Kai Xin San ameliorates scopolamine-induced cognitive dysfunction.

Kai Xin San (KXS, containing ginseng, hoelen, polygala, and acorus), a traditional Chinese herbal compound, has been found to regulate cognitive dysfunction; however, its mechanism of action is still unclear. In this study, 72 specific-pathogen-free male Kunming mice aged 8 weeks were randomly divided into a vehicle control group, scopolamine group, low-dose KXS group, moderate-dose KXS group, high-dose KXS group, and positive control group. Except for the vehicle control group and scopolamine groups (which received physiological saline), the doses of KXS (0.7, 1.4 and 2.8 g/kg per day) and donepezil (3 mg/kg per day) were gastrointestinally administered once daily for 2 weeks. On day 8 after intragastric treatment, the behavioral tests were carried out. Scopolamine group and intervention groups received scopolamine 3 mg/kg per day through intraperitoneal injection. The effects of KXS on spatial learning and memory, pathological changes of brain tissue, expression of apoptosis factors, oxidative stress injury factors, synapse-associated protein, and cholinergic neurotransmitter were measured. The results confirmed the following. (1) KXS shortened the escape latency and increased residence time in the target quadrant and the number of platform crossings in the Morris water maze. (2) KXS increased the percentage of alternations between the labyrinth arms in the mice of KXS groups in the Y-maze. (3) Nissl and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining revealed that KXS promoted the production of Nissl bodies and inhibited the formation of apoptotic bodies. (4) Western blot assay showed that KXS up-regulated the expression of anti-apoptotic protein Bcl-2 and inhibited the expression of pro-apoptotic protein Bax. KXS up-regulated the expression of postsynaptic density 95, synaptophysin, and brain-derived neurotrophic factor in the cerebral cortex and hippocampus. (5) KXS increased the level and activity of choline acetyltransferase, acetylcholine, superoxide dismutase, and glutathione peroxidase, and reduced the level and activity of acetyl cholinesterase, reactive oxygen species, and malondialdehyde through acting on the cholinergic system and reducing oxidative stress damage. These results indicate that KXS plays a neuroprotective role and improves cognitive function through reducing apoptosis and oxidative stress, and regulating synapse-associated protein and cholinergic neurotransmitters.

Pharmacokinetics of beta-asarone in rabbit blood, hippocampus, cortex, brain stem, thalamus and cerebellum.

beta-Asarone has significant pharmacological effects on the central nervous system. As a potential therapeutic agent to manage brain diseases, analysis of the pharmacokinetics of beta-asarone in brain is necessary. We used cardio-perfusion method to exclude the beta-asarone in the brain blood. The brain was divided into five regions: hippocampus, cortex, brain stem, thalamus and cerebellum, and pharmacokinetic differences were investigated. We found that concentration-time profile of beta-asarone in blood, hippocampus, cortex, brain stem and cerebellum could be adequately described by a first-order equation, consistent with a linear two-compartmental model, but a first-order equation with a linear one-compartmental model in thalamus. The half lives of beta-asarone in blood, hippocampus, cortex, brain stem, thalamus and cerebellum were 1.3801, 1.300, 1.937, 7.142, 2.832 and 8.149 h, respectively. Gender differences do not significantly influence plasma pharmacokinetics of beta-asarone.

[Compound Xuanju capsule improves sex hormones and sex organ indexes in castrated male rats].

OBJECTIVE: To investigate the effects of Compound Xuanju Capsule on the levels of sex hormones and the weight of sexual organs in castrated male rats. METHODS: A randomized model control trail was performed in 60 young male SD rats of SPF grade, of which 12 were included in the normal control group, and the others were castrated and randomly divided into a model control group and a high-dose, a median-dose and a low-dose Xuanju group. The control groups received intragastric administration of normal saline, and the model groups solution of Compound Xuanju Capsule, all for 20 days. Then we determined by radioimmunoassay the levels of testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in the peripheral blood of the rats, and measured the weights of the epididymis, preputial gland, seminal vesicle, prostate and levator ani muscle. RESULTS: The T levels were remarkably lower in the castrated groups than in the normal controls, and significantly higher in the three Xuanju groups than in the model controls (P < 0.01). Both LH and FSH levels were increased in the model control and Xuanju groups as compared with the normal control group, the former with statistically significant difference (P < 0.05) and the latter without. In comparison with the normal controls, the model control rats showed a marked reduction in the indexes of the preputial gland, seminal vesicle, prostate and levator ani muscle, and the high-dose Xuanju group exhibited a significant increase in the seminal vesicle index as compared with the model controls (P < 0.05). There were no statistically significant differences in the indexes of preputial gland, prostate and levator ani muscle among different dose groups (P > 0.05). CONCLUSION: Compound Xuanju Capsule can elevate T and LH levels in the peripheral blood of male SD rats and improve the indexes of their sex organs, which may be an important mechanism behind its effect on ED.

[Effects of beta-asarone on expression of FOS and GAD65 in cortex of epileptic rat induced by penicillin].

OBJECTIVE: To study effects of beta-asarone on expression of FOS and GAD65 in cortex of epileptic rat induced by penicillin. METHODS: The epileptic animal models were induced by penicillin. The rats were randomly divided into beta-asarone of high (100 mg/kg), medium (50 mg/kg), low (25 mg/kg) dose group, positive control group (Phenytoin sodium), negative control group (matrix). The medicine was administered orally. The effects of beta-asarone on expression of FOS and GAD65 in cortex of epileptic rat were detected by immuohistochemistry method. RESULTS: beta-asarone could raise expression of FOS and reduce expression of GAD65 obviously. There were significant differences between negative control group and beta-asarone group. And it showed significant dose-effect relationship. CONCLUSION: Up-regulation of FOS may be a effective link of anti-epileptic effect of beta-asarone; reduced expression of GAD65 may be a follow-up impact of beta-asarone treatment.

[Effects of beta-asarone on expression of c-fos in kindling epilepsy rat brain].

OBJECTIVE: To study the effects of beta-asarone on expression of immediately early gene c-fos in kindling epilepsy rat brain. METHOD: The rats were randomly divided in to beta-asarone groups (200, 100, 50 mg x kg(-1) x d(-1)), difetoin control group (36 mg x kg(-1)) and model group. The remedy was administered orally. The effects were observed in kindling epilepsy model induced by penicillin, then the expression of c-fos were determined by western blot (hippocampus) and immunohistochemical techniques (cortex). RESULT: Beta-asarone could significantly increase the expression of c-fos in kindling epilepsy rat brain, and show its quantity-effect relation. The expression of c-fos in hippocampus was (1139.45 +/- 155.56), (1109.56 +/- 134.03), (1103.73 +/- 235.82) CNT x mm2 in beta-asarone groups, 920.54 +/- 203.20 in model control group, and 1106.26 +/- 186.24 in difetoin group, respectively. The number of c-fos positive cell was 87.1 +/- 2.2, 76.3 +/- 1.3 and 59.9 +/- 1.3 in beta-asarone groups, 39.3 +/- 2.6 in model control group, and 95.2 +/- 1.1 in difetoin group, respectively. CONCLUSION: Beta-asarone can obviously increase the expression of c-fos in epilepsy rat brain. It is one of important response to epilepsy.

[Protective effects of beta-asarone on cultured rat cortical neurons damage induced by glutamate].

OBJECTIVE: To study the protective effects of beta-asarone on cultured rat cortical neurons damage induced by glutamate. METHODS: The protective effects of beta-asarone on cultured rat cortical neurons after glutamate intoxication were observed with morphology, extent of damage, livability, Intracellular calcium concentration and apoptosis ratio. RESULTS: Morphological changes, LDH leakage and intracellular calcium concentration increasing, cell survival decreasing were observed in cultured rat cortical neurons exposured to glutamate; 7.5, 15, 30 microg/ml beta-asarone could increase cell survival, decrease LDH leakage and apoptosis ratio; 15, 30 microg/ml beta-asarone could reduce intracellular calcium concentration. CONCLUSION: The results suggest that beta-asarone prevents the toxicity of glutamate, and it maybe attribute to its effect of anticalcium.

[Effects of annao tablet on S100B and NPY of cortex in chronic epilepsy rats].

OBJECTIVE: To study the effects of Annao tablet (main component is beta-asarone) on S100B and NPY of cortex in chronic epilepsy rats. METHOD: The remedy was administered orally. The effects were observed in convulsion model induced by PG, then S100B protein and NPY of cortex were determined. RESULT: Annao tablet could depress the epileptic degree, postpone spasm latent period and reduce the wet dog sample (WDS) times. The remedy could decline S100B and NPY of cortex in chronic epilepsy rats. CONCLUSION: Annao tablet has obvious antiepileptic effects and can reduce the nerve cell damage induced by epilepsy.

[Study on GC-MS fingerprint analysis in rhizome of volatile oil of Acorus tatarinowii].

OBJECTIVE: To establish the method of fingerprint analysis on volatile oil in rhizome of Acorus tatarinowii by GC-MS, and to study the main characteristic components. METHOD: The main components of 10 samples were determined by GC-MS. RESULT: The injector temperature was 250 degrees C. The interface temperature was 230 degrees C. The column flow was 1.3 mL x min(-1). The column pressure was 80 kPa. The detector volt was 1.4 kV. The temperature rate was 3 degrees C x min(-1). And the main characteristic components were composed of the methyleugenol (2.13%), cis-methylisoeugenol (4.48%), trans-methylisoeugenol (0.82%), gamma-asarone (4.51%), beta-asarone (66.15%), alpha-asarone (6.35%). And the RSD of precision and reproducibility and stability was almost in the range of 5%. CONCLUSION: The method is reliable, accurate and can be used for fingerprint analysis of volatile oil of Acorus tatarinowii.

[Pharmacokinetics of beta-asarone in rats].

AIM: To study the pharmacokinetics of beta-asarone in rats. METHODS: The concentration of beta-asarone in serum and organs were measured by HPLC after i.g. administration, the pharmacokinetics was analyzed with DAS software regarding the organs as independent system. RESULTS: The pharmacokinetics of beta-asarone can be described as first order process of one-compartment model. In the serum, T(1/2), Tpeak and Cmax were 54 min, 12 min and 3.19 mg x L(-1), respectively. The procedure in the organs was similar to that in serum. CONCLUSION: The absorption, distribution and elimination of beta-asarone are very rapid, and it is easy to pass through blood brain barrier. Brain is an important organ of distributing of beta-asarone.