Pectic polysaccharides from Lilium brownii and Polygonatum odoratum exhibit significant antioxidant effects in vitro.

Two pectic polysaccharides (WLBP-A3-c and WPOP-A-c) were isolated from traditional Chinese medicines Lilium brownii and Polygonatum odoratum, respectively. Monosaccharide composition, FT-IR, NMR and enzymatic analyses indicated that both WLBP-A3-c (59 kDa) and WPOP-A-c (33 kDa) contained homogalacturonan (HG), rhamnogalacturonan I (RG-I), and rhamnogalacturonan II (RG-II) domains, with mass ratios of 76.0: 17.2:6.8 and 76.8:10.6:12.6, respectively. Two RG-I domains WLBP-A3-c-DE1 and WPOP-A-c-DE1, correspondingly obtained from WLBP-A3-c and WPOP-A-c by enzymatic hydrolysis, were composed of repeating units of [→2)-α-L-Rhap-(1 â†’ 4)-α-D-GalpA-(1→] with highly branched neutral sugar side chains at the O-4 position of Rhap, which contained arabinan, galactan, arabinogalactan I and II (AG-I and AG-II) side chains in different proportions. By comparison, WPOP-A-c exhibited higher scavenging effects against DPPH, ABTS and hydroxy radicals than WLBP-A3-c, probably because WPOP-A-c had higher contents of GalA residues and HG domains and lower molecular weight. Among three domains of WPOP-A-c, HG domain possessed the strongest activity in decreasing ROS production and promoting SOD activity, resulting in the effective protection of HepG2 cells against H2O2-induced oxidative stress. Our study provides evidence that pectins rich in HG domains from Lilium brownii and Polygonatum odoratum exhibit significant antioxidant effects, which hold potential for the application in the field of healthcare products.

Dual crosslinking of folic acid-modified pectin nanoparticles for enhanced oral insulin delivery.

Pectin-based drug delivery systems hold great potential for oral insulin delivery, since they possess excellent gelling property, good mucoadhesion and high stability in the gastrointestinal (GI) tract. However, lack of enterocyte targeting ability and premature drug release in the upper GI tract of the susceptible ionic-crosslinked pectin matrices are two major problems to be solved. To address these issues, we developed folic acid (FA)-modified pectin nanoparticles (INS/DFAN) as insulin delivery vehicles by a dual-crosslinking method using calcium ions and adipic dihydrazide (ADH) as crosslinkers. In vitro studies indicated insulin release behaviors of INS/DFAN depended on COOH/ADH molar ratio in the dual-crosslinking process. INS/DFAN effectively prevented premature insulin release in simulated GI fluids compared to ionic-crosslinked nanoparticles (INS/FAN). At an optimized COOH/ADH molar ratio, INS/DFAN with FA graft ratio of 18.2% exhibited a relatively small particle size, high encapsulation efficiency and excellent stability. Cellular uptake of INS/DFAN was FA graft ratio dependent when it was at/below 18.2%. Uptake mechanism and intestinal distribution studies demonstrated the enhanced insulin transepithelial transport by INS/DFAN via FA carrier-mediated transport pathway. In vivo studies revealed that orally-administered INS/DFAN produced a significant reduction in blood glucose levels and further improved insulin bioavailability in type I diabetic rats compared to INS/FAN. Taken together, the combination of dual crosslinking and FA modification is an effective strategy to develop pectin nano-vehicles for enhanced oral insulin delivery.

Antiarrhythmic effects of ginsenoside Rg2 on calcium chloride-induced arrhythmias without oral toxicity.

BACKGROUND: Malignant arrhythmias require drug therapy. However, most of the currently available antiarrhythmic drugs have significant side effects. Ginsenoside Rg2 exhibits excellent cardioprotective effects and appears to be a promising candidate for cardiovascular drug development. So far, the oral toxicity and antiarrhythmic effects of Rg2 have not been evaluated. METHODS: Acute oral toxicity of Rg2 was assessed by the Limit Test method in mice. Subchronic oral toxicity was determined by repeated dose 28-day toxicity study in rats. Antiarrhythmic activities of Rg2 were evaluated in calcium chloride-induced arrhythmic rats. Antiarrhythmic mechanism of Rg2 was investigated in arrhythmic rats and H9c2 cardiomyocytes. RESULTS: The results of toxicity studies indicated that Rg2 exhibited no single-dose (10 g/kg) acute oral toxicity. And 28-day repeated dose treatment with Rg2 (1.75, 3.5 and 5 g/kg/d) demonstrated minimal, if any, subchronic toxicity. Serum biochemical examination showed that total cholesterol in the high-dose cohort was dramatically decreased, whereas prothrombin time was increased at Day 28, suggesting that Rg2 might regulate lipid metabolism and have a potential anticoagulant effect. Moreover, pretreatment with Rg2 showed antiarrhythmic effects on the rat model of calcium chloride induced arrhythmia, in terms of the reduced duration time, mortality, and incidence of malignant arrhythmias. The antiarrhythmic mechanism of Rg2 might be the inhibition of calcium influx through L-type calcium channels by suppressing the phosphorylation of Ca2+/calmodulin-dependent protein kinase II. CONCLUSION: Our findings support the development of Rg2 as a promising antiarrhythmic drug with fewer side effects for clinical use.

Gelatin-crosslinked pectin nanofiber mats allowing cell infiltration.

Pectin nanofiber mats are promising tissue engineering scaffolds but suffer from poor cell infiltration. In this study, gelatin, a collagen derived cell adhesive protein, was used to crosslink the electrospun nanofibers of periodate oxidized pectin. Cell culture experiment results demonstrated that cells were able to grow into the gelatin-crosslinked pectin nanofiber mats rather than only spread on mat surface. The nanofiber mats showed moderate mechanical strength, with a maximum tensile strength of up to 2.3 MPa, an ultimate tensile strain of up to 15%, and were capable of degrading gradually over 4 weeks or even longer periods in simulated body fluids. Thus, gelatin-crosslinked pectin nanofiber mats hold a great potential for soft tissue regeneration.

Cross-Linked Pectin Nanofibers with Enhanced Cell Adhesion.

Polysaccharides display poor cell adhesion due to the lack of cell binding domains. This severely limits their applications in regenerative medicine. This study reports novel cross-linked pectin nanofibers with dramatically enhanced cell adhesion. The nanofibers are prepared by at first oxidizing pectin with periodate to generate aldehyde groups and then cross-linking the nanofibers with adipic acid dihydrazide to covalently connect pectin macromolecular chains with adipic acid dihydrazone linkers. The linkers may act as cell binding domains. Compared with traditional Ca2+-cross-linked pectin nanofibers, the pectin nanofibers with high oxidation/cross-linking degree exhibit much enhanced cell adhesion capability. Moreover, the cross-linked pectin nanofibers exhibit excellent mechanical strength (with Young's modulus ∼10 MPa) and much enhanced body degradability (degrade completely in 3 weeks or longer time). The combination of excellent cell adhesion capability, mechanical strength, and body degradability suggests that the cross-linked pectin nanofibers are promising candidates for in vivo applications such as tissue engineering and wound healing. This cross-linking strategy may also be used to improve the cell adhesion capability of other polysaccharide materials.

Pectinate nanofiber mat with high absorbency and antibacterial activity: A potential superior wound dressing to alginate and chitosan nanofiber mats.

Polysaccharides including pectin, alginate and chitosan are fabricated into dressings of micrometer-scaled architecture (micro- fiber or particle) and widely applied in wound treatments clinically. This work characterized and compared the properties of electrospun nanofibrous dressings of these polysaccharides. We found that although the three polysaccharide nanofiber mats had comparable mechanical strength and vapour permeability, the pectinate nanofiber mat could absorb 1.2 times and 3.6 times more exudates than the alginate and chitosan nanofiber mats, respectively, within less time. Moreover, the pectinate nanofiber mat showed much higher antibacterial activity (73.1%) than the alginate and chitosan nanofiber mats (11.8% and 17.1%, respectively). Further examinations demonstrated that the superior absorbency and antibacterial activity of the pectinate nanofiber mat were associated with the moderate extent of swelling of pectinate nanofibers under hydrated conditions. All these results suggest that the pectinate nanofiber mat might be a superior wound dressing to the alginate and chitosan nanofiber mats.

Reducing the content of carrier polymer in pectin nanofibers by electrospinning at low loading followed with selective washing.

Nanofibers of natural polymers represent an essential class of materials in biomedicine. Pectin is a plant-sourced anionic polysaccharide widely used in food products and biomedicine owning to its abundance, biocompatibility and inherent bioactivity. However, current electrospun pectin nanofibers are suffered from high content of carrier polymer, which may lead to low integrity and mechanical strength as well as in vivo toxicity. We report here a strategy to reduce the content of carrier polymer, polyethylene oxide (PEO) in our study, in pectin nanofibers, via electrospinning at low loading followed with selective washing. With improved electrospinning condition, we first enabled electrospinning of pectin nanofibers at low PEO loading. Then the PEO was removed by washing with a selective solvent to give pectin nanofibers containing only 1.5% PEO. The strategy was versatile to pectins from various sources and of various degree of esterification. The pectin nanofibers exhibited Young's modulus as high as 358.5MPa. In view of their rich bioactivity, the pectin nanofibers of low content of carrier polymer are promising materials for a wide range of biomedical applications.

Multifunctional gold nanostar conjugates for tumor imaging and combined photothermal and chemo-therapy.

Uniform gold nanostars (Au NS) were conjugated with cyclic RGD (cRGD) and near infrared (NIR) fluorescence probe (MPA) or anti-cancer drug (DOX) to obtain multi-functional nanoconstructs, Au-cRGD-MPA and Au-cRGD-DOX respectively. The NIR contrast agent Au-cRGD-MPA was shown to have low cytotoxicity. Using tumor cells and tumor bearing mice, these imaging nanoparticles demonstrated favorable tumor-targeting capability mediated by RGD peptide binding to its over-expressed receptor on the tumor cells. The multi-therapeutic analogue, Au-cRGD-DOX, integrates targeting tumor, chemotherapy and photo-thermotherapy into a single system. The synergistic effect of photo-thermal therapy and chemotherapy was demonstrated in different tumor cell lines and in vivo using S180 tumor-bearing mouse models. The viability of MDA-MB-231 cells was only 40 % after incubation with Au-cRGD-DOX and irradiation with NIR light. Both tail vein and intratumoral injections showed Au-cRGD-DOX treated mice exhibiting the slowest tumor increase. These results indicate that the multifunctional nanoconstruct is a promising combined therapeutic agent for tumor-targeting treatment, with the potential to enhance the anti-cancer treatment outcomes.