Magnolol Reduces Renal Ischemia and Reperfusion Injury via Inhibition of Apoptosis.

Magnolol, a constituent of the bark of Magnolia officinalis, has been reported to decrease myocardial stunning and infarct size. In this study, we investigated whether magnolol can reduce renal ischemia and reperfusion (I/R) injury. Renal I/R, induced by a 60-min occlusion of bilateral renal arteries and a 24-h reperfusion, significantly increased blood urea nitrogen (BUN) and creatinine levels, and caused histological damage to the kidneys of rats. Apoptosis, as evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and caspase-3 activation, was significantly increased in the kidneys. Furthermore, serum levels of tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were significantly elevated, while the interleukin-10 (IL-10) level was suppressed. However, intravenous pretreatment with magnolol at doses of 0.003[Formula: see text]mg/kg and 0.006[Formula: see text]mg/kg 10[Formula: see text]min before renal I/R significantly limited the increases of BUN, creatinine, the histological damage, and apoptosis in the kidneys. The increases in TNF-[Formula: see text], IL-1ß, and IL-6, and the decrease in IL-10 were also significantly inhibited. Additionally, magnolol increased Bcl-2 and decreased Bax in the kidneys. Phosphorylation of the prosurvival kinases, including Akt and extracellular signal-regulated kinases 1 and 2 (ERK1/2), was elevated, while phosphorylation of the pro-apoptotic mitogen-activated protein kinases, including p38 and c-Jun N-terminal kinase (JNK), was suppressed. In conclusion, magnolol reduces renal I/R injury. The underlying mechanisms for this effect might be related to the prevention of apoptosis, possibly via the inhibition of both extrinsic and intrinsic apoptotic pathways, including the reduction of TNF-[Formula: see text] production and the modulation of pro- and anti-apoptotic signaling elements.

A high-cholesterol, n-3 polyunsaturated fatty acid diet causes different responses in rats and hamsters.

This study was designed to investigate the response to a high-cholesterol, n-3 polyunsaturated fatty acid (PUFA) or n-6 PUFA diet in rats and hamsters. Animals were fed n-3 or n-6 PUFA with a cholesterol-free diet, or with a diet enriched with cholesterol (0.5%, w/w) for 2 weeks. In rats and hamsters fed a cholesterol-free diet, plasma cholesterol, triglycerides and very-low-density lipoprotein (VLDL)-triglyceride levels in n-3 PUFA group were significantly lower than those in n-6 PUFA group. In contrast, when diets were supplemented with 0.5% cholesterol, the plasma cholesterol- and triglyceride-lowering effect of dietary n-3 PUFA disappeared. In hamsters fed with the atherogenic diet (0.5% dietary cholesterol) for 2 weeks, n-3 PUFA induced hypercholesterolemia more than n-6 PUFA, the increase being in the VLDL and low-density lipoprotein (LDL) fractions. Our data thus indicate that elevation of VLDL- and LDL-cholesterol in hamsters by n-3 PUFA, compared with n-6 PUFA, is dependent on 0.5% dietary cholesterol supplementation. In rats, on the other hand, dietary n-3 PUFA did not induce hypercholesterolemia more than n-6 PUFA when 0.5% cholesterol was supplemented. Although the effects of n-3 PUFA on plasma cholesterol, triglycerides and VLDL-triglycerides were similar in hamsters and rats, the interactive effects of n-3 PUFA and cholesterol on plasma and lipoprotein cholesterol levels differed in the two species. It was also found that plasma triglycerides, cholesterol and lipoprotein cholesterol levels in hamsters are higher than in rats in the presence and absence of dietary cholesterol. In addition, cholesterol feeding induces hypertriglyceridemia and hypercholesterolemia only in hamsters. Moreover, liver triglyceride concentrations increased in rats fed a cholesterol-rich diet and hepatic triglyceride levels of the n-3 PUFA-fed rats were significantly lower than those in the n-6 PUFA-fed rats in the presence and absence of dietary cholesterol. However, triglycerides did not accumulate in the liver in hamsters fed a cholesterol-rich diet and hepatic triglyceride levels of the n-3 PUFA-fed hamsters were not significantly different from those in the n-6 PUFA-fed hamsters in the presence and absence of dietary cholesterol. Therefore, these studies confirm marked species differences in response to the interactive effects of dietary n-3 PUFA and cholesterol.