褐藻胶(Alginate)又称海藻酸盐，是一种从褐藻细胞壁中提取的天然多糖醛酸，是唯一一种在单体分子中含有羧基的多糖，其分子式为(C6H7NaO6)n。褐藻胶通过1,4-糖苷键将α-L-古罗糖醛酸(α-L-guluronicacid，G)和β-D-甘露糖醛酸(β-D-mannuronicacid，M)连接成聚合长链，因此褐藻胶的组合方式主要有3种：只有M组成的多聚β-D-甘露糖醛酸片段(Polymannuronate, PM)，只由G组成的多聚α-L-古罗糖醛酸片段(Polyguluronate，PG)，以及由G和M组成的共聚物(Heteropolymer，PolyMG)。组成褐藻胶的M和G在结构上互为差向异构体，主要在C5位上羧基位置的不同，且M和G的比率与其生物活性密切相关[1]。

Alginate is a natural polysaccharide aldehyde acid extracted from the cell wall of brown algae, and it is the only polysaccharide that contains a carboxyl group in the monomer molecule with the molecular formula (C6H7NaO6)n. Alginate connects α-L-α-L-gulonicacid (G) and β-D-mannuronicacid (M) into polymeric long chains, so there are three main combinations of alginate: polymannuronate, polyguluronate and heteropolymer. The M and G of alginate are structurally different from each other, mainly in the position of the carboxyl group at the C5 position, and the ratio of M and G is closely related to their biological activities.

图：褐藻胶的结构

图：褐藻寡糖结构

随着研究的深入，褐藻胶被认为是一种具有重要的免疫刺激、抗凝血、抗病毒和抗癌活性的大分子化合物，然而褐藻胶分子量大、黏性大、难以跨越细胞膜和多重生物屏障，进而限制了褐藻胶的开发和应用[2]。近年来，通过糖苷键水解或生物/有机合成获得的低分子量的褐藻寡糖(Alginateoligosaccharides，AOS)受到了研究者们的广泛关注，其不仅分子量较低，黏性小，易于吸收，而且表现出较强的生物活性[3]，包括免疫调节[4]、益生元[5]、抗炎[6]、抗细胞凋亡[7]、抗氧化[8]甚至抗肿瘤[9]等。

With the in-depth research, alginate is considered as a macromolecular compound with important immunostimulatory, anticoagulant, antiviral and anticancer activities. However, the large molecular weight, viscosity and difficulty in crossing cell membranes and multiple biological barriers of alginate in turn limit the development and application of alginate. In recent years, low molecular weight alginate oligosaccharides (AOS) obtained by glycosidic bond hydrolysis or bio/organic synthesis have received much attention from researchers, which not only have low molecular weight, low viscosity and easy absorption, but also exhibit strong biological activities, including immunomodulation, prebiotics, anti-inflammation, anti-apoptosis, antioxidant and even anti-tumor, etc.

3.1 抗肿瘤活性

3.1 Anti-tumor activity

AOS可通过抑制肿瘤细胞增殖和迁移，以及调节免疫防御反应等发挥抗肿瘤活性。已有研究证明AOS可通过抑制Hippo/YAP/c-Jun信号通路来减弱人前列腺癌细胞的增殖、迁移和侵袭。

AOS can exert anti-tumor activity by inhibiting tumor cell proliferation and migration, as well as regulating immune defense response. It has been demonstrated that AOS can attenuate the proliferation, migration and invasion of human prostate cancer cells by inhibiting the Hippo/YAP/c-Jun signaling pathway.

3.2 免疫调节功能

3.2 Immunomodulation

天然多糖和寡糖具有作为免疫调节剂的潜力。AOS在免疫调节中关键功能之一是诱导细胞因子的活性。在动物试验中发现，AOS可提高断奶仔猪血清中白介素(Interleukin，IL)-6、IL-10、免疫球蛋白(Immunoglobulin，Ig)和IgA浓度，并提高了小肠中分泌型免疫球蛋白A的含量，进而表明AOS可提高免疫球蛋白和细胞因子，增强断奶仔猪的免疫功能。

Natural polysaccharides and oligosaccharides have the potential to act as immunomodulators. One of the key functions of AOS in immunomodulation is the induction of cytokine activity. In animal tests, AOS was found to increase the serum concentrations of Interleukin (IL)-6, IL-10, immunoglobulin and IgA in weaned piglets and to increase the content of secretory immunoglobulin A in the small intestine, thus indicating that AOS can increase immunoglobulin and cytokines and enhance weaned piglets’ immunity.

3.3 抗氧化活性

3.3 Antioxidant activity

AOS具有清除自由基的作用，可作为抗氧化剂。AOS的抗氧化活性与AOS中G和M的相对含量无关。C5羧基的方向是G和M之间唯一的结构差异，它们的空间排列不会影响AOS的抗氧化活性，但其制备方法、浓度和分子量可影响AOS的抗氧化活性。

AOS has the effect of scavenging free radicals and can be used as an antioxidant. The antioxidant activity of AOS is independent of the relative contents of G and M. The orientation of the C5 carboxyl group is the only structural difference between G and M. Their spatial arrangement does not affect the antioxidant activity of AOS, but the preparation method, concentration and molecular weight can affect the antioxidant activity of AOS.

3.4 抗炎症活性

3.4 Anti-inflammatory activity

炎症是机体抵御病原体入侵的重要防御机制，可激活机体固有免疫细胞。然而，慢性或过度炎症可出现在慢性疾病过程中，如炎症性肠病、风湿性多肌痛、关节炎、糖尿病、心血管疾病和神经退行性疾病。通过不同的降解方法制备的AOS的抗炎效果明显不同。AOS可通过抑制TLR4/NF-κB和NOD1/NF-κB信号通路，进而提高断奶仔猪的肠道抗炎功能。氧化降解法制备的AOS与使用其他方法制备的AOS相比，具有更强的炎症抑制作用。

Inflammation is an important defense mechanism of the body against pathogenic invasion and activates the body’s intrinsic immune cells. However, chronic or excessive inflammation can occur in chronic disease processes, such as inflammatory bowel disease, rheumatic polymyalgia, arthritis, diabetes, cardiovascular disease and neurodegenerative disease. The anti-inflammatory effects of AOS prepared by different degradation methods are significantly different. AOS could improve intestinal anti-inflammatory function in weaned piglets by inhibiting TLR4/NF-κB and NOD1/NF-κB signaling pathways. AOS prepared by the oxidative degradation method shows stronger inflammation inhibition compared with that prepared by other methods.

AOS是一种有开发前途的天然添加剂，阐明AOS的结构与生物活性之间的关系将有助于靶向制备具有所需组成和结构特征的AOS，从而应用于食品、药品和饲料添加剂等领域。但是，目前对AOS的结构与生物活性之间关系的研究还不够深入，大部分研究集中在AOS混合物的生物活性上，并多以体外模型研究为主，从而限制了AOS的进一步开发和利用。

AOS is a promising natural additive, and elucidating the relationship between the structure and biological activity of AOS will help to target the preparation of AOS with the desired composition and structural characteristics for applications in food, pharmaceuticals and feed additives. However, the relationship between the structure and bioactivity of AOS has not been studied deeply enough, and most of the studies have focused on the bioactivity of AOS mixtures and mostly on in vitro models, thus limiting the further development and utilization of AOS.

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参考文献

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投稿者：刘亚文 博士研究生

审核导师：傅鹏程 教授