Effects of magnolol (5,5′-diallyl-2,2′-dihydroxybiphenyl) on diabetic nephropathy in type 2 diabetic Goto-Kakizaki rats

Department of Herbal Pharmaceutical Development, Korea Institute of Oriental Medicine, 461-24 Jeonmin-dong, Yuseong-gu, Daejeon 305-811, Republic of Korea.
Life Sciences (Impact Factor: 2.7). 02/2007; 80(5):468-75. DOI: 10.1016/j.lfs.2006.09.037
Source: PubMed


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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    • "Several studies have focused on the pharmacological features of MG or HK such as anti-inflammatory [13], antioxidative stress [18], and cardiovascular protective attributes [19]. It is reported that MG reduced fasting blood glucose and plasma insulin levels in type 2 diabetic rats [20] and increased the glucose uptake in 3T3-L1 adipocytes [21] [22]. In addition, both HK and MG stimulated glucose uptake in insulinsensitive and insulin-resistant murine and human adipocytes via an insulin signaling pathway [21] and protected tissues and cells against a variety of oxidative stressors [23]. "
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    ABSTRACT: Obesity is caused by a combination of both genetic and environmental risks. Disruption in energy balance is one of these risk factors. In the present study, the preventive effect on high-fat diet- (HFD-) induced obesity and insulin resistance in mice by Magnolia bioactive constituent 4-O-methylhonokiol (MH) was compared with Magnolia officinalis extract BL153. C57BL/6J mice were fed by normal diet or by HFD with gavage-administered vehicle, BL153, low-dose MH, and high-dose MH simultaneously for 24 weeks, respectively. Either MH or BL153 slightly inhibited body-weight gain of mice by HFD feeding although the food intake had no obvious difference. Body fat mass and the epididymal white adipose tissue weight were also mildly decreased by MH or BL153. Moreover, MH significantly lowered HFD-induced plasma triglyceride, cholesterol levels and activity of alanine transaminase (ALT), liver weight and hepatic triglyceride level, and ameliorated hepatic steatosis. BL153 only significantly reduced ALT and liver triglyceride level. Concurrently, low-dose MH improved HFD-induced hyperinsulinemia and insulin resistance. Furthermore, the infiltration of mast cells in adipose tissue was decreased in MH or in BL153 treatment. These results suggested that Magnolia bioactive constituent MH might exhibit potential benefits for HFD-induced obesity by improvement of lipid metabolism and insulin resistance.
    Oxidative medicine and cellular longevity 05/2014; 2014:965954. DOI:10.1155/2014/965954 · 3.36 Impact Factor
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    • "Recently, the studies demonstrated that constituents of Magnolia such as HON and MAG have anti-inflammatory [9] [10] [11], -oxidative [12] [13], and -apoptotic effects [13] [14]. Moreover, another study showed that MAG reduced fasting blood glucose and plasma insulin levels in type 2 diabetic model without altering body weight [15] and increased glucose uptake in 3T3-L1 adipocytes [16]. However, the effects of Magnolia officinalis on heart of obesity induced by HFD still remain unclear. "
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    ABSTRACT: Magnolia as an herbal material obtained from Magnolia officinalis has been found to play an important role in anti-inflammation, antioxidative stress, and antiapoptosis. This study was designed to investigate the effect of Magnolia extract (BL153) on obesity-associated lipid accumulation, inflammation, oxidative stress, and apoptosis in the heart. C57BL/6 mice were fed a low- (10 kcal% fat) or high-fat (60 kcal% fat) diet for 24 weeks to induce obesity. These mice fed with high-fat diet (HFD) were given a gavage of vehicle, 2.5, 5, or 10 mg/kg body weight BL153 daily. The three doses of BL153 treatment slightly ameliorated insulin resistance without decrease of body weight gain induced by HFD feeding. BL153 at 10 mg/kg slightly attenuated a mild cardiac hypertrophy and dysfunction induced by HFD feeding. Both 5 mg/kg and 10 mg/kg of BL153 treatment significantly inhibited cardiac lipid accumulation measured by Oil Red O staining and improved cardiac inflammation and oxidative stress by downregulating ICAM-1, TNF- α , PAI-1, 3-NT, and 4-HNE. TUNEL staining showed that BL153 treatment also ameliorated apoptosis induced by mitochondrial caspase-3 independent cell death pathway. This study demonstrates that BL153 attenuates HFD-associated cardiac damage through prevention of HFD-induced cardiac lipid accumulation, inflammation, oxidative stress, and apoptosis.
    Oxidative Medicine and Cellular Longevity 02/2014; 2014:205849. DOI:10.1155/2014/205849 · 3.36 Impact Factor
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    • "Immunohistochemistry was performed as previously described [33]. Antibodies were a mouse anti-CML (TransGenic, Kobe, Japan), a mouse anti-8-hydroxygluanine (8-OHdG) antibody (Santa Cruz Biotechnology, CA, USA) and a rabbit anti-synaptopodin (Santa Cruz Biotechnology, CA, USA). "
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    ABSTRACT: Renal lipid accumulation exhibits slowly developing chronic kidney disease and is associated with increased oxidative stress. The impact of exercise on the obese- and oxidative stress-related renal disease is not well understood. The purpose of this study was to investigate whether a high-fat diet (HFD) would accelerate d-galactose-induced aging process in rat kidney and to examine the preventive effect of regular exercise on the obese- and oxidative stress-related renal disease. Oxidative stress was induced by an administration of d-galactose (100 mg/kg intraperitoneally injected) for 9 weeks, and d-galactose-treated rats were also fed with a high-fat diet (60% kcal as fat) for 9 weeks to induce obesity. We investigated the efficacy of regular exercise in reducing renal injury by analyzing Nε-carboxymethyllysine (CML), 8-hydroxygluanine (8-OHdG) and apoptosis. When rats were fed with a HFD for 9 weeks in d-galactose-treated rats, an increased CML accumulation, oxidative DNA damage and renal podocyte loss were observed in renal glomerular cells and tubular epithelial cells. However, the regular exercise restored all these renal changes in HFD plus d-galactose-treated rats. Our data suggested that long-term HFD may accelerate the deposition of lipoxidation adducts and oxidative renal injury in d-galactose-treated rats. The regular exercise protects against obese- and oxidative stress-related renal injury by inhibiting this lipoxidation burden.
    Acta histochemica et cytochemica official journal of the Japan Society of Histochemistry and Cytochemistry 08/2013; 46(4):111-9. DOI:10.1267/ahc.13012 · 1.39 Impact Factor
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