Chemical Constituents from the Fruits of Amomum kravanh and Their Role in Activating Alcohol Dehydrogenase.

Alcoholism is a worldwide health problem, and diseases caused by alcoholism are killing people every year. Amomum kravanh is a traditional Chinese medicine used to relieve hangovers. However, whether its bioactive components improve alcohol metabolism is not clear. In this study, ten new (amomumols A-J, 1-10) and thirty-five known (11-45) compounds were isolated from the fruits of Amomum kravanh by an activity-guided separation. Ten novel compounds were identified as four sesquiterpenoids (1-4), three monoterpene derivatives (5-7), two neolignans (8, 9), and a novel norsesquiterpenoid (10) with a new C14 nor-bisabolane skeleton. Their structures were determined by the comprehensive analysis of high-resolution electrospray ionization mass spectrometry (HRESIMS), nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD) calculation. The effects of all isolated compounds on the activity of alcohol dehydrogenase were evaluated in vitro, and it was found that eight compounds (11, 12, 15, 18, 26, and 36-38) exhibited significant activation effects on the alcohol dehydrogenase at 50 µM.

GDH promotes isoprenaline-induced cardiac hypertrophy by activating mTOR signaling via elevation of α-ketoglutarate level.

Numerous studies reveal that metabolism dysfunction contributes to the development of pathological cardiac hypertrophy. While the abnormal lipid and glucose utilization in cardiomyocytes responding to hypertrophic stimuli have been extensively studied, the alteration and implication of glutaminolysis are rarely discussed. In the present work, we provide the first evidence that glutamate dehydrogenase (GDH), an enzyme that catalyzes conversion of glutamate into ɑ-ketoglutarate (AKG), participates in isoprenaline (ISO)-induced cardiac hypertrophy through activating mammalian target of rapamycin (mTOR) signaling. The expression and activity of GDH were enhanced in cultured cardiomyocytes and rat hearts following ISO treatment. Overexpression of GDH, but not its enzymatically inactive mutant, provoked cardiac hypertrophy. In contrast, GDH knockdown could relieve ISO-triggered hypertrophic responses. The intracellular AKG level was elevated by ISO or GDH overexpression, which led to increased phosphorylation of mTOR and downstream effector ribosomal protein S6 kinase (S6K). Exogenous supplement of AKG also resulted in mTOR activation and cardiomyocyte hypertrophy. However, incubation with rapamycin, an mTOR inhibitor, attenuated hypertrophic responses in cardiomyocytes. Furthermore, GDH silencing protected rats from ISO-induced cardiac hypertrophy. These findings give a further insight into the role of GDH in cardiac hypertrophy and suggest it as a potential target for hypertrophy-related cardiomyopathy.

[Effect of salvianolic acid A on anesthetized canine experimental myocardial infarction].

Salvianolic acid A (SAA), one of the major active water-soluble salvianolic acids of traditional Chinese medicine Salvia miltiorrhiza Bunge, has been reported to be effective on anti-myocardial ischemia, anti-oxidation and anti-thrombus. This study aimed to investigate appropriate administration route on dogs with acute myocardial ischemia(AMI). Twenty-four dogs were randomized into four groups (n=6), model, oral administration of SAA (8 mg•kg⁻¹), intravenous administration of SAA (4 mg•kg⁻¹), intravenous administration of Herbesser(0.5 mg•kg⁻¹) as positive drug group. AMI model was established by ligating left anterior descending coronary arteries(LAD) of dogs. Changes of ST segment were determined by epicardial electrocardiogram(ECG), coronary blood flow (CBF) and myocardial oxygen consumption were measured by ultrasonic Doppler flow meter, serum creatine kinase (CK) and lactate dehydrogenase (LDH) were observed by fully automatic biochemical analyser. Myocardial infarct size was assessed by nitro blue tetrazolium (NBT) staining. Both oral and intravenous administration of SAA reduced the myocardial infarct area/left ventricle area significantly [(16.73±6.52)% and (13.19±2.38)%, compared with (24.35±4.89)% in model group, P<0.01). Oral administration of SAA improved the ECG performance of Σ-ST from 30-190 min after ischemia (P<0.05-0.01), while intravenous SAA had a rapid onset (10-190 min after ischemia, P<0.05-0.01). Compared with model group, oral and intravenous SAA both decreased serum CK and LDH significantly (P<0.05-0.01), while the difference of intravenous administration is more significant. SAA protects myocardium in canine experimental myocardial infarction models. Intravenous administration of SAA alleviates myocardial infarction with greater significance than oral route.

[Studies on therapeutic effects of zhenzhu qishi wan on stroke and hypertension of SHRsp].

OBJECTIVE: To study the effect of Zhenzhu Qishi Wan on blood pressure(BP), body weight(BW), stroke and survival rate of stroke-prone spontaneously hypertension rats(SHRsp). METHOD: 8-week-old SHRsp was randomly divided into three groups: control group, Zhenzhu Qishi Wan prevention group and therapy group (n = 10). SHRsp of prevention group were treated with Zhenzhu Qishi Wan by ig 150 mg.kg-1 per day for 6 weeks, and therapy group were given the same treatment two weeks later. Behavior and stroke were observed everyday; BW were weighted every week; BP were estimated every 2 weeks. Time of the first cerebral seizure of SHRsp was recorded. RESULT: Zhenzhu Qishi Wan had obvious preventive and therapeutic effect on genetic hypertension. The BP of prevention and therapy groups were significantly lower than that of control group (P < 0.05 [symbol: see text] P < 0.01). The drug ameliorated general behavior of SHRsp, BW of prevention group increased faster than that of control group(P < 0.05 or P < 0.01), and BW of therapy group were also heavier than that of control group at the age of 14 weeks(P < 0.05). When the experiment ended, 60% SHRsp of control group showed stroke and 20% of them were dead, while only 20% SHRsp in each of Zhenzhu Qishi Wan-treated groups showed stroke and none of them died. CONCLUSION: Zhenzhu Qishi Wan had significant hypotensive effect, and some protective effect on the stroke caused by hypertension.