Inhibitory Effect of LGS and ODE Isolated from the Twigs of Syringa oblata subsp. dilatata on RANKL-Induced Osteoclastogenesis in Macrophage Cells

Osteoblasts and osteoclasts play a pivotal role in maintaining bone homeostasis, of which excessive bone resorption by osteoclasts can cause osteoporosis and various bone diseases. However, current osteoporosis treatments have many side effects, and research on new treatments that can replace these treatments is ongoing. Therefore, in this study, the roles of ligustroside (LGS) and oleoside dimethylester (ODE), a natural product-derived compound isolated from Syringa oblata subsp. dilatata as a novel, natural product-derived osteoporosis treatments were investigated. In the results of this study, LGS and ODE inhibited the differentiation of receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced RAW264.7 cells into osteoclasts without cytotoxicity, and down-regulated the activity of TRAP, a specific biomarker of osteoclasts. In addition, it inhibited bone resorption and actin ring formation, which are important functions and features of osteoclasts. Also, the effects of LGS and ODE on the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) and phosphoinositide 3-kinases (PI3K)/ protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) signaling pathways that play important roles in osteoclast differentiation were evaluated. In the results, LGS and ODE downregulated the phosphorylation of RANKL-induced MAPK and PI3K/Akt/mTOR proteins in a concentration-dependent manner, translocation of NF-κB into the nucleus was inhibited. As a result, the compounds LGS and ODE isolated from S. oblate subsp. dilatata effectively regulated the differentiation of RANKL-induced osteoclasts and inhibited the phosphorylation of signaling pathways that play a pivotal role in osteoclast differentiation. Therefore, these results suggest the possibility of LGS and ODE as new natural product treatments for bone diseases caused by excessive osteoclasts.     

Metal catalysed reactions of β,β′-tricarbonyl derivatives with isocyanates

The reactions of β,β′-tricarbonyl derivatives with isocyanates are catalysed by 2 mol % transition metal acetylacetonates (e.g., [Co(acac)₂] and [Zn(acac)₂]) at room temperature. 3-Oxo-1,5-pentanedioic acid dimethylester (1) reacts with RNCO (R=Et, CH₂CHCH₂, CH₂Ph, Ph, 4-Cl-Ph) to give 1:1 adducts involving the formation of a new C-C bond between the intercarbonylic methylene and the isocyanato group. Under similar conditions 2,4,6-heptanetrione (2) reacts with the same isocyanates to afford pyridinone and pyranone derivatives resulting from the cyclisation of unstable 1:1 and 1:2 adducts.     

Reduction of a bilindione-10-thiol-adduct as a model of the reduction step of the biliverdin reductase system

Summary Biliverdin dimethyl ester and its 10-thioethanol addition product are reduced by LiBH₄ with similar reaction velocities as derived from NMR experiments. This reaction serves as a model of the biliverdin reductase system. According to this model the addition of the enzyme thiol group to position 10 of biliverdin primarily serves as the binding and orienting mode. It is obviously not intended as such to accelerate the velocity of the reduction step.

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Die Reduktion eines Bilindion-10-thioladduktes als Modellreaktion für den Reduktionsschritt des Biliverdinreduktase-Systems (Kurze Mitt.)

Zusammenfassung Biliverdindimethylester und sein 10-Thioethanoladdukt werden, wie durch NMR-Experimente gezeigt werden konnte, durch LiBH₄ mit vergleichbaren Geschwindigkeiten reduziert. Diese Reaktion dient als ein Modell für das Biliverdinreduktasesystem. Entsprechend diesem Modell dient die Addition der Enzym-Thiolgruppe in Position 10 des Biliverdins in erster Linie der Bindung und Orientierung und ist als solche nicht in Hinblick auf eine Reaktionsbeschleunigung der Reduktion konzipiert.

     

藻红胆素二甲酯甲醇加成物的形成和结构

藻红蛋白是红藻(Rhodophyta)、蓝绿藻(Cyanophyta)和隐藻(Cryptophyta)中类囊体外光合辅助色素,它是由开链四吡咯化合物和脱辅蛋白共价键结合而成。研究这些开链四吡咯化合物的化学性质及其衍生物的形成对藻胆蛋白的光生物现象和性质是很有价值的。我们从海滨采集的条斑紫菜(Porphyra