Biomedical and Clinical Importance of Mussel-Inspired Polymers and Materials

The substance secreted by mussels, also known as nature’s glue, is a type of liquid protein that hardens rapidly into a solid water-resistant adhesive material. While in seawater or saline conditions, mussels can adhere to all types of surfaces, sustaining its bonds via mussel adhesive proteins (MAPs), a group of proteins containing 3,4-dihydroxyphenylalanine (DOPA) and catecholic amino acid. Several aspects of this adhesion process have inspired the development of various types of synthetic materials for biomedical applications. Further, there is an urgent need to utilize biologically inspired strategies to develop new biocompatible materials for medical applications. Consequently, many researchers have recently reported bio-inspired techniques and materials that show results similar to or better than those shown by MAPs for a range of medical applications. However, the susceptibility to oxidation of 3,4-dihydroxyphenylalanine poses major challenges with regard to the practical translation of mussel adhesion. In this review, various strategies are discussed to provide an option for DOPA/metal ion chelation and to compensate for the limitations imposed by facile 3,4-dihydroxyphenylalanine autoxidation. We discuss the anti-proliferative, anti-inflammatory, anti-microbial activity, and adhesive behaviors of mussel bio-products and mussel-inspired materials (MIMs) that make them attractive for synthetic adaptation. The development of biologically inspired adhesive interfaces, bioactive mussel products, MIMs, and arising areas of research leading to biomedical applications are considered in this review.     

New Kunitz-Type HCRG Polypeptides from the Sea Anemone Heteractis crispa

Sea anemones are a rich source of Kunitz-type polypeptides that possess not only protease inhibitor activity, but also Kv channels toxicity, analgesic, antihistamine, and anti-inflammatory activities. Two Kunitz-type inhibitors belonging to a new Heteractis crispa RG (HCRG) polypeptide subfamily have been isolated from the sea anemone Heteractis crispa. The amino acid sequences of HCRG1 and HCRG2 identified using the Edman degradation method share up to 95% of their identity with the representatives of the HCGS polypeptide multigene subfamily derived from H. crispa cDNA. Polypeptides are characterized by positively charged Arg at the N-terminus as well as P1 Lys residue at their canonical binding loop, identical to those of bovine pancreatic trypsin inhibitor (BPTI). These polypeptides are shown by our current evidence to be more potent inhibitors of trypsin than the known representatives of the HCGS subfamily with P1Thr. The kinetic and thermodynamic characteristics of the intermolecular interactions between inhibitors and serine proteases were determined by the surface plasmon resonance (SPR) method. Residues functionally important for polypeptide binding to trypsin were revealed using molecular modeling methods. Furthermore, HCRG1 and HCRG2 possess anti-inflammatory activity, reducing tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) secretions, as well as proIL-1β expression in lipopolysaccharide (LPS)-activated macrophages. However, there was no effect on nitric oxide (NO) generation.     

Briarenolides U–Y,New Anti-Inflammatory Briarane Diterpenoids from an Octocoral Briareum sp. (Briareidae)

Five new 13,14-epoxybriarane diterpenoids, briarenolides U–Y (1–5), were isolated from the octocoral Briareum sp. The structures of briaranes 1–5 were elucidated by spectroscopic methods. Briarenolides U–Y (1–5) were found to significantly inhibit the expression of the pro-inflammatory inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein of the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells.     

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为了解艾纳香油的抗炎作用机理,为其开发应用提供参考,将60只昆明种小鼠(SPF级)随机分为艾纳香油高(40％)、中(20％)、低(10％)剂量组,氢化可的松组,模型对照组和溶剂对照组,用二甲苯致炎,采用紫外可见分光光度法测定致炎耳组织中前列腺素E2 (PGE2)和血清中丙二醛(MDA)的含量,并采用超氧化物歧化酶(SOD)试剂盒测定血清SOD活性.结果表明:与模型对照组相比,艾纳香油高、中、低剂量组对二甲苯所致的小鼠耳肿胀均有显著抑制作用(P＜0.05),降低PGE2含量,其中低剂量组可极显著降低致炎耳组织中PGE2含量(P＜0.01);艾纳香油高、低剂量组均显著提高血清SOD的活性(P＜0.05),艾纳香油可降低血清MDA含量(P＞0.05).艾纳香油具有一定的抗炎作用,可能与降低炎症区域PGE2含量和提高机体抗氧化损伤有关.     

Streptoglycerides E–H,Unsaturated Polyketides from the Marine-Derived Bacterium Streptomyces specialis and Their Anti-Inflammatory Activity

Four new streptoglycerides E–H (1–4), with a rare 6/5/5/-membered ring system, were isolated from a marine-derived actinomycete Streptomyces specialis. The structures of 1–4 were elucidated by detailed analysis of HRESIMS, 1D and 2D NMR data and ECD spectra as well as comparison of their spectroscopic data with those reported in literature. Compounds 1–4 showed significant anti-inflammatory activity by inhibiting lipopolysaccharide (LPS)-induced nitric oxide (NO) production in Raw 264.7 cells with IC₅₀ values ranging from 3.5 to 10.9 µM. Especially, 2 suppressed mRNA expression levels of iNOS and IL-6 without cytotoxicity.     

九里香叶的抗炎镇痛作用研究

采用小鼠扭体试验、热板法、二甲苯致耳朵肿胀法和角叉菜胶致足肿胀法研究了九里香[Murrayaexotica(L.)]叶的镇痛抗炎作用。结果表明,九里香叶醇提物可有效抑制醋酸致小鼠的扭体反应,延长小鼠的痛阈值,显著抑制二甲苯及角叉菜胶诱导的肿胀。表明中药九里香叶醇提物具有显著的抗炎、镇痛药理学作用,为中药九里香的二次开发提供了有益的科学依据。     

Oxygenated Theonellastrols: Interpretation of Unusual Chemical Behaviors Using Quantum Mechanical Calculations and Stereochemical Reassignment of 7α-Hydroxytheonellasterol

A total of eight new oxygenated 4-exo-methylene sterols, 1–8, together with one artifact 9 and six known sterols 11–16, were isolated from the marine sponge Theonella swinhoei collected from the Bohol province in Philippines. Structures of sterols 1–8 were determined from 1D and 2D NMR data. Among the sterols, 8α-hydroxytheonellasterol (4) spontaneously underwent an allylic 1,3-hydroxyl shift to produce 15α-hydroxytheonellasterol (9) as an artifact; this was rationalized by quantum mechanical calculations of the transition state. In addition, the 1,2-epoxy alcohol subunit of 8α-hydroxy-14,15-β-epoxytheonellasterol (5) was assigned using the Gauge-Independent Atomic Orbital (GIAO) NMR chemical shift calculations and subsequent DP4+ analysis. Finally, comparison of the ¹³C chemical shifts of isolated 7α-hydroxytheonellasterol (6) with the reported values revealed significant discrepancies at C-6, C-7, C-8, and C-14, leading to reassignment of the C-7 stereochemistry in the known structure.     

Anti-Inflammatory Effect of Sulfated Polysaccharides Isolated from Codium fragile In Vitro in RAW 264.7 Macrophages and In Vivo in Zebrafish

In this study, the anti-inflammatory activity of sulfated polysaccharides isolated from the green seaweed Codium fragile (CFCE-PS) was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and zebrafish. The results demonstrated that CFCE-PS significantly increased the viability of LPS-induced RAW 264.7 cells in a concentration-dependent manner. CFCE-PS remarkably and concentration-dependently reduced the levels of inflammatory molecules including prostaglandin E₂, nitric oxide (NO), interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6 in LPS-stimulated RAW 264.7 cells. In addition, in vivo test results indicated that CFCE-PS effectively reduced reactive oxygen species, cell death, and NO levels in LPS-stimulated zebrafish. Thus, these results indicate that CFCE-PS possesses in vitro and in vivo anti-inflammatory activities and suggest it is a potential ingredient in the functional food and pharmaceutical industries.     

新型中兽药“黄金二白散”药效学研究

[目的]考察“黄金二白散”的抑菌及消炎作用.[方法]采用小鼠耳肿胀法和平板打孔法进行了“黄金二白散”的抗炎试验和体外抑菌试验.[结果]抗炎试验,小鼠耳平均肿胀度低剂量组为（1.25±177;0.78） mg,中剂量组为（0.51±177;0.38） mg,高剂量组为（0.42±177;0.35） mg,试验3组与空白对照组相比,差异极显著;体外抑菌试验,“黄金二白散”对金黄色葡萄球菌的抑菌值为21.7 mm,对痢疾杆菌的抑菌值为17.4 mm,对绿脓杆菌的抑菌值为14.6 mm,对大肠杆菌的抑菌值为16.4 mm,对变形杆菌的抑菌值为28.3 mm.[结论]“黄金二白散”具有一定的抗炎作用,对金黄色葡萄球菌、痢疾杆菌、绿脓杆菌、大肠杆菌、变形杆菌等细菌皆敏感,具有广谱抗菌作用,且与庆大霉素相比,抑菌效果更佳.