Sulfated Derivatives Research Articles

Effects of sulfation and carboxymethylation on Cyclocarya paliurus polysaccharides: Physicochemical properties, antitumor activities and protection against cellular oxidative stress

The Cyclocarya paliurus polysaccharide (CP) was chemically modified to produce sulfated derivatives (S-CP) and carboxymethylated derivatives (CM-CP). Subsequently, the antioxidant activity, cytoprotective effect and antitumor activity of these derivatives were investigated to establish the relationship between their structure and functional activity. The results found that chemical modifications resulted in remarkable variations in the chemical compositions and apparent structures of CP. S-CP with the highest amount of glucose had the strongest antioxidant capacity to scavenge DPPH• and HO•, but CM-CP was lower than CP in terms of HO• scavenging. More importantly, S-CP and CM-CP more effectively protected RAW264.7 from H2O2-induced damage compared to CP by reducing the secretion of lactate dehydrogenase (LDH), intracellular reactive oxygen species (ROS) and malondialdehyde (MDA), enhancing phagocytosis and superoxide dismutase (SOD) levels, and suppressing abnormal apoptosis. Further experiments showed that the anti-apoptotic effect of S-CP and CM-CP was in intimate association with down-regulation of Caspase-9/3 activities and alleviation of cell cycle arrest in the S phase. In addition, S-CP and CM-CP decreased the cell viability of tumor cells. These findings suggest that the type of functional group plays important roles in the biological function of the derivatives and provide a theoretical basis for the development of novel natural anti-oxidants or low-toxicity anti-tumor drugs.

The regulate function of polysaccharides and oligosaccharides that with sulfate group on immune-related disease

• Sulfate carbohydrate include polysaccharides and oligosaccharides, which have immunomodulatory effects. • Carbohydrate with sulfate groups can be divided into endogenous and exogenous, according to the different sources, have different ways of action. • Sulfate polysaccharides and oligosaccharides have great potential in medicine and health food industry. Sulfate polysaccharide is a kind of polyanionic linear macromolecular compound which contained sulfate groups. In vivo, most of them combine with proteins to form proteoglycans. The oligosaccharides obtained by degradation from polysaccharides would have different biological activities. Sulfate polysaccharides and oligosaccharides have immunomodulatory activity, which can be involved in activating immune cell recognition, controlling immune cell activity and reducing the side effects caused by inflammatory reactions. Polysaccharides treated with sulfate can act on multiple targets of the immune systems, affecting the occurrence and development of diseases and even cancer. In this article, polysaccharide and oligosaccharide containing sulfate groups were classified as endogenous and exogenous, and sulfated derivatives. And their biological activities in immune regulation were reviewed. Polysaccharides and oligosaccharides or the derivatives after sulfuric acid modification would have relatively unique biological activities due to the negative charge of the sulfate group and the change of their solubility.

Evidence for Indoxyl Sulfate as an Inducer of Oxidative Stress in Patients With Diabetes.

Indoxyl sulfate is a metabolite of tryptophan and its urinary level reflects the status of bacterial flora in the intestine. Indoxyl sulfate possesses prooxidant properties and is implicated in various diseases including chronic kidney disease and cardiovascular diseases. However, the relation of urinary indoxyl sulfate to oxidative stress is not known. The association of urinary indoxyl sulfate levels with urinary levels of oxidative stress markers, 15-isoprostane F2t and pteridine derivatives, was investigated in 255 patients with type 2 diabetes. Indoxyl sulfate and pteridine derivatives were measured by using spectrofluorometry. Urinary levels of indoxyl sulfate, pteridines, and 15-isoprostane F2t showed a normal distribution after logarithmic transformation but not before it, and they were thus used for parametric analysis after logarithmic transformation. Urinary indoxyl sulfate levels were significantly correlated (p<0.01) with urinary 15-isoprostane F2t and pteridine levels [Pearson's correlation coefficients: 0.503 (15-isoprostane F2t) and 0.562 (pteridines)]. These associations were also found in multivariable analysis after adjusting for age, sex, insulin therapy for diabetes, body mass index, mean arterial pressure, hemoglobin A1c, estimated glomerular filtration rate, urinary albumin, and histories of smoking and alcohol drinking. Urinary indoxyl sulfate levels showed associations with urinary levels of oxidative stress markers, and the associations were independent of age, sex, insulin therapy for diabetes, body mass index, blood pressure, glycemic status, renal function, smoking, and alcohol drinking. Indoxyl sulfate appears to be an important determinant of redox balance in patients with diabetes.

Directions of Genetic Changes Induced by New Dimethyl Sulfate Derivatives in Oil Flax

Directions of Genetic Changes Induced by New Dimethyl Sulfate Derivatives in Oil Flax

Разработка гидрофильного геля на основе сульфатированного арабиногалактана

Introduction. The modern pharmaceutical market offers a very limited range of medicines for the prevention and treatment of chronic venous insufficiency. The original pharmacologically active compound based on the potassium salt of the sulfated derivative of arabinogalactan (Agsular®) is an analog of heparin. Aim. Development of a hydrophilic gel based on Agsular®. Materials and methods. Model compositions were prepared according to traditional methods of gels preparation. The physical and chemical properties of the obtained samples were evaluated by methods of potentiometry, dynamic rheology and dynamic light scattering. The microbiological purity of the gels during storage was also evaluated. Results. The optimal composition of the hydrophilic gel containing Agsular® (1.5%) as the active substance is substantiated. This is a water-aerosil-glycerol-containing composition (the mixture ratio being 1:2:13 respectively). Studies of pH, dynamic viscosity and zeta potential confirm the stability of this gel. The introduction of a preservative (Nipagin 0.1%) ensures the microbiological purity of the gel during storage. Conclusion. The developed hydrophilic gel is a promising mean of prevention and treatment of chronic venous insufficiency.

Assessment of Anti-microbial and Anti-oxidant Activities of Modified Guar Gum

Apart from drug delivery potential of polysaccharides or their chemical derivatives, some chemically modified polysaccharides particularly sulfated polysaccharides showed significant biological property. In this study, guar gum was sulfated by reacting with various ratios of CSA (chlorosulfonic acid) and pyridine to obtain the product with different degree of sulfation (DS). The sulfated guar gum derivatives were examined by FTIR, NMR and degree of sulfation analysed and were further evaluated for their potential antibacterial activity by agar diffusion method. Results obtained from the study indicated that derivatives having higher degree of sulfation exhibited moderate activity against the selected bacterial strains at 200 µg∙ml − 1 . However, the sulfated guar gum did not show any significant antifungal activity at any concentration studied. The sulfated guar gum demonstrated dose-dependent DPPH and H 2 O 2 scavenging activity with maximum activity noted at 2 mg∙ml − 1 concentration. The sulfation of partially oxidized guar gum caused significant improvement of antioxidant activity to that observed for non-oxidized sulfated guar gum derivative. This study revealed that the extent of sulfation and molecular weight had significant impact on antimicrobial and antioxidant activities of guar gum.

Food Xanthan Polysaccharide Sulfation Process with Sulfamic Acid.

Xanthan is an important polysaccharide with many beneficial properties. Sulfated xanthan derivatives have anticoagulant and antithrombotic activity. This work proposes a new method for the synthesis of xanthan sulfates using sulfamic acid. Various N-substituted ureas have been investigated as process activators. It was found that urea has the greatest activating ability. BBD of xanthan sulfation process with sulfamic acid in 1,4-dioxane has been carried out. It was shown that the optimal conditions for the sulfation of xanthan (13.1 wt% sulfur content) are: the amount of sulfating complex per 1 g of xanthan is 3.5 mmol, temperature 90 °C, duration 2.3 h. Sulfated xanthan with the maximum sulfur content was analyzed by physicochemical methods. Thus, in the FTIR spectrum of xanthan sulfate, in comparison with the initial xanthanum, absorption bands appear at 1247 cm−1, which corresponds to the vibrations of the sulfate group. It was shown by GPC chromatography that the starting xanthan gum has a bimodal molecular weight distribution of particles, including a high molecular weight fraction with Mw > 1000 kDa and an LMW fraction with Mw < 600 kDa. It was found that the Mw of sulfated xanthan gum has a lower value (~612 kDa) in comparison with the original xanthan gum, and a narrower molecular weight distribution and is characterized by lower PD values. It was shown by thermal analysis that the main decomposition of xanthan sulfate, in contrast to the initial xanthan, occurs in two stages. The DTG curve has two pronounced peaks, with maxima at 226 and 286 °C.

Metabolic Subtyping of Adrenal Tumors: Prospective Multi-Center Cohort Study in Korea.

BackgroundConventional diagnostic approaches for adrenal tumors require multi-step processes, including imaging studies and dynamic hormone tests. Therefore, this study aimed to discriminate adrenal tumors from a single blood sample based on the combination of liquid chromatography-mass spectrometry (LC-MS) and machine learning algorithms in serum profiling of adrenal steroids.MethodsThe LC-MS-based steroid profiling was applied to serum samples obtained from patients with nonfunctioning adenoma (NFA, n=73), Cushing’s syndrome (CS, n=30), and primary aldosteronism (PA, n=40) in a prospective multicenter study of adrenal disease. The decision tree (DT), random forest (RF), and extreme gradient boost (XGBoost) were performed to categorize the subtypes of adrenal tumors.ResultsThe CS group showed higher serum levels of 11-deoxycortisol than the NFA group, and increased levels of tetrahydrocortisone (THE), 20α-dihydrocortisol, and 6β-hydroxycortisol were found in the PA group. However, the CS group showed lower levels of dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) than both the NFA and PA groups. Patients with PA expressed higher serum 18-hydroxycortisol and DHEA but lower THE than NFA patients. The balanced accuracies of DT, RF, and XGBoost for classifying each type were 78%, 96%, and 97%, respectively. In receiver operating characteristics (ROC) analysis for CS, XGBoost, and RF showed a significantly greater diagnostic power than the DT. However, in ROC analysis for PA, only RF exhibited better diagnostic performance than DT.ConclusionThe combination of LC-MS-based steroid profiling with machine learning algorithms could be a promising one-step diagnostic approach for the classification of adrenal tumor subtypes.

Sulphation and Hydrolysis Improvements of Bioactivities, and Immuno-Modulatory Properties of Edible Amanita hemibapha Subspecies javanica (Corner and Bas) Mucilage Polysaccharide as a Potential in Personalized Functional Foods.

In this study, the mucilage polysaccharide (MP) from Amanita hemibapha subspecies javanica was prepared by hot water extraction and ethanol precipitation and then fractionated using anion-exchange chromatography equipped with a DEAE Sepharose fast flow column. The most immune-enhancing polysaccharide fraction 2 (MPF2) was subjected to a structural modification such as hydrolysis or over-sulphation. The sulphate and molecular weight (Mw) of over-sulphated (OS1-3) and hydrolysed (HS1-3) derivatives of MPF2 differed between 9.85% and 14.2% and 32.8 and 88.1 × 103 g/mol, respectively. Further, the immune-enhancing properties of MPF2 and its derivatives were tested on RAW264.7 and NK cells through various in vitro assays. Interestingly, a low molecular weight of HS1-3 significantly increased the nitric oxide (NO) production (p < 0.05) more than MPF2, indicating that Mw is a major factor in RAW264.7 cell stimulation. In addition, RAW264.7 cells produced various cytokines by up-regulating mRNA expression levels and the activation of nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. On the other hand, OS1-3-treated natural killer (NK) cells induced cytotoxicity in HepG2 cells through the expression of IFN-γ, Grandzyme-B, perforin, NKp30, and FasL. These results demonstrated that sulphate derivatives play an important role in NK cell activation. Further, this study also explores how polysaccharide binds to RAW264.7 and NK cells. MPF2 and HS3 may activate RAW264.7 cells via binding to TLR4 receptors, and OS2 could be activated through the CR3 signalling pathways.

Conformational Properties of Glycosaminoglycan Disaccharides: A Molecular Dynamics Study.

The structure and conformation of glycosaminoglycans (GAGs) are of central importance to understand the mechanisms behind their functions in biological systems. Due to the inherent chemical and structural heterogeneity of GAGs, focusing on longer, naturally existing GAG chains hinders drawing conclusions on the influence of the chemical functionalization on the basic conformational degree of freedom, that is, the dynamic shape of glycosidic linkage present in the particular disaccharide repeating unit. In the present study, we have considered the complete set of 106 GAG-related disaccharides, being potential building blocks for longer GAG chains (including hyaluronan, chondroitin, keratan, dermatan, and heparan). Both the unfunctionalized units and all possible combinations of either partially or fully sulfated derivatives contribute to this number. The unbiased and enhanced sampling molecular dynamics simulations provide a link to understand the influence of sulfation on the conformational properties of GAG glycosidic linkages. Residue-residue hydrogen bonding is not significant for either the glycosidic linkage conformation or its flexibility. It was found that in the majority of cases, the dominating conformation of the linkage is weakly affected by sulfation and the main role is played by the steric and stereoelectronic effects. However, there exist numerous cases where sulfation increases the contribution of alternative conformations to a nonnegligible extent and, in some rare cases (restricted to disaccharides building heparan), leads to the reorientation of the glycosidic linkage. The identified sulfation sites, being the most important in this context, are C6 and C3 at the GlcNAc residue. Finally, the full set of free energy maps relying on the glycosidic dihedral angle values for diverse GAG disaccharides are provided; they may be used for further studies, focused on longer GAG chains.

Modification of Arabinogalactan Isolated from Larix sibirica Ledeb. into Sulfated Derivatives with the Controlled Molecular Weights.

The process of sulfation of arabinogalactan—a natural polysaccharide from Larix sibirica Ledeb.—with sulfamic acid in 1,4-dioxane using different activators has been studied for the first time. The dynamics of the molecular weight of sulfated arabinogalactan upon variation in the temperature and time of sulfation of arabinogalactan with sulfamic acid in 1,4-dioxane has been investigated. It has been found that, as the sulfation time increases from 10 to 90 min, the molecular weights of the reaction products grow due to the introduction of sulfate groups without significant destruction of the initial polymer and sulfation products. Sulfation at 95 °C for 20 min yields the products with a higher molecular weight than in the case of sulfation at 85 °C, which is related to an increase in the sulfation rate; however, during the further process occurring under these conditions, sulfation is accompanied by the destruction and the molecular weight of the sulfated polymer decreases. The numerical optimization of arabinogalactan sulfation process has been performed. It has been shown that the optimal parameters for obtaining a product with a high sulfur content are a sulfamic acid amount of 20 mmol per 1 g of arabinogalactan, a process temperature of 85 °C, and a process time of 2.5 h.

Preparation and characterization of sulfated inulin-type fructans from Jerusalem artichoke tubers and their antitumor activity

The modification of polysaccharides is important for enhancing their biological activities. In this study, a pure inulin-type fructan, denoted as Jerusalem artichoke polysaccharide (P-JAP), was purified from Jerusalem artichoke tubers and modified by sulfation via treatment with a sulfur trioxide-pyridine complex to produce its sulfated derivative (S-JAP). Fourier-transform infrared spectroscopic analysis confirmed the successful introduction of sulfate groups. The inhibitory effects of S-JAP on the proliferation of human liver hepatocellular carcinoma (HepG2) cells was evaluated via a CCK-8 assay, and the pro-apoptotic effects were assessed using annexin V-FITC/PI double staining. The inhibition rates of various concentrations of S-JAP on HepG2 cells after 24, 48, and 72 h were significantly higher than those of P-JAP; moreover, S-JAP succeeded in promoting cell apoptosis. Thus, the sulfate-modified polysaccharide extracted from Jerusalem artichoke tubers was shown to exhibit effective antitumor activity with potential for further development.

Sulfation of Diethylaminoethyl-Cellulose: QTAIM Topological Analysis and Experimental and DFT Studies of the Properties.

Sulfated cellulose derivatives are biologically active substances with anticoagulant properties. In this study, a new sulfated diethylaminoethyl (DEAE)-cellulose derivative has been obtained. The effect of a solvent on the sulfation process has been investigated. It is shown that 1,4-dioxane is the most effective solvent, which ensures the highest sulfur content in DEAE-cellulose sulfate under sulfamic acid sulfation. The processes of sulfamic acid sulfation in the presence of urea in 1,4-dioxane and in a deep eutectic solvent representing a mixture of sulfamic acid and urea have been compared. It is demonstrated that the use of 1,4-dioxane yields the sulfated product with a higher sulfur content. The obtained sulfated DEAE-cellulose derivatives have been analyzed by Fourier transform infrared spectroscopy, X-ray diffractometry, and scanning electron and atomic force microscopy, and the degree of their polymerization has been determined. The introduction of a sulfate group has been confirmed by the Fourier transform infrared spectroscopy data; the absorption bands corresponding to sulfate groups have been observed in the ranges of 1247–1256 and 809–816 cm–1. It is shown that the use of a deep eutectic solvent leads to the side carbamation reactions. Amorphization of DEAE-cellulose during sulfation has been demonstrated using X-ray diffractometry. The geometric structure of a molecule in the ground state has been calculated using the density functional theory with the B3LYP/6-31G(d, p) basis set. The reactive areas of DEAE-cellulose and its sulfated derivatives have been analyzed using molecular electrostatic potential maps. The thermodynamic parameters (heat capacity, entropy, and enthalpy) of the target sulfation products have been determined. The HOMO–LUMO energy gap, Mulliken atomic charges, and electron density topology of the title compound have been calculated within the atoms in molecule theory.

Chemically Sulfated Polysaccharides from Agaricus blazei Murill: Synthesis, Characterization and Anti-HIV Activity.

AIDS, caused by HIV-1, is one of the most dangerous infectious diseases in the world. Therefore, it is necessary to develop new drugs with more potent bioactivities, less toxicity and higher tolerability for controlling the viral load, particularly by using the raw materials that are widely available. Agaricus blazei Murill (AbM), known in China as jisongrong, is of great importance as a food source and as a health-promoting supplement for immunomodulation. The polysaccharides of AbM exhibit various biological activities, such as regulating cellular immunity and providing anti-oxidative, anti-infective, and anti-inflammatory effects. At present, to our knowledge, no report has explored the chemically sulfated and anti-HIV-1 activity of AbM polysaccharides. Herein, the sulfated AbM polysaccharides with different sulfur contents were prepared by the chlorosulfonic acid-pyridine method. The characteristics of sulfated derivatives were established by the determination of the sulfur content, the relative molecular weight, and the Fourier-transform infrared spectroscopy. The anti-HIV activities of the sulfated AbM polysaccharides were evaluated by CCK-8 and the single-cycle pseudovirus infection (TZM-bl) assay. The sulfated AbM polysaccharides had strong antiviral properties, and the half-maximal inhibitory concentrations approached that of the positive control, azidothymidine. Sulfated modification of AbM polysaccharides can increase their anti-HIV pharmacological activity, which makes them promising alternative candidates as bioactive macromolecules for biomedical applications in HIV/AIDS.

In vitro osteogenic activities of sulfated derivative of polysaccharide extracted from Tamarindus indica L.

Osteoporosis, one of the most serious public health concerns caused by an imbalance between bone resorption and bone formation, has a major impact on the population. Therefore, finding the effective osteogenic compounds for the treatment of osteoporosis is a promising research approach. In our study, tamarind (Tamarindus indica L.) seed polysaccharide (TSP) extracted from tamarind seed was subjected to synthesize its sulfate derivatives. The 1H NMR, FT-IR, SEM, monosaccharide compositions and elemental analysis data revealed that tamarind seed polysaccharide sulfate (TSPS) was successfully prepared. As the result, TSPS showed potent effects on inducing osteoblast differentiation via increasing alkaline phosphatase (ALP) activity up to 20% after 10days and bone mineralization approximately 58% after four weeks at concentration of 20μg/mL, whereas no statistically increase for both ALP activity and bone mineralization was observed in TSP treatment. Furthermore, TSPS enhanced expression of several marker genes in bone formation. Overall, the obtained data provided novelty on osteogenic compounds originated from TSP of T.indica, as well as scientific fundamentals on drug development and bone tissue engineering for the treatment of osteoporosis and other bone-related diseases.

Chemical composition and biological activities of aqueous extracts and their sulfated derivatives of pea peel (Pisum sativum L.)

Agro-industrial wastes are an important natural reservoir of bioactive compounds that could be used to obtain useful by-products. The objective of our study was to evaluate the anticoagulation, fibrinolytic, antioxidant, antiproliferative and prebiotic activity of six aqueous extracts of P. sativum waste and their sulfated derivatives, with particular attention to the content of certain bioactive compounds. Three sulfated extracts exhibited significant anticoagulation activity at 2 mg/ml. Alkaline insoluble sulfated extract showed the highest anticoagulation activity at a concentration of 800 μg/ml, which had a clotting time of 50.11 min. All aqueous extracts exhibited high free radical scavenging activity using DPPH (ranging from 91 to 98.6%) than sulfated ones. They had also good prebiotic properties as they promoted the growth of the two tested probiotics up to 260%. All extracts exhibited also relevant in vitro antiproliferative activity using MTT assay. Sulfated alkaline soluble and insoluble extracts had potent activities against HepG-2 cancer cell lines (55.8 and 52.8%, respectively) compared to Doxorubicin® (52.6%), while sulfated acidic insoluble, neutral soluble and alkaline soluble extracts had potent activities against MCF-7 cancer cell lines (73.4, 72.4 and 72.8%, respectively) compared to Doxorubicin® (72%) with low IC50 values. To author's knowledge, this is the first report investigating the anticoagulation activity of isolated pea peel extracts.

Synthesis optimization, DFT and physicochemical study of chitosan sulfates

Chitosan is an important biologically active amino polysaccharide. Water-soluble sulfated chitosan derivatives are widely used as anticoagulant and antiviral drugs. In this study, new methods for sulfamic acid sulfation of chitosan in the presence of urea in 1,4-dioxane and in a deep eutectic solvent representing a mixture of sulfamic acid and urea have been proposed. Mathematical models of sulfation of chitosan in these systems have been built. The obtained sulfated chitosan derivatives have been investigated by Fourier-transform infrared spectroscopy, X-ray diffractometry, atomic force microscopy, gel permeation chromatography, elemental analysis, and the density functional theory. The introduction of the sulfate group into the chitosan molecule was proven by infrared spectroscopy. When using the sulfamic acid/urea mixture, side reactions of carbamation of chitosan have been observed. It has been established from the atomic force microscopy data that the sulfated chitosan film surface consists of spherical particles partially agglomerated with each other. According to the gel permeation chromatography data, sulfated chitosan obtained in different systems, but under the same conditions (temperature and time), has different molecular weight distributions. The molecular weight distribution curve of the sulfated chitosan obtained in the sulfamic acid‒urea‒1,4-dioxane system is significantly shifted to the high-molecular region (Mw ~ 36.6 kDa), while the sulfated chitosan obtained in the sulfamic acid/urea deep eutectic solvent (Mw ~ 27.2 kDa). The density functional theory calculation of chitosan sulfates in the B3LYP/6-31G(d, p) basis set have been made.

Enantioseparation of solriamfetol and its major impurity phenylalaninol by capillary electrophoresis using sulfated gamma cyclodextrin.

R-solriamfetol is a recently approved drug used for the treatment of excessive sleepiness associated with narcolepsy and sleep apnea. Herein, a capillary electrophoretic method was developed, enabling the simultaneous analysis of the API and its S-enantiomer in addition to the enantiomers of its major impurity phenylalaninol. Twenty-nine different cyclodextrins (CDs), including native, neutral, and charged ones were screened as potential chiral selectors, and the best results were obtained with sulfated CDs. Randomly sulfated-β-CD exhibited outstanding enantioresolution, the peaks of phenylalaninol enantiomers inserted between the two peaks of solriamfetol enantiomers, while sulfated-γ-CD (S-γ-CD) showed remarkable resolution values in a much shorter analysis time with the optimal enantiomer migration order. Among the single isomer sulfated CD derivatives, substituent dependent enantiomer migration order reversal could also be observed in the case of heptakis(6-O-sulfo)-β-CD (HS-β-CD) or heptakis(2,3-O-dimethyl-6-O-sulfo)-β-CD (HDMS-β-CD) with R-,S-solriamfetol, and heptakis(2,3-O-diacetyl-6-O-sulfo)-β-CD (HDAS-β-CD) resulting S-,R-solriamfetol migration order. The sulfated-γ-CD system was chosen for method optimization applying orthogonal experimental design. The optimized method (45mM Tris-acetate buffer, pH 4.5, 4mM S-γ-CD, 21°C, +19.5kV) was capable for the baseline separation of solriamfetol and phenylalaninol enantiomers within 7min. The optimized method was validated according to the ICH guidelines and successfully applied for the analysis of pharmaceutical preparation (Sunosi® 75mg tablet), thus it may serve as a routine procedure for the laboratories of regulatory authorities as well as in Pharmacopoeias.

Analysis of Unusual Sulfated Constituents and Anti-infective Properties of Two Indonesian Mangroves, Lumnitzera littorea and Lumnitzera racemosa (Combretaceae)

Lumnitzera littorea and Lumnitzera racemosa are mangrove species distributed widely along the Indonesian coasts. Besides their ecological importance, both are of interest owing to their wealth of natural products, some of which constitute potential sources for medicinal applications. We aimed to discover and characterize new anti-infective compounds, based on population-level sampling of both species from across the Indonesian Archipelago. Root metabolites were investigated by TLC, hyphenated LC-MS/MS and isolation, the internal transcribed spacer (ITS) region of rDNA was used for genetic characterization. Phytochemical characterization of both species revealed an unusual diversity in sulfated constituents with 3,3’,4’-tri-O-methyl-ellagic acid 4-sulfate representing the major compound in most samples. None of these compounds was previously reported for mangroves. Chemophenetic comparison of L. racemosa populations from different localities provided evolutionary information, as supported by molecular phylogenetic evidence. Samples of both species from particular locations exhibited anti-bacterial potential (Southern Nias Island and East Java against Gram-negative bacteria, Halmahera and Ternate Island against Gram-positive bacteria). In conclusion, Lumnitzera roots from natural mangrove stands represent a promising source for sulfated ellagic acid derivatives and further sulfur containing plant metabolites with potential human health benefits.

Impact of binding mode of low-sulfated hyaluronan to 3D collagen matrices on its osteoinductive effect for human bone marrow stromal cells.

Synthetically sulfated hyaluronan derivatives were shown to facilitate osteogenic differentiation of human bone marrow stromal cells (hBMSC) by application in solution or incorporated in thin collagen-based coatings. In the presented study, using a biomimetic three-dimensional (3D) cell culture model based on fibrillary collagen I (3D Col matrix), we asked on the impact of binding mode of low sulfated hyaluronan (sHA) in terms of adsorptive and covalent binding on osteogenic differentiation of hBMSC. Both binding modes of sHA induced osteogenic differentiation. Although for adsorptive binding of sHA a strong intracellular uptake of sHA was observed, implicating an intracellular mode of action, covalent binding of sHA to the 3D matrix induced also intense osteoinductive effects pointing towards an extracellular mode of action of sHA in osteogenic differentiation. In summary, the results emphasize the relevance of fibrillary 3D Col matrices as a model to study hBMSC differentiation in vitro in a physiological-like environment and that sHA can display dose-dependent osteoinductive effects in dependence on presentation mode in cell culture scaffolds.