iridoids and aucubigenin

The advances in the research on pharmacological activities of aucubin have been summarized in the last ten years. Aucubin is one of active components of Chinese medicinal herbs such as Eucommia ulmoides and has been shown wide pharmacological activities including hepatoproective, antitoxicanti-inflammatory, antioxidant, antiaging, antiosteoporosis and neurotrophic and should be further researched and utilized.

Topics: Aging; Animals; Anti-Inflammatory Agents; Antioxidants; Eucommiaceae; Glucosides; Iridoid Glucosides; Iridoids; Molecular Structure; Plants, Medicinal; Pyrans

X-ray diffraction analyses of iridoid glycoside aucubin (1) and its aglycone aucubigenin (2) are reported. It was found that crystals of 1 are orthorhombic, with P2(1)2(1)2(1) space group, both cyclopentane ring and pyran ring adopt envelope conformations, and the Glc moiety is in the (4)C(1) conformation. Crystals of 2 are monoclinic, with space group P2(1), the cyclopentane and pyran rings also adopt the envelope conformation. The absolute configurations of 1 and 2 were also determined. Intensive O-H . . . O hydrogen bonds in both crystal lattices were observed.

Topics: Crystallography, X-Ray; Glucosides; Hydrogen Bonding; Iridoid Glucosides; Iridoids; Pyrans

The iridoid glucoside aucubin can irreversibly bind to proteins through the formation of its aglycone. In view of a possible involvement of these protein adducts in the toxicity of aucubin, we investigated the mechanism of binding of aucubin to proteins. [3H]aucubin in itself did not result in binding to protein whereas it covalently bound to rat serum albumin as a function of exposure time and dose in the presence of beta-glucosidase. The rate and extent of protein binding were significantly increased in the presence of the imine-trapping agent sodium cyanide. Oral administration of [3H]aucubin to rats showed that the total radioactivity in plasma remained at a similar level for up to 6 h once peak level was reached, suggesting that a considerable amount of radioactivity might be covalently associated with plasma proteins. The levels of radioactivity in the liver and kidney after oral dosing were higher than those after i.v. dosing. These results indicate that the open-chain aglycone of aucubin can form an imine bond with a nucleophilic site of the protein and these irreversible bindings may partially contribute to its biological and toxic effects.

Topics: Administration, Oral; Animals; beta-Glucosidase; Blood Proteins; Dose-Response Relationship, Drug; Glucosides; Imines; Injections, Intravenous; Iridoid Glucosides; Iridoids; Kidney; Liver; Male; Protein Binding; Pyrans; Rats; Rats, Sprague-Dawley; Serum Albumin; Sodium Cyanide; Tissue Distribution; Tritium

The inhibition of ethoxy coumarin O-deethylase (ECOD) activity by aucubin and its aglycone was examined in a microsomal system and in freshly isolated hepatocytes. Aucubin was found to be inactive but the aglycone was found to be a potent time-dependent inhibitor of ECOD activity in both systems. The close structural similarity between the aglycone of aucubin and glutaraldehyde suggests a similar mechanism of enzyme inhibition through protein cross-linking by Schiff reactions. The similarity between the 2 compounds was demonstrated through their closely similar binding spectra to bovine serum albumin. The biological activities reported for the aglycone are suggested to be due to this similarity to glutaraldehyde.

Topics: 7-Alkoxycoumarin O-Dealkylase; Animals; Cattle; Cross-Linking Reagents; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Glucosides; Glutaral; In Vitro Techniques; Iridoid Glucosides; Iridoids; L-Lactate Dehydrogenase; Male; Microsomes, Liver; Molecular Structure; Protein Binding; Pyrans; Rats; Rats, Wistar; Schiff Bases; Serum Albumin, Bovine; Spectrophotometry, Ultraviolet