Piperidine alkaloids from Piper retrofractum Vahl. protect against high-fat diet-induced obesity by regulating lipid metabolism and activating AMP-activated protein kinase

The fruits of Piperretrofractum Vahl. have been used for their anti-flatulent, expectorant, antitussive, antifungal, and appetizing properties in traditional medicine, and they are reported to possess gastroprotective and cholesterol-lowering properties. However, their anti-obesity activity remains unexplored. The present study was conducted to isolate the anti-obesity constituents from P. retrofractum Vahl. and evaluate their effects in high-fat diet (HFD)-induced obese mice. Piperidine alkaloids from P. retrofractum Vahl. (PRPAs), including piperine, pipernonaline, and dehydropipernonaline, were isolated as the anti-obesity constituents through a peroxisome proliferator-activated receptor δ (PPARδ) transactivation assay. The molecular mechanism was investigated in 3T3-L1 adipocytes and L6 myocytes. PRPA treatment activated AMP-activated protein kinase (AMPK) signaling and PPARδ protein and also regulated the expression of lipid metabolism-related proteins. In the animal model, oral PRPA administration (50, 100, or 300 mg/kg/day for 8 weeks) significantly reduced HFD-induced body weight gain without altering the amount of food intake. Fat pad mass was reduced in the PRPA treatment groups, as evidenced by reduced adipocyte size. In addition, elevated serum levels of total cholesterol, low-density lipoprotein cholesterol, total lipid, leptin, and lipase were suppressed by PRPA treatment. PRPA also protected against the development of nonalcoholic fatty liver by decreasing hepatic triglyceride accumulation. Consistent with the in vitro results, PRPA activated AMPK signaling and altered the expression of lipid metabolism-related proteins in liver and skeletal muscle. Taken together, these findings demonstrate that PRPAs attenuate HFD-induced obesity by activating AMPK and PPARδ, and regulate lipid metabolism, suggesting their potential anti-obesity effects.     

Sodium Pentaborate Pentahydrate ameliorates lipid accumulation and pathological damage caused by high fat diet induced obesity in BALB/c mice

BackgroundObesity is one of the most popular topic in the field of research. In order to defeat this highly widespread disease, the mechanism of fat accumulation at the molecular level and its elimination are crucial. The use of boron has been showing promising results during the recent years.MethodsIn this study, anti-obesity potential of Sodium Pentaborate Pentahydrate (SPP) used as a dietary supplement on BALB/c mice fed with a high-fat diet was evaluated. Mice were divided into four groups with different diets, consisting of a normal diet, a high-fat diet (HFD) (containing 60 % fat), a HFD-supplemented with 0.5 mg/g body weight (BW) of SPP and a HFD-supplemented with 1.5 mg/g body weight (BW) of SPP. The animals were then observed for 10 weeks and physically monitored, and were sacrificed at the end of the experiment for physical and physicochemical evaluation.ResultsAccording to the physical parameters measured -body weight, food and water intake ratios-, the results indicate that SPP decreased weight gain in a dose dependent manner. Measurement of the hormone levels in the blood and fat accumulation in organs of mice also supported the anti-obesity effects of SPP. Expressions of adipogenesis related genes were also negatively regulated by SPP administration in white adipose tissue (WAT) tissue.ConclusionThese findings promise a treatment approach and drug development that can be used against obesity when SPP is used in the right doses. As a future aspect, clinical studies with SPP will reveal the effect of boron derivatives on obesity.     

Withaferin A exerts an anti-obesity effect by increasing energy expenditure through thermogenic gene expression in high-fat diet-fed obese mice

BackgroundThe enhancement of energy expenditure has attracted attention as a therapeutic target for the management of body weight. Withaferin A (WFA), a major constituent of Withania somnifera extract, has been reported to possess anti-obesity properties, however the underlying mechanism remains unknown.PurposeTo investigate whether WFA exerts anti-obesity effects via increased energy expenditure, and if so, to characterize the underlying pathway.MethodsC57BL/6 J mice were fed a high-fat diet (HFD) for 10 weeks, and WFA was orally administered for 7 days. The oxygen consumption rate of mice was measured at 9 weeks using an OxyletPro™ system. Hematoxylin and eosin (H&E), immunohistochemistry, immunoblotting, and real-time PCR methods were used.ResultsTreatment with WFA ameliorated HFD-induced obesity by increasing energy expenditure by improving of mitochondrial activity in brown adipose tissue (BAT) and promotion of subcutaneous white adipose tissue (scWAT) browning via increasing uncoupling protein 1 levels. WFA administration also significantly increased AMP-activated protein kinase (AMPK) phosphorylation in the BAT of obese mice. Additionally, WFA activated mitogen-activated protein kinase (MAPK) signaling, including p38/extracellular signal-regulated kinase MAPK, in both BAT and scWAT.ConclusionWFA enhances energy expenditure and ameliorates obesity via the induction of AMPK and activating p38/extracellular signal-regulated kinase MAPK, which triggers mitochondrial biogenesis and browning-related gene expression.     

Chitooligosaccharides antagonize the cytotoxic effect of glucosamine

Chitooligosaccharides (COS) are partially hydrolyzed compounds derived from chitosan that exhibit a number of biological activities, including antitumor, antibacterial and antifungal properties. In this work, we examined the cytotoxicity of pure COS and oligomers A, B and C (solutions composed of different amounts of COS) produced by enzymatic hydrolysis using a crude enzyme extract produced by the fungus Metarhrizium anisopliae. The antiproliferative effect of these molecules was analyzed using tumor cell lines (HepG2 and HeLa cells) and in a normal cell line (3T3). The antioxidant activity was analyzed in several in vitro experiments. Glucosamine showed higher toxicity (approximately 92%) to all cell lines studied. However, the oligomers obtained after hydrolysis demonstrated no toxic effects on the normal cells (3T3). Furthermore, we showed that a small amount of other COS can decrease the cytotoxic effect of glucosamine against 3T3 cells, indicating that glucosamine could be used as an antitumor drug in the presence of other COS. In addition, different effects were found in antiproliferative assays, which depended on the COS composition in the oligomers (A, B and C), showing that a combination of them may be essential for developing antineoplastic drugs. Superoxide anion scavenging was the main antioxidant activity demonstrated by the COS and oligomers. This activity was also dependent on the oligomer composition of the chitosan hydrolysates. Further work will identify the ideal proportions of COS and glucosamine for maximizing the effects of these biological activities.     

Recombinant expression of a chitosanase and its application in chitosan oligosaccharide production

Recently, considerable attention has been focused on chitosan oligosaccharides (COSs) due to their various biological activities. COSs can be prepared by enzymatic degradation of chitosan, which is the deacetylation product of chitin, one of the most abundant biopolymers in nature. In the current study, we recombinantly expressed a chitosanase and used it for COS preparation. A bacillus-derived GH8 family chitosanase with a 6×His tag fused at its N-terminal was expressed in the Escherichia coli strain BL21(DE3) as a soluble and active form. Its expression level could be as high as 500 mg/L. Enzymatic activity could reach approximately 140,000 U/L under our assay conditions. The recombinant chitosanase could be purified essentially to homogeneity by immobilized metal-ion affinity chromatography. The enzyme could efficiently convert chitosan into monomer-free COS: 1 g of enzyme could hydrolyze about 100 kg of chitosan. Our present work has provided a cheap chitosanase for large-scale COS production in industry.     

Separation of chitooligosaccharides and the potent effects on gene expression of cell surface receptor CR3

Chitooligosaccharides were prepared through hydrolysis of colloidal chitosan by enzyme source from Aspergillus fumigatus BSF114. Chitosan pentamer (COS5) and chitosan hexamer (COS6) were isolated and purified from COS by the ultra-filtration, nano-filtration, ethanol precipitation and the CM-Sephadex C-25 column. COS5 consisted of (GlcN)₄ (59.84%) and (GLcN)₅ (40.16%). COS6, however, mainly consisted of (GLcN)₆ (93.11%) and (GLcN)₅ (6.89%). Effects of COS5 and COS6 in vivo and in vitro on gene expression of cell surface CR3 receptor were investigated by relatively quantitative RT-PCR and ELISA. The results showed that the expression of CR3 mRNA could be promoted by both COS5 and COS6. The promotion effect caused by COS6 was greater than that of COS5.     

Effect of dietary chitosans on trace iron, copper and zinc in mice

Dietary chitosans with different molecular weight M_w and the degree of deacetylation DDA (high molecular weight chitosan HCS with M_w 7.60 × 10⁵ and DDA 85.5%, middle molecular weight chitosan MCS with M_w 3.27 × 10⁴ and DDA 85.2%, chito-oligomer COS with M_w 0.99 × 10³ and DDA 85.7% and water-soluble chitosan WSC with M_w 3.91 × 10⁴ and DDA 52.6%) were used at the 1.05% level to feed mice for 90 days. Afterwards no pathological symptoms, clinical signs or deaths were observed. The body weight of mice in chitosan group and control group showed no significant difference. Although HCS, COS and WSC had no significant effect on the level of Fe, Zn and Cu in the tested mice’s liver, spleen, heart and kidney, MCS significantly increased the level of Fe, Zn and Cu in liver. Therefore dietary ingestion of chitosan did not depress the level of Fe, Zn and Cu in mice.     

Growth and osteogenic differentiation of adipose-derived and bone marrow-derived stem cells on chitosan and chitooligosaccharide films

Very low molecular weight chitooligosaccharide (COS, 1.4 kDa) and high molecular weight chitosan (1000 kDa) were comparatively studied in terms of physical and biological characteristics. Thin films of COS, chitosan and gelatin were prepared and crosslinked by dehydrothermal treatment at 140 °C for 24 h. COS film presented more hydrophilic property than chitosan film. Behaviors of rat adipose-derived stem cells (ASCs) and bone marrow-derived stem cells (MSCs) were investigated on COS and chitosan films, comparing to those on gelatin film. The results on cell spreading suggested that both ASCs and MSCs preferred to attach on COS film than chitosan film with 6–7 times larger cell areas. Numbers of both stem cells proliferated on COS film were approximately 3-fold higher than those on chitosan film. In addition, COS film enhanced osteogenic differentiating potential of MSCs, as observed from the alkaline phosphatase activity and calcium deposition. Therefore, in this work, COS was shown to be a more favorable material for the growth and osteogenic differentiation of both ASCs and MSCs, compared to high molecular weight chitosan.     

Paecilomyces tenuipes extracts affect lipid and glucose metabolic parameters similarly to Cordyceps militaris extracts

Ascocarps of some species of the genus Cordyceps have long been used as a traditional medicine and food source for promoting human health. The compound cordycepin, isolated from C. militaris ascocarps (CE), show similar health effects to CE. In this study, we investigated and compared the anti-obesity and antidiabetic effects of dietary CE and Paecilomyces tenuipes ascocarps (PE) in mice. In addition, we investigated their effects on the expression of genes related to the regulation of obesity and diabetes. We found that dietary CE and PE suppressed body weight gain and fat accumulation in the liver and adipocyte tissues of mice fed a high-fat diet (HFD). Enzyme and lipid profiles induced by HFD returned to normal with CE or PE treatment. Dietary CE or PE reduced fasting blood glucose and serum insulin levels in HFD-fed mice. Finally, we show that CE and PE treatment restored to normal the hyperlipidemia- and hyperglycemia-related gene expressions in HFD-fed mice. These results indicate that dietary CE or PE exert their anti-obesity and antidiabetic effects by regulating adipogenesis and insulin signaling pathways. Finally, we show that dietary CE or PE have similar anti-obesity and antidiabetic effects even when included in a normal mouse diet. Although cordycepin is not found in PE, PE treatment improves lipid and glucose metabolic parameters in a manner similar to CE. We find that PE provides alternative potential therapeutic treatments for obesity and diabetes.     

Comparison of main chemical composition of Plantago asiatica L. and P. depressa Willd. seed extracts and their anti-obesity effects in high-fat diet-induced obese mice

BackgroundNowadays, the pharmacological effects of Plantaginis semen was getting more and more attention because of the great effect of treating diuresis, hypertension, hyperlipidemia, and hyperglycemia. According to the Chinese Pharmacopoeia, Plantaginis semen is the seed of Plantago asiatica L. or P. depressa Willd. This was verified by examining chemical composition differences in a preliminary experiment, predicting their differences in pharmacology.PurposeIn this study, we aimed to compared the the differences in main components and anti-obesity effects of Plantago asiatica L. seed extract (PASE) and P. depressa Willd. seed extract (PDSE).Study design and methodsThe ultra-performance liquid chromatography–mass spectrometry (UPLC–MS) analysis was used to characterize and compare the differences chemical constituents of PASE and PDSE. The difference therapeutic effects between PASE and PDSE on obesity and associated metabolic disorders was investigated by high-fat (HF) diet induced mice model.ResultsThe fingerprint of Plantaginis semen were established by screening and identified 15 main components, including iridoids, phenethanol glycosides, flavonoids, guanidines, and fatty acids. Pentahydroxy flavanone was observed only in PDSE but not in PASE. The quantitative analysis results indicated that the main bioactive components in PASE were geniposidic acid and acteoside; their concentrations were three times higher in PASE than in PDSE. In anti-obesity effects, the result show the levels of fasting blood glucose were improved in both PASE and PDSE when compared with the HF group, while the PASE is show a significant effect then the PDSE group and improved the glucose tolerance but not in PDSE. The results also displayed that the Plantaginis semen did not modify food intake or body weight but decreased abdominal white/brown adipocyte size, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-c), hepatic TG and TC, fecal TG and TC concentrations when compared with the HF group. Among these indicators, serum TG, liver TG, fecal TC and TG levels were significantly improved in PASE compared with PDSE. The results indicated that PASE treatment more effectively improved lipid and glucose metabolism in HF diet-induced obese mice than did PDSE.ConclusionAs Plantaginis semen sources, P. asiatica L. seeds demonstrated more bioactive components and favorable metabolic disorder treatment outcomes than did P. depressa Willd. seeds.     

Protective effect of chitosan oligosaccharides against FcɛRI-mediated RBL-2H3 mast cell activation

The activation of mast cells by immunoglobulin E-mediated stimuli is considered as a central event in allergic responses. In this regard, chitosan oligosaccharides (COS) of two different molecular weight ranges (1–3 kDa and 3–5 kDa) were investigated for their capabilities against the activation of RBL-2H3 mast cell sensitized with dinitrophenyl-specific immunoglobulin E antibody and stimulated by antigen dinitrophenyl-bovine serum albumin. It was found that COS significantly inhibited RBL-2H3 cell degranulation via attenuating the releases of histamine and β-hexosaminidase. Moreover, the inhibitory activity of COS was accompanied by a reduction in intracellular Ca²⁺ elevation. Notably, the expression of immunoglobulin Fc epsilon receptor I (Fc?RI) in RBL-2H3 cells was down-regulated by COS treatment in a dose-dependent manner. The suppressive effect of COS on RBL-2H3 cell activation suggested that COS may be potential candidates of novel inhibitors against allergic reactions.     

Attenuation of pro-inflammatory mediators in LPS-stimulated BV2 microglia by chitooligosaccharides via the MAPK signaling pathway

Chitooligosaccharides (COS), depolymerized products of chitosan, has received considerable attention as bioactive material due to their biocompatible, biodegradable, non-toxic and non-allergenic natures. In this study, COS of four different molecular weight ranges (<1, 1-3, 3-5 and 5-10 kDa) were investigated for their abilities to modulate inflammatory mediators in lipopolysaccharides (LPS)-stimulated BV2 microglia. At the concentration of 500 μg/ml, COS attenuate the productions of nitric oxide (NO) and prostaglandin E₂ (PGE₂) by inhibiting inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions. Furthermore, the release and expression levels of inflammatory cytokines; including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were also attenuated by COS. Notably, the inhibitory activity of COS depends significantly on its molecular weight, with lower molecular weight showed higher activity. In addition, the suppressive effects on the phosphorylation of JNK and p38 mitogen-activated protein kinase (MAPK) by COS were confirmed. These results indicate that COS could be used as an inhibitor in regulating microglial inflammatory responses. Moreover, COS may assist therapeutic treatment of neurodegenerative diseases which accompanied with microglial activation.     

The antimicrobial action of low-molar-mass chitosan,chitosan derivatives and chitooligosaccharides on bifidobacteria

The crude fractions of chitooligosaccharides (COS) and low-molar-mass chitosans (LMWC) were prepared by enzyme hydrolysis of chitosan (CS). Specific growth rate of B. adolescentis, B. bifidum, B. breve, B. catenulatum, B. infantis and B. longum ssp. longum was determined in the presence of 0.025 and 0.5 % COS (<5 kDa), LMWC (5–10 kDa), and 0.025, 0.1 and 0.5 % of CS, chitosan succinate and chitosan glutamate in vitro. Minimum inhibitory concentrations (MIC; assayed by colony counting on TPY agar plates) of COS-LMWC and CS ranged from 0.025 % to 0.75 % of CS-LMWC. The growth of all bifidobacterial strains in the presence of chitosan, its derivatives and LMWC decreased at a concentration of 0.025 %; the bacterial growth was completely inhibited at a concentration of 0.5 %. COS did not show any inhibitory effect, an increased growth rate was even observed in the case of B. bifidum, B. catenulatum and B. infantis.     

Stronger anti-obesity effect of white ginseng over red ginseng and the potential mechanisms involving chemically structural/compositional specificity to gut microbiota

BackgroundGinseng has therapeutic potential for treating obesity and the associated gut microbiota dysbiosis. However, whether white ginseng and red ginseng, the two kinds of commonly used processed ginseng, possess different anti-obesity effects remains unknown.PurposeAnti-obesity effects of water extracts of white ginseng and red ginseng (WEWG and WERG) were compared, and the potential mechanisms were discussed.MethodsChemical profiles of WEWG and WERG were characterized by ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS) and high performance liquid chromatography coupled with evaporative light scattering detector (HPLC-ELSD). Anti-obesity effects of WEWG/WERG were examined by determining fat accumulation, systemic inflammation, enteric metabolic disorders and gut microbiota dysbiosis in high-fat diet (HFD)-fed obese mice.ResultsBoth WEWG and WERG exerted anti-obesity effects, with WEWG stronger than WERG. Compared to WERG, WEWG contained less contents of carbohydrates (polysaccharides, oligosaccharides, free monosaccharides) and ginsenosides, but chemical structures or compositions of these components in WEWG were characteristic, i.e. narrower molecular weight distribution and higher molar ratios of glucose residues of polysaccharides; higher content ratios of oligosaccharides DP2–3 (di-/tri-saccharides)-to-oligosaccharides DP4–7 (tetra-/penta-/hexa-/hepta-saccharides), sucrose-to-melibiose, maltose-to-trehalose and high-polar-to-low-polar ginsenosides. WEWG better ameliorated fat accumulation, enteric metabolic disorders and gut microbiota dysbiosis in HFD-fed obese mice than WERG.ConclusionThe stronger anti-obesity effect of white ginseng appears to correlate with differences in its chemical profile as compared to red ginseng. The carbohydrates and ginsenosides in WEWG potentially present more structural and compositional specificity to the obesity-associated gut bacteria, allowing more beneficial effects of WEWG on the gut microbiota dysbiosis. This consequently better alleviates the enteric metabolic disorders and systemic inflammation, thereby contributing to the stronger anti-obesity effect of WEWG as compared to WERG.     

Prawn Shell Chitosan Has Anti-Obesogenic Properties,Influencing Both Nutrient Digestibility and Microbial Populations in a Pig Model

The potential of natural products to prevent obesity have been investigated, with evidence to suggest that chitosan has anti-obesity effects. The current experiment investigated the anti-obesity potential of prawn shell derived chitosan on a range of variables relevant to obesity in a pig model. The two dietary treatment groups included in this 63 day study were: T1) basal diet and T2) basal diet plus 1000 ppm chitosan (n = 20 gilts per group (70 ± 0.90 kg). The parameter categories which were assessed included: performance, nutrient digestibility, serum leptin concentrations, nutrient transporter and digestive enzyme gene expression and gut microbial populations. Pigs offered chitosan had reduced feed intake and final body weight (P< 0.001), lower ileal digestibility of dry matter (DM), gross energy (GE) (P< 0.05) and reduced coefficient of apparent total tract digestibility (CATTD) of gross energy and nitrogen (P<0.05) when compared to the basal group. Fatty acid binding protein 2 (FABP2) gene expression was down-regulated in pigs offered chitosan (P = 0.05) relative to the basal diet. Serum leptin concentrations increased (P< 0.05) in animals offered the chitosan diet compared to pigs offered the basal diet. Fatness traits, back-fat depth (mm), fat content (kg), were significantly reduced while lean meat (%) was increased (P<0.05) in chitosan supplemented pigs. Pigs offered chitosan had decreased numbers of Firmicutes in the colon (P <0.05), and Lactobacillus spp. in both the caecum (P <0.05) and colon (P <0.001). Bifidobacteria populations were increased in the caecum of animals offered the chitosan diet (P <0.05). In conclusion, these findings suggest that prawn shell chitosan has potent anti-obesity/body weight control effects which are mediated through multiple biological systems in vivo.     

Quirks of dye nomenclature. 12. Victoria’s rainbow

ABSTRACT

The identities of 18 dyes whose names begin with “Victoria” are described using their chemical structures, names and numerical identifiers. All are synthetic dyes originally synthesized in Germany during the late 19^th century as colorants for textiles. Brief manufacturing details are included. All the colors of the rainbow are represented except indigo. Unusual properties including explosive tendency or toxicity are noted. Some of the applications as stains and for food coloring, anti-obesity medication and pigments for ball pen inks also are discussed     

结节乳头体在小鼠运动和摄食中的作用及机制研究

目的:探讨结节乳头体在小鼠运动和摄食中的作用及机制。方法:选择雄性ddy小鼠,180-200 g,通过单侧植入电极损毁TMN-E2区。采用荧光金逆行追踪方法检测小鼠Me5与TMN之间的神经纤维联系;采用免疫组化方法检测小鼠TMN中组氨酸脱羧酶(HDC)免疫反应阳性细胞数;采用旷场试验箱记录小鼠全天、夜间以及白天的自主活动和摄食摄水;采用PCR检测小鼠穹窿周和下丘脑外侧区的orexin m RNA的表达。结果:荧光金逆行追踪实验显示小鼠Me5可向TMN-E2发出神经纤维投射。单侧TMN损毁,两侧TMN中HDC反应阳性细胞显著减少(P0.05),且损毁侧比未损毁侧HDC免疫反应阳性细胞数减少(P0.05)。TMN损毁对小鼠24 h自主活动和摄食摄水无明显影响。单侧TMN损毁,小鼠从暗期到光期的自主活动和摄食摄水显著减少(P0.05)。单侧TMN损毁,小鼠正常昼夜活动摄食节律无显著改变。单侧TMN损毁,小鼠穹隆周和下丘脑外侧区白天的orexin m RNA表达显著减少(P0.05)。结论:Me5与TMN之间存在神经通路,该通路可能通过调节穹隆周区或下丘脑外侧区的orexin神经元的激活从而调控摄食及相关行为的昼夜节律。     

Multi-Functional Roles of Chitosan as a Potential Protective Agent against Obesity

Chitosan, a natural polysaccharide comprising copolymers of glucosamine and N-acetylglucosamine, has been shown to have anti-obesity properties. Two experiments (Exp. 1 and Exp. 2) were performed to determine the role of chitosan on dietary intake, body weight gain, and fat deposition in a pig model, as well as identifying potential mechanisms underlying the anti-obesity effect of chitosan. In Exp. 1, the nutrient digestibility experiment, 16 pigs (n = 4/treatment) were randomly allocated to one of four dietary treatments as follows: 1) basal diet; 2) basal diet plus 300 ppm chitosan; 3) basal diet plus 600 ppm chitosan; 4) basal diet plus 1200 ppm chitosan. The main observation was that crude fat digestibility was lower in the 1200 ppm chitosan group when compared with the control group (P<0.05). In Exp. 2, a total of 80 pigs (n = 20/treatment) were offered identical dietary treatments to that offered to animals in Exp. 1. Blood samples were collected on day 0, day 35 and at the end of the experiment (day 57). Animals offered diets containing 1200 ppm chitosan had a lower daily dietary intake (P<0.001) and body weight gain (P<0.001) from day 35 to 57 when compared with all the other treatment groups. Animals offered diets containing 1200 ppm chitosan had a significantly lower final body weight (P<0.01) when compared with all the other treatment groups. The decreased dietary intake observed in the 1200 ppm chitosan group was associated with increased serum leptin concentrations (P<0.001) and a decrease in serum C-reactive protein (CRP) concentrations (P<0.05). In conclusion, the results of this study highlight novel endocrine mechanisms involving the modulation of serum leptin and CRP concentrations by which chitosan exhibits anti-obesity properties in vivo.     

Evaluation of the antimutagenic potential of chitosan oligosaccharide: Rec, Ames and Umu tests

Two types of chitosan oligosaccharides (COS), COS I (1-kDa < MW < 3-kDa) and COS II (3-kDa < MW < 5-kDa), were tested for antimutagenic activities against chemical mutagens using Umu gene expression, Ames, and Bacillus subtilis Rec mutagenicity tests. At the highest chitosan oligosaccharide dose (1 mg) tested, mutagenic activity of indirect-acting mutagen was inhibited by 50% in the Umu gene expression system and in the Ames test. Chitosan oligosaccharide (0.01, 0.1 and 1 mg) also suppressed 4-nitroquinoline-N-oxide (NQO)-induced mutagenicity in the B. subtilis Rec^– assay.     

Effects of chitosan oligosaccharides on neutrophils from glycogen-induced peritonitis mice model

To investigate the effects of chitosan oligosaccharides (COS) on the neutrophils from glycogen-induced peritonitis mice model, the production of superoxide and hydrogen peroxide, myeloperoxidase (MPO) release as well as apoptosis were measured. We found that 100 μg/ml COS supplementation could induce the production of superoxide and hydrogen peroxide by neutrophils, meanwhile, COS promoted the apoptosis of peritoneal neutrophils, whereas the MPO release was decreased. Furthermore, superoxide dismutase (SOD) administration could abolish the pro-apoptotic effects mediated by COS. These results demonstrated that COS exerted pro-apoptotic effects on neutrophils, and superoxide played an important role in neutrophil apoptosis caused by COS. By the use of inhibitors of PLD and PI3K respectively, administration of 1-butanol and wortamannin decreased the generation of superoxide stimulated by COS. The production of superoxide caused by COS resulted from the activation of PLD and PI3K to some extent.