• Herbal Formula Science
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• v.21 no.2
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• pp.144-157
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• 2013

Objectives : The aim of this study was to evaluate the efficacy of Hwangnyeonhaedok-tang (HH) and Geongangbuja-tang (GB) on the plasma hormone level in mice exposed to cold stress. HH and GB are the representative prescriptions of cold and hot property, respectively. Methods : We established cold condition by confining ICR mice to a $4^{\circ}C$ cage for 24 hours, ICR mice were given a HH (100, 300, 1000 mg/kg) or GB (100, 300, 1000 mg/kg) extract orally twice a day for three consecutive days. From the second day, they were given cold stress ($4^{\circ}C$) for twenty four hours. To measure the plasma corticosterone, insulin, thyroxine, epinephrine and norepinephrine levels of mice, their blood samples were collected from cardiac puncture, immediately centrifuged at $4^{\circ}C$. The protein level of HSP70 and JNK was examined using western blot analysis in cortex and hypothalamus. Results : Oral administration of GB more significantly reduced plasma corticosterone level raised by cold stress than HH. Gardeniae Fructus (CJ), the constituent of HH, significantly increased the thyroxine level. Western blot analysis showed that cold stress-induced Heat shock protein 70 (HSP70) expression was increased by HH and GB, HH decreased JNK expression and GB increased JNK expression dose-depently in hypothalamus. Scutellariae Radix (HG), Zingiberis Rhizoma (GG) and Aconiti Tuber (BJ) decreased HSP70 in hypothalamus and GG, BJ decreased HSP70 in cortex as well. Conclusions : These results suggest Geongangbuja-tang (GB) is more effective for ameliorating the stress response caused by cold stress.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.24 no.1
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• pp.121-141
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• 2011

Objective : This Experimental study was done to investigate the Effect of Taklisodok-um and Hwangryunhaedok-tang(TH) on Atopic Dermatitis. Methods : We assessed effects of TH on the IgE, IL-4, IL-5, IL-6, IgM, IgG1, IFN-${\gamma}$ in vivo, on the IL-4, IL-5, CCR3 in the skin tissues of ear and dorsum with NC/Nga mice. And we assessed effects of TH on the COX-2, IL-$1{\beta}$, TNF-${\alpha}$, IL-6 with RAW 264.7 cell. Results and Conclusion : 1. IgE, IL-4, IL-5, IL-6, IgM, IgGl levels in the serum of TH treated NC/Nga mouse group were decreased compared to the untreated control mice. IFN-r showed a increase in the experimental group compared to the untreated control group. The spleen weight of TH treated NC/Nga mice was decreased compared to the untreated control group. 2. mRNA expression levels of IL-4, IL-5 and CCR3 in the skin tissues of TH treated NC/Nga mice were decreased, and expression levels of IL-6 in the skin tissues of TH treated NC/Nga mice were decreased compared to the untreated control group. IFN-${\gamma}$ mRNA expression levels were increased compared to the untreated control group. 3. Judged from that IL-$1{\beta}$, TNF-${\alpha}$, IL-6 express of gene, effect of inflammatory Cytokines revelation were decreased compared to the untreated control group. 4. Depend on the strength of TH, inflammatory RAW 264.7 in the serum of TH were inhibited compared to the untreated control serum that leaded a COX-2 activity model. 5. Histological observation of the ear and skin tissues showed that the extents of inflammation and infiltrated immune cells in the epidermis and dermis of TH treated NC/Nga mice were highly reduced compared to the untreated control group.

• Journal of Acupuncture Research
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• v.29 no.1
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• pp.89-101
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• 2012

Objectives : The purpose of this study was find out the therapeutic effects of its exclusive use on the rat with allergic rhinitis. Materials and Methods : Thirty Sprague-Dawley rats were divided into three group : normal group, control group and sample group. To induce the allergic rhinitis in control group and sample group, rats were sensitized intraperitoneally with 0.1% ovalumin solution 3 times at intervals of 1 week. Then intranasal sensitization was performed by diffusing 0.1% ovalumin solution 3 times at intervals of 2 days. After that time, rats in the sample group were administered by $Yonghyang$($LI_{20}$) subcutaneously to treat the inflammation. Results : 1. The anti-oxidant effects of $Hwangryunhaedok-tang$ extract was dose-dependantly increased. 2. The RAW 264.7 cells were treated with LPS for 1 hours prior to the addition of indicated concentrations ($0.4,-1.0mg/m{\ell}$) of HHT, and the cells were further incubated for 24 hours. The LPS-induced iNOS mRNA expression and NO production were dose-dependantly decreased in HHT treated RAW 264.7 cells. 3. The number of eosinophil in HP noticeably decreased than CON and this decrease had probability. The infiltration of eosinophil in HP noticeably decreased than CON. 4. The damaged mucosa as disruption of cilia in respiratory cell and vacant mucose secreting cell were increased CON, but HP same as normal configuration. Decrease of PAS positive cell were shown in CON, but goblet cell occupied with neutral mucous were shown in HP. Decrease of mucosal stress(HSP70). Decrease of perennial sign(PPAR-${\gamma}$). Decrease of icthing and sneezing intricate neurotransmitter-(substance P). 5. The anti-inflammation of HHT pharmacopuncture for AR caused mucosa comes to result as belows. Decrease of pre-inflammation cytokine(TNF-${\alpha}$). Decrease of transcription factor (NF-${\kappa}B$ p65). Decrease of transcription factor inhibitor(p-$I{\kappa}B$). Decrease of inflammation cytokine(iNOS). Conclusions : The results may suggest that administration treatment using $Hwangryunhaedok-tang$ pharmacopucnture decreases the inflammatory response on an animal model with allergic rhinitis.

• Journal of Korean Medicine Rehabilitation
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• v.26 no.2
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• pp.51-59
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• 2016

Objectives We studied long-term preservation in stability of a mixed preparation of distilled and 70% alcohol extracted Hwangnyunhaedok-tang pharmacopuncture to establish standards for expiration date and quality control. Methods Three lots of consecutively prepared Hwangnyunhaedok-tang pharmacopuncture were each tested in triplicate to a total 5 tests at 3 month intervals over a period of 12 months for analysis of appearance, pH, specific gravity, index component content, endotoxins, microbial sterility, residual organic solvents, heavy metals, and pesticides. Items with no difference by elapsed time were tested at the initial and final timepoints, and data of items with potential difference by elapsed time were analyzed for trends to establish individual quality control standards. Results All tested items were stable over the study period, and therefore the expiration date was set as 12 months. pH quality control standards were set as 3.66~5.69, and that of specific gravity as 0.802~1.203, respectively. In index component content standards, berberine was set at $4.96{\sim}8.98{\mu}g/vial$, baicalin at $6.47{\sim}10.31{\mu}g/vial$, and geniposide at $116.03{\sim}189.55{\mu}g/vial$, respectively. Standards for other items with no difference by elapsed time were set according to general Korean herbal medicine standards in the Korean Pharmacopoeia. Conclusions Manageable expiration date and quality control standards were established through long-term preservation testing of Hwangnyunhaedok-tang pharmacopuncture, furthering standardization of Korean medicine pharmacopuncture.

• Journal of Korean Traditional Oncology
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• v.16 no.1
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• pp.1-14
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• 2011

Background and Objectives : This study is an observational study of nonequivalent control group based on time lag design in order to determine the effectiveness of gargling Hwangryunhaedok-tang (HRHDT) on stomatitis caused by chemotherapy. Methods : The study period is from July 1st, 2010 to September 30th, 2010. The subjects are 13 patients who fit the profile of the study and who are admitted in the tumor department of the regional cancer center of C University Hospital which is located in Chung-Joo City. When stomatitis occurs after chemotherapy, the level of stomatitis is assessed using oral assessment guide score and oral discomfort score. Then mix 5 g of powered HRHDT and 60 ml of distilled water, and 15 ml of the solution is given to patients 4 times per day to gargle for 1 minute. For the control group, 60 ml of Chlorohexidin gargling solution is used; everyday for one week, 4 times per day, 15 ml per gargle and gargled for 1 minute. Oral Assessment Guide score and Oral Discomfort Score are assessed at same hour everyday. Crosstabulation analysis $X^2$(${\rho}$) was used to examine the demographic characteristics and difference of the two groups by using SPSS/WIN 12.0. For mean and standard deviation, descriptive statistical analysis was used. T-test was used to determine the difference of the oral discomfort scores. Result : The study has shown that the Oral Assessment Guide score of the experimental group has decreased more with more regularity. On the third day, the score of the control group is 20.16 and the score of the experimental group was 18.75, which showed a statistically significant difference with the level of significance of p<0.05. Oral Discomfort Score of the control group's score was 13.60 on the first day and 6.80 on the seventh day and the experimental group's score was 13.00 on the first day and 2.25 on the seventh day. The experimental group's score 2.25 is statistically significantly lower than the control group's score of 6.80 with the level of significance of p<0.05. Conclusions : The HRHDT gargling solution showed more regular effectiveness compared to Chlorohexidin solution on chemotherapy-caused stomatitis. Therefore this study has shown that HRHDT gargling solution can be used as an alternative medicine.

• The Journal of Korean Medicine
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• v.23 no.4
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• pp.161-168
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• 2002

Objectives: Hwangryunhaedok-tang (Huang-lian-jie-du-tang, HRHDT, 黃連解毒湯) is a traditional Korean herbal medicine that is formulated with Coptidis Rhizoma, Phellodendri Cortex, Scutellariae Radix and Gardeniae Fructus. HRHDT is cold (寒) and bitter (苦) in nature and has general properties of clearing heat and detoxifying (淸熱解毒), strengthening the stomach and settling the liver (健胃平肝), and reducing inflammation, fever and swelling. This formula can prevent and treat artherosclerosis, hyperplasia of the endothelium, cerebral fluid circulation, cerebral vascular deterioration through aging, impairment of neurotransmitters, or disruption of the functioning of the cerebral cortex following infection or trauma. The purpose of the study reported here was to determine the neuroprotective effect of HRHDT on global ischemia induced by 4-vessel occlusion in Wistar rats. Methods: HRHDT extract was lyophilized after extraction with 85% methanol and 100% water. Rats were induced to 10 minutes of forebrain ischemia by 4-vessel occlusion (4-VO) and reperfused again. HRHDT was administered with a dose of 100 mg/kg, and 500 mg/kg of 85% methanol extracts and 100 mg/kg of 100% water extracts, respectively, at 0 min and 90 min after 4-VO. Rats were killed at 7 days after ischemia and the number of CA1 pyramidal neurons was counted in hippocampal sections stained with cresyl violet. Results: Body temperature of animals showed no significant difference between saline-treated groups and HRHDT extracts-treated groups until 5 hours of reperfusion. This result indicated that neuroprotective effects of HRHDT extracts were not due to hypothermic effects. The administration of HRHDT showed a significant neuroprotective effect on hippocampal CA1 neurons at 7 days after ischemia compared to the saline-treated group (P<0.001). HRHDT methanol extracts of 100 mg/kg, 500 mg/kg and HRHDT water extracts of 100 mg/kg showed 88.5%, 98.3% and 95.1 % neuroprotection, respectively. Conclusions: The results of this study demonstrate that administration of HRHDT is highly effective in reducing neuronal damage in response to transient global cerebral ischemia. HRHDT may involve many mechanisms that might account for its high degree of efficacy. A number of factors including free radicals, glutamate, calcium overload, NO, and various cytokines have been proposed to have an important role in causing neuronal death after short periods of global ischemia. Further studies are needed to know the neuroprotective mechanisms of HRHDT.

• The Journal of Korean Medicine
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• v.32 no.5
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• pp.100-113
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• 2011

Objectives: Brain edema is brain swelling that occurs due to the accumulation of excess water in the brain parenchyma. AQP4 and AQP9 are water-channel proteins expressed strongly in the brain and control water fluxes into and out of the brain parenchyma. This study was conducted to evaluate effect of Hwangnyeonhaedok-tang on brain edema and intracerebral hemorrhage. Methods: Intracerebral hemorrhage was induced by intrastriatal injection of type IV collagenase(0.23 U/${\mu}l$, 0.1 ${\mu}l$/min) into Sprague-Dawley rat brains. Hwangnyeonhaedok-tang water extract(1,000 mg/kg) was administered orally three times every 20 hours from 4 hours after ICH operation. Then hematoma volume, brain edema percentage, and water content of brain tissue were measured. Immuno-histochemistry was performed for AQP4 and AQP9 expressions in the brain sections and area % of immuno-labeling was analyzed with image analyzing system. Results: 1. Water extract of Hwangnyeonhaedok-tang reduced hematoma volume of ICH induced rat. 2. Water extract of Hwangnyeonhaedok-tang reduced MPO positive neutrophils in the perihematoma of the ICH induced rat. 3. Water extract of Hwangnyeonhaedok-tang reduced brain edema percentage and water content of brain tissue of ICH induced rat. 4. Water extract of Hwangnyeonhaedok-tang reduced AQP4 immuno-positive cells in the perihematoma of the ICH induced rat. 5. Water extract of Hwangnyeonhaedok-tang reduced AQP9 immuno-positive cells in the perihematoma of the ICH induced rat. Conclusions: These results suggest that Hwangnyeonhaedok-tang decreases intracerebral hemorrhage and brain edema by means of downregulating AQP4 and AQP9 expressions in the brain.

• Korean Journal of Acupuncture
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• v.19 no.2
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• pp.63-78
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• 2002

Kupunggibodan(KU), Gamisamul-tang(GA) and Whangryunhaedok-tang(WH) are clinically the most popular prescriptions as an herbal medicine in the treatment of ischemia. In order to compare and evaluate their protective effects on the ischema-induced cognitive deficits by middle cerebral artery occlusion (MCAO), we examined its ability to improve ischemia-induced cell loss and impairements of learning and memory in the Morris water maze and eight-arm radial arm maze. Focal cerebral ischemia produced a marked cell loss, decrease in acetylcholinesterase(AchE) reactivity in the hippocampus, and learning and memory deficits in two behavioral tasks. Pretreatment with WH (100 mg/kg, p.o.) produced a substantial increase in acquisition in the Morris water maze. Pretreatment with KU increased the perfomance of the resention test in the Morris water maze. WH, KU and GA caused a significant improvement in choice accuracy in radial arm maze test. WH was superior to KU and GA in perfomance of the radial arm maze test. Consistent with behavioral data, staining with cresyl violet showed that pretreatments with WH, but not KU and GA significantly recovered the ischemia-induced cell loss in the hippcampal CA1 area. In addition, pretreatments with WH and KU recovered the ischemia-induced reduction of AchE reactivity in the hippocampal CA1 area. These results demonstrated that KU, GA and WH have protective effects against ischimea-induced learning and memory impairments and that the efficacy was the order of WH>KU>GA in tratment of ischemia induced memory deficits. The present studies provide an evidence of KU, GA and WH as putative treatment of vascular dementia. Supported by a fund from the Ministry of Health and Welfare(HMP-00-OO-04-0004), and the Brain Korea 21 Project from Korean Ministry of Education, Korea.

• Korean Journal of Acupuncture
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• v.36 no.4
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• pp.230-240
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• 2019

Objectives : This research was performed to investigate the effects of Hwangryunhaedok-tang decoction and Hwangryunhaedok-tang Pharmacopuncture at BL10 on cognition and memory impairment in a mouse dementia model induced by scopolamine. Methods : Fifty ICR mice were divided into 6 groups : Normal group (n=5), Control group (n=9), Positive control group for pharmacopuncture group (n=9, Donepezil 0.75 mg/kg), Positive control group for oral administration group (n=9, Donepezil 5 mg/kg), Pharmacopuncture group (n=9, Hwangryunhaedok-tang Pharmacopuncture undiluted solution 10 ml/kg), and Oral administration group (n=9, Hwangryunhaedok-tang 200 mg/kg). For a mouse dementia model, 1 mg/kg scopolamine was intraperitoneally administered to ICR mice. Hwangryunhaedok-tang pharmacopuncture was administered on BL10 for 4 weeks at intervals of 2 days. Hwangryunhaedok-tang decoction was given orally for 4 weeks every day. Morris water maze and passive avoidance test were conducted followed by measurement of acetylcholine concentration, acetylcholinesterase activity, and the amount of BDNF and p-CREB in the brain. Results : 1. In the Morris water maze test, the time spent staying around the platform significantly increased in the pharmacopuncture group and oral administration group than in the control group. 2. In the passive avoidance test, the time spent in the bright room significantly increased in the pharmacopuncture group and oral administration group than in the control group. 3. The level of acetylcholine in brains increased in the pharmacopuncture group and oral administration group than in the control group. Also, the activity of acetylcholinesterase decreased in the pharmacopuncture group and oral administration group than in the control group. 4. The expression of BDNF and p-CREB decreased in the control group, but increased in the pharmacopuncture group and oral administration group. Conclusions : These results suggest that Hwangryunhaedok-tang decoction and Hwangryunhaedok-tang pharmacopuncture at BL10 may have cognition and memory-enhancing effect in scopolamine-induced dementia in ICR mice via controlling the content of acetylcholine and the activity of acetylcholinesterase, and activating BDNF and p-CREB.

• Herbal Formula Science
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• v.28 no.2
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• pp.157-167
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• 2020

Objectives : The purpose of this clinical study was to investigate the efficacy and safety of Hwangryunhaedok-tang on the gastritis treatment. Methods : A total of 20 subjects who visited Pusan National University Hospital from April 2nd, 2019 to September 2nd, 2019 were included. In this study, we evaluated the individual symptoms through questionnaires, laboratory test, BIA (Bioelectrical Impedance Analysis), and adverse reaction according to medication. Statistical analysis was performed with paired t-test and Wilcoxon Signed Rank test. Statistical significance was achieved if the probability was less than 5% (p < 0.05). Results : After medications, the total score of individual symptoms, primary outcome, was significantly decreased. In particular, individual symptoms such as upper abdominal pain, bloating, heartburn and trim showed significant improvement. However, no statistically significant differences were found in nausea/vomiting and anorexia. In additions, the laboratory test showed a statistically significant decrease in total cholesterol, but no statistically significant differences in results of BIA. In the safety evaluation, adverse reactions were not reported. Conclusions : Considering this results, we have confirmed the possibility of Hwangryunhaedok-tang to the gastritis treatment.