Therapeutic effect and mechanism of breviscapine on cisplatin-induced nephrotoxicity in mice

Objective:To observe the protective effect of breviscapineon mice with cisplatin-induced nephrotoxicity.Methods:Mice were given a single injection of cisplalin(8 mg/kg,up.);then,breviscapine was given to mice at 25 mg/kg and 50 mg/kg doses,respectively,once a day for seven days.Renal tissue structure was observed after animals were sacrificed.Blood urea nitrogen(BUN),serum creatinine(Scr),lipid peroxide(MDA) and superoxide dismutase(SOD) serum levels were detected;and MDA,glutathione peroxidase,and SOD levels in the renal cortex were detected.Results:Compared with the blank control group(BCG),the kidney pathological damage of mice in the model control group(MCG) was more severe.After applying different doses of breviscapine,different degrees of renal injury improvement appeared.Compared with the BCG,the serum levels of Scr and BUN in the MCG increased to(89.92±6.78) μmoL/L and(15.32±4.53) mmoL/L.The differences were statistical significant(P<0.01).Compared with the MCG,the serum levels of Scr and BUN in the Bre low-dose groups and Bre high-dose groups decreased significantly(P<0.05).Compared with the BCG,the MDA levels in serum and in the renal cortex in the MCG significantly increased,while the SOD levels significantly decreased.Both the differences were statistically significant(P<0.01).In the Bre low-dose groups and Bre high-dose groups,MDA levels in serum and in the renal cortex significantly decreased,while SOD and glutathione peroxidase levels in the renal cortex significantly increased,compared with the MCG;and the differences were statistically significant(P<0.05).Conclusions:Breviscapine can reduce cisplatin induced renal toxicity in mice and it's possible through inhibition of renal tubule cell lipid peroxidation and reduces the nephrotoxicity of cisplatin.

Breviscapine alleviates hepatic injury and inhibits PKC-mRNA and its protein expression in brain-dead BA-Ma mini pigs

BACKGROUND: Brain-dead donors are the main sources for organ transplantation, but many studies show that brain-death affects the organ's function after transplantation. This study was undertaken to investigate liver injury after brain-death in BA-Ma mini pigs and the protective effects of breviscapine on hepatic function and on PKC-alpha mRNA and its protein expression. METHODS: Fifteen BA-Ma mini pigs were equally divided into 3 groups at random: brain-dead (group B), breviscapine pretreated (group P), and control (group Q. The brain-dead model was established by increasing intracranial pressure in a modified, slow and intermittent way. At 3, 6, 12, 18 and 24 hours after the initial brain-death, the levels of serum AST, ALT, TNF-alpha, IL-1 beta, and IL-6 were determined. The changes in hepatic tissues were assessed, and the expression of PKC-alpha and PKC-alpha mRNA was detected by immunohistochemistry and RTPCR, respectively. RESULTS: The levels of AST and ALT in groups B and P began to increase 12 hours after brain-death, while the values in group P were lower than those in group B (P<0.05). The levels of IL-1 beta, IL-6, and TNF-alpha in groups B and P at 3, 6, 12 and 18 hours were lower than those in group B (P<0.05). At 6, 12 and 24 hours, the expressions of PKC-a mRNA and PKC-a protein in group P were lower than those in group B (P<0.05). The degree of injury to hepatic cells in group P was milder than that in group B. CONCLUSIONS: Breviscapine inhibits the degree of PKC-alpha mRNA transcription and its protein translation, decreases the release of inflammatory factors, and thus alleviates hepatic injury during brain-death.

Breviscapine reduces neuronal injury caused by traumatic brain injury insult:partly associated with suppression of interleukin-6 expression

Breviscapine,extracted from the herb Erigeron breviscapus,is widely used for the treatment of cardiovascular diseases,cerebral infarct,and stroke,but its mechanism of action remains unclear.This study established a rat model of traumatic brain injury induced by controlled cortical impact,and injected 75 μg breviscapine via the right lateral ventricle.We found that breviscapine significantly improved neurobehavioral dysfunction at 6 and 9 days after injection.Meanwhile,interleukin-6 expression was markedly down-regulated following breviscapine treatment.Our results suggest that breviscapine is effective in promoting neurological behavior after traumatic brain injury and the underlying molecular mechanism may be associated with the suppression of interleukin-6.

Clinical Observation on Breviscapine in Treating Hypertension Patients Complicated with Micro-albuminuria of Renal Impairment

Objective: To evaluate the efficacy of Breviscapine on essential hypertension (EH) patients complicated with micro-albuminuria of renal impairment. Methods: Seventy-six EH patients were randomly assigned to the control group and the treated group, the former was given amlodipine, captopril/uropidil and the latter was given in addition Breviscapine intravenously dripped for 2 treatment courses. The indexes of serum creatinine (Cr), blood urea nitrogen (BUN), blood and urinary β 2-microglobulin (β 2-MG), and quantitative determination of 24 hrs urinary protein were evaluated before and after treatment. Results: In the control group, compared with before treatment, the quantitative determination of 24 hrs urinary protein got reduced significantly ( P <0.05), while in the treated group, both urinary β 2-MG and quantitative determination of 24 hrs urinary protein got lowered significantly ( P <0.05 and P <0.01). But after treatment, compared with the control group, urinary β 2-MG and quantitative determination of 24 hrs urinary protein in the treated group were obviously reduced ( P <0.05). Conclusion: Besides lowering blood pressure effectively, Breviscapine could improve the renal function significantly and reduce the urinary micro-albuminuria, hence showing promising effect on renal protection.

Analysis on Common Compatibility Contraindications of Breviscapine for Injection

[Objectives]To analyze the common compatibility contraindications of breviscapine for injection,and to provide references for clinical rational drug use.[Methods]The pH distribution of the combined drugs in the report on the compatibility contraindications of breviscapine for injection and was analyzed.[Results]Breviscapine for injection may become turbid or precipitated when mixed with drugs whose pH are lower;it can make the liquid discoloration in a strong alkaline solution.[Conclusions]Breviscapine for injection should not be combined with drugs whose pH are lower,especially drugs with pH lower than 4.2.Breviscapine for injection should not be used with drugs with strong alkaline.It is recommended to use Breviscapine for injection separately.

Analysis of 8611 Cases of Adverse Reaction Reports of Breviscapine for Injection

[Objectives]To analyze the occurrence rules and factors influencing adverse reactions of breviscapine for injection,explore potential drug risks,and guide the clinical rational medication.[Methods]The retrospective analysis method was used to analyze the case reports of adverse reactions of breviscapine for injection,and analyze the gender and age distribution of the cases,the patient's medication status,the adverse reactions involving organ/system damage and clinical manifestations,the occurrence time,duration,and outcome of the adverse reactions.[Results]Adverse reactions of breviscapine for injection were mainly concentrated in middle-aged and elderly patients aged 45 and above,accounting for 85.35%;in the gender distribution,females were higher than males;adverse reactions involved multiple organ/system damages.Among them,75.86%of patients had adverse reactions after the first medication,and 11.77%of reported patients had concomitant medications.[Conclusions]The adverse reactions caused by breviscapine for injection may be related to the patient's age,gender and irrational medication.

THE EFFECTS OF BREVISCAPIN ON AT－Ⅲ ACTIVITY， tPA AND PAI IN DOGS DURING ACUTE MYOCARDIAL ISCHEMIA

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EFFECTS OF BREVISCAPIN ON MYOCARDIAL REOXYGENATION DAMAGE: AN EXPERIMENTAL STUDY

By means of Langendor ff isolated-heart perfusion technique, a model of cardiac global hypoxia/reoxygenation was prepared. Breviscapin (100mg/L in perfusate) effectively reduced the myocardial hypoxic perfusion and reoxygenation damage with respect to lowering myocardial CPK release, indicating a membrane-protective effect of the drug. After 50min hypoxic perfusion. Breviscapin-treated grup showed relatively higher myocardial activity of superoxide dismutase and glutathione peroxidase comparing to the control group. After 5min reoxygenation, the level of myocardial malondialdehyde-like substance in the treated group was lower than that in the control group indicating less free radical accumulated in the myocardium of treated group.

Effect of breviscapine on fractalkine expression in chronic hypoxic rats

Fractalkine （FKN） is the only known chemokine that fulfils the dual functions of an adhesive molecule and a soluble chemoattractant.1 FKN expression was reported increase in lungs of patients with severe pulmonary arterial hypertension,2 suggesting that FKN may participate in pathogenesis of pulmonary hypertension. Breviscapine is a flavonoid extracted from Erigeron breviscapus （Vant.） Hand. Mazz. Breviscapine can prevent the development of hypoxic pulmonary hypertension^3 but the mechanism is unknown. This study evaluated the role of FKN in the pathogenesis of hypoxic pulmonary hypertension and the effect of breviscapine on FKN in hypoxic pulmonary hypertension.