Hyung-Sup Bae

An fMRI study of neuronal specificity of an acupoint: electroacupuncture stimulation of Yanglingquan (GB34) and its sham point.

The neuronal specificity of acupoints has not been entirely supported by the results of fMRI studies. The objective of this study was to investigate the neuronal specificity of an acupoint with electroacupuncture stimulation (EAS) using functional magnetic resonance imaging (fMRI). Functional MR imaging of the entire brain was performed in 12 normal healthy subjects during EAS of GB34 (Yanglingquan) and its sham point over the left leg in counter-balanced order. Anatomically, both GB34 and its sham point belong to the L5 spinal segment. EAS at the left GB34 specifically activated the right putamen, caudate body, claustrum, thalamus, cerebellum, as well as the left caudate body, ventral lateral thalamus, and cerebellum, all related to motor function. EAS at the sham point of the left GB34 specifically activated the right BA6, BA8, BA40, BA44, thalamus, as well as the left thalamus and cerebellum. Taken together, these findings suggest that EAS at an acupoint and its sham point, in the same spinal segment, induced specific cerebral response patterns. These findings support neuronal specificity of the acupoint studied. EAS at GB34 appears to be more related to motor function than EAS at its sham point, suggesting specificity of the GB34 acupoint. The results of this study provide neurobiological evidence for the existence of acupoint specificity, although further studies are necessary to better understand this phenomenon.

Fecal metabolic activities of herbal components to bioactive compounds.

The herbal components should be transformed to bioactive compounds by the intestinal bacteria and then expressed the pharmacological action of herbal medicines. Human fecal enzyme activities related to the metabolism of herbal components were measured. The metabolic activities of puerarin, poncirin, glycyrrhizin, ginsenoside Rb1 and ginsenoside Rb2 to their bioactive compounds were 3.5 ±1.18, 333.1 ±183.64, 95.7 ± 107.1, 28.6 ± 10.32 and 20.8 ±13.3 umol/ h/g, respectively. The profile of these metabolic activities of glycyrrhizin and ginsenosides were not changed even if herbal extracts, water extract of Glycyrrhizae Radix and Ginseng Radix, instead of the isolated compounds were used. All the enzyme activities tested were not different between male and female, and between ages. However, the difference of these enzyme activities in individuals was significant. These results suggest that the metabolic activity of herbal components to bioactive compounds may be a factor of constitutional classification, and could be available for constitutional classifications, if the constitutional herbal medicines were used.

Modulation of natural killer cell activity affected by electroacupuncture through lateral hypothalamic area in rats.

Electroacupuncture (EA) has been reported to modulate natural killer cell (NK cell) activities. Also it is well known that hypothalamus directly mediates the effects of EA on analgesia. Especially lateral hypothalamic area (LHA) is related to splenic NK cell activities. In order to investigate the relationship between hypothalamus and effects of EA on NK cell activity, lesions have been made bilaterally at LHA of Spraque-Dawley rats. Subsequently, NK cell cytotoxities of normal and lesioned rats were measured with (51)Cr release immunoassay after EA stimulation for 2 and 14 days. NK cell activity of EA group was significantly higher than sham group. In addition, lesions abolished effects of EA on NK cell activity. These results strongly suggest that LHA is closely related to increase of NK cell activity induced by EA.

Effects of GV20 Acupuncture on Cerebral Blood Flow Velocity of Middle Cerebral Artery and Anterior Cerebral Artery Territories, and CO2 Reactivity During Hypocapnia in Normal Subjects

OBJECTIVES Acupuncture has been gaining popularity among practitioners of modern medicine as an alternative and complementary treatment. However, the mechanism of its therapeutic effect still remains uncertain. The present study chose the GV20 acupoint to evaluate acupoint effectiveness, hypothesizing that its stimulation induces cerebrovascular responses. DESIGN AND SETTING The effects of GV20 acupuncture treatment on middle cerebral artery (MCA) and anterior cerebral artery (ACA) blood flow velocities, and CO(2) reactivity during hypocapnia were evaluated in 10 healthy male subjects (mean age 25.6 ± 0.8 years). Measurements were done at rest and during hypocapnia, and were repeated four times each at different cerebral artery territories with an interval of 1 week. MCA and ACA blood flow velocities were measured with a transcranial Doppler flowmeter. Blood flow velocity was corrected to 40 mm Hg of end-tidal CO(2) partial pressure (P(ETCO2)), and was expressed as CV40. CO(2) reactivity was measured as percent change in mean blood flow velocity/mm Hg P(ETCO2). RESULTS Mean MCA and ACA blood flow velocities at rest, CV40, and CO(2) reactivity during hypocapnia increased significantly after GV20 acupuncture treatment, whereas mean arterial blood pressure and pulse rate at rest did not change significantly. The increases in MCA and ACA blood flow velocity were associated with improved CO(2) reactivity after GV20 acupuncture treatment. CONCLUSIONS The data suggest that GV20 acupuncture treatment increases cerebral blood flow. The results of this small-scale study provide preliminary evidence for acupuncture effectiveness.

A Preliminary Study on the Inhibitory Effect of Chunghyul-dan on Stroke Recurrence in Patients with Small Vessel Disease

Abstract Objective: Chunghyul-dan is a combinatorial herbal medicine, and previous works reported that it had therapeutic effects for microangiopathy, which is a major part in the progression of small vessel disease, as having anti-hypertensive, anti-hyperlipidemic, anti-apoptotic, anti-oxidative and anti-inflammatory activities. Therefore, we examined the inhibitory effect of Chunghyul-dan on stroke recurrence in patients with small vessel disease. Methods: We prescribed Chunghyul-dan 600 mg a day to the patients with small vessel disease, and monitored stroke recurrence, drug compliances and adverse effect for 2 years. And then we performed follow-up brain MRI to find new vascular lesion after 2 years of Chunghyul-dan medication. As for the control, we recruited the subjects who had been managed with antiplatelet agents from a western medical hospital, and compared the rate of stroke recurrence. Results: There were 148 subjects who had been treated with Chunghyul-dan for 2 years, and new vascular events were found in three subjects. On the other hand, 208 subjects were managed with anti-platelet agents for 2 years in a Western medical hospital, and 17 of them had stroke recurrence. Therefore, 2 years of Chunghyul-dan medication reduced the odds ratio of stroke recurrence by 77% compared to the anti-platelet agents managed control. The inhibition rate increased to 79%, when adjusted for other relevant risk factors for stroke occurrence. During the study, no adverse effect was detected. Conclusion: We suggest that Chunghyul-dan could be useful for inhibition of stroke recurrence by preventing the progression of microangiopathy. Further study with a randomized controlled trial is needed to confirm this suggestion.

Hepatoprotective Activity of Reduohanxiao-tang (Yuldahanso-tang) is Related to the Inhibition of β-Glucuronidase

Beta-glucuronidase-inhibitory and hepatoprotective effects of Reduohanxiao-tang (Yuldahanso-tang), which has been used for liver diseases and stroke, on carbon tetrachloride (CCl4)-induced hepatotoxicity of rats were investigated. Reduohanxiao-tang potently inhibited beta-glucuronidases. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactic acid dehydrogenase (LDH) levels of the CCl4 group orally treated with Reduohanxiao-tang (100 mg/kg) were lowered to 54%, 71.5% and 66.1% of the CCl4-treated control group, respectively. Among the ingredients of the Reduohanxiao-tang, the rhizomes of Pueraria thunbergiana and Scutellaria baicalensis potently inhibited beta-glucuronidases and protected against CCl4-induced liver injury. Orally administered puerarin, which is a main component of Pueraria thunbergiana, showed potent hepatoprotective activity, but did not inhibit beta-glucuronidase. However, daidzein, which is produced from puerarin by human intestinal bacteria, potently inhibited beta-glucuronidase. These results suggest that beta-glucuronidase inhibition by herbal medicines may protect against CCl4-induced liver injury.

Acupuncture for Cerebral Vasospasm After Subarachnoid Hemorrhage: A Retrospective Case–Control Study

OBJECTIVES To examine the possibility of acupuncture as a new promising treatment to prevent delayed cerebral vasospasm, retrospective comparison was done of patient outcomes in patients with subarachnoid hemorrhage (SAH) treated with and without acupuncture. MATERIALS AND METHODS Twenty (20) patients with SAH were treated after their ruptured aneurysms had been secured. Acupuncture treatments were applied to the bilateral Zusanli (ST36) and Neiguan (PC6) once a day for 2 weeks, starting within 3 days of the aneurysm rupture. The incidence of angiographic vasospasm and delayed ischemic neurological deficit (DIND), the patients functional status at discharge, and mortality rate were analyzed. Patient outcomes were compared with those of an age- and severity-matched comparison group composed of patients treated in the hospital without acupuncture. RESULTS None of the patients who received acupuncture died. Angiographic vasospasms occurred in 5 patients (25.0%) and DIND in 2 (10%). In terms of functional impairment, the modified Rankin score at discharge was ≤2 in 7 patients (35%). In the control group, angiographic vasospasms occurred in 10 patients (55.6%) and DIND in 7 (38.9%), similar to the reported incidence in conventionally treated patients. CONCLUSIONS Patients with SAH who received acupuncture had a significantly lower incidence of DIND and significantly improved function at discharge, suggesting that acupuncture is effective in preventing cerebral vasospasm. In light of these promising results, a randomized controlled trial is warranted to determine the efficacy of acupuncture in a clinical setting.

Paeonol attenuates inflammation-mediated neurotoxicity and microglial activation.

Chronic activation of microglial cells endangers neuronal survival through the release of various proinflammatory and neurotoxic factors. The root of Paeonia lactiflora Pall has been considered useful for the treatment of various disorders in traditional oriental medicine. Paeonol, found in the root of Paeonia lactiflora Pall, has a wide range of pharmacological functions, including anti-oxidative, anti-inflammatory and neuroprotective activities. The objective of this study was to examine the efficacy of paeonol in the repression of inflammation-induced neurotoxicity and microglial cell activation. Organotypic hippocampal slice cultures and primary microglial cells from rat brain were stimulated with bacterial lipopolysaccharide. Paeonol pretreatment was performed for 30 minutes prior to lipopolysaccharide addition. Cell viability and nitrite (the production of nitric oxide), tumor necrosis factor-alpha and interleukin-1beta products were measured after lipopolysaccharide treatment. In organotypic hippocampal slice cultures, paeonol blocked lipopolysaccharide-related hippocampal cell death and inhibited the release of nitrite and interleukin-1beta. Paeonol was effective in inhibiting nitric oxide release from primary microglial cells. It also reduced the lipopolysaccharide-stimulated release of tumor necrosis factor-alpha and interleukin-1β from microglial cells. Paeonol possesses neuroprotective activity in a model of inflammation-induced neurotoxicity and reduces the release of neurotoxic and proinflammatory factors in activated microglial cells.

Effect of Uwhangchungsimwon on expression of nitric oxide synthase and vascular cell adhesion molecule-1 in human endothelial cells.

For molecular biological characterization of the effects of Uwhangchungsimwon (UC) on the expression of nitric oxide synthase (NOS) gene and cell adhesion-regulating gene, vascular cell adhesion molecule-1 (VCAM-1), the human endothelial cell line (ECV304) was treated with the extract of UC and transcription of genes was examined using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. UC showed a transcription-activating effect on the NOS gene and a suppressing effect on the VCAM-1 gene in human endothelial cells, and these effects were found in a dose- and time-dependent manner. Down-regulation of VCAM-1 expression by UC was directly mediated by increased nitric oxide (NO) production, which was associated with increased NOS gene transcription. This study strongly suggests that the clinical effects of UC on stroke might be derived at least in part from its ability to induce NOS expression, which was followed by significant reduction of VCAM-1 expression.

Effects of Uwhangchungsimwon on cell viability, proliferation, and gene expression of human neuronal cell line IMR32

Uwhangchungsimwon (pill, UC) is one of the traditional Korean medical prescriptions that has been most frequently used for stroke. To characterize the effects of UC on human neuronal cells, the human neuroblastoma cell line IMR32 was treated with UC, and cell viability, cell proliferation, apoptosis, and gene expression were analyzed. The effect of UC on recovery of cell viability was analyzed following stress induction by nutrient depletion or cold shock. Flow cytometric analysis of the cell cycle showed that UC inhibits cell cycle progression of IMR32 in a dose- and time-dependent manner. UC was also identified to increase cell viability and suppress apoptosis induction by a DNA-damaging agent, etoposide. Quantitative RT-PCR analysis revealed that expressions of the p53 tumor suppressor gene and its downstream effect, Waf1, are stimulated whereas expressions of positive cell cycle regulators, c-Myc, c-Fos, and Cyclin D1 were repressed by UC treatment. Moreover, while expression levels of apoptosis inhibitors, Bcl-2 and Bcl-XL were increased following UC treatment, that of an apoptosis promoter, Bax, was decreased. In addition, expression of BMP-7, which has been recently demonstrated to improve the motor neuron recovery from stroke, was induced by UC while it was not detected in untreated cells. Taken together, our data suggest that the pharmacoclinical effects of UC might be derived in part from its negative regulation of cell proliferation and apoptosis through the transcriptional control of related genes.