Sang Kwan Moon

Neuroprotective effects of an herbal medicine, Yi-Gan San on MPP+/MPTP-induced cytotoxicity in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE A traditional herb, Yi-Gan San, has been widely used for the management of neurodegenerative disorders in traditional East Asian Medicine. AIM OF THE STUDY The present study investigated the neuroprotective effects of Yi-Gan San in 1-methyl-4-phenylpyridine/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced cytotoxicity in vitro and in vivo and sought to clarify its underlying mechanisms. MATERIALS AND METHODS The effect of Yi-Gan San on 1-methyl-4-phenylpyridine was measured in terms of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays, caspase-3 activity, and western blot analysis of phosphorylated Akt, one of the survival-related signaling proteins in SH-SY5Y cells. The effects of Yi-Gan San were also confirmed in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonian mouse model using a rotarod test and tyrosine hydroxylase-immunohistochemistry. RESULTS Pretreatment of Yi-Gan San with 1-methyl-4-phenylpyridine showed a significant protective effect on SH-SY5Y cells and significantly decreased the level of caspase-3 activity compared to the values for the 1-methyl-4-phenylpyridine-treated cells. This process increased the protein expressions of phosphorylated Akt, and an inhibitor of phosphatidylinositol 3-kinase (PI3K)/Akt, LY294002, significantly decreased this protective effect of Yi-Gan San. In the mouse Parkinsons disease model, treatment with Yi-Gan San also significantly improved motor functioning and prevented dopaminergic loss related to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine challenge. CONCLUSION Using both in vitro and in vivo methods, this study revealed that Yi-Gan San has neuroprotective effects and rescues dopaminergic neurons from 1-methyl-4-phenylpyridine/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity, possibly via the PI3K/Akt pathway.

Intradermal acupuncture on shen-men and nei-kuan acupoints in patients with insomnia after stroke.

This is the first study that focuses on the effects of intradermal acupuncture on insomnia after stroke. We enrolled hospitalized stroke patients with insomnia and assigned them into a real intradermal acupuncture group (RA group) or a sham acupuncture group (SA group) by randomization. The RA group received intradermal acupuncture on shen-men (He-7) and nei-kuan (EH-6) for 2 days, and the SA group received sham acupuncture on the same points. The effectiveness was measured by the Morning Questionnaire (MQ), Insomnia Severity Index (ISI), and Athens Insomnia Scale (AIS). These scales were examined by an independent, blinded neurologist before, and 1 and 2 days after treatment, repeatedly. Thirty subjects (15 in the RA group and 15 in the SA group) were included in the final analysis. The RA group showed more improvement on insomnia than the SA group. Repeated measures analysis detected that there were significant between-subjects effects in the MQ, the ISI and the AIS. In conclusion, we suggest that intradermal acupuncture on shen-men and nei-kuan is a useful treatment for post stroke-onset insomnia.

Cytoprotective mechanism of baicalin against endothelial cell damage by peroxynitrite

To evaluate the mechanism responsible for the cytoprotective effects of baicalin, an antioxidant flavonoid isolated from Scutellaria baicalensis, we investigated its effects against peroxynitrite (ONOO−)‐induced endothelial cell (EC) damage. Baicalin showed efficient antioxidative actions by its ability to scavenge ONOO− and inhibit ONOO−‐mediated nitrotyrosine formation in vitro. Using an EC (YPEN‐1) culture system, baicalin exhibited cytoprotective effects against cell death by ONOO− that was induced exogenously with tert‐butyl hydroperoxide (t‐BHP) in the YPEN‐1 model. Baicalin was also found to reduce the intracellular precursors of ONOO−, NO˙ and O2− in the t‐BHP‐treated ECs. Evidence from Western blotting further revealed down‐regulated expressions of iNOS and COX‐2, endogenous sources of NO˙ and O2− by baicalin treatment. In addition, pre‐incubation of baicalin with EC suppressed t‐BHP‐induced nuclear factor kappa‐B binding activity as determined by the transfection assay and Western blot analysis, further indicating baicalins inhibition of iNOS and COX‐2 expression. Based on the present data, we propose that baicalin scavenges ONOO− and protects cells against injury. Based on these data, it was concluded that baicalin is potentially a useful antioxidant against ONOO− and NO˙ and an inhibitor of iNOS and COX‐2.

Efficacy and Safety of Chunghyul-dan (Qingwie-dan) in Patients with Hypercholesterolemia

Chunghyul-dan has inhibitory effects on HMG-CoA reductase and pancreatic lipase. We investigated whether Chunghyul-dan has therapeutic effects on humans with hypercholesterolemia. This study was a case-control, open-labeled clinical study. Subjects were treated with Chunghyul-dan (600 mg/day) or Atorvastatin (10 mg/day) for 8 weeks. Serum lipids were checked at baseline after 4 and 8 weeks of medication. While, Chunghyul-dan showed significant lipid-lowering effects, it was less effective than Atorvastatin. In comparison with the histological controls, Chunghyul-dans effects were superior to placebo. On safety assessment, there was no adverse effect with the use of Chunghyul-dan in hepatic or renal toxicity. In conclusion, we suggest that Chunghyul-dan is a useful herbal medicine for hypercholesterolemia.

The Effect of Low versus High Frequency Electrical Acupoint Stimulation on Motor Recovery After Ischemic Stroke by Motor Evoked Potentials Study

Electrical acupoint stimulation (EAS) has been used to treat motor dysfunction of stroke patients with reportedly effective results. When we operate EAS treatment, we can modulate the intensity and frequency of stimulation. The purpose of this study is to evaluate the effect of different frequencies in treating motor dysfunction of ischemic stroke patients with EAS. The subjects of this study were 62 ischemic stroke patients with motor dysfunction in Kyunghee oriental medical center. They have been hospitalized after 1 week to 1 month from onset. They were treated with 2 Hz or 120 Hz EAS for 2 weeks, and had motor evoked potentials (MEPs) tests before and after 2 weeks of EAS treatment. We measured latency, central motor conduction time (CMCT) and amplitude of MEPs. After 2 weeks of treatment, we compared MEPs data of the affected side between the 2 Hz group and the 120 Hz group. The 2 Hz group showed more significant improvement than the 120 Hz group in latency, CMCT and amplitude (p = 0.008, 0.002, 0.002). In the case of the affected side MEPs data divided by normal side MEPs data, the 2 Hz group also showed higher improvement rate than the 120 Hz group in latency, CMCT and amplitude with significant differences (p = 0.003, 0.000, 0.008). These results suggest that low frequency EAS activates the central motor conduction system better than high frequency EAS, and EAS with low frequency could be more helpful for motor recovery after ischemic stroke than that with high frequency.

Effects of Moxibustion on the Recovery of Post-Stroke Urinary Symptoms

This study was conducted to test the effectiveness of moxibustion therapy for patients with post-stroke urinary symptoms using International Prostate Symptom Score (IPSS). Stroke patients with urinary symptoms were enrolled and assigned into the moxibustion group (MO group) and the control group by stratified randomization. The MO group received moxibustion treatment on Zhong-Ji (CV-3), Guan-Yuan (CV-4) and Qi-Hai (CV-6) for 10 days, and the control group did not receive it. The effectiveness of urinary symptoms and activities of daily living were measured by IPSS and Barthel Index (BI), respectively. These scales were examined by an independent blinded neurologist before treatment, and 10 days after therapy. Thirty nine subjects (20 in the MO group and 19 in the control group) were included in the final analysis. The MO group showed more improvement on urinary symptoms than the control group. In conclusion, we suggest that moxibustion on Zhong-Ji (CV-3), Guan-Yuan (CV-4) and Qi-Hai (CV-6) is effective to post-stroke urinary symptoms.

Anti-hypertensive Effect of Chunghyul-dan (Qingxue-dan) on Stroke Patients with Essential Hypertension

Hypertension is one of the modifiable risk factors for stroke. Lowering blood pressure is helpful for primary and secondary prevention of stroke. This study is aimed to assess the efficacy of Chunghyul-dan on stroke patients with stage 1 hypertension using 24 hours ambulatory blood pressure monitoring (24ABPM). Forty hospitalized stroke patients with stage 1 hypertension were included in the study and they were randomly assigned into two groups: group A was treated with Chunghyul-dan 1200 mg once a day for 2 weeks, while group B was not. Twelve subjects were dropped out because of unexpected early discharge or data errors, thus the remaining 28 subjects were included in the final analysis (15 in group A and 13 in group B). Blood pressure was monitored every 30 minutes for 24 hours at baseline and 2 weeks after medication. Blood pressure, pulse rate, trough/peak ratio (TPR) [the value calculated by dividing the blood pressure change at trough (22 to 24 hours after drug intake) by the change at peak (2 adjacent hours with a maximal blood pressure reduction between the second and eighth hour after drug intake)] and smoothness index (SI) (the value calculated as the ratio between the average of the 24 hours, treatment-induced blood pressure changes and its standard deviation) were compared to assess the efficacy of Chunghyul-dan. To assess the safety of Chunghyul-dan, any adverse effects during medication period were monitored. There was no significant difference in the baseline assessment between the two groups. Systolic blood pressure was lower in group A than in group B (141.37+/-8.96 mmHg versus 132.28+/-9.46 mmHg, P = 0.03), while diastolic blood pressure and pulse rate had no significant difference between the two groups. Systolic TPR and SI was 0.87 and 1.04 in group A, respectively. This suggests that Chunghyul-dan have anti-hypertensive effect on stroke patients with stage 1 hypertension.

Safety and efficacy assessment of Chungpyesagan-tang for acute ischemic Stroke

Chungpyesagan-tang is one of the most well-known traditional herbal formulations frequently used for treatment of acute stroke in Korea. Therefore, this study aims to assess the clinical safety and efficacy of chungpyesagan-tang on acute ischemic stroke. We recruited acute cerebral infarction subjects within 1 week after onset time. Then, we prescribed chungpyesagan-tang to an Oriental medical treatment group (OM-group) for 2 weeks and enrolled a Western medical treatment group (WM-group) which received only Western biomedical care as a control. In this study, the OM-group was composed of 75 subjects. However, 14 of them dropped out, as two had progressive stroke while 12 complained of diarrhea. Thus, 61 cases were included in the analysis and compared to the 76 cases of the WM-group. The improvement of OM-group was better than that of the WM-group according to the National Institute of Health Stroke Scale (NIHSS), but not by the Modified Barthel Index (MBI). There were no definite abnormalities on labortory safety asessment. Therefore, we suggest that chungpyesagan-tang may have therapeutic effects, acting to reduce the severity of stroke and improving functional recovery without definite hepatic or renal toxicity when given for the first 2 weeks after a stroke.

Hwangryunhaedogtang (Huanglianjiedutang) Treatment for Pathological Laughter after Stroke and Importance of Patterns Identification: A Preliminary Study

This study was to test the importance of patterns identification (PI) and the effectiveness of hwangryunhaedogtang (huanglianjiedutang) (HT) treatment for patients with post stroke pathological laughter (PL). Fourteen subjects were enrolled. Eight subjects diagnosed with Yang Excess patterns (YEP) were assigned into group A and 6 subjects who had no YEP to group B. HT was administrated 3 times a day for 14 days to both groups. The duration of PL at one time, the frequency of PL in a day, and pathological laughter scale (PLS) were the primary outcome measures. Barthel index (BI) was the secondary outcome measure. The duration and the frequency of PL in group A were significantly decreased from 10.88 +/- 4.67 to 6.63 +/- 4.07 sec and from 6.38 +/- 2.72 to 3.00 +/- 1.77 times, respectively (p = 0.01) after 14 days administration of HT. PLS in group A was also significantly lowered from 9.13 +/- 1.73 to 4.75 +/- 0.71 points (p = 0.01). However, significant differences were not observed in BI in group A and in the primary and secondary outcome measures in group B. The duration and the frequency of PL and PLS were more markedly reduced in group A than in group B (p = 0.01, 0.02, and < 0.01, respectively). These results suggested that HT could be effective on subjects with post stroke PL diagnosed as YEP and PI, that prescription of herbal medications to such patients should be considered.

Chunghyul-Dan (Qingxie-Dan) Improves Arterial Stiffness in Patients with Increased baPWV

Arterial stiffness is an important, independent determinant of cardiovascular risk. Pulse wave velocity (PWV) has been used as a valuable index of arterial stiffness and as a surrogate marker for atherosclerosis. Chunghyul-dan (CHD) has anti-hyperlipidemic activity, anti-inflammatory activity and anti-atherogenic effects. To determine its clinical effect on increased arterial stiffness, we examined whether CHD improves arterial stiffness in patients with increased brachial-ankle PWV (baPWV). Thirty-five subjects with increased baPWV (> 1400 cm/sec) were recruited and randomized to a treatment group (20 subjects) or a control group (15 subjects). The treatment group was administered CHD at a dose of 600 mg three times a day for 8 weeks, and the control group received no medication (observation only). baPWV was assessed using a pulse pressure analyzer at baseline and after 8 weeks. Blood pressure and serum lipid profile were monitored in the treatment group. Our results indicate that baPWV was lowered significantly in the treatment group after 8 weeks of medication (p < 0.05), but not in the control group. Moreover, there were no significant changes in blood pressure and serum lipids profile except triglyceride level suggesting that the effect is largely independent of CHDs lipid-lowering effect or a blood pressure change. In conclusion, CHD appears to improve arterial stiffness in patients with increased PWV.