Experimental study on the antifatigue effect of icariin.

Fatigue is a serious disturbance to human health, especially in people who have a severe disease such as cancer, or have been infected with COVID-19. Our research objective is to evaluate the anti-fatigue effect and mechanism of icariin through a mouse experimental model. Mice were treated with icariin for 30 days and anti-fatigue effects were evaluated by the weight-bearing swimming test, serum urea nitrogen test, lactic acid accumulation and clearance test in blood and the amount of liver glycogen. The protein expression levels of adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1-α) in the skeletal muscle of mice in each group were measured by western blotting. Results showed that icariin prolonged the weight-bearing swimming time of animals, reduced the serum urea nitrogen level after exercise, decreased the blood lactic acid concentration after exercise and increased the liver glycogen content observably. Compared to that in the control group, icariin upregulated AMPK and PGC1-α expression in skeletal muscle. Icariin can improve fatigue resistance in mice and its mechanism may be through improving the AMPK/PGC-1α pathway in skeletal muscle to enhance energy synthesis, decreasing the accumulation of metabolites and slowing glycogen consumption and decomposition.

Na (+) /Ca (2+) Exchanger 3 is Downregulated in the Hippocampus and Cerebrocortex of Rats with Hyperthermia-induced Convulsion.

BACKGROUND: Na + /Ca 2+ exchanger (NCX) plays a crucial role in pentylenetetrazol-induced convulsion. However, it is unclear whether NCX is critically involved in hyperthermia-induced convulsion. In this study, we examined the potential changes in NCX3 in the hippocampus and cerebrocortex of rats with hyperthermia-induced convulsion. METHODS: Twenty-one Sprague Dawley rats were randomly assigned to control group, convulsion-prone group and convulsion-resistant group (n = 7 in each group). Whole-cell patch-clamp method was used to record NCX currents. Both the Western blotting analysis and immunofluorescence labeling techniques were used to examine the expression of NCX3. RESULTS: NCX currents were decreased in rats after febrile convulsion. Compared to the control group, NCX3 expression was decreased by about 40% and 50% in the hippocampus and cerebrocortex of convulsion-prone rats, respectively. Furthermore, the extent of reduction in NCX3 expression seemed to correlate with the number of seizures. CONCLUSIONS: There is a significant reduction in NCX3 expression in rats with febrile convulsions. Our findings also indicate a potential link between NCX3 expression, febrile convulsion in early childhood, and adult onset of epilepsy.

Anti-fibrotic effects of neferine on carbon tetrachloride-induced hepatic fibrosis in mice.

The effects of neferine, a bisbenzylisoquinline alkaloid extracted from the seed embryo of the Chinese traditional medicine Nelumbo nucifera Gaertn, on carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice were evaluated. Adult male Kunming mice were administered with CCl4 1 ml/kg via intraperitoneal injection twice a week for 8 weeks. At the beginning of the 9th week, mice were treated with normal saline, colchicine (0.1 mg/kg), and neferine (5, 10, 20 mg/kg) via intraperitoneal injection once a day for 2 weeks. The liver index and histological examination, plasma ALT/AST levels, hydroxyproline and TGF-ß1 content of liver tissue were examined. In the model group, the liver index, the hydroxyproline content of liver tissue and plasma ALT/AST levels were increased, and a high expression of TGF-ß1 was observed. The abnormal changes could be improved by neferine in a dose-dependent manner. Our data showed that neferine had an antifibrosis effect on CCl4-induced hepatic fibrosis in mice, possibly partly due to the decreased expression of TGF-ß1 in the liver.

The relationship between frequency dependence of action potential duration and the expression of TRPC3 in rabbit ventricular myocardium.

BACKGROUND/AIMS: Cardiac action potential duration (APD) is regulated by heart rate, leading to the trans-membrane movement of inorganic ions. Whether the alteration of heart rate can affect the expression of transient receptor potential canonical channels (TRPCs), further studies should be made. We investigated the changes of APD at different stimulus frequencies and their influences on the expression of TRPCs in rabbit ventricular myocardium. METHODS: Monophasic action potential (MAP) was recorded by contact electrode technique in different programmed stimulus frequencies on rabbit ventricular epicardium in vivo, and the expression of TRPCs was detected using RT-PCR and Western blot. RESULTS: At the frequency range of 4.5-7.5 Hz, APD gradually shortened with the increase of stimulus frequency, showing the property of significant frequency dependence in rabbit ventricular myocardium in vivo. Compared with 4.5 Hz group, TRPC3 mRNA and protein expression increased in 6 Hz and 7.5 Hz groups by way of frequency dependence. Both amiodarone (AM) and neferine (Nef) could prolongate APD and showed characters of frequency independence at the designed frequency. In contrast with 4.5 Hz control group, it was Nef treatment group rather than AM treatment group that could obviously increase the expression of TRPC3 mRNA and protein. CONCLUSIONS: At the frequency range of 4.5-7.5 Hz, frequency-dependent shortening of APD was associated with the expression of TRPC3. AM and Nef exhibited frequency-independent lengthening of the APD. Nef may prolong APD via the increasement of TRPC3.

Upregulation of TRPC1 contributes to contractile function in isoproterenol-induced hypertrophic myocardium of rat.

AIMS: The transient receptor potential canonical channel 1 (TRPC1) is a crucial component of the stretch-activated ion channels (SACs). The objective of this research was to demonstrate the contribution of TRPC1 in maintaining cardiac contractile function in the hypertrophic myocardium. METHODS: Hypertrophic rat hearts were induced by injecting isoproterenol intraperitoneally, and the expressions of TRPC1/3/6 and Na(+)/Ca(2+) exchanger 1 (NCX1) proteins were analyzed by Western blot. The intracellular calcium images, the action potential of myocardium, the length-dependent contractile force of ventricle muscle and the cardiac output of isolated heart were investigated. RESULTS: The expression of TRPC1 was increased in the hypertrophic myocardium. After being stretched, the ascendant amplitude of the increase in the intracellular calcium ion concentration ([Ca(2+)]i) in the hypertrophic myocardium was higher than that in the normal myocardium. The increase of the APD50 and the amplitude of the membrane potential depolarization were more significant in the hypertrophic myocardium after the activation of SACs. When the heart preparations were perfused with Tyrode's solution, there was no difference in the cardiac systolic function between the cardiac hypertrophy group and the control group. Gadolinium, a SACs blocker, reduced the length-dependent contractile force and suppressed the ascending limb of the Frank-Starling curves in the hypertrophic heart. CONCLUSIONS: The upregulation of TRPC1 contributes to the contractile function in the hypertrophic myocardium by increasing [Ca(2+)]i through the SACs.