Xiaoyaosan decoction, a traditional chinese medicine, inhibits oxidative-stress-induced hippocampus neuron apoptosis in vitro.

Xiaoyaosan (XYS) decoction is a famous prescription for the treatment of mental disorders in China. In this experiment, we explored the way in which XYS decoction-reverse hippocampus neuron apoptosis in vitro. We used XYS decoction-containing serum to treat oxidative-stress-induced hippocampus neuron apoptosis and used immunofluorescence to determine the concentration of free calcium, mitochondrial membrane potential, and apoptotic rate of neuron. Results showed that 3-hour oxidative stress decrease mitochondrial membrane potential, increase the concentration of free calcium and apoptotic rate of neuron via triggering pathological changes of nucleus such as karyorrhexis, karyopyknosis. Low, medium, high dose of XYS-decoction-containing serum could reverse these phenomenon, and the effect of low-dose XYS-decoction-containing serum was significant in improving mitochondrial membrane potential and apoptotic rate of neuron. These findings suggest that XYS decoction may be helpful in reducing oxidative-stress-induced hippocampus neuron apoptosis.

Norcantharidin Induces HL-60 Cells Apoptosis In Vitro.

Norcantharidin (NCTD) is the demethylated form of cantharidin, which is the active substance of mylabris, and is known to have anticancer potentials. The aim of this paper was to assess the apoptosis-inducing effect of NCTD on HL-60 cells. Methods. The effects of NCTD were detected by flow cytometer on the cell toxicity, cell cycle, and apoptosis of HL-60 cells cultured in vitro. Results. After 48-hour treatment with NCTD, the growth of HL-60 cells was inhibited significantly. The summit of apoptosis appeared after 24 hours. The percentage of the cells in G(1) phase decreased and then increased in S and G(2)+ M phase, while the S and G(2)+ M phases were blocked after treatment with 5, 10, and 50 µmol/L NCTD for 24 hours. Conclusions. NCTD can induce the apoptosis of HL-60 cells and inhibit the fissiparism, and the domino effect was obviously correlated with the time and dosage.

Effects of Xiaoyaosan on Stress-Induced Anxiety-Like Behavior in Rats: Involvement of CRF1 Receptor.

Background. Compared with antidepressant activity of Xiaoyaosan, the role of Xiaoyaosan in anxiety has been poorly studied. Objective. To observe the effects of Xiaoyaosan on anxiety-like behavior induced by chronic immobilization stress (CIS) and further explore whether these effects were related to CRF1R signaling. Methods. Adult male SD rats were randomly assigned to five groups (n = 12): the nonstressed control group, vehicle-treated (saline, p.o.) group, Xiaoyaosan-treated (3.854 g/kg, p.o.) group, vehicle-treated (surgery) group, and antalarmin-treated (surgery) group. Artificial cerebrospinal fluid (0.5 µL/side) or CRF1R antagonist antalarmin (125 ng/0.5 µL, 0.5 µL/side) was bilaterally administered into the basolateral amygdala in the surgery groups. Except for the nonstressed control group, the other four groups were exposed to CIS (14 days, 3 h/day) 30 minutes after treatment. On days 15 and 16, all animals were subjected to the elevated plus-maze (EPM) and novelty suppressed feeding (NSF) test. We then examined the expression of CRF1R, pCREB, and BDNF in the amygdala. Results. Chronic pretreatment with Xiaoyaosan or antalarmin significantly reversed elevated anxiety-like behavior and the upregulated level of CRF1R and BDNF in the amygdala of stressed rats. pCREB did not differ significantly among the groups. Conclusions. These results suggest that Xiaoyaosan exerts anxiolytic-like effects in behavioral tests and the effects may be related to CRF1R signaling in the amygdala.

The Protective Effects of Salidroside from Exhaustive Exercise-Induced Heart Injury by Enhancing the PGC-1 α -NRF1/NRF2 Pathway and Mitochondrial Respiratory Function in Rats.

OBJECTIVE: To test the hypothesis that salidroside (SAL) can protect heart from exhaustive exercise-induced injury by enhancing mitochondrial respiratory function and mitochondrial biogenesis key signaling pathway PGC-1α-NRF1/NRF2 in rats. METHODS: Male Sprague-Dawley rats were divided into 4 groups: sedentary (C), exhaustive exercise (EE), low-dose SAL (LS), and high-dose SAL (HS). After one-time exhaustive swimming exercise, we measured the changes in cardiomyocyte ultrastructure and cardiac marker enzymes and mitochondrial electron transport system (ETS) complexes activities in situ. We also measured mitochondrial biogenesis master regulator PGC-1α and its downstream transcription factors, NRF1 and NRF2, expression at gene and protein levels. RESULTS: Compared to C group, the EE group showed marked myocardium ultrastructure injury and decrease of mitochondrial respiratory function (P < 0.05) and protein levels of PGC-1α, NRF1, and NRF2 (P < 0.05) but a significant increase of PGC-1α, NRF1, and NRF2 genes levels (P < 0.05); compared to EE group, SAL ameliorated myocardium injury, increased mitochondrial respiratory function (P < 0.05), and elevated both gene and protein levels of PGC-1α, NRF-1, and NRF-2. CONCLUSION: Salidroside can protect the heart from exhaustive exercise-induced injury. It might act by improving myocardial mitochondrial respiratory function by stimulating the expression of PGC-1α-NRF1/NRF2 pathway.

Effect of xiaoyaosan decoction on learning and memory deficit in rats induced by chronic immobilization stress.

Xiaoyaosan (XYS) decoction is a famous prescription which can protect nervous system from stress and treat liver stagnation and spleen deficiency syndrome (LSSDS). In this experiment, we observed the effect of XYS decoction on chronic immobilization stress (CIS) induced learning and memory deficit in rats from behaviors and changes of proteins in hippocampus. We used XYS decoction to treat CIS induced learning and memory deficit in rats with rolipram as positive control, used change of body weight and behavioral tests to determine whether the rats have LSSDS and have learning and memory deficit or not. We used Western blotting to determine the content of postsynaptic density protein 95 (PSD-95) and synaptophysin (SYP) in hippocampus. Results showed that XYS could improve the situation of slow weight gain induced by CIS, improve the ability of learning and memory, reverse the symptom of liver stagnation and spleen deficiency syndrome (LSSDS) in rats, and increase the levels of PSD-95 and SYP on the hippocampal nerve synapses. These findings suggested that XYS decoction may be helpful in reversing CIS induced learning and memory deficit by increasing the levels of PSD-95 and SYP on the hippocampal nerve synapses and improving synaptic plasticity.

Comparative study on effects of Xiaoyao Powder and its modified prescription on plasma metabolomics of rats with chronic immobilization stress.

OBJECTIVE: To determine the changes in the levels of endogenous metabolites in rats with chronic immobilization stress (CIS) taking Xiaoyao Powder (XYP) and its modified prescription version, which lacks the volatile oils extracted from Herba Menthae. METHODS: Twenty-four experimental male SD rats were randomly divided into 4 groups of 6 rats each: control, model, XYP-1 (containing volatile oils from Herba Menthae), and XYP-2 (lacking volatile oils). All rats except control group rats were subjected to CIS 3 h per day for 21 consecutive days. Groups XYP-1 and XYP-2 were given the extracted XYS with or without volatile oils (3.854 g/kg; suspended in distilled water) via gavage 1 h before CIS each day for 21 days. Rats were anesthetized using intraperitoneal injection of pentobarbital sodium (40 mg/kg) on the 22nd day. Observations were made using a Varian INOVA 600 MHz NMR spectrometer at 27 °C. Carr-Purcell-Meiboom-Gill (CPMG) and longitudinal eddy-delay (LED) were applied, resulting in spectra showing only the signals from micro- and macro-metabolites. RESULTS: Compared to controls, rats subjected to CIS showed increased levels of plasma metabolites, such as acetic acid, choline, N-glycoprotein (NAC), saturated fatty acid, and blood sugars. Levels of low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and unsaturated fatty acids were decreased. The biochemical effects of XYS were characterized by elevated levels of VLDL, LDL, threonine, methionine, and glutamic acid in plasma. CONCLUSION: Some common and characteristic metabolites on the anti-CIS of XYP and its modified prescription were obtained. The metabolomics technology is a valuable tool and may be used to identify the specific metabolites and potential biomarkers of therapeutic effect of Chinese medicinal prescriptions.