Propylene Glycol Alginate Sodium Sulfate Research Articles

Pretreatment with propylene glycol alginate sodium sulfate ameliorated concanavalin A-induced liver injury by regulating the PI3K/Akt pathway in mice

AimsPropylene glycol alginate sodium sulfate (PSS), a sulfated polysaccharide possesses anti-inflammatory effects. Here, we investigated the effect of PSS on concanavalin A (Con A)-induced liver injury in mice and examined the underlying mechanisms. Main methodsBalb/C mice were injected intravenously with Con A (25mg/kg) to generate a model of acute liver injury. PSS (25 or 50mg/kg) was injected intraperitoneally 1h before the Con A administration. The levels of serum liver enzymes, inflammatory cytokines, and other marker proteins were determined, and liver injury was assessed histopathologically 2, 8, and 24h after Con A injection. Key findingsPretreatment with PSS reduced the levels of serum liver enzymes, inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, and attenuated histopathological damage in Con A-induced liver injury in mice. The effects of Con A were mediated by apoptosis and autophagy, as indicated by changes in protein and gene expression of related factors after Con A injection. PSS activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway and showed a protective function against apoptosis and autophagy. SignificancePSS ameliorated Con A-induced liver injury by downregulating inflammatory cytokines including TNF-α and IL-1β and regulating apoptosis and autophagy via the PI3K/Akt pathway.

PropyleneGlycolAlginateSodiumSulfateAlleviates Cerulein-InducedAcutePancreatitisbyModulating theMEK/ERKPathwayinMice.

Previous studies have focused on the effects of propylene glycol alginate sodium sulfate (PSS) against thrombosis, but the anti-inflammatory potential is unknown. Therefore, we specifically focused on the protective effects of PSS on cerulein-induced acute pancreatitis (AP) using a mouse model, and investigated the mechanism of PSS on autophagy and apoptosis via the Mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. Cerulein (100 ug/kg) was used to induce AP by ten intraperitoneal injections at hourly intervals in Balb/C mice. Pretreatment with vehicle or PSS was carried out 1 h before the first cerulein injection and two doses (25 mg/kg and 50 mg/kg) of PSS were injected intraperitoneally. The severity of AP was assessed by pathological score, biochemistry, pro-inflammatory cytokine levels, myeloperoxidase (MPO) activity and MEK/ERK activity. Furthermore, pancreatic histological scores, serum amylase and lipase activities, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β interleukin (IL)-6 levels, and MPO activity were significantly reduced by PSS via up-regulated MEK/ERK activity. The representative molecules of apoptosis and autophagy, such as Bcl-2, Bax, Lc-3, Beclin-1, P62, were remarkably reduced. Taken together, these results indicate that PSS attenuates pancreas injury by inhibiting autophagy and apoptosis through a mechanism involving the MEK/ERK signaling pathway.

Study on quality control of sulfated polysaccharide drug, propylene glycol alginate sodium sulfate (PSS)

The combination of biological and chemical analysis methods was developed to improve quality control of propylene glycol alginate sodium sulfate (PSS), a sulfated polysaccharide drug. The allergic and anticoagulant assays revealed that PSS fractions with higher Mw and lower M/G ratio may have allergic response and bleeding risks. HPLC with pre-column derivatization, HPGPC and IC methods were combined to analyze 10 batches of PSS samples from different manufacturers. The results showed that the quality of these PSSs varied greatly which in turn led to the unstable anticoagulant activity and side effects. The study indicated that PSS with high purity, M/G ratio above 1.5, Mw of ∼9kD and DS of 9.0–13.0% can ensure clinical efficacy and low incidence of adverse drug reactions. In conclusion, the combined methods would be in favor of guiding manufacture and quality control of PSS to guarantee its effectiveness and safety.

Anticoagulant and antithrombotic activities of low-molecular-weight propylene glycol alginate sodium sulfate (PSS)

Propylene glycol alginate sodium sulfate (PSS), a sulfated polysaccharide derivative, has been used as a heparinoid drug to prevent and treat hyperlipidemia and ischemic cardio-cerebrovascular diseases in China for nearly 30 years. To extend the applications of PSS, a series of low-molecular-weight PSSs (named FPs) were prepared by oxidative-reductive depolymerization, and the antithrombotic activities were investigated thoroughly in vitro and in vivo. The bioactivity evaluation demonstrated a positive correlation between the molecular weight and the anticoagulant and antithrombotic activities of FPs. FPs could prolong the APTT and clotting time and reduce platelet aggregation significantly. FPs could also effectively inhibit factor IIa in the presence of AT-III and HC-II. FPs decreased the wet weights and lengths of the thrombus and increased occlusion times in vivo. FP-6k, a PSS fragment with a molecular weight of 6 kDa, is an optimal antithrombotic candidate for further study and showed little chance for hemorrhagic action.

In vitro fermentation of alginate and its derivatives by human gut microbiota

Alginate (Alg) has a long history as a food ingredient in East Asia. However, the human gut microbes responsible for the degradation of alginate and its derivatives have not been fully understood yet. Here, we report that alginate and the low molecular polymer derivatives of mannuronic acid oligosaccharides (MO) and guluronic acid oligosaccharides (GO) can be completely degraded and utilized at various rates by fecal microbiota obtained from six Chinese individuals. However, the derivative of propylene glycol alginate sodium sulfate (PSS) was not hydrolyzed. The bacteria having a pronounced ability to degrade Alg, MO and GO were isolated from human fecal samples and were identified as Bacteroides ovatus, Bacteroides xylanisolvens, and Bacteroides thetaiotaomicron. Alg, MO and GO can increase the production level of short chain fatty acids (SCFA), but GO generates the highest level of SCFA. Our data suggest that alginate and its derivatives could be degraded by specific bacteria in the human gut, providing the basis for the impacts of alginate and its derivates as special food additives on human health.

Anticoagulant and FGF/FGFR signal activating activities of the heparinoid propylene glycol alginate sodium sulfate and its oligosaccharides

Propylene glycol alginate sodium sulfate (PSS), prepared by chemical sulfation of alginate, has been used for treating cardiovascular diseases in China for nearly 30 years. In the current study, the PSS was hydrolyzed partially by an environment-friendly solid phase acid degradation method, and then separated by using a Bio-Gel P6 chromatographic column. Thirteen PSS oligosaccharide fractions were obtained and characterized by ESI-MS. The results of different coagulation assays showed that a high molecular weight and a higher degree of sulfation were essential for the anticoagulant activity of the PSS because the PSS oligosaccharides exhibited no detectable anticoagulant activity. In contrast, not only PSS but also certain oligosaccharides showed significant activities in stimulation of FGF1, 2, 7, 8, 9 or 10 induced cell proliferation in FGFR1c-expressing BaF3 cells. Such properties made the PSS and its oligosaccharides promising compounds in the regulation of FGF-dependent development, treatment of cancer, and wound healing processes.

Efficacy of Heparinoid PSS in Treating Cardiovascular Diseases and Beyond-A Review of 27 Years Clinical Experiences in China.

Propylene glycol alginate sodium sulfate (PSS) is the world's first oral heparinoid approved by Chinese Food and Drug Administration in 1987. Propylene glycol alginate sodium sulfate is produced by modifying partially hydrolyzed alginate, one of the most abundant marine polysaccharides isolated from brown algae, by epoxypropane esterification and by chemical sulfation. It is used for treating and preventing cardiovascular-related diseases. The low cost (US$1.29/100 tablets, ∼4 tablets/day), remarkable clinical effects, and convenient oral administration make PSS an ideal long-term prevention drug. Propylene glycol alginate sodium sulfate is available in most drug stores in China, and millions of patients take PSS routinely during the past 27 years. The 22 784 reported clinical cases as well as the structure, preparation, clinical efficacy, adverse reactions, pharmacokinetics, pharmacodynamics, and future perspectives of PSS based on the results of peer-reviewed publications will be discussed. This review should bring the knowledge of PSS gained in China to the world to stimulate in depth academic and clinical studies of PSS.

Preparation, characterization and pharmacokinetics of fluorescence labeled propylene glycol alginate sodium sulfate

A rapid and sensitive fluorescence labeling method was developed and validated for the microanalysis of a sulfated polysaccharide drug,namely propylene glycol alginate sodium sulfate (PSS), in rat plasma. Fluorescein isothiocyanate (FITC) was selected to label PSS, and 1, 6-diaminohexane was used to link PSS and FITC in order to prepare FITC-labeled PSS (F-PSS) through a reductive amination reaction. F-PSS was identified by UV-Vis, FT-IR and 1H-NMR spectrum. The cell stability and cytotoxicity of F-PSS were tested in Madin-Darby canine kidney (MDCK) cells. The results indicated that the labeling efficiency of F-PSS was 0.522% ± 0.0248% and the absolute bioavailability was 8.39%. F-PSS was stable in MDCK cells without obvious cytotoxicity. The method was sensitive and reliable; it showed a good linearity, precision, recovery and stability. The FITC labeling method can be applied to investigating the absorption and metabolism of PSS and other polysaccharides in biological samples.

Determination of M/G ratio of propylene glycol alginate sodium sulfate by HPLC with pre-column derivatization

A reliable high performance liquid chromatography with pre-column derivatization method was developed for the determination of the mannuronic acid (M)/guluronic acid (G) ratio of propylene glycol alginate sodium sulfate (PSS). The hydrolysis conditions of PSS were investigated by four degradation methods based on the degree of destruction of M and G, and the chromatographic separation conditions were also optimized. A satisfactory resolution of M and G was achieved with a KP-C18 column using 0.1mol/L phosphate buffer (pH 7.0)-acetonitrile (83/17, v/v) as a mobile phase, after PSS was hydrolyzed with 0.1mol/L sulfuric acid and labeled with 1-phenyl-3-methyl -5-pyrazolone. The M/G ratio of PSS determined by this method was in good accordance with that obtained by the 1H NMR method with a desulfurization strategy. Our method is rapid, sensitive, accurate and reproducible. The limit of detection was found to be 0.25μg/mL for M and 0.40μg/mL for G.

An HPLC Method for Microanalysis and Pharmacokinetics of Marine Sulfated Polysaccharide PSS-Loaded Poly Lactic-co-Glycolic Acid (PLGA) Nanoparticles in Rat Plasma

This study was aimed at developing a sensitive and selective HPLC method with postcolumn fluorescence derivatization for the detection of propylene glycol alginate sodium sulfate (PSS) in rat plasma. Plasma samples were prepared by a simple and fast ultrafiltration method. PSS was extracted from rat plasma with d-glucuronic acid as internal standard. Isocratic chromatographic separation was performed on a TSKgel G2500 PWxL column with the mobile phase of 0.1 M sodium sulfate at a flow rate of 0.5 mL/min. Analyte detection was achieved by fluorescence detection (FLD) at 250 nm (excitation) and 435 nm (emission) using guanidine hydrochloride as postcolumn derivatizing reagent in an alkaline medium at 120 °C. The calibration curve was linear over a concentration range of 1–500 μg/mL, and the lower limit of detection (LLOD) was found to be 250 ng/mL. This validated method was applied successfully to the pharmacokinetic study of PSS and PSS-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (PSS-NP) in rat plasma after a single intravenous (PSS only) and oral administration (PSS and PSS-NP). Significant differences in the main pharmacokinetic parameters of PSS and PSS-NP were observed. The relative bioavailability of PSS-NP was 190.10% compared with PSS which shows that PSS-NP can improve oral bioavailability.