apatite formation ability of the scaffold was confirmed via scanning electron microscopy, X-ray diffraction and Fourier transforming infrared spectroscopy, after 28 days soaking in simulated body fluid. The scaffold was able to deliver 93% of the loaded drug, Quercetin, during 120 h in phosphate-buffered solution, in a sustainable manner. The MTT assay using human bone mesenchymal stem cells showed 84% cell viability of the Quercetin-loaded scaffold. The expression of the osteogenic genes including Col I, Runx-2, BGLAP (gene of osteocalcin), bFGF, SP7 (gene of osterix) and SPP1 (gene of osteopontin) were all upregulated when Quercetin was loaded on the scaffold, which indicates the synergetic effect of the drug and the scaffold.

Tragacanth gum coating suppresses the disassembly of cell wall polysaccharides and delays softening of harvested mango (Mangifera indica L.) fruit.

Mango is a climacteric fruit and is prone to high perishability. The rapid softening and ripening (due to degradation and disassembly of cell wall polysaccharides) are the major limitations in extending the storability of the harvested mango fruits. Various types of gum-based edible coatings have been reported for the shelf life extension of mango fruits. Tragacanth gum (TCG) also has appropriate coating properties. Its use as an edible coating has been reported on certain fruits. However, the effect of TCG coating in the regulation of harvested mango fruits ripening and softening has not been reported yet. So, the objective of this work was to investigate the effect of TCG (control, 0.5 %, 1 % and 1.5 %) coating on postharvest softening and ripening of harvested mango fruits. TCG coating affected the ripening and softening of mango in a dose-dependent manner. Results exhibited that mango fruits coated with 1.5 % TCG showed substantially lower disease incidence and weight loss. The 1.5 % TCG-coated mangoes showed substantially lower ethylene biosynthesis and respiration rate peaks as well as superoxide anion and hydrogen peroxide contents compared with the control. In the same way, 1.5 % TCG-coated mango fruits had markedly higher total chlorophyll content and lower L*, b* and a* along with substantially lower total carotenoids in peel tissues. Mango fruits coated with 1.5 % TCG exhibited markedly lower water-soluble pectin and higher chelate-soluble pectin, Na2CO3-soluble pectin, protopectin, cellulose and hemicellulose in flesh tissues compared with control. The activity of polygalacturonase (PG), cellulase (CX), pectin methylesterase (PME), ß-galactosidase (ß-Gal) and ß-glucosidase (ß-Glu) were significantly lower in flesh of 1.5 % TCG treated fruits along with substantially higher firmness in contrast with control. In addition, 1.5 % TCG coating treatment showed significantly higher activity of antioxidative enzymes and delayed the increase in soluble solids content (SSC) and ripening index (RI) along with considerably higher titratable acidity (TA) compared with the untreated control. So, pre-storage TCG based edible coating (1.5 %) could be applied to delay ripening and softening in mango fruit industry under postharvest ambient conditions.

Characterization and optimization of de-esterified Tragacanth-chitosan nanocomposite as a potential carrier for oral delivery of insulin: In vitro and ex vivo studies.

Oral administration of insulin is one of the most challenging topics within this area, because insulin is degraded in stomach before it enters the bloodstream. In this study, for the first time, a nano-carrier for controlled and targeted oral delivery of insulin was developed using de-esterified Tragacanth and chitosan. The fabricated nanoparticles were synthesized using coacervation technique and their properties were optimized using response surface methodology. The effect of experimental variables on the particle size and loading efficiency was examined. In addition, the interactions between components were analyzed using Fourier transform infrared. The thermal stability of nanoparticles was studied by thermal gravimetric analysis. The insulin loading efficiency was measured and in vitro release profile and ex vivo insulin permeability was determined. Optimized nanoparticles showed spherical shape with a size less than 200 nm and zeta potential of +17 mV. Owing to their nanoscale dimensions and mucoadhesiveness, nanoparticles were synthesized using medium molecular weight of Chitosan. The insulin loading efficacy for the system was 6.4%, released under simulated gastrointestinal conditions in a pH-dependent manner. Based on all of the obtained results, it can be concluded that these nanoparticles can potentially be utilized as a carrier for the oral insulin delivery.

Gum Tragacanth (GT): A Versatile Biocompatible Material beyond Borders.

The use of naturally occurring materials in biomedicine has been increasingly attracting the researchers' interest and, in this regard, gum tragacanth (GT) is recently showing great promise as a therapeutic substance in tissue engineering and regenerative medicine. As a polysaccharide, GT can be easily extracted from the stems and branches of various species of Astragalus. This anionic polymer is known to be a biodegradable, non-allergenic, non-toxic, and non-carcinogenic material. The stability against microbial, heat and acid degradation has made GT an attractive material not only in industrial settings (e.g., food packaging) but also in biomedical approaches (e.g., drug delivery). Over time, GT has been shown to be a useful reagent in the formation and stabilization of metal nanoparticles in the context of green chemistry. With the advent of tissue engineering, GT has also been utilized for the fabrication of three-dimensional (3D) scaffolds applied for both hard and soft tissue healing strategies. However, more research is needed for defining GT applicability in the future of biomedical engineering. On this object, the present review aims to provide a state-of-the-art overview of GT in biomedicine and tries to open new horizons in the field based on its inherent characteristics.

Tragacanth gum-based multifunctional hydrogels and green synthesis of their silver nanocomposites for drug delivery and inactivation of multidrug resistant bacteria.

This study investigated natural polymer-based stimuli-responsive hydrogels (TGIAVE) and their silver nanocomposites (TGIAVE-Ag). The hydrogels were composed of tragacanth gum, N-isopropyl acrylamide, and 2-(vinlyoxy) ethanol and were prepared via simple redox polymerization using N,N'-methylene-bis-acrylamide as a crosslinker and potassium persulfate as an initiator. The TGIAVE-Ag were synthesized via a green method involving an aqueous extract of Terminalia bellirica seeds. Structural, thermal, crystallinity, morphology, and size characteristics of the TGIAVE and TGIAVE-Ag were investigated by FTIR, UV-Vis, XRD, DSC, SEM, EDS, DLS, and TEM. To understand the physicochemical interaction and diffusion characteristics of TGIAVEs, network parameters such as zero-order, first-order, Hixson-Crowell, Higuchi, and Korsmeyer-Peppas values were calculated by assessing swelling data. TGIAVE hydrogels at pH 1.2 and 7.4 and temperatures of 25 and 37 °C may be used for time-dependent controlled release of 5-fluorouracil, an anticancer drug, TGIAVE-Ag may be applied for the inactivation of multidrug resistant (MDR) bacteria.

Tragacanth gum coating modulates oxidative stress and maintains quality of harvested apricot fruits.

Tragacanth gum is a polysaccharide-based complex with a good coating property. However, its use in postharvest storage of fresh fruits and vegetables is very limited. In the current work, the effect of tragacanth gum (1%) was investigated on postharvest quality of apricot fruits during storage at 20 ± 1 °C for 8 days. Apricot fruits coated with tragacanth gum coating showed significantly reduced weight loss, decay and electrolyte leakage, hydrogen peroxide and malondialdehyde production. Tragacanth gum coating suppressed increase in total soluble solids and showed higher titratable acidity compared with control. The coated fruits had higher total phenolics and ascorbic acid along with greater 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity in contrast with control. Postharvest application of tragacanth gum coating maintained markedly higher activities of ascorbate peroxidase (APX), catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD) enzymes activities as compared with control. In addition, tragacanth gum application suppressed polygalacturonase (PG), pectin methylesterase (PME), and cellulase (CX) enzymes activities, thereby suppressed softening of apricot fruits. Sensory quality attributes such as taste, juiciness, aroma, appearance, and overall acceptability were also significantly higher in tragacanth gum coated fruits compared with control. In conclusion, tragacanth gum coating could be considered suitable for postharvest quality conservation of apricot fruits.

Antibacterial tragacanth gum-based nanocomposite films carrying ascorbic acid antioxidant for bioactive food packaging.

Food packaging has a pivotal share to improve protection, safety and shelf-life time of foods and bioproducts. Herein, we prepared bioactive nanocomposite films that composed of tragacanth (TG), polyvinyl alcohol, ZnO nanoparticles (NPs) and ascorbic acid (AA) using glycerol as a plasticizer and citric acid as a cross-linker for food packaging. The SEM images showed a homogenous distribution of ZnO NPs with low aggregation in nanocomposite films. The water solubility of nanocomposite films reduced from 15.65 % to 10.81 with increasing of TG and ZnO NPs contents. The incorporation of AA and ZnO NPs into nanocomposite films improved antioxidant activity from 50 % to 66 % in 95 % ethanolic solution. Also, the nanocomposite films showed good antibacterial activity against Gram-negative and -positive bacteria. Soil degradation rate of nanocomposite films increased from 80 % to 91.46 as the wt% of TG increased. Therefore, prepared nanocomposite films could be employed as a promising candidate for food packaging applications.

Green fabrication of chitosan/tragacanth gum bionanocomposite films having TiO2@Ag hybrid for bioactivity and antibacterial applications.

Common materials used in tissue engineering are not cost-effective and natural origin. Hence, we designed green, safe, and antibacterial bionanocomposite (bio-NC) films based on polysaccharides, chitosan (CS) and gum tragacanth (GT) for the bone tissue engineering. For this aim, different percentages of titanium dioxide nanoparticles (TiO2 NPs) and green silver (Ag)-doped TiO2 NPs (TiO2@Ag hybrid) were employed as nanofiller to improve the properties of the CS-GT film. Moreover, the physicochemical characteristics of the bio-NC films were examined with a field-emission scanning electron microscope (FE-SEM), Fourier transform infrared, X-ray diffraction, and transmission electron microscopy (TEM). The FE-SEM images showed a rough surface for the CS-GT/TiO2@Ag bio-NC films, and TEM images showed better dispersion of TiO2@Ag hybrid than TiO2 NPs into the CS-GT matrix. Also, these bio-NC films were considered for the bioactivity test and the results showed formation of hydroxyapatite on the surface of the prepared bio-NC films. Furthermore, addition of GT led to an increase in the bioactivity of the CS-GT blend. Finally, antibacterial behavior of the prepared bio-NC films was investigated against Escherichia coli and Staphylococcus aureus bacteria with/without ultraviolet irradiation and the results indicated better antibacterial performance for the CS-GT/TiO2@Ag bio-NC film (TiO2:Ag = 1:1) under both conditions.

Novel pH-sensitive alginate hydrogel delivery system reinforced with gum tragacanth for intestinal targeting of nutraceuticals.

The present study utilizes the novel combination of Gum tragacanth (GT) and sodium alginate (SA) to reinforce SA hydrogel beads. The composite hydrogel beads were encapsulated with phenolic compounds extracted from Basella sps. The rheological studies conferred increased elastic property of GT incorporated formulations. Higher swelling behavior was observed in simulated intestinal fluid (SIF) with increasing GT content in SA formulations. SA-GT composite hydrogels revealed increased encapsulation efficiency with sustained release of phenolic compounds in SIF. GT incorporated hydrogel beads exhibited increased biodegradation (up to 82% weight loss) in biodegradation media (in vitro). FTIR study found no molecular interaction between SA and GT. TGA analysis revealed that GT incorporation did not affect the thermal behavior of SA. Furthermore, SA-GT encapsulated hydrogels showed remarkable cytotoxicity against osteosarcoma cells. Thus our findings suggest SA-GT gel formulation could be used as a promising delivery system for drugs and nutraceutical compounds.

Removal of NO3- ions from water using bioadsorbent based on gum tragacanth carbohydrate biopolymer.

In this study, functionalized hydrogel bioadsorbents were produced from gum tragacanth (GT) carbohydrate and quaternary ammonium salt (TMSQA) as a crosslinker. The prepared bioadsorbents were used for the removal of NO3- ions from water through the electrostatic and ion exchange mechanism and antibacterial activity. The effect of quaternary ammonium content on the adsorption capacity was studied. The bioadsorbents were characterized by using FE-SEM, energy dispersive X-Ray (EDX), FT-IR, and TGA techniques. The equilibrium time and the most effective pH value for maximum NO3- removal (20 mg g-1) were 21 min and 7, respectively. A series of isotherms and kinetics models were undertaken and the obtained data were fitted well to the Langmuir isotherm and pseudo-second-order rate kinetic. The thermodynamic study confirmed the suitability of NO3- removal by the as-prepared bioadsorbent at room temperature, and also the negative value of ΔGº = -89.1 kJ mol-1 demonstrating the spontaneous nature of adsorption.

Fabrication and characterization of PVA/Gum tragacanth/PCL hybrid nanofibrous scaffolds for skin substitutes.

In this work three dimensional biodegradable nanofiberous scaffolds containing poly(ε-caprolactone) (PCL), poly(vinyl alcohol) (PVA) and gum tragacanth (GT) were successfully fabricated through two nozzles electrospinning process. For this purpose, PVA/GT blend (Blend: B) solution (60:40wt%) was injected from one syringe and poly(ε-caprolactone) solution from the other one. Presence of PVA and PCL in the formulation improved the electrospinning process of GT solution and mechanical properties of the fabricated nanofibers. Scanning electron microscopy (SEM) results showed uniform PVA/GT-PCL blend-hybrid (Blend-Hybrid: B-H) nanofibers with the diameter ranging about 132±27nm. Hybrid nanofibers were evaluated by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) tests. The antibacterial activities of the PVA/GT-PCL (B-H) nanofibers were conducted against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus and results indicated that the hybrid nanofibers were 95.19% antibacterial against S. aureus bacterium. NIH 3T3 fibroblast cells growth and MTT assay were carried out on the scaffolds. Hydrophilicity nature, favorable mechanical properties of the fabricated hybrid nanofibers, along with their structure in biological media, biocompatibility, as well as antibacterial property indicate scaffolds prepared are suitable for tissue engineering.

Electron beam irradiation crosslinked hydrogels based on tyramine conjugated gum tragacanth.

In the present study, electron beam irradiation was applied to prepare a chemically crosslinked hydrogel based on tyramine conjugated gum tragacanth. Then, the gel content, swelling behavior and cytotoxicity of the hydrogels were evaluated. The gel content of the hydrogels was in the range of 75-85%. Equilibrium swelling degree of the hydrogels decreased from 51 to 14 with increasing polymer concentration and irradiation dose. Moisture retention capability of the hydrogels after 5h incubation at 37°C was in the range of 45-52 that is comparable with of commercial hydrogels. The cytotoxicity analysis showed the good biocompatibility of hydrogels. These results indicated that electron beam irradiation is a promising method to prepare chemically crosslinked tyramine conjugated gum tragacanth hydrogels for biomedical applications. Also, the versatility of electron beam irradiation for crosslinking of a variety of polymers possessing tyramine groups was demonstrated.

Effect of gum tragacanth on rheological and physical properties of a flavored milk drink made with date syrup.

Date syrup as a nutritional additive and safe alternative to added sugar is one of the best choices for milk flavoring. In this study, a flavored milk beverage was formulated using date syrup for flavoring the product and gum tragacanth to obtain an acceptable mouth feel. Steady shear and dynamic oscillatory rheological properties of the samples contained 3 concentrations (0, 0.1, 0.2, and 0.3%, wt/wt) of 2 types of gum tragacanth (Astragalus gossypinus and Astragalus rahensis) which at 3°C, were studied. Particle size distribution and colorimetric assays were determined by laser diffractometry and using reflection spectrometer, respectively. Sensory analysis was performed with 25 semitrained panelists, using a 5-point hedonic scale. The results showed that viscoelastic properties, flow behavior parameters, particle size, and color parameters (L*, a*, and b*, where L* represents lightness, a* represents the redness/greenness quality of the color, and b* represents the yellowness and blueness quality of the colors) were significantly affected by the concentration of the gum tragacanth and the severity of this effect was influenced by the type of gum. The use of appropriate type and concentration of gum tragacanth in date milk formulation can improve the texture and mouth feel by affecting on particle size and the flow behavior of this product.

Enzymatic depolymerization of gum tragacanth: bifidogenic potential of low molecular weight oligosaccharides.

Gum tragacanth derived from the plant "goat's horn" (Astragalus sp.) has a long history of use as a stabilizing, viscosity-enhancing agent in food emulsions. The gum contains pectinaceous arabinogalactans and fucose-substituted xylogalacturonans. In this work, gum tragacanth from Astragalus gossypinus was enzymatically depolymerized using Aspergillus niger pectinases (Pectinex BE Color). The enzymatically degraded products were divided into three molecular weight fractions via membrane separation: HAG1 < 2 kDa; 2 kDa < HAG2 < 10 kDa; HAG3 > 10 kDa. Compositional and linkage analyses showed that these three fractions also varied with respect to composition and structural elements: HAG1 and HAG2 were enriched in arabinose, galactose, and galacturonic acid, but low in fucose and xylose, whereas HAG3 was high in (terminal) xylose, fucose, and 1,4-bonded galacturonic acid, but low in arabinose and galactose content. The growth-stimulating potential of the three enzymatically produced gum tragacanth fractions was evaluated via growth assessment on seven different probiotic strains in single-culture fermentations on Bifidobacterium longum subsp. longum (two strains), B. longum subsp. infantis (three strains), Lactobacillus acidophilus , B. lactis, and on one pathogenic strain of Clostridium perfringens . The fractions HAG1 and HAG2 consistently promoted higher growth of the probiotic strains than HAG3, especially of the three B. longum subsp. infantis strains, and the growth promotion on HAG1 and HAG2 was better than that on galactan (control). HAG3 completely inhibited the growth of the C. perfringens strain. Tragacanth gum is thus a potential source of prebiotic carbohydrates that exert no viscosity effects and which may find use as natural functional food ingredients.

The utilization of gum tragacanth to improve the growth of Rhodotorula aurantiaca and the production of gamma-decalactone in large scale.

The production of gamma-decalactone and 4-hydroxydecanoic acid by the psychrophilic yeast R. aurantiaca was studied. The effect of both compounds on the growth of R. aurantiaca was also investigated and our results show that gamma-decalactone must be one of the limiting factors for its production. The addition of gum tragacanth to the medium at concentrations of 3 and 4 g/l seems to be an adequate strategy to enhance gamma-decalactone production and to reduce its toxicity towards the cell. The production of gamma-decalactone and 4-hydroxydecanoic acid was significantly higher in 20-l bioreactor than in 100-l bioreactor. By using 20 g/l of castor oil, 6.5 and 4.5 g/l of gamma-decalactone were extracted after acidification at pH 2.0 and distillation at 100 degrees C for 45 min in 20- and 100-l bioreactors, respectively. We propose a process at industrial scale using a psychrophilic yeast to produce naturally gamma-decalactone from castor oil which acts also as a detoxifying agent; moreover the process was improved by adding a natural gum.

Whey protein concentrate and gum tragacanth as fat replacers in nonfat yogurt: chemical, physical, and microstructural properties.

The effect of whey protein concentrate (WPC) and gum tragacanth (GT) as fat replacers on the chemical, physical, and microstructural properties of nonfat yogurt was investigated. The WPC (7.5, 15, and 20 g/L) and GT (0.25, 0.5, 0.75, and 1 g/L) were incorporated into the skim milk slowly at 40 to 45 degrees C with agitation. The yogurt mixes were pasteurized at 90 degrees C for 10 min, inoculated with 0.1% starter culture, and incubated at 42 degrees C to pH 4.6, then refrigerated overnight at 5 degrees C. A control nonfat yogurt and control full fat yogurt were prepared as described, but without addition of WPC and GT. Increasing amount of WPC led to the increase in total solids, total protein, acidity, and ash content, whereas GT did not affect chemical parameters. Increasing WPC caused a more compact structure consisting of robust casein particles and large aggregates. Firmness was increased and susceptibility to syneresis was decreased as WPC increased. No significant difference was observed for firmness and syneresis of yogurt fortified with GT up to 0.5 g/L compared with control nonfat yogurt. Increasing the amount of gum above 0.5 g/L produced softer gels with a greater tendency for syneresis than the ones prepared without it. Addition of GT led to the coarser and more open structure compared with control yogurt.

Reduction of saliva-promoted adhesion of Streptococcus mutans MT8148 and dental biofilm development by tragacanth gum and yeast-derived phosphomannan.

The aim of this study was to investigate materials which reduce saliva-promoted adhesion of Streptococcus mutans onto enamel surfaces, and their potential in preventing dental biofilm development. The effects of hydroxyapatite (HA) surface pretreatment with hydrophilic polysaccharides on saliva-promoted S. mutans adhesion in vitro and de novo dental biofilm deposition in vivo were examined. Saliva-promoted adhesion of S. mutans MT8148 was significantly reduced by pretreatment of the HA surface with tragacanth gum (TG) and yeast-derived phosphoglycans. Extracellular phosphomannan (PM) from Pichia capsulata NRRL Y-1842 and TG reduced biofilm development on lower incisors in plaque-susceptible rats when administered via drinking water at concentrations of 0.5% and 0.01%, respectively. The inhibitory effect of TG on de novo dental biofilm formation was also demonstrated when administered via mouthwash in humans. It is concluded that TG and yeast-derived PM have the potential for use as anti-adherent agents and are effective in reducing de novo dental biofilm formation.

Antiviral activities of tragacanthin polysaccharides on Punta Toro virus infections in mice.

Tragacanthin polysaccharides from Astragalus brachycentrus (AV208) and Astragalus echidnaeformis (AV212) plants, which are devoid of in vitro antiviral activity, were evaluated in a mouse model of Punta Toro virus (PTV) infection. The PTV (a phlebovirus member of the Bunyaviridae family of viruses) is a model for studying the treatment of Rift Valley fever and hantavirus infections. Single intraperitoneal treatments with 12.5-200 mg/kg/day doses of AV212 given 24 h before or 4 and 24 h after virus inoculation protected the majority of mice from mortality. Single treatments with AV208 were ineffective when given 24 h before the virus challenge; however, protection was afforded when treatments were administered at 4 and 24 h following virus inoculation. In a follow-up study, AV208 treatments of 1.6-50 mg/kg/day given 24 h subsequent to virus exposure caused reductions in mortality, liver infection scores, liver and spleen virus titers, and serum transaminases. The polysaccharides did not activate lymphocytes or natural killer cells, nor was interferon induced in treated mice. However, mice pretreated with fumed silica (a macrophage poison) and infected with the PTV were not protected by subsequent administration of AV208 or AV212 at 50 mg/kg, providing evidence that activation of peritoneal macrophages by the polysaccharides affords protection to infected animals. These compounds should be considered for the potential treatment of significant human infections induced by bunyaviruses and hantaviruses.