lignans and Hypoglycemia

The natural health product, BeneFlax, is a standardized flaxseed [Linum usitatissimum L. (Linaceae)] lignan enriched product with evidence of product quality and known quantity of the bioactive component, lignan. The acceptance of this natural health product for its various health benefits requires greater evidence of its safety in the general population.. We determined whether flaxseed lignan causes clinical hypoglycemia or hypotension in healthy older adults as an important aspect of safety.. Participants aged 49-87 years were randomized in a double-blind trial to receive flaxseed lignan (543 mg/day in BeneFlax) or placebo while completing a 6-month walking program. The 94 participants who completed the study were stratified by age (<65 years versus ≥65 years) and treatment category to determine whether older adults were more susceptible to adverse effects.. After 6 months of treatment, average plasma glucose level (5.4 ± 0.6 mmol/L), systolic blood pressure (127 ± 14 mm Hg), and diastolic blood pressure (80 ± 9 mm Hg) were within normal clinical range. Controlling for sex and body mass index covariates resulted in no observed differences between plasma glucose or blood pressure measurements between treatment or age groups (p > 0.05). No incidents of hypoglycemia or hypotension were observed during BeneFlax treatment, suggesting that 543 mg falls at or below the no observable adverse effect level (NOAEL).. These data suggest the flaxseed lignan product BeneFlax does not pose a risk of hypoglycemia or hypotension in healthy adults aged 49-87 years.

Topics: Age Factors; Aged; Aged, 80 and over; Blood Glucose; Blood Pressure; Dietary Supplements; Double-Blind Method; Female; Flax; Humans; Hypoglycemia; Hypotension; Lignans; Male; Middle Aged; No-Observed-Adverse-Effect Level

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

Our previous studies demonstrated that magnolol protects neurons against chemical hypoxia by KCN in cortical neuron-astrocyte mixed cultures (14). In the present study, we examined whether the neuroprotective effect of magnolol involve modulating inflammatory mediators, prostaglandin E2 (PGE2) and nitric oxide (NO), induced by KCN (hypoxia) or KCN plus lipopolysaccharide (LPS). In glucose-absent (hypoglycemia) media, KCN or KCN plus LPS induced increases in lactate dehydrogenase (LDH) activity by 32% and 34%, and PGE2 production by 12% and 32%, respectively. Both LDH and PGE2 increases were suppressed by 100 microM magnolol. In addition, although KCN or LPS alone did not increase NO generation, KCN plus LPS increased NO generation. This increase was reduced by 100 microM magnolol or 10 microM L-NAME, but the LDH increase and PGE2 production were not reduced by L-NAME. These findings suggest that the protective effects of magnolol against brain damage by KCN or KCN plus LPS in hypoglycemic media may involve inhibition of PGE2 production, but inhibition of NO generation may not be important.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Biphenyl Compounds; Cell Hypoxia; Cells, Cultured; Cerebral Cortex; Culture Media; Dinoprostone; Enzyme Inhibitors; Hypoglycemia; L-Lactate Dehydrogenase; Lignans; Lipopolysaccharides; Neurons; Neuroprotective Agents; NG-Nitroarginine Methyl Ester; Nitric Oxide; Potassium Cyanide; Rats; Rats, Sprague-Dawley

The protective effect of magnolol, a component of Magnolia officinalis, against hypoxia-induced cell injury in cortical neuron-astrocyte mixed cultures was examined. Exposure of the cells to chemical hypoxia (0.5 mM KCN) produced morphological changes in neurons but not in astrocytes. KCN induced dose- and time-dependent increases in release of LDH and decreases in viable cell number. Treatment with magnolol (10 and 100 microM) significantly reduced the KCN-induced LDH release in a concentration-dependent manner. A higher concentration (750 microM) magnolol was toxic. Nuclear condensation was not observed in KCN-treated cells, suggesting that chemical hypoxia-induced cell death was via necrosis, rather than via apoptosis. This is the first report demonstrating that magnolol protects neurons against chemical hypoxic damage or necrotic cell death in cortical neuron-astrocyte mixed cultures.

Topics: Animals; Astrocytes; Biphenyl Compounds; Cell Death; Cell Hypoxia; Cell Survival; Cells, Cultured; Central Nervous System Depressants; Fluorescent Dyes; Hypoglycemia; Indoles; L-Lactate Dehydrogenase; Lignans; Neurons; Neurotoxins; Potassium Cyanide; Rats; Rats, Sprague-Dawley