lignans and Ischemia

Magnolol is a component of the bark of Magnolia officinalis, which is a traditional herbal remedy used in China. In this study, we investigated whether magnolol can reduce myocardial injury induced by renal ischemia and reperfusion (I/R).. Renal I/R was elicited by a 60-minute occlusion of the bilateral renal arteries and a 24-hour reperfusion in Sprague-Dawley rats. Magnolol was administered intravenously 10 minutes before renal I/R to evaluate its effects on myocardial injury induced by renal I/R.. Renal I/R significantly increased the serum levels of creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and cardiac troponin I and caused myocardial damage. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive nuclei and caspase-3 activation was significantly increased in the myocardium, indicating increase of apoptosis. Echocardiography revealed left ventricular dysfunction, as evidenced by reduction of left ventricular ejection fraction and left ventricular fractional shortening. Furthermore, serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were significantly elevated, while the IL-10 level was suppressed. However, intravenously, pretreatment with magnolol at doses of 0.003 and 0.006 mg/kg 10 minutes before renal I/R significantly prevented the increases of CPK, LDH, and cardiac troponin I levels, as well as the histological damage and the apoptosis in the myocardium. Echocardiography showed significant improvement of left ventricular function. Furthermore, the increases in TNF-α, IL-1β, and IL-6 and the decrease in IL-10 were significantly limited, while Bcl-2 was increased and Bax was decreased in the myocardium. Phosphorylation of Akt and extracellular signal-regulated kinases 1 and 2 was increased, while phosphorylation of p38 and c-Jun N-terminal kinase was reduced.. Magnolol reduces myocardial injury induced by renal I/R. The underlying mechanisms for this effect might be related to modulation of the production of pro- and anti-inflammatory cytokines and the limiting of apoptosis.

Topics: Animals; Apoptosis; Biphenyl Compounds; Interleukin-10; Interleukin-6; Ischemia; Lignans; Myocardial Reperfusion Injury; Myocardium; Rats; Rats, Sprague-Dawley; Reperfusion; Reperfusion Injury; Stroke Volume; Troponin I; Tumor Necrosis Factor-alpha; Ventricular Function, Left

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-1β (IL-1β), 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-1β, 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.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Biphenyl Compounds; Blood Urea Nitrogen; Creatinine; Dose-Response Relationship, Drug; Infusions, Intravenous; Interleukin-10; Interleukin-1beta; Interleukin-6; Ischemia; JNK Mitogen-Activated Protein Kinases; Kidney; Lignans; Male; Mitogen-Activated Protein Kinase 3; Phosphorylation; Phytotherapy; Proto-Oncogene Proteins c-bcl-2; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; Tumor Necrosis Factor-alpha

In the present study, the potential antioxidant and anti-inflammatory effects of Acanthopanax divaricatus vat. albeofructus (AE) and acanthoside-D (AD) isolated from AE against hepatic ischemia-reperfusion (I/R) injury were investigated in a rat model. Male Sprague-Dawley rats (200-220 g) were randomized into seven groups: normal controls; sham-operated controls; I/R injury model; I/R injury model with AE pretreatment at 150, 300, and 600 mg/kg body weight; and I/R injury model with AD pretreatment at 600 μg/kg body weight (equivalent to high dose of AE). The AE and AD pretreatments were administered orally for 2 weeks prior to I/R injury surgery. All rats recovered for 1 week with AE and AD treatment after surgery. Compared to the normal control groups, the I/R injury model group without supplemental treatment showed a significantly lower level of serum superoxide dismutase (SOD) and significantly higher levels of tumor necrosis factor-alpha (TNF-α, interleukin (IL)-6, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), as well as lactate dehydrogenase (LDH) activity. The I/R-induced decrease in SOD and increases in TNF-α and IL-6 were resolved, at least partially, by AE and AD treatments, as evidenced by significantly higher antioxidant activities and significantly lower inflammatory cytokine levels in the treatment groups as compared to the I/R injury model group. The AE and AD treatment groups also showed significantly higher levels of serum IL-10 than I/R injury model group. Histological examination revealed that the AE and AD treated groups had less extensive liver necrosis than I/R injury model group. Concomitantly, AE lowered the I/R-induced increases in AST, ALT, ALP levels and LDH activity. In conclusion, AE and AD are capable of alleviating I/R-induced hepatic injury by inhibiting inflammatory cell infiltration, thereby mitigating the release of inflammatory cytokines and balancing the oxidant-antioxidant status mediated by p38 MAPK and JNK/SAPK signaling.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Eleutherococcus; Furans; Glucosides; Ischemia; L-Lactate Dehydrogenase; Lignans; Liver; Male; MAP Kinase Kinase 4; p38 Mitogen-Activated Protein Kinases; Plant Extracts; Rats; Rats, Sprague-Dawley; Reperfusion Injury

We used cinnamophilin, a novel dual inhibitor of thromboxane synthase and thromboxane A2 (TXA2) receptor, and superoxide dismutase (SOD) with catalase to examine their protective effect against reperfusion injury in rat skeletal muscle. In 5 groups of 6 wistar rats three hours of ischaemia were induced in one hind limb by application of a tourniquet to the proximal thigh; the contralateral limb served as an internal, nonischaemic control. The first group did not receive any drug nor was it reperfused. In the other four groups, normal saline (reperfusion control), dimethylsulphoxide (DMSO), cinnamophilin, or SOD with catalase was given before removal of the tourniquet and one hour of reperfusion followed. Skeletal muscle injury was measured by a quantitative spectrophotometric assay of triphenyltetrazolium chloride (TTC) reduction and by muscle weight gain. One hour of reperfusion significantly (p<0.05) lowered TTC reduction in ischaemic limbs in the reperfusion control group in comparison with the rats in 3h ischaemia alone. Among the four reperfusion groups, only the cinnamophilin group had significantly lower decrease of TTC reduction and significantly lower muscle weight gain. These results demonstrate the protective effect of cinnamophilin against reperfusion injury of the ischaemic skeletal muscle in rats.

Topics: Animals; Catalase; Female; Guaiacol; Hindlimb; Ischemia; Lignans; Muscle, Skeletal; Random Allocation; Rats; Rats, Wistar; Receptors, Thromboxane; Reperfusion Injury; Superoxide Dismutase; Thromboxane-A Synthase; Tissue Survival