Growth hormone releasing hormone agonist enhances cell survival and anti-apoptosis of bone marrow derived mesenchymal stem cells via activating STAT3 signaling pathway to promote angiogenesis of hindlimb ischemia

Objectives: Obesity is associated with cardiac inflammation, oxidative stress, apoptotic cell death, resulting in cardiac hypertrophy cardiac dysfunction. Magnolia as a herbal material obtained from Magnolia officinalis has been found to play an important role in anti-inflammation, anti-oxidative stress, and anti-apoptosis. In our previous study, we found that the extract of Magnolia (BL153) attenuated cardiac lipid accumulation, inflammation, oxidative stress, apoptotic cell death and cardiac hypertrophy in high-fat-diet (HFD) -induced obese mice. However, the extract contains some toxic ingredients that may limit the use of the Magnolia extract. In the present study, we investigated the preventive effect on of HFD-induced obesityassociated insulin resistance, lipid accumulation and inflammation in the heart by BL153 bioactive constituent, 4-O-methylhonokiol (MH), using BL153 as a reference. Methods: C57BL/6J mice, 8 weeks of age, were treated with vehicle, BL153 (5mg/kg), MH (0.5mg/kg) or MH (1.0mg/kg) by gavage daily, during 24weeks of normal (10 kcal% fat) fat diet or HFD (60 kcal% fat) feeding. At the endpoint blood glucose, glucose tolerance, plasma triglyceride and cardiac function were assessed. Cardiac lipid accumulation was measured by Oil Red O staining. Cardiac fibrosis, inflammation, and oxidative damage were assessed by Western blot. Results: 0.5mg/kg MH treatment significantly ameliorated insulin resistance with slightly decreased of body weight gain induced by HFD feeding. MH significantly attenuated HFD-induced hypertriglyceridemia and hypercholesteremia. MH treatments ameliorated cardiac hypertrophy. MH treatments also attenuated cardiac lipid accumulation through inhibiting the expression of fatty acid translocase / D36 and evaluating the expression of peroxisome proliferator-activated receptor g coactivator 1 a (PGC1a) and suppressed oxidative stress markers (malondialdehyde) by increasing nuclear-factor-E2-related-factor-2 (Nrf2) and inflammation markers (tumor necrosis factor-a and plasminogen activator inhibitor-1). Conclusions: Our study indicated that MH ameliorated HFD associated cardiac hypertrophy cardiac lipid accumulation, inflammation, oxidative stress via downregulation of CD36 and upregulation of PGC1a and Nrf2.