AIM: To study the protective effects of crocetin on the doxorubicin-induced damage in rats with myocardial mitochondria. METHODS: Rats were given intraperitoneal injection of doxorubicin to induce cardiotoxicity. After continuous oral administration of crocetin, the rats were sacrificed, and myocardial mitochondria were isolated. The mitochondrial membrane potential (MMP), O~-_2. production, the activity of respiratory chain complex IV and glutathione peroxidase (GSH-PX), and DNA fragmentation were determined. The expression level of COII gene was determined through RT-PCR. RESULTS: Crocetin increased the activity of respiratory chain complex IV and GSH-PX, MMP and the expression level of COII and decreased DNA fragmentation and superoxide anion radical O~-_2. production in rats with myocardial mitochondria. CONCLUSION: Crocetin may decrease the damage in rat myocardial mitochondria induced by doxorubicin.

Object To study the protective effect of crocetin on myocardial ischemia induced by isoproterenol (ISO). Methods Myocardial ischemia was induced by subcutaneous injection of ISO (30 mg/kg for two days, once a day). The experimental animals were randomly divided into the normal group, ISO group, positive control group and three crocetin groups (25, 50, 100 mg/kg). Cardiac indexes were examined. The level of LDH, CK, MDA in serum were measured. The content of MDA, GSH-Px and the ATPase activity heart and mitochondria were assayed by colorimetric analysis. The histopathological change of myocardia was investigated by HE staining. Results Compared with the model group, crocetin can significantly reduce the cardiac indexes, obviously decrease the level of MDA, LDH and CK in the serum. Crocetin can significantly increase the activities of Na +, K +-ATPase; Ca 2+ , Mg 2+ -APTase; GSH-Px. The histopathological changes confirmed the protective effects of crocetin on the myocardial injury. Conclusion Crocetin could alleviate the acute myocardial ischemia induced by ISO in rats.

Object To study the influence of crocetin on the activity of ATPase and the content of hydroxyproline in the myocardial hypertrophy rats induced by overload pressure. Methods Abdominal aortic ligation was used to establish the myocardial hypertrophy model in rats. The rats were divided into two groups: 1) The early term group which included five groups: sham-operation group, model group, Captopril groups, crocetin 100, 50 mg/kg groups. 2) The long term group which also included five groups as the same as the early term groups. Heart indexes were examined. The ATPase activity of heart and the content of hydroxyproline in heart were assayed by colorimetric analysis. Results Compared with the model group, crocetin can significantly reduce the cardiac indexes, increase the activities of Na +, K +-ATPase; Ca 2+ , Mg 2+ -ATPase and markedly decrease the content of hydroxyproline in heart. Conclusion Crocetin could prevent the remodeling of cardiac hypertrophy induced by overload pressure. The ATPase may play an important role in myocardial hypertrophy induced by overload pressure.

Object To study the cardio-protective effect of crocetin on primary culture cardiac myocyte injured by hydroxyl free radicals. Methods After adding crocetin, primary culture cardiac myocyte was injured by 0.5 mmol/L hydroxyl free radicals which were generated by Fenton systems. The activity of lactic dehydrogenase (LDH) and mitochondrion succinic dehydrogenase (MSD) was observed. Mitochondrion membrane potential (MMP) was detected by Rh123. The ratio of cardiac myocyte apoptosis was investigated by flow cytometry and DNA ladder electrophoresis. Results Compared with the model group, crocetin significantly decreased the activity of LDH in culture supernatant and the ratio of cardiac myocyte apoptosis, markedly increased the activity of MSD and MMP. Conclusion Crocetin has the protective effect on the apoptosis of cardiac myocyte injured by hydroxyl free radical.

Objective To study the protection of crocetin on myocardial ischemia-reperfusion injury and the possible mechanism involved. Methods Infarction model: Coronary occlusion was maintained for 45 min and reperfused for 180 min to produce infarction model. Creatine kinase (CK) and lactate dehydrogenase (LDH) activity in serum of infarction groups were analyzed at baseline (before ischemia), 5, 60, and 180 min after reperfusion. Stunned model: Stunned model was achieved by ligating the left anterior descending branch of coranary artery for 15 min. Na+, K+-ATPase, and Ca2+, Mg2+-ATPase activity, total adenosine content (TAC), and energy charge (EC) in ischemic and nonischaemic myocardial tissue and malondialdehyde (MDA) in serum of stunned groups were analyzed at the end of 180 min of reperfusion. Haemodynamic parameters including heart rate, left ventricular end-systolic and end-diastolic pressure, ejection fraction, maximum and minimum dp/dt, maximum and minimum dV/dt, and stroke work, were monitored at baseline, 5, 30, 90, and 180 min after reperfusion. Results Crocetin could attenuate the infarction ratio, relieve stunning in a dose-dependent manner, and decrease the CK and LDH activities in serum. Crocetin (50 mg/kg) could improve the heart function, ameliorate myocardial stunning degree, and increase the level of ATP and EC in myocardial tissue. Conclusion Crocetin could protect myocardium from ischemia and following reperfusion, then prevent the myocardial infarction and relieve myocardial stunning. The underlying mechanism may be partly attributed to the improvement of energy restoration and free radical scavenging effect.

Aim To study the effects of luteolin on the expression of TGF-?1 mRNA in rats with pulmonary fibrosis, and elaborate the molecular mechanism of luteolin in pulmonary fibrosis therapy. Methods The model of pulmonary fibrosis was established through instilling bleomycin intratracheally. After luteolin treatment, the pulmonary index and the content of hydroxyproline (HYP) were observed. The levels of TGF-?1 mRNA in pulmonary tissues were determined with RT-PCR. Results The pulmonary index and the content of HYP decreased markedly in pulmonary fibrosis rats treated with luteolin. Furthermore, luteolin inhibited evidently the expression of TGF-?1 mRNA in lung tissues with pulmonary fibrosis. Conclusion The molecular mechanism of luteolin in pulmonary fibrosis therapy was associated with inhibition of the expression of TGF-?1 mRNA.

AIM: To study the effect of crocetin on the formation of advanced glycation end products(AGEs) and receptor for AGEs(RAGE) protein expression in diabetic rats induced by streptozotocin(STZ).METHODS: Rats were injected STZ in tail vessel with a dose of 45(mg?kg~(-1)).3 d later,the rats whose blood glucose were over(11.1)(mmol?L~(-1)) were regarded as diabetic rats,and were divided randomly into two groups: diabetic mellitus(DM) group,crocetin(50(mg?kg~(-1)),po) group.At the same time,8 normal rats were regarded as control group.After 21 d treatment,The levels of fasting blood glucose(FBG),serum fructosamine(FMN) and glycosylated hemoglobin(GHb) were measured.The contents of AGEs in aorta and mesenteric vessel were detected by fluorospectrophotometry.HE staining for mesenteric aorta was performed,and RAGE protein expression was studies with immunohistochemical method.RESULTS: Compared with DM group,crocetin did not decrease the level of FBG.However,it could decrease the levels of FMN and GHb in blood and AGEs in aorta and mesenteric vessel(P