Effects of magnolol (5,5'-diallyl-2,2'-dihydroxybiphenyl) on diabetic nephropathy in type 2 diabetic Goto-Kakizaki rats.
ABSTRACT We investigated the effect of magnolol (5,5'-diallyl-2,2'-dihydroxybiphenyl), a marker compound isolated from the cortex of Magnolia officinalis, in non-obese type 2 diabetic Goto-Kakizaki (GK) rats. The rats were treated orally with magnolol (100 mg/kg body weight) once a day for 13 weeks. In magnolol-treated GK rats, fasting blood glucose and plasma insulin were significantly decreased, and the pancreatic islets also showed strong insulin antigen positivity. Urinary protein and creatinine clearance (Ccr) were significantly decreased. Pathological examination revealed the prevention of the glomeruli enlargement in magnolol-treated GK rats. The overproduction of renal sorbitol, advanced glycation endproducts (AGEs), type IV collagen, and TGF-beta1 mRNA were significantly reduced in magnolol-treated GK rats. Thus based on our findings, the use of magnolol could result in good blood glucose control and prevent or retard development of diabetic complications such as diabetic nephropathy.
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ABSTRACT: Diabetic nephropathy (DN) has become the leading cause of end stage failure, but no renoprotective treatment has been very available for use in DN. Astragalus saponin I (AS I), a component extracted from Astragalus membranaceus BUNGE, was studied in experimental DN induced by administration of streptozotocin in male rats. The early DN rats were treated with 3 doses of AS I for 8 weeks to analyze its efficacy with different parameters. By comparison with vehicle-treated DN rats, the renal hypertrophy, the oxidative stress intensity, and the blood glucose level of DN rats were ameliorated by AS I. Also, the microalbuminuria level, advanced glycated end-products either in serum or in kidney cortex, and the aldose reductase activity were significantly reduced. Furthermore, the expression of transforming growth factor beta1 mRNA in kidney cortex by RT-PCR analysis was markedly declined. Both the relative grade of mesangium hyperplasia by microscopical observation and the thickness of glomerular base membrane by electron microscope measurement were decreased significantly. Therefore, the results suggest that AS I has therapeutic effects on several pharmacological targets in the progress of DN and is a potential drug for prevention of early stage DN.Journal of Pharmacological Sciences 07/2004; 95(2):256-66. · 2.15 Impact Factor
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ABSTRACT: 1. Free radicals mediate cerebral ischaemic injury associated with heatstroke. Magnolol, an active component of Magnolia officinalis, is 1000-fold more potent than alpha-tocopherol in inhibiting lipid peroxidation in rat mitochondria. The aim of the present study was to ascertain whether magnolol attenuated cerebral ischaemic injury and free radical formation associated with heatstroke. 2. Urethane-anaesthetized rats were exposed to heat stress (ambient temperature 42 degrees C) to induce heatstroke. Controlled rats were exposed to 24 degrees C. Mean arterial pressure, cerebral perfusion pressure and cerebral blood flow after the onset of heatstroke were all significantly lower than in control rats. However, colonic temperature, intracranial pressure, heart rate, cerebral free radicals, lipid peroxidation and the neuronal damage score were greater after the onset of heatstroke. 3. Magnolol (20 or 40 mg/kg, i.v.) significantly attenuated the heatstroke-induced hyperthermia, arterial hypotension, intracranial hypertension, cerebral ischaemia and neuronal damage and increased free radical formation and lipid peroxidation in the brain. The extracellular concentrations of ischaemic (e.g. glutamate and lactate/pyruvate ratio) and damage (e.g. glycerol) markers in the corpus striatum were increased after the onset of heatstroke. Magnolol significantly attenuated the increase in striatal ischaemia and damage markers associated with heatstroke. 4. Thus, it appears that magnolol has impressive effects against heatstroke reactions.Clinical and Experimental Pharmacology and Physiology 01/2003; 30(5-6):387-92. · 2.16 Impact Factor
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ABSTRACT: In type 2 diabetes, chronic hyperglycemia has been suggested to be detrimental to beta-cell function, causing reduced glucose-stimulated insulin secretion and disproportionately elevated proinsulin. In the present study, we investigated the effect on several beta-cell functions of prolonged in vitro exposure of human pancreatic islet cultures to high glucose concentrations. Islets exposed to high glucose levels (33 mmol/l) for 4 and 9 days showed dramatic decreases in glucose-induced insulin release and in islet insulin content, with increased proportion of proinsulin-like peptides relative to insulin. The depletion in insulin stores correlated with the reduction in insulin mRNA levels and human insulin promoter transcriptional activity. We also demonstrated that high glucose dramatically lowered the binding activity of pancreatic duodenal homeobox 1 (the glucose-sensitive transcription factor), whereas the transcription factor rat insulin promoter element 3b1 activator was less influenced and insulin enhancer factor 1 remained unaffected. Most of these beta-cell impairments were partially reversible when islets first incubated for 6 days in high glucose were transferred to normal glucose (5.5 mmol/l) concentrations for 3 days. We conclude that cultured human islets are sensitive to the deleterious effect of high glucose concentrations at multiple functional levels, and that such mechanisms may play an important role in the decreased insulin production and secretion of type 2 diabetic patients.Diabetes 07/1999; 48(6):1230-6. · 7.90 Impact Factor