Anti-inflammatory Activity of Guluronate Oligosaccharides Obtained by Oxidative Degradation from Alginate in Lipopolysaccharide-Activated Murine Macrophage RAW 264.7 Cells

Zhou, Rui; Shi, Xu-Yang; Gao, Yan; Cai, Nan; Jiang, Zedong; Xu, Xu

doi:10.1021/jf503548a

Cited by 115 publications

(74 citation statements)

References 37 publications

(86 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…With lower molecular weights and viscosities compared with the polymer, alginate oligosaccharide (AOS) appears to possess more physiological activities. For example, AOS prepared by oxidative degradation, which has a carboxyl group at the reducing end, displays anti-inflammatory and neuroprotective effects 14, 15 . Additionally, AOS prepared by enzymatic degradation, which has an unsaturated terminal structure with a C4-C5 double bond, exhibits various immuno-stimulation 16 , anti-tumour 17 , antioxidant and neuroprotective activities 18 .…”

Section: Introductionmentioning

confidence: 99%

Identification and activation of TLR4-mediated signalling pathways by alginate-derived guluronate oligosaccharide in RAW264.7 macrophages

Fang

Zheng

et al. 2017

Sci Rep

Self Cite

143

View full text Add to dashboard Cite

Alginate, a natural acidic polysaccharide extracted from marine brown seaweeds, is composed of different blocks of β-(1, 4)-D-mannuronate (M) and its C-5 epimer α-(1, 4)-L-guluronate (G). Alginate-derived guluronate oligosaccharide (GOS) readily activates macrophages. However, to understand its role in immune responses, further studies are needed to characterize GOS transport and signalling. Our results show that GOS is recognized by and upregulates Toll-like receptor 4 (TLR4) on RAW264.7 macrophages, followed by its endocytosis via TLR4. Increased expression of TLR4 and myeloid differentiation protein 2 (MD2) results in Akt phosphorylation and subsequent activation of both nuclear factor-κB (NF-κB) and mechanistic target of rapamycin (mTOR). Moreover, GOS stimulates mitogen-activated protein kinases (MAPKs); notably, c-Jun N-terminal kinase (JNK) phosphorylation depends on TLR4 initiation. All these events contribute to the production of inflammatory mediators, either together or separately. Our findings also reveal that GOS induces cytoskeleton remodelling in RAW264.7 cells and promotes macrophage proliferation in mice ascites, both of which improve innate immunity. Conclusively, our investigation demonstrates that GOS, which is dependent on TLR4, is taken up by macrophages and stimulates TLR4/Akt/NF-κB, TLR4/Akt/mTOR and MAPK signalling pathways and exerts impressive immuno-stimulatory activity.

show abstract

Section: Introductionmentioning

confidence: 99%

Identification and activation of TLR4-mediated signalling pathways by alginate-derived guluronate oligosaccharide in RAW264.7 macrophages

Fang

Zheng

et al. 2017

Sci Rep

Self Cite

143

View full text Add to dashboard Cite

show abstract

“…Alginate oligosaccharide (AOS), produced by depolymerizing alginate using different degradation methods including enzymatic degradation, acid hydrolysis and oxidative degradation, has been proven to exert several pharmacological activities, including anti-oxidative [11], anti-apoptotic [12], anti-inflammatory [13] and anti-proliferative effects [14]. Nevertheless, whether AOS is protective against acute DOX cardiotoxicity is not yet clear, and the underlying mechanisms need to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Alginate Oligosaccharide Prevents Acute Doxorubicin Cardiotoxicity by Suppressing Oxidative Stress and Endoplasmic Reticulum-Mediated Apoptosis

Guo

Shi

et al. 2016

Marine Drugs

View full text Add to dashboard Cite

Doxorubicin (DOX) is a highly potent chemotherapeutic agent, but its usage is limited by dose-dependent cardiotoxicity. DOX-induced cardiotoxicity involves increased oxidative stress and activated endoplasmic reticulum-mediated apoptosis. Alginate oligosaccharide (AOS) is a non-immunogenic, non-toxic and biodegradable polymer, with anti-oxidative, anti-inflammatory and anti-endoplasmic reticulum stress properties. The present study examined whether AOS pretreatment could protect against acute DOX cardiotoxicity, and the underlying mechanisms focused on oxidative stress and endoplasmic reticulum-mediated apoptosis. We found that AOS pretreatment markedly increased the survival rate of mice insulted with DOX, improved DOX-induced cardiac dysfunction and attenuated DOX-induced myocardial apoptosis. AOS pretreatment mitigated DOX-induced cardiac oxidative stress, as shown by the decreased expressions of gp91 (phox) and 4-hydroxynonenal (4-HNE). Moreover, AOS pretreatment significantly decreased the expression of Caspase-12, C/EBP homologous protein (CHOP) (markers for endoplasmic reticulum-mediated apoptosis) and Bax (a downstream molecule of CHOP), while up-regulating the expression of anti-apoptotic protein Bcl-2. Taken together, these findings identify AOS as a potent compound that prevents acute DOX cardiotoxicity, at least in part, by suppression of oxidative stress and endoplasmic reticulum-mediated apoptosis.

show abstract

“…The anti-inflammatory activity mechanism of guluronate oligosaccharides prepared by oxidative degradation (GOS-OD) may involve the inhibition of the binding of LPS to the cell surface and attenuation of LPS-induced expression of TLR4 and cluster of differentiation 14. These changes, in turn, can inhibit the activation of NF-κB and MAPK signaling pathways [77]. Similarly, the treatment of BV2 cells by AOS (oxidative degradation, molecular weight: 1500 Da, concentration: 50-500 µg/mL) markedly inhibits the LPS-activated synthesis and secretion of TNF-α, IL-6, and IL-1β, as well as the amyloid β-protein (Aβ)-activated production of TNF-α, IL-6, and IL-12.…”

Section: Anti-inflammatory Activitymentioning

confidence: 99%

Advances in Research on the Bioactivity of Alginate Oligosaccharides

et al. 2020

View full text Add to dashboard Cite

Alginate is a natural polysaccharide present in various marine brown seaweeds. Alginate oligosaccharide (AOS) is a degradation product of alginate, which has received increasing attention due to its low molecular weight and promising biological activity. The wide-ranging biological activity of AOS is closely related to the diversity of their structures. AOS with a specific structure and distinct applications can be obtained by different methods of alginate degradation. This review focuses on recent advances in the biological activity of alginate and its derivatives, including their anti-tumor, anti-oxidative, immunoregulatory, anti-inflammatory, neuroprotective, antibacterial, hypolipidemic, antihypertensive, and hypoglycemic properties, as well as the ability to suppress obesity and promote cell proliferation and regulate plant growth. We hope that this review will provide theoretical basis and inspiration for the high-value research developments and utilization of AOS-related products.2 of 26 the 4 C 1 conformation and are linked by β-1,4-glycosidic bond, while in pG, all G residues are in the 1 C 4 conformation and are linked by an α-1,4-glycosidic bond. These features are responsible for the differences in their higher-order structure. For example, pG exhibits an egg-box-like conformation and usually forms stiffer 2-fold screw helical chains when dissolved in water, while pM forms belt chains through intra-molecular hydrogen bonds. Due to these dissimilarities, pM and pG, as well as their derivatives, will exhibit different activities [12].As the most abundant marine biomass and low-cost material, alginate has been extensively used in the food and medical industries. The widespread utilization is also driven by its favorable chemical properties and versatile activities. However, the applications of alginate have been greatly limited due to its high molecular weight and low bioavailability. Therefore, the degradation of high molecular weight polysaccharides into low molecular weight poly-or oligosaccharides is considered of great significance for improving their bioavailability, increasing the body's absorption of drugs, and fully utilizing the efficacy of polysaccharides. Recently, the degradation products of alginate, i.e., alginate oligosaccharides (AOS), have attracted increasing attention due to their biological activities and excellent solubility in water [13]. AOS can be depolymerized by different degradation methods, including enzymatic degradation, acid hydrolysis, and oxidative degradation [14]. Alginate lyases have been isolated from a wide range of organisms, including algae, marine invertebrates, and marine and terrestrial microorganisms, which can degrade alginate into unsaturated oligosaccharides by β-elimination [15,16]. Moreover, due to differences in degradation patterns, G content (G/M ratio), molecular weight, and spatial conformation of degradation products, AOS possess a variety of biological activities. They have anti-tumor properties [17], counteract oxidation [8], regulate immune respo...

show abstract

Anti-inflammatory Activity of Guluronate Oligosaccharides Obtained by Oxidative Degradation from Alginate in Lipopolysaccharide-Activated Murine Macrophage RAW 264.7 Cells

Cited by 115 publications

References 37 publications

Identification and activation of TLR4-mediated signalling pathways by alginate-derived guluronate oligosaccharide in RAW264.7 macrophages

Identification and activation of TLR4-mediated signalling pathways by alginate-derived guluronate oligosaccharide in RAW264.7 macrophages

Alginate Oligosaccharide Prevents Acute Doxorubicin Cardiotoxicity by Suppressing Oxidative Stress and Endoplasmic Reticulum-Mediated Apoptosis

Advances in Research on the Bioactivity of Alginate Oligosaccharides

Contact Info

Product

Resources

About