hetacillin and secoisolariciresinol

Hypoglycemic effects of the H(2)O and MeOH extracts of the wood of Taxus yunnanensis were examined in streptozotocin (STZ)-induced diabetic rats. The H(2)O extract significantly lowered the fasting blood glucose level by 33.7% at a 100mg/kg dose on intraperitoneal administration. From the active H(2)O extract of the wood, three lignans, i.e., isotaxiresinol (1), secoisolariciresinol (2) and taxiresinol (3), were isolated as major components. These lignans were further tested for their hypoglycemic effects on the same experimental model. At a dose of 100mg/kg (i.p.), isotaxiresinol (1) reduced the fasting blood glucose level of diabetic rats by 34.5%, while secoisolariciresinol (2) and taxiresinol (3) reduced by 33.4% and 20.9%, respectively. The blood glucose lowering effects of 1 and 2 were stronger than the mixture of tolbutamide (200mg/kg) and buformin (1mg/kg) used as a positive control, which lowered fasting blood glucose level by 24.0%.

Topics: Animals; Blood Glucose; Butylene Glycols; Diabetes Mellitus, Experimental; Furans; Hypoglycemia; Lignans; Male; Molecular Structure; Plant Extracts; Rats; Rats, Wistar; Taxus; Wood

The H2O, H2O/MeOH (1:1) extracts from the wood of Taxus yunnanensis showed a remarkable inhibitory effect on induced histamine release from the human basophilic cell line, KU812. The eleven constituents purified from the wood extracts of Taxus yunnanensis were tested by an in vitro histamine release inhibition assay. Among them, secoisolarciresinol and taxiresinol were found to show inhibitory activities. A new neolignan, 2-[2-hydroxy-5-(3-hydroxypropyl)-3-methoxyphenyl]-1-(4-hydroxy-3-methoxyphenyl)propane-1,3-diol, was isolated from the wood of Taxus yunnanensis.

Topics: Anti-Allergic Agents; Butylene Glycols; Calcimycin; Carbon Isotopes; Cell Line; Chromatography, High Pressure Liquid; Deuterium; Drugs, Chinese Herbal; Furans; Histamine Release; Humans; Lignans; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Phenols; Plant Bark; Plant Extracts; Propylene Glycols; Spectrophotometry, Infrared; Taxoids; Taxus; Wood

The effects of secoisolariciresinol (1) and isotaxiresinol (2), two major lignans isolated from the wood of Taxus yunnanensis, on tumor necrosis factor-alpha (TNF-alpha)-dependent hepatic apoptosis induced by D-galactosamine (d-GalN)/lipopolysaccharide (LPS) were investigated in mice. Co-administration of d-GalN (700 mg/kg) and LPS (10 microg/kg) resulted in a typical hepatic apoptosis characterized by DNA fragmentation and the formation of apoptotic bodies. Serum glutamic pyruvic transaminase (sGPT) and glutamic oxaloacetic transaminase (sGOT) levels were also raised at 8 h after d-GalN/LPS intoxication due to a severe necrosis of hepatocytes. Pre-administration of 1 or 2 (50, 10 mg/kg, i.p.) 12 and 1 h before d-GalN/LPS significantly reduced DNA fragmentation and prevented chromatin condensation, apoptotic body formation and hepatitis. Pro-inflammatory cytokines such as TNF-alpha and interferon-gamma (IFN-gamma) secreted from LPS-activated macrophages are important mediators of hepatocyte apoptosis in this model. Pre-treatment with 1 or 2 significantly inhibited the elevation of serum TNF-alpha and IFN-gamma levels. In a separate experiment, both lignans had a significant dose-dependent protective effect on d-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes and TNF-alpha-mediated cell death in murine L929 fibrosarcoma cells. These results indicated that 1 and 2 prevent d-GalN/LPS-induced hepatic injury by inhibiting hepatocyte apoptosis through the blocking of TNF-alpha and IFN-gamma production by activated macrophages and direct inhibition of the apoptosis induced by TNF-alpha.

Topics: Alanine Transaminase; Animals; Apoptosis; Aspartate Aminotransferases; Butylene Glycols; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Drug Therapy, Combination; Furans; Galactosamine; Injections, Intraperitoneal; Interferon-gamma; Lignans; Lipopolysaccharides; Liver; Male; Mice; Mice, Inbred Strains; Phytotherapy; Plant Extracts; Plants, Medicinal; Taxus; Tumor Necrosis Factor-alpha