• Journal of Acupuncture Research
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• v.26 no.5
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• pp.19-28
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• 2009

Objectives : We tried to investigate the effects of Panax Ginseng Radix pharmacopuncture and Zizyphi Spinosi Semen pharmacopuncture on human body with the Heart Rate Variability (HRV) in adult man. As well as we tried to investigate how safe Panax Ginseng Radix and Zizyphi Spinosi Semen pharmacopuncture on the the human being. Methods : We investigated on 44 healthy volunteers consisted of 16 subjects in Panax Ginseng Radix pharmacopuncture group, 13 subjects in Zizyphi Spinosi Semen pharmacopuncture group and 15 subjects in Normal Saline. We ruled out subjects who wasn't stable by rest, with in the limit of normal heart beat(60-120cycle/min). Study form was a randomized, clinical trial. Each group was injected Panax Ginseng Radix pharmacopuncture, Zizyphi Spinosi Semen pharmacopuncture and Normal Saline $0.2m{\ell}$ at $GB_{21}$(Kyonjong). We measured HRV on 7 times : before and after injection per 5 minutes during 30 minutes. The SPSS 13.0 for windows was used to analyze the data by the paired t-test(in the group) and Anova test(among the groups) were used to verify the result. Results : 1. After Panax Ginseng Radix pharmacopuncture injection, SDNN was significantly high, pNN50 was significantly low, Ln(TP) was significantly high, Ln(VLF) was significantly high, Ln(LF) was significantly high at 30 minutes. 2. After Zizyphi Spinosi Semen pharmacopuncture injection, Complexity was significantly low, Ln(VLF) was significantly high at 30 minutes. 3. HRV-index made a significant difference between the Zizyphi Spinosi Semen pharmacopuncture and normal saline at 5 minutes(p=0.02). 4. There wasn's any pain the injected region and whole body, rubefaction, uredo, nausea, vomiting, colic, headache, dizziness within 24 hours. Measured data and mean value of Mean-HRV was within normal range. Conclusions : The results suggested that and Panax Ginseng Radix pharmacopuncture in healthy adult man tended to activate the vagus nervous system within normal range.

• Journal of Pharmacopuncture
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• v.12 no.3
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• pp.31-40
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• 2009

Objective : This study was to investigate the effects of distilled Cervi Pantotrichum Cornu Pharmacopuncture and Zizyphi Spinosi Semen Pharmacopuncture on autonomic nervous system with Heart Rate Variability(HRV). Purpose of the trial was to observe what influence distilled Cervi Pantotrichum Cornu Pharmacopuncture and Zizyphi Spinosi Semen Pharmacopuncture have on the autonomic nervous system. Methods : 60 healthy male volunteers were divided into three groups which consist of two experimental groups such as Cervi Pantotrichum Cornu Pharmacopuncture and Zizyphi Spinosi Semen Pharmacopuncture, and a control group. Study design was a randomized, placebo-controlled, double-blind clinical trial. 20 subjects in experimental group were injected distilled Cervi Pantotrichum Cornu Pharmacopuncture at $GB_{21}$(Kyonjong), 20 subjects in other experimental group were injected distilled Zizyphi Spinosi Semen Pharmacopuncture and 20 subjects in control group were injected Normal Saline at $GB_{21}$(Kyonjong). One volunteer of each groups were excluded from analysis because of error during measuring HRV. At the end of the study 57 volunteers completed HRV analysis. HRV was measured by QECG-3:LXC3203(LAXTHA Inc. Korea) at P0, P1, P2, P3, P4, P5 and P6 and its time-course dependent change in each group was analyzed using paired t-test, and the difference of HRV fluctuation among two experimental group and a control was evaluated by one way ANOVA(p<0.05). Results : A. Time Domain Analysis 1. Analysis of Mean HRV, SDNN and Complexity After injection of distilled Cervi Pantotrichum Cornu Pharmacopuncture, Mean HRV was significantly decreased only at 20 minutes after injection. SDNN was significantly increased from 15 minute after injection. Complexity was significantly decreased only at 15 minute after injection. After injection of distilled Zizyphi Spinosi Semen Pharmacopuncture, Complexity was significantly decreased at 10, 15 and 30 minutes after injection. 2. Analysis of HRV index, pNN50 After injection of distilled Cervi Pantotrichum Cornu Pharmacopuncture, pNN50 was significantly decreased at 15, 20 and 25 minutes after injection. Compared with Normal Saline injection, distilled Cervi Pantotrichum Cornu Pharmacopuncture and Zizyphi Spinosi Semen Pharmacopuncture showed significant difference on HRV index and pNN50 at 5 minutes after injection. B. Frequency Domain Analysis 1. Analysis of Ln(TP), Ln(VLF) After injection of distilled Cervi Pantotrichum Cornu Pharmacopuncture, Ln(TP) was significantly increased at 15 and 30 minutes after injection. Ln(VLF) was significantly increased at 10, 15 and 30 minutes after injection. After injection of distilled Zizyphi Spinosi Semen Pharmacopuncture, Ln(VLF) was significantly increased only at 30 minutes after injection. Compared with Normal Saline injection, distilled Cervi Pantotrichum Cornu Pharmacopuncture showed significant difference on Ln(TP) after 5 minutes of injection. Conclusions : Our results suggest that Cervi Pantotrichum Cornu Pharmacopuncture and Zizyphi Spinosi Semen Pharmacopuncture in healthy adult man tend to activate the autonomic nervous system and sympathetic nervous system compared to Normal Saline within normal range.

• Herbal Formula Science
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• v.22 no.1
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• pp.33-45
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• 2014

Objectives : Zizyphi spinosi Semen is widely used for treating insomnia in korea and other oriental country. This study is analyzing combination tendency of Zizyphi spinosi Semen in herbal formula for treating insomnia. Methods : Herbal formulas for treating insomia were searched in "The Prescription Dictionary of Traditional Chinese Medicine", and checked in each literary source. Then, the herbal formula was divided in two groups : FCZ(The formula group containing Zizyphi spinosi Semen) and FWZ(The formula group without Zizyphi spinosi Semen). FCZ and FWZ were compared by following criteria; i) Prevalence of herbal formula by period ii) Prevalence of medicinal material's effects iii) Prevalence of medicinal material iv) Prevalence of the nature of midicinals v) Prevalence of flavor of medicinals vi) Prevalence of meridian entry. Results : 116 Herbal formula met our criteria, and herbal formulas were divided in two groups : FCZ(n=59), FWZ(n=57). The result of prevalence in FCZ is following; Herbal formula prevalence increased as time passed to the Qing(淸) dynasty. Tonifying and replenishing medicinal(補益藥), tranquillizing medicinal (安神藥), and inducing diuresis to drain dampness medicinal(利水滲濕藥) are the three most prevalent types of materia medica. In specifically, Panax ginseng radix(人蔘), Liriopis Tuber(麥門冬), Angelicae Gigantis Radix(當歸), Poria Cocos(茯神), Glycyrrhizae Radix(甘草), Poria cocos(茯神), Polygalae Radix(遠志), Thuja Orientalis L.(柏子仁), Paeonia Japonica(白芍藥), and HgS(硃砂) are combined frequently. The most prevalent nature of medicinals were 'warm microwarm(溫 微溫)' and flavor of medicinals was normal(平). Meridian entrys that frequently combined were heart(心), spleen(脾), and liver(肝). Conclusion : We found combination tendency of Zizyphi Semen in herbal formula for treating insomnia.

• Journal of Food Hygiene and Safety
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• v.27 no.2
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• pp.141-145
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• 2012

Zizyphi spinosi semen (Z. spinosi) has been used in traditional Chinese medicine for the treatment of rheumatoid arthritis and wounds. However, toxicity in high doses was often observed due to the presence of alkaloids. This study was conducted to investigate the potential genotoxicity of Z. spinosi in vitro and in vivo. This was examined by the Bacterial reverse mutation (Ames) test using Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA, Chromosomal aberration was investigated using Chinese hamster lung cells and the micronucleus test using mice. Z. Spinosi did not induce mutagenicity in the Ames test, and it did not produce chromosomal aberration in Chinese hamster lung cells with and without metabolic activation, nor in the micronucleated polychromatic erythrocytes in the bone marrow cells in mice. Based on these results, it is concluded that Z. spinosi does not have mutagenic potential under the conditions examined in each study.

• Biomolecules & Therapeutics
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• v.12 no.3
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• pp.151-156
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• 2004

This study was carried out to evaluate the putative anxiolytic-1ike effects of the aqueous extracts of Sanjoin-tang (SJIT) and its ingredients using the elevated plus maze (EPM) test in mice. SJIT consists of five herbs, namely, Zizyphi Spinosi Semen (roasted), Glycyrrhizae Radix, Cnidii Rhizoma, Anemarrhenae Rhizoma, and Hoelen. The aqueous extracts of SJIT and each herbal drug were orally administered to ICR mice, 1 hr before evaluating behavioral activity in the EPM test, respectively. Repeated treatments (for 3 days) of the aqueous extract of SJIT (400 mg/kg) significantly increased time-spend in the open arms and arms entries into the open arms in the EPM test. Zizyphi Spinosi Semen (400 mg/kg), an ingredient of SJIT, significantly increased timespent in the open arms and arm entries into the open arms (P < 0.05). However, the other ingredient of SJIT did not show any anxiolytic-like behaviors. In addition, the anxiolytic-like effects of Zizyphi Spinosi Semen were blocked by pindolol (lO mg/kg), a $5-HT_{1A}$ receptor antagonist. These results suggest that Zizyphi Spinosi Semen (roasted) as an ingredient of SJIT plays a crucial anxiolytic role, and it acts via the serotonergic nervous system.

• Biomolecules & Therapeutics
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• v.16 no.3
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• pp.261-269
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• 2008

This experiment was performed to investigate the anxiolytic-like effects of cyclopeptide fraction alkaloids of Zizyphi Spinosi Semen (CFAZ), by using the experimental paradigms of anxiety, and compared with those of a known anxiolytic, diazepam. CFAZ (8.0 mg/kg, p.o.) increased the percentage of time spent on the open arms and the number of open arms entries in the elevated plus-maze test, increased the number of head dips in the hole-board test, and increased the percentage of center zone ambulatory time in the open-field box. However, CFAZ has no effect on the locomotor activity, while diazepam (2.0 mg/kg, p.o.) significantly reduced locomotor activity. CFAZ did not influence the grip force in the grip strength meter test, either. From the molecular experiments, CFAZ increased chloride influx in cultured cerebellar granule cells. In addition, $GABA_A$ receptors $\gamma$-subunit were over-expressed by CFAZ in cultured cerebellar granule cells. It is concluded that CFAZ may have anxiolytic-like effects, and these effects may be mediated by $GABA_A$ receptors.

• Natural Product Sciences
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• v.18 no.2
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• pp.67-75
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• 2012

Zizyphi Spinosi Semen (ZSS) have been widely used for the treatment of insomnia in Asia. This experiment was performed to investigate whether methanol extract of ZSS (MEZSS) has hypnotic effects through the ${\gamma}$-amino butyric acid (GABA)ergic systems. MEZSS inhibited the locomotor activity. MEZSS enhanced pentobarbital-induced sleep behaviors. However, MEZSS itself did not induce sleep at higher dose, similar to muscimol. On the other hand, both pentobarbital and MEZSS increased the non rapid eye move (NREM) sleep, especially reducing the -wave electroencephalogram (EEG) activity in REM sleep. MEZSS showed similar effects with muscimol on potentiating chloride influx induced by pentobarbital. MEZSS significantly increased GABAA receptors ${\gamma}$-subunit expression and slightly decreased ${\beta}$-subunit expression in hypothalamus and thalamus, showing that subunit-expression was similar to diazepam. In addition, MEZSS enhanced the expression of glutamic acid decarboxylase (GAD). In conclusion, it is suggested that MEZSS might augment pentobarbital-induced sleep behaviors through the modification of GABAergic systems.

• Korean Journal of Pharmacognosy
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• v.7 no.2
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• pp.115-118
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• 1976

The effects of the ether extract of Zizyphi spinosi semen and lithium chloride on the serum ceruloplasmin level in blood of rabbits were examined. An oral dose 1gm/kg/day of the ether extract and oral dose of lithium chloride 1 Meq/kg/day with 1gm/kg/day of the ether extract were administered respectively to rabbits for eight days, The results are: 1)Serum ceruloplasmin level in blood of the rabbits treated with the ether extract was higher than that of the control group. 2)The level of the rabbits treated with both the ether extract and lithium chloride was higher than that of the control. 3)The administration of lithium chloride alone also increased ceruloplasmin blood level.

• YAKHAK HOEJI
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• v.15 no.2
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• pp.53-63
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• 1971

A water-soluble basic extract was obtained from Zizyphi spinosi semen and tested on its sedative and psychotropic activities. In a 2.2m $\times$ 2.2m $\times$ 0.8m open-field, the effect of the extract on unlearned emotional responses of mice was determined. Intraperitoneal injection of 5mg/kg, 10mg/kg, and 20mg/kg of the extract caused to show less often the frequency of ambulation, rearing and exploration and more the frequency of lying and sleeping than that of placebo control, meprobamate and chlordiazepoxide treated groups. In a standard shuttle box, the effect of the extract on learned emotional responses was determined. Intraperitoneal injection of 10mg/kg of the extract caused to show less conditioned response, secondary conditioned response and defecation than either placebo control or pre- and post-treated sessions with the extract throughout the acquisition and extinction of conditioned avoidance response. Intraperitoneal injection of 10mg/kg of the extract showed similar sedative actions with that of 1.25mg/kg of chlorpromazine. The extract shows major tranquilizer-like effect as chlorpromazine.

• Korean Journal of Pharmacognosy
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• v.31 no.1
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• pp.23-27
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• 2000

The effect of seventy kinds of medicinal plants on the activities of GABA-metabolizing enzymes as glutamate dehydrogenase I (GDH I), glutamate dehydrogenase II (GDH II), GABA transaminase (GABA-T), succinic semialdehyde dehydrogenase (SSADH) and succinic semialdehyde reductase (SSAR) were estimated. The following plants extracts from Acori graminei Rhizoma, Longnae Arillus, Gastrodiae Herba, Lycii Fructus, Ligusticum officinale, Ferula assafoetida, Corydalis Tuber, Eucommiae Cortex, Zizyphi spinosi Semen activated the activity of GDH I to more than 35%, and the following ones from Visci Ramulus, Ligusticum officinale, Myristicae Semen, Ferulae Resina, Scolopendrae Corpus, Corydalis Tuber, Eucommiae Cortex, Zizyphi spinosi Semen did that of GDH II. The plant extracts from Cynanchi Radix, Astragali Semen, Angelicae dahuricae Radix, Biotae orientalis Folium, Uncariae Ramulus et Uncus, Polygalae Radix, Cynomorii Herba inhibited that of GABA-T to 35% and over, and the following ones from Hyoscyamus niger, Cynanchi Radix, Acori graminei, Caesalpiniae Lignum, Cannabis Semen, Sedum aizoon, Sedum kamtschaticum, Schisandrae Fructus, Lilii Bulbus, Biotae orientalis Folium, Uncariae Ramulus et Uncus, Myristicae Semen, Akebiae Fructus, Cynomorii Herba, Buddleiae Flos, Mucunae Caulis, Zizyphi Fructus, Paeoniae Radix rubra did that of SSADH to 70% and over; the following ones from, Caesalpiniae Lignum, Sedum kamtschaticum, Schisandrae Fructus, Astragali Semen, Angelicae dahuricae Radix, Dioscorea nipponica, Myristicae Semen, Akebiae Fructus, Cynomorii Herba, Scutellariae Radix did that of SSAR.