5-6-dehydrokawain and 7-8-dihydro-5-6-dehydrokawain

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 from Alpinia zerumbet rhizomes, 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.

Topics: Alkaline Phosphatase; Alpinia; Animals; Cell Differentiation; Cell Line; Cell Proliferation; Core Binding Factor Alpha 1 Subunit; Gene Expression Regulation; Homeodomain Proteins; Humans; Macrophages; Mice; Osteoblasts; Osteogenesis; p38 Mitogen-Activated Protein Kinases; Plant Extracts; Pyrones; Rhizome; RNA, Messenger; Sp7 Transcription Factor; Transcription Factors

Obesity and its related disorders have become leading metabolic diseases. In the present study, we used 3T3-L1 adipocytes to investigate the anti-obesity activity of hispidin and two related compounds that were isolated from Alpinia zerumbet (alpinia) rhizomes. The results showed that hispidin, dihydro-5,6-dehydrokawain (DDK), and 5,6-dehydrokawain (DK) have promising anti-obesity properties. In particular, all three compounds significantly increased intracellular cyclic adenosine monophosphate (cAMP) concentrations by 81.2% ± 0.06%, 67.0% ± 1.62%, and 56.9% ± 0.19%, respectively. Hispidin also stimulated glycerol release by 276.4% ± 0.8% and inhibited lipid accumulation by 47.8% ± 0.16%. Hispidin and DDK decreased intracellular triglyceride content by 79.5% ± 1.37% and 70.2% ± 1.4%, respectively, and all three compounds inhibited glycerol-3-phosphate dehydrogenase (GPDH) and pancreatic lipase, with hispidin and DDK being the most potent inhibitors. Finally, none of the three compounds reduced 3T3-L1 adipocyte viability. These results highlight the potential for developing hispidin and its derivatives as anti-obesity compounds.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Alpinia; Animals; Anti-Obesity Agents; Cell Survival; Cyclic AMP; Glycerol; Glycerolphosphate Dehydrogenase; Lipase; Lipids; Mice; Obesity; Plant Extracts; Pyrones; Triglycerides

The chemical composition of kava (Piper methysticum) lactones and various phytochemicals obtained following the sonication of ground kava roots extracted in the solvents hexane, chloroform, acetone, ethanol, methanol and water, respectively, was analyzed. Eighteen kava lactones, cinnamic acid bornyl ester and 5,7-dimethoxy-flavanone, known to be present in kava roots, were identified, and seven compounds, including 2,5,8-trimethyl-1-naphthol, 5-methyl-1-phenylhexen-3-yn-5-ol, 8,11-octadecadienoic acid-methyl ester, 5,7-(OH)(2)-4'-one-6,8-dimethylflavanone, pinostrobin chalcone and 7-dimethoxyflavanone-5-hydroxy-4', were identified for the first time. Glutathione (26.3 mg/g) was found in the water extract. Dihydro-5,6-dehydrokavain (DDK) was present at a higher level than methysticin and desmethoxyyagonin, indicating that DDK is also a major constituent of kava roots. Acetone was the most effective solvent in terms of maximum yield and types of kava lactones isolated, followed by water and chloroform, whereas hexane, methanol, and ethanol were less effective as solvents. Total phenolic and antioxidant activity varied among the extracting solvents, with acetone and chloroform producing the highest effects, followed by water, while methanol, ethanol and hexane were less effective.

Topics: Antioxidants; Biphenyl Compounds; Chalcones; Chromatography, High Pressure Liquid; Free Radical Scavengers; Gas Chromatography-Mass Spectrometry; Glutathione; Kava; Lactones; Phenols; Picrates; Plant Extracts; Plant Roots; Pyrans; Pyrones; Solvents; Sonication

The syntheses and biological activities of dihydro-5,6-dehydrokawain derivatives against plant pathogenic fungi and termites were investigated. Dihydro-5,6-dehydrokawain was isolated by a simple method without chromatography from the leaves of Alpinia speciosa K. SCHUM. The white crystalline compound obtained was identified as dihydro-5,6-dehydrokawain (1) by instrumental analyses. 4-Hydroxy-6-(2-phenylethyl)-2H-pyran-2-one (3) was prepared by hydrolyzing dihydro-5,6-dehydrokawain. Three dihydro-5,6-dehydrokawain derivatives were synthesized by reacting 3 with phosphoric agents. Among the synthesized compounds, dimethyl [6-(2-phenylethyl)-2-oxo-2H-pyran-4-yl]phosphorothionate (4) had the strongest antifungal activity of 91% at 100 ppm against Corticium rolfsii.

Topics: Animals; Antifungal Agents; Insecta; Insecticides; Molecular Structure; Plants, Medicinal; Pyrones; Structure-Activity Relationship

Topics: Animals; Anti-Ulcer Agents; Drugs, Chinese Herbal; Male; Mice; Pyrones; Rats

5,6-Dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK) inhibited the aggregation and ATP release of rabbit platelets induced by arachidonic acid and collagen, without affecting those induced by ADP, PAF and thrombin. This inhibition was reversible and in a concentration-dependent manner. The IC50 of DK and DDK on arachidonate-induced platelet aggregation were calculated to be about 10 and 60 micrograms/ml, respectively. Thromboxane B2 formation caused by arachidonic acid was also suppressed by both antiplatelet agents. DK inhibited the intracellular calcium concentration rised by arachidonic acid, but not that by collagen or thrombin. DK also inhibited the secondary, but not the primary aggregation of human platelet-rich plasma induced by ADP and epinephrine. It is concluded that the antiplatelet effect of both DK and DDK is due to the inhibition of thromboxane A2 formation.

Topics: Adenosine Triphosphate; Animals; Blood Platelets; Drugs, Chinese Herbal; Humans; In Vitro Techniques; Platelet Aggregation; Platelet Aggregation Inhibitors; Pyrans; Pyrones; Rabbits; Thromboxane B2

Topics: Animals; Anti-Ulcer Agents; Guinea Pigs; Male; Mice; Mice, Inbred ICR; Plants, Medicinal; Pyrans; Pyrones; Rats; Rats, Inbred Strains; Stomach Ulcer; Taiwan