Search

In this study, we explored anti-inflammatory compounds from the brown alga Dictyopteris polypodioides and isolated 7 meroterpenoids. Their anti-inflammatory activities were evaluated using the lipopolysaccharide-stimulated mouse macrophage cell line, RAW264. Yahazunol (1) exhibited similar nitric oxide (NO) production inhibitory activity as zonarol (2), which has previously been shown to be an anti-inflammatory compound. Yahazunol (1), zonarol (2), and isozonarol (3) inhibited not only NO production but also inducible nitric oxide synthase, interleukin-6, and C-C motif chemokine ligand 2 mRNA expression in RAW264 cells. The structure-activity relationships of the 11 compounds, including their synthetic analogs, revealed the significance of the hydroquinone moiety in the anti-inflammatory activity of these sesquiterpenoids in RAW264 cells. Diacetylated zonarol (9) exhibited an activity comparable to that of zonarol as a result of intracellular deacetylation. These results provide new insights into the anti-inflammatory activity of hydroquinone-containing natural products. [ABSTRACT FROM AUTHOR]

Brown algae contain a β-glucan called laminaran that exhibits various biological activities, such as immune-enhancing, anti-cancer, and antioxidant properties. The laminaran content in brown algae varies depending on species, habitat, and season. When developing a laminaran-containing functional food using brown algae or its extract, accurate quantitative methods to determine laminaran content in a variety of brown algae and foodstuffs are required. In this study, we examined the applicability of the existing sodium hypochlorite extracting and enzymatic digesting (SEED) assay for the determination of the laminaran content of the brown alga Eisenia bicyclis. The laminaran content of E. bicyclis could be determined using the SEED assay. Furthermore, we developed a rapid and concise acid extraction enzymatic method. This method can specifically extract total water-soluble β-glucan (laminaran) and selectively convert it to glucose. The generated glucose content was determined using the glucose oxidase/peroxidase method. The validation test using brown algae E. bicyclis and Sargassum horneri revealed that the acid extraction-enzymatic method is accurate, precise, and applicable to the determination of the laminaran content in these brown algae. Furthermore, developed method was also applicable to laminaran-added processed foods. [ABSTRACT FROM AUTHOR]

An imbalance between bone resorption by osteoclasts and bone formation by osteoblasts can cause bone loss and bone-related disease. In a previous search for natural products that increase osteogenic activity, we found that 5,6-dehydrokawain ( 1 ) from Alpinia zerumbet promotes osteoblastogenesis. In this study, we synthesized and evaluated series of 5,6-dehydrokawain analogs. Our structure-activity relationships revealed that alkylation of para or meta position of aromatic ring of 1 promote osteogenic activity. Among the potential analogs we synthesized, ( E )-6-(4-Ethylstyryl)-4-methoxy-2 H -pyran-2-one ( 14 ) and ( E )-6-(4-Butylstyryl)-4-methoxy-2 H -pyran-2-one ( 21 ) both significantly up-regulated Runx2 and Osterix mRNA expression at 10 µM. These osteogenic activities could be mediated by bone morphogenetic protein (BMP) and activation of p38 MAPK signaling pathways. Compounds 14 and 21 also inhibited RANKL-induced osteoclast differentiation of RAW264 cells. These results indicated that novel 5,6-dehydrokawain analogs not only increase osteogenic activity but also inhibit osteoclast differentiation, and could be potential lead compounds for the development of anti-osteoporosis agents. [ABSTRACT FROM AUTHOR]

Bone homeostasis is maintained by balancing bone formation and bone resorption, but an imbalance between them is associated with various bone-related diseases such as osteoporosis and rheumatoid arthritis. We found that 5,6-dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK), which were isolated as promising compounds fromAlpinia zerumbetrhizomes,promote differentiation of osteoblastic MC3T3-E1 cells. DK and DDK increased the alkaline phosphatase activity and matrix mineralization of MC3T3-E1 cells. DK exerts larger effects than DDK. The gene expression of runt-related transcription factor 2 and osterix, which are essential transcription factors in the early period of osteoblast differentiation, was significantly increased by DK treatment. The mRNA level of distal-less homeobox 5 was also enhanced by DK treatment, and DK activated the p38 mitogen-activated protein kinase pathway. Therefore, DK may have clinical potential for preventing osteoporosis, and could be considered as a potential anabolic therapeutic agent. 5,6-Dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK) fromAlpinia zerumbetrhizomes, promote differentiation of osteoblastic MC3T3-E1 cells. [ABSTRACT FROM AUTHOR]

Osteoporosis with bone loss is widely recognized as a major health problem. Bone homeostasis is maintained by balancing bone formation and bone resorption. The imbalance caused by increased bone resorption over bone formation can lead to various bone-related diseases such as osteoporosis and rheumatoid arthritis. Osteoclasts are the principal cells responsible for bone resorption and the main targets of anti-resorptive therapies. However, excessive inhibition of osteoclast differentiation may lead to inhibition of osteoblast differentiation. Therefore, it is important to screen for new compounds capable of inhibiting bone resorption and enhancing bone formation. Toddalia asiatica (L.) Lam. has been utilized traditionally for medicinal purposes such as the treatment of rheumatism. Currently, the extract is considered to be a good source of pharmacological agents for the treatment of bone-related diseases, but the active compounds have yet to be identified. We investigated whether toddaculin, derived from Toddalia asiatica (L.) Lam., affects both processes by inhibiting bone resorption and enhancing bone formation. Towards this end, we used pre-osteoclastic RAW 264 cells and pre-osteoblastic MC3T3-E1 cells. We found that toddaculin not only inhibited the differentiation of osteoclasts via activation of the NF-κB, ERK 1/2, and p38 MAPK signaling pathways, but it also induced differentiation and mineralization of osteoblasts by regulating differentiation factors. Thus, toddaculin might be beneficial for the prevention and treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

There are marine cytotoxic bromotriterpenoids, named the thyrsiferol family that are structurally characterized by some tetrahydropyran (THP) and tetrahydrofuran (THF) rings. The thyrsiferol family belongs to natural products that are often difficult to determine their stereostructures even by the current, highly advanced spectroscopic methods, especially in acyclic systems including stereogenic tetrasubstituted carbon centers. In such cases, it is effective to predict and synthesize the possible stereostructures. Herein, to elucidate ambiguous stereostructures and unassigned absolute configurations of aplysiol B, laurenmariannol, and saiyacenol A, members of the thyrsiferol family, we carried out their asymmetric chemical syntheses featuring 6‐exo and 5‐exo oxacyclizations of epoxy alcohol precursors and 6‐endo bromoetherification of a bishomoallylic alcohol. In this paper, we report total assignments of their stereostructures through their asymmetric chemical syntheses and also their preliminary cytotoxic activities against some tumor cells. These results could not have been achieved without depending on asymmetric total synthesis. [ABSTRACT FROM AUTHOR]

An investigation of anti-oxidative compounds from the brown alga Dictyopteris undulata has led to the isolation and identification of isozonarol, isozonarone, chromazonarol, zonaroic acid and isozonaroic acid. Their structures were identified by comparison of MS and NMR spectra. Full NMR assignment and absolute configuration of isozonaroic acid are described. Isozonarol showed the most potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity among the compounds isolated. [ABSTRACT FROM AUTHOR]

As a Japanese folk medicine, Tithonia diversifolia is used for cardiovascular disease prevention and health maintenance. We isolated T. diversifolia‐derived orizabin based on the nitric oxide production inhibitory effect. This study aimed to consider orizabin as a novel functional compound with anti‐atherosclerotic activity. Orizabin significantly inhibited the adhesion of THP‐1 cells to human umbilical vein endothelial cells (HUVECs) and suppressed the mRNA expression of adhesion molecules in HUVECs. In Phorbol 12‐myristate 13‐acetate stimulated THP‐1 cells, orizabin suppressed macrophage differentiation, CD36 expression (1% at 10 μM), and NFκB transcriptional activity. Furthermore, orizabin suppressed oxidized low‐density lipoprotein (oxLDL) uptake in macrophages and the Akt phosphorylation. On the contrary, we revealed that phosphatidylinositol‐3,4,5‐trisphosphate 3‐phosphatase (PTEN) mRNA and protein expression were promoted significantly by orizabin (mRNA, 270‐fold at 10 μM). Our study presented the possibility that T. diversifolia‐derived orizabin is novel anti‐atherosclerotic compound via the suppression of Akt phosphorylation, and T. diversifolia may be effective as a new crop for vascular health maintenance. Practical applications: In this study, the differentiation of monocytes was suppressed without any toxicity, it was obvious in the image, and the oxLDL uptake in monocytes was clearly suppressed by orizabin. Our findings presented that T. diversifolia‐derived compound orizabin specifically contributes to the promotion of PTEN expression and suppression of Akt signal in cells, and acts to suppress inflammation by suppression of NFκB transcriptional activity. As a component derived from food, it has a strong function and can be used to maintain the health for blood vessels. It is also a finding that deserves to expand production currently being carried out on a small scale. Furthermore, the promoting effect of PTEN known as a cancer suppressor in orizabin may result in further use for pharmaceuticals research. Orizabin can be safely used as a food‐derived compound for maintaining human health. [ABSTRACT FROM AUTHOR]

Configuration determination, cytotoxicity, natural products, structure elucidation, total synthesis The escaping fish are illustrating the feeding deterrence property of aplysiol B. More information can be found in the Communication by Keisuke Nishikawa, Yoshiki Morimoto et al. GLO:BDBM/03jan22:asia202101276-toc-0001.jpg PHOTO (COLOR): . gl GLO:BDBM/03jan22:asia202101276-toc-0001.jpg PHOTO (COLOR): . gl Keywords: configuration determination; cytotoxicity; natural products; structure elucidation; total synthesis EN configuration determination cytotoxicity natural products structure elucidation total synthesis 1 1 1 01/05/22 20220103 NES 220103 B Total assignments of stereostructures b of marine cytotoxic bromotriterpenoids, aplysiol B (laurenmariannol) and saiyacenol A derived from a sea hare or red alga, have been accomplished through their asymmetric syntheses from the known epoxide to elucidate their ambiguous stereostructures. [Extracted from the article]

Feroniellin analogs isolated from Feroniella lucida possess a furanocoumarin skeleton connected to monoterpenic five‐ to seven‐membered ethereal rings by an ether linkage and exhibit a broad spectrum of biological activities. In this contribution, we intended to establish a "ring‐size‐divergent" synthetic strategy for the monoterpenic five‐ to seven‐membered ethereal rings through the chemical sythesis of feroniellins. The short and comprehensive synthesis of feroniellins was achieved in only two steps from easily available bergamottin based on the "ring‐size‐divergent" strategy. In addition, these syntheses resulted in revision of the proposed structures for feroniellins A and B and the determination of all the absolute configurations of feroniellins; their preliminary anti‐inflammatory activities were investigated as well. [ABSTRACT FROM AUTHOR]

Biomimetic epoxide‐opening cascades of polyepoxides enable the efficient and rapid construction of polyether frameworks. Herein, we show that the epoxide‐opening cascade cyclization that affords tetrahydrofuran products in acidic aqueous media produces tetrahydropyran (THP) in neutral water. THP formation proceeded by simply heating polyepoxides in neutral water and followed a different cyclization mode from those observed so far. The novel cascade cyclization in H2O was applied to the synthesis of a new nerolidol‐type sesquiterpenoid, resulting in revision of the proposed structure and determination of the absolute configuration. [ABSTRACT FROM AUTHOR]

Biomimetic epoxide‐opening cascades of polyepoxides enable the efficient and rapid construction of polyether frameworks. Herein, we show that the epoxide‐opening cascade cyclization that affords tetrahydrofuran products in acidic aqueous media produces tetrahydropyran (THP) in neutral water. THP formation proceeded by simply heating polyepoxides in neutral water and followed a different cyclization mode from those observed so far. The novel cascade cyclization in H2O was applied to the synthesis of a new nerolidol‐type sesquiterpenoid, resulting in revision of the proposed structure and determination of the absolute configuration. [ABSTRACT FROM AUTHOR]

The enantioselective total syntheses of lepadiformine marine alkaloids, azatricyclic natural products isolated from marine tunicates, were completed. These alkaloids have a unique chemical structure characterized by the trans-1-azadecalin (AB ring system) fused with the spirocyclic ring (AC ring system). Here we found that a cycloisomerization reaction from functionalized linear substrates to a 1-azaspiro[4.5]decane framework corresponding to the AC ring in lepadiformines is promoted by a catalytic amount of mercury(II) triflate (Hg(OTf)2). The total syntheses of (−)-lepadiformines A and B were achieved in 28 % and 21 % overall yields, respectively, through the novel cycloisomerization reaction. The syntheses of (+)- and (−)-lepadiformine C hydrochloride salts also enabled us to determine the absolute configuration of natural lepadiformine C. It has been found that a phenomenon of enantiodivergence occurs in lepadiformine alkaloids from a single species of marine tunicate, Clavelina moluccensis. The cytotoxic activities of synthesized lepadiformine hydrochloride salts and their synthetic intermediates were evaluated. [ABSTRACT FROM AUTHOR]

Highlights from the article: Titelbild: Critical Switching of Cyclization Modes of Polyepoxides in Acidic Aqueous Media and Neutral Water: Synthesis and Revised Structure of a Nerolidol-Type Sesquiterpenoid (Angew. Im Titelbild steht eine Schienenweiche für diesen divergierenden Verlauf der Polyepoxid-Cyclisierung, wobei der rechte Waggon die THP-Bildung beim Erhitzen in neutralem Wasser darstellt. Eine Alkyl-MOF-basierte Methan-Nanofalle mit gegenüberliegenden offenen Metallzentren und dichten Alkylgruppen wird von S. Ma, Z. Niu et al. in ihrer Zuschrift auf S. 10244 vorgestellt.

A phenomenon of enantiodivergence was found in lepadiformine marine alkaloids isolated from a single species marine tunicate Clavelina moluccensis. The enantioselective total syntheses have been achieved by key mercury(II) triflate‐catalyzed cycloisomerization reaction from a functionalized linear substrate to a 1‐azaspiro[4.5]decane compound, and cytotoxic activities of synthesized lepadiformines and their synthetic intermediates were also evaluated. More information can be found in the Full Paper by Y. Morimoto et al. on page 9535. [ABSTRACT FROM AUTHOR]