Metabolites with Anti-Inflammatory Activity from the Mangrove Endophytic Fungus Diaporthe sp. QYM12

One new diterpenoid, diaporpenoid A (1), two new sesquiterpenoids, diaporpenoids B–C (2,3) and three new α-pyrone derivatives, diaporpyrones A–C (4–6) were isolated from an MeOH extract obtained from cultures of the mangrove endophytic fungus Diaporthe sp. QYM12. Their structures were elucidated by extensive analysis of spectroscopic data. The absolute configurations were determined by electronic circular dichroism (ECD) calculations and a comparison of the specific rotation. Compound 1 had an unusual 5/10/5-fused tricyclic ring system. Compounds 1 and 4 showed potent anti-inflammatory activities by inhibiting the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW264.7 cells with IC₅₀ values of 21.5 and 12.5 μM, respectively.     

Cellular Signal Transductions and Their Inhibitors Derived from Deep-Sea Organisms

Not only physiological phenomena but also pathological phenomena can now be explained by the change of signal transduction in the cells of specific tissues. Commonly used cellular signal transductions are limited. They consist of the protein–tyrosine kinase dependent or independent Ras-ERK pathway, and the PI3K-Akt, JAK-STAT, SMAD, and NF-κB-activation pathways. In addition, biodegradation systems, such as the ubiquitin–proteasome pathway and autophagy, are also important for physiological and pathological conditions. If we can control signaling for each by a low-molecular-weight agent, it would be possible to treat diseases in new ways. At present, such cell signaling inhibitors are mainly looked for in plants, soil microorganisms, and the chemical library. The screening of bioactive metabolites from deep-sea organisms should be valuable because of the high incidence of finding novel compounds. Although it is still an emerging field, there are many successful examples, with new cell signaling inhibitors. In this review, we would like to explain the current view of the cell signaling systems important in diseases, and show the inhibitors found from deep-sea organisms, with their structures and biological activities. These inhibitors are possible candidates for anti-inflammatory agents, modulators of metabolic syndromes, antimicrobial agents, and anticancer agents.     

Cherbonolides M and N from a Formosan Soft Coral Sarcophyton cherbonnieri

Two new isosarcophine derivatives, cherbonolides M (1) and N (2), were further isolated from a Formosan soft coral Sarcophyton cherbonnieri. The planar structure and relative configuration of both compounds were established by the detailed analysis of the IR, MS, and 1D and 2D NMR data. Further, the absolute configuration of both compounds was determined by the comparison of CD spectra with that of isosarcophine (3). Notably, cherbonolide N (2) possesses the unique cembranoidal scaffold of tetrahydrooxepane with the 12,17-ether linkage fusing with a γ-lactone. In addition, the assay for cytotoxicity of both new compounds revealed that they showed to be noncytotoxic toward the proliferation of A549, DLD-1, and HuCCT-1 cell lines. Moreover, the anti-inflammatory activities of both metabolites were carried out by measuring the N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLF/CB)-induced generation of superoxide anion and elastase release in the primary human neutrophils. Cherbonolide N (2) was found to reduce the generation of superoxide anion (20.6 ± 6.8%) and the elastase release (30.1 ± 3.3%) in the fMLF/CB-induced human neutrophils at a concentration of 30 μM.     

阿魏酸抗LPS诱导的奶牛子宫内膜上皮细胞炎性作用

[目的]为了探明阿魏酸的抗炎机制.[方法]采用组织块培养法获得奶牛子宫内膜上皮细胞.用噻唑蓝(MTT法)检测细胞活力.采用荧光定量PCR方法,分别对对照组、模型组、药物作用高、中、低剂量组在LPS作用3h、6h炎症基因IL-1β、IL-6、IL-8和TNF-α的mRNA变化进行检测.[结果]阿魏酸在一定浓度范围内对细胞增殖无显著影响.药物预处理细胞能够显著降低LPS诱导的IL-1β、IL-6、IL-8和TNF-α的mRNA表达.[结论]阿魏酸能够显著降低LPS刺激细胞后炎症细胞因子的表达,说明阿魏酸是通过抑制炎症因子的表达发挥其抗炎作用.     

Anti-Inflammatory Concentrate Enriched with Substituted Oligofucans Derived from Brown Seaweed Turbinaria conoides (J. Agardh) Kützing and Its Safety Assessment on Wistar Rats

ABSTRACT

Aqueous extract of the seaweed Turbinaria conoides was purified to obtain an oligofucan-enriched seaweed concentrate (OESC). Oligofucans isolated were characterized as two types with (→1)-fucose-(2,3-diSO₃^?)-(1→4)-fucose-(2-SO₃^?)-(1→3)-fucose-(2,3-diSO₃^?)-(1→4)-fucose-(2-SO₃^?, 3-OAc)-(4→) and (→1)-fucose-(3-SO₃^?)-(1→4)-fucose-(2-SO₃^?)-(1→4)-fucose-(3-SO₃^?)-(1→4)-fucose-(2-SO₃^?)-(4→) motifs. A 90-day accelerated shelf-life study (50°C) showed that OESC maintained its antioxidant properties (free radical scavenging, reducing, lipid peroxidation inhibition, and chelating activities) even after 30 days. In vitro COX-2 and 5-LOX inhibitory properties of OESC (67.2 and 95.2%, respectively) showed no significant variation even at the 30th day. OESC significantly mitigated the carrageenan-induced inflammation in rats at 0–2 h (59.7–70.3% inhibition), which were greater compared to the synthetic NSAID aspirin. The safety of OESC has been assessed by acute (14 days) and subchronic (90 days) oral toxicity studies, which showed no toxicity-related significant changes in renal or hepatic function, hematological indices, and serum biochemical parameters in the OESC-treated Wistar rats. No histopathological alterations were observed in the vital organs of rats treated with OESC. LD₅₀ and sub-chronic no-observed-adverse-effect level (NOAEL) for this concentrate were found to be > 5,000 and 2,000?mg/kg BW, respectively. Hence, oligofucan-enriched seaweed concentrate is safe to consume without any adverse effects in the body.     

New Drimane Sesquiterpenes and Polyketides from Marine-Derived Fungus Penicillium sp. TW58-16 and Their Anti-Inflammatory and α-Glucosidase Inhibitory Effects

Marine fungi-derived natural products represent an excellent reservoir for the discovery of novel lead compounds with biological activities. Here, we report the identification of two new drimane sesquiterpenes (1 and 2) and six new polyketides (3–8), together with 10 known compounds (9–18), from a marine-derived fungus Penicillium sp. TW58-16. The planar structures of these compounds were elucidated by extensive 1D and 2D NMR, which was supported by HR-ESI-MS data. The absolute configurations of these compounds were determined by experimental and calculated electronic circular dichroism (ECD), and their optical rotations compared with those reported. Evaluation of the anti-inflammatory activity of compounds 1–18 revealed that compound 5 significantly inhibited the release of nitric oxide (NO) induced by lipopolysaccharide (LPS) in RAW264.7 cells, correlating with the inhibition of expression of inducible nitric oxide synthase (iNOS). In addition, we revealed that compounds 1, 3–6, 14, 16, and 18 showed strong α-glucosidase inhibitory effects with inhibition rates of 35.4%, 73.2%, 55.6%, 74.4%, 32.0%, 36.9%, 88.0%, and 91.1%, respectively, which were comparable with or even better than that of the positive control, acarbose. Together, our results illustrate the potential of discovering new marine-based therapeutic agents against inflammation and diabetes mellitus.     

紫甘蓝花色苷及其复合体的抗炎活性研究

为了探究紫甘蓝花色苷—3-二糖-5-D-吡喃葡糖苷矢车菊素(cyanidin-3-diglcoside-5-glcoside,Cy)及其复合体对鼠源单核-巨噬细胞RAW264.7的抗炎活性,首先采用紫甘蓝花色苷碱水解产物中的Cy为原料,模拟天然蓝花中结构相对稳定的花色苷复合体存在形式,与芦丁(rutin)及2种不同金属离子(Mg~(2+)和Fe~(3+))构建5种Cy复合体;然后通过建立脂多糖(LPS)诱导的鼠源单核-巨噬细胞RAW264.7炎症模型,评价Cy复合体构建前后对Cy抗炎活性的影响。结果表明,Cy可以显著性抑制RAW264.7细胞上清液中NO释放及细胞内炎症相关基因iNOS、IL-1β、IL-6和TNF-α的mRNA的表达(P0.05)。在构建的复合体中,与Cy相比,Cy-Fe~(3+)、Cy-rutin-Fe~(3+)、Cy-Mg~(2+)和Cy-rutin-Mg~(2+)复合体的抗炎活性均显著提高(P0.05)。其中,Cy-Mg~(2+)和Cy-rutinMg~(2+)复合体的抗炎活性高于Cy-Fe~(3+)和Cy-rutin-Fe~(3+)复合体,而Cy-Mg~(2+)复合体的抗炎活性最强。由这些结果可以得出Cy及其复合体均具有显著的抗炎活性,且Cy复合体的抗炎活性高于Cy。Cy复合体有望开发成为一种新型食品添加剂,辅助干预炎症反应及其引起的相关疾病。     

中药生物碱的提取及抗炎作用研究

为探讨自拟中药复方"宫炎净"总生物碱、简化复方总生物碱以及益母草生物碱对小鼠的抗炎作用,将实验小鼠分为生理盐水、地塞米松、复方"宫炎净"总生物碱、简化复方总生物碱以及益母草生物碱组,依据建立小鼠耳廓肿胀、腹腔毛细血管通透性、足趾肿胀以及肉芽肿炎症模型来评估各组药物的抗炎效果。结果表明,复方"宫炎净"总生物碱组与简化复方总生物碱能够显著抑制二甲苯所致小鼠耳廓肿胀率、降低小鼠腹腔毛细血管通透性、抑制蛋清所致小鼠足趾肿胀率、降低棉球所致小鼠肉芽组织增生,均与益母草生物碱组差异显著(P0.05),并与地塞米松组差异不显著(P0.05)。结果显示,复方"宫炎净"总生物碱组与简化复方总生物碱抗炎效果相差不大,简化复方可作为临床用药组方使用。     

抗菌消炎胶囊中知母薄层鉴别方法的改进

[目的]改进抗菌消炎胶囊中知母的薄层鉴别方法。[方法]以知母阴性、菝葜皂苷元为对照品,采用不同展开溶剂系统进行薄层色谱鉴别。[结果]改进后方法薄层色谱斑点清晰,重现性好,专属性好,阴性对照无干扰。[结论]改进后的方法快捷简便、重复性好、毒性小,可作为抗菌消炎胶囊中知母的鉴别方法。     

Topical anti-inflammatory plant species: Bioactivity of Bryonia dioica, Tamus communis and Lonicera periclymenum fruits

The practice of rubbing different plant material juices or extracts into the skin to relieve pain and rheumatic symptoms is deeply rooted in folk medicine and has been used for a long time. Several common species, usually available in agroecosystems of the Iberian Peninsula, were/are used for topical medicinal preparations as reported in recent ethnobotanical surveys. Based on these studies, the fruits of three relevant species (Bryonia dioica or white-bryony, Lonicera periclymenum or common honeysuckle and Tamus communis or black-bryony) were gathered and different analyses and assays were performed in order to characterize their phytochemical composition and to find biologically active compounds for pharmaceutical application. Black-bryony ripened fruits revealed the highest antioxidant properties which are in agreement to its highest concentration in phenolics, flavonoids, ascorbic acid, tocopherols and lycopene. The studied fruits revealed interesting antioxidant properties and bioactive phytochemicals that could provide scientific evidence for their folk uses as anti-inflammatory species.