Odookeanynes A and B, Acetylene-Containing Lipopeptides from an Okeania sp. Marine Cyanobacterium.

Odookeanynes A (1) and B (2), two acetylene-containing lipopeptides, were isolated from an Okeania sp. marine cyanobacterium collected in Okinawa, Japan. Their structures were elucidated by spectroscopic analysis and Marfey's analysis of acid hydrolysates. Odookeanynes A (1) and B (2) dose-dependently promoted the differentiation of mouse 3T3-L1 preadipocytes in the presence of insulin.

Beneficial effects of a nobiletin-rich formulated supplement of Sikwasa (C. depressa) peel on cognitive function in elderly Japanese subjects; A multicenter, randomized, double-blind, placebo-controlled study.

BACKGROUND: Nobiletin exerts beneficial effects on cognitive function in various animal models of Alzheimer's disease. The present study aimed to investigate the benefits and safety of a combination food of nobiletin-rich extract from C. depressa peel for healthy elderly subjects. METHODS: The nobiletin-containing test food (Nobilex®) comprised high-purity nobiletin powder combined with dried root powder of K. parviflora and dried lead powder of P. japonicum and was administered to elderly Japanese subjects once a day for 16 weeks. The Japanese version of the Wechsler Memory Scaled-Revised (WMS-R) was used as a primary evaluation item for the assessment of global memory. Data from a protocol-matched population (Per Protocol Set: PPS) (n = 108) were analyzed. RESULTS: The scores of "general memory" or "visual memory" in the indices of WMS-R were significantly higher in the nobiletin-containing test food group than in the placebo group. The difference in the total WMS-R score was significantly higher in the test-food group (9.0 ± 7.20) than in the placebo group (5.9 ± 7.70). An age-stratified analysis of the WMS-R test showed similar changes in subjects aged ≦74 years to those in the overall subject population. In the stratified analysis involving subjects with an MMSE-J score of between 24 and 28, the "figural memory" subscale score in WMS-R was significantly higher in the test food group than in the placebo group. CONCLUSION: The present results indicate that the nobiletin-containing test food is beneficial for improving memory dysfunction in healthy elderly subjects.

Effect of methoxyflavones contained in Kaempferia parviflora on CRE-mediated transcription in PC12D cells.

The cAMP-response element (CRE) is critical in the formation of long-term memory. To prove the pharmacological effects of the methoxyflavones-rich residue (MRR) and its constituent methoxyflavones (1-9) extracted from the rhizomes of Kaempferia parviflora on the nervous system, we examined the effects of the MRR and methoxyflavones (1-9) on CRE-mediated transcription in PC12D cells. The MRR increased CRE-mediated transcription in PC12D cells. In addition, among methoxyflavones (1-9) isolated from MRR, compounds 1-4 increased CRE-mediated transcription. These results suggest that K. parviflora and methoxyflavone might be very useful materials for preventing and recovering from cognitive decline.

Irijimasides A-E, Macrolide Glycosides from an Okeania sp. Marine Cyanobacterium.

Irijimasides A-E (1-5), a series of new 14-membered macrolide glycosides, were isolated from a marine cyanobacterium collected in Okinawa. The gross structures of 1-5 were established by spectroscopic analysis, including 2D NMR, while absolute stereostructures were determined based on NOESY spectra, chemical derivatization, and ECD data. All five macrolides suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP) activity in mouse RAW264 macrophage cells, indicating that these compounds inhibit osteoclast formation.

Antimicrobial and antibiofilm activities of prenylated flavanones from Macaranga tanarius.

BACKGROUND: The emergence of antibiotic resistant microorganisms presents a worldwide problem that requires novel antibiotic and non-antibiotic strategies, and biofilm formation is a mechanism of drug resistance utilized by diverse microorganisms. The majority of microorganisms live in biofilms that help their survival against starvation, antimicrobial agents, and immunological defense systems. Therefore, it is important novel compounds be identified that inhibit biofilm formation and cell survival without drug resistance. STUDY DESIGN: In this study, the antimicrobial and antibiofilm activities of five prenylated flavanones (Okinawan propolins) isolated from fruits of Macaranga tanarius (L.) were investigated against 14 microorganisms including 10 pathogens. RESULTS: Of these five propolins, propolin D at 5-10 µg/ml significantly inhibited biofilm formation by three Staphylococcus aureus strains, a Staphylococcus epidermidis strain, and a Candida albicans with MICs from 10 to 50 µg/ml, and in C. albicans, propolin D was found to inhibit biofilm formation by reducing cell aggregation and downregulated the expressions of hypha/biofilm-related genes including ECE1 and HWP1. Interestingly, at sub-MIC concentrations (10-50 µg/ml), propolin D significantly inhibited biofilm formation by enterohemorrhagic E. coli O157:H7, uropathogenic E. coli O6:H1, and Acinetobacter baumannii without affecting planktonic cell growth, but did not inhibit biofilm formation by a commensal E. coli K-12 strain, three probiotic Lactobacillus plantarum strains, or two Pseudomonas aeruginosa strains. And, propolin D reduced fimbriae production by E. coli O157:H7 and repressed gene expression of curli fimbriae genes (csgA and csgB). Also, propolin D was minimally toxic in a Caenorhabditis elegans nematode model. CONCLUSION: These findings show that prenylated flavanones, especially propolin D from Macaranga tanarius (Okinawan propolis), should be considered potential candidates for the development of non-toxic antibacterial and antifungal agents against persistent microorganisms.

Inhibition of Biofilm Formation by Candida albicans and Polymicrobial Microorganisms by Nepodin via Hyphal-Growth Suppression.

Candida albicans is an opportunistic pathogenic yeast and is responsible for candidiasis. It readily colonizes host tissues and implant devices, and forms biofilms, which play an important role in pathogenesis and drug resistance. In this study, the antibiofilm, antihyphal, and antivirulence activities of nepodin, isolated from Rumex japonicus roots, were investigated against a fluconazole-resistant C. albicans strain and against polymicrobial-microorganism-biofilm formation. Nepodin effectively inhibited C. albicans biofilm formation without affecting its planktonic cell growth. Also, Rumex-root extract and nepodin both inhibited hyphal growth and cell aggregation of C. albicans. Interestingly, nepodin also showed antibiofilm activities against Candida glabrata, Candida parapsilosis, Staphylococcus aureus, and Acinetobacter baumannii strains and against dual biofilms of C. albicans and S. aureus or A. baumannii but not against Pseudomonas aeruginosa. Transcriptomic analysis performed by RNA-seq and qRT-PCR showed nepodin repressed the expression of several hypha- and biofilm-related genes (ECE1, HGT10, HWP1, and UME6) and increased the expression of several transport genes (CDR4, CDR11, and TPO2), which supported phenotypic changes. Moreover, nepodin reduced C. albicans virulence in a nematode-infection model and exhibited minimal cytotoxicity against the nematode and an animal cell line. These results demonstrate that nepodin and Rumex-root extract might be useful for controlling C. albicans infections and multispecies biofilms.

Ypaoamides B and C, Linear Lipopeptides from an Okeania sp. Marine Cyanobacterium.

Two new pyrrolinone-containing lipopeptides, ypaoamides B (1) and C (2), were isolated from an Okeania sp. marine cyanobacterium collected in Okinawa. Their structures were determined by spectroscopic analysis and Marfey's analysis of acid hydrolysates. Ypaoamides B (1) and C (2) stimulated glucose uptake in cultured rat L6 myotubes. In particular, ypaoamide B (1) showed potent activity and activated AMP-activated protein kinase.

Three New Malyngamides from the Marine Cyanobacterium Moorea producens.

Three new compounds of the malyngamide series, 6,8-di-O-acetylmalyngamide 2 (1), 6-O-acetylmalyngamide 2 (2), and N-demethyl-isomalyngamide I (3), were isolated from the marine cyanobacterium Moorea producens. Their structures were determined by spectroscopic analysis and chemical derivatization and degradation. These compounds stimulated glucose uptake in cultured L6 myotubes. In particular, 6,8-di-O-acetylmalyngamide 2 (1) showed potent activity and activated adenosine monophosphate-activated protein kinase (AMPK).