• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.1
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• pp.104-110
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• 2002

Citri Reticulatae Viride Pericarpium extract(CRVP) have been used in oriental medicine for many centuries as a therapeutic agent for Soothing the liver and regulating the circulation of qi(疏肝理氣), and promoting digestion and removing stagnated food(消積化滯). The effects of CRVP on the vascular system is not known. The purpose of this Study was to investigate the effects of CRVP on the pial arterial diameter and regional cerebral blood flow(rCBF) in normal rats and ischemic cerebrovascular pathologic model rats. The changes in rCBF was determinated by Laser-Doppler Flowmetry(LDF), and the changes in pial arterial diameter were determinated by video microscopy methods and video analyzer. The results were as follows ; 1. Pial arterial diameter was significantly increased by CRVP in a dose-dependent manner. 2. Pretreatment with L-NNA significantly inhibited CRVP induced increased rCBF and pial arterial diameter. 3. Both the methylene chloride fraction and the hexane fraction of CRVP dose-dependently improved the altered cerebral hemodynamics of cerebral ischemic animal by increasing rCBF. 4. Pretreatment with L-NNA and indomethacin significantly inhibited CRVP(MC) induced increased rCBF. 5. Pretreatment with L-NNA and indomethacin significantly inhibited CRVP(hexane) induced increased rCBF. 6. Pretreatment with CRVP maredly stabilized the changes rCBF and pial arterial diameter during the period of cerebral reperusion. In conclusion, CRVP causes a diverse response of rCBF and pial arterial diameter, and CRVP dose-dependently improved the altered cerebral hemodynamics of cerebral ischemic animal by increasing rCBF and pial arterial diameter. These results suggest that the improvement of cerebral hemodynamics is also mediated by nitric oxide synthase and cyclooxygenase.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.6
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• pp.1475-1478
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• 2003

Purpose : We hope to evaluate the effectiveness of Citri Reticulatae Viride Pericarpium for the bronchial asthma using assesment on the vascular endothelial growth factor after Citri Reticulatae Viride Pericarpium was intravenously administered OVA-sensitized and -challenged mice. Material and methods: Eleven female mice, 8-10 weeks of age and free of murine specific pathogens, were used. Of the eleven mice, one mouse was not sensitized and ten mice were sensitized by intraperitoneal injection of OVA. Of the sensitized mice, three mice didn't administrate Citri Reticulatae Viride Pericarpium and seven mice administrated Citri Reticulatae Viride Pericarpium. Mice were sensitized on days 1 and 14 by intraperitoneal injection of 20 ㎍ OVA. On days 21, 22, and 23 after the initial sensitization, the mice were challenged for 30 minutes with an aerosol of 1 % OVA in saline. Citri Reticulatae Viride Pericarpium administered 200mg/kg in the tail of the mouse, one time per day, for 7 days, beginning 14 days after first sensitization. Bronchoalveolar lavage was performed 72 hours after the last challenge, and level of VEGF in the BAL fluid were measured by Western blot analysis. Results: Western blot analysis revealed that VEGF protein levels were increased in the all three mice which were challenge with OVA without administered Chung-pi compared the normal mouse. However, in the groups of the administered Chung-pi, the VEGF protein level markedly decreased in six of seven mice. Conclusion : Citri Reticulatae Viride Pericarpium might be effect the treatment of the bronchial asthma as a inhibition of the VEGF.

• The Journal of Korean Obstetrics and Gynecology
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• v.28 no.2
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• pp.40-54
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• 2015

Objectives : In the theory of Korean medicine, Citri Reticulatae Viride Pericarpium (CRVP) can soothe the liver to break qi stagnation, eliminate mass and relieve dyspepsia. This study was carried out to investigate the effects of CRVP on the apoptotic cell death in breast cancer cells. Methods : In the present experiment, the effects of CRVP on proliferation rates, type of cell death, cell cycle distribution, and intracellular oxidative stress were investigated using MDA-MB-231 cells in vitro. In addition, the effects on expression levels of caspase 3, caspase 9, Bax and Bcl-2 were also investigated. Results : Treatment with CRVP decreased proliferation rates in a dose dependent manner. ID50 (50% inhibitory dosage) was 175.4 μg/ml. In the CRVP treated group, cell volumes showed smaller than non-treated normal. In addition, CRVP increased percentage of apoptotic and sub G1 arrested cells respectively. 200 μg/ml of CRVP treatment increased intracellular ROS level significantly. Finaly the expression level of caspase 3 and Bax/Bcl-2 ratio were elevated by treatment with CRVP respectively. Conclusions : These results suggest that CRVP can trigger intrinsic apoptotic pathway in MDA-MB-231 cells.

• The Journal of Korean Medicine
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• v.17 no.2 s.32
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• pp.296-302
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• 1996

Pericarpium Citri Nobilis Viride, a traditional herb medicine, has been used in Korea and China for many centuries as a treatment for respiratory disease. The purpose of the present study was to determine the effect of Pericarpium Citri Nobilis Viride on histamine-induced tracheal smooth muscle contraction in rats. Guinea pigs(500g , female) were killed by $CO_2$ exposure and a segment (8-10mm) of the thoracic trachea from each guinea pig was cut into equal segments and mounted 'in pairs' in a tissue bath. Contractile force was measured with force displacement transducers under 0.5g loading tension. The dose of histamine which evoked 50% of maximal response $(ED_{50})$ was obtained from cumulative dose response curves for histamine $(10^{-7}-10^{-4}M)$. Contractions evoked by histamine ($ED_{50}$) were inhibited significantly by Pericarpium Citri Nobilis Viride. The mean percent inhibition was 53.7% (P<0.05) after 1.5mg／ml Pericarpium Citri Nobilis Viride, and 87.7% (P<0.01) after 5.0mg／ml Pericarpium Citri Nobilis Viride. Propranolol $(10^{-7}M)$ slightly but significantly attenuated the inhibitory effects of Pericarpium Citri Nobilis Viride. Following treatment with propranolol the mean present inhibition caused by 1.5 and 5.0mg／ml Pericarpium Citri Nobilis Viride. Indomethacin and methylene blue $(10^{-7}M)$ did not significantly alter the inhibitory effect of Pericarpium Citri Nobilis Viride These results indicate that Pericarpium Citri Nobilis Viride can relax histamine-induced contraction of guinea pig tracheal smooth muscle, and that this inhibition involves in part symphathetic nerve system.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.4
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• pp.416-421
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• 2006

Among the oriental medicine compounds, sulfur is known as a heat-generation material in a human body. Heat-generation reaction results in the consumption of energy source. Some oriental herbs are used to treat obesity and blood lipid composition. Therefore, we hypothesized that a sulfur containing oriental medicine compound, called as Hangbisan, could help weight loss of experimental rats. This study was designed to observe the change of weight of Sprague-Dawley (SD) rats that had been fed with high-fat diet containing 10% cellulose or Hangbisan for 9 weeks. Hangbisan affected the weight loss of rats as reducing the level of plasma cholesterol and triglyceride and increasing the level of HDL-cholesterol. Thus, this study revealed Hangbisan have an anti-obesity effect and a potential role for anti-obesity agent in the application of oriental medicine compounds.

• The Journal of Pediatrics of Korean Medicine
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• v.20 no.1
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• pp.181-194
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• 2006

Objective : Author evaluate the effects of Citri Reticulatae Viride Pericarpium for the bronchial asthma using assesment of the vascular endothelial growth factor after Citri Reticulatae Viride Peicarpium was intravenously administered Ovalbumine(OVA)-sensitized and -challenged mice. Material and Methods : Twenty-four female mice, 8-10 weeks old and free of murine specific pathogens, were sensitized by intraperitoneal injection of OVA. Of the sensitized mice, ten mice didn't administrate Citri Reticulatae Viride Pericarpium and the other ten mice administrated Citri Reticulatae Viride Pericarpium. Mice were sensitized on the first and fourteen days introspectional injection of 20 ${\mu}g$ OVA. After$21^{st}\;22^{th}\;and\;23^{rd}$, the initial sensitization, the mice were challenged for 30 minutes with an aerosol of 1% OVA in saline. Citri Reticulatae Viride Pericarpium administered 200mg/kg in the tail of the mouse, one a day, for 7 days and beginning 14 days after first sensitization. Bronchoalveolar lavage was performed 72 hours after the last challenge, and total cell numbers in the BAL fluid were count. Also, lever of VEGF in the BAL fluid was measured by Enzyme immunoassays and Western blot analysis. Results: Total cell numbers in BAL fluid were significantly greater than from 72 hrs after OVA inhalation compared with cell numbers in the control group. However, there was no difference of the total cell numbers between OVA-challenge groups without Citri Reticulatae Viride Pericarpium, and OVA-challenge with Citri Reticulatae Viride Pericarpium. Enzyme immunoassay revealed that VEGF levels in the BAL fluids were significantly increased 72 hrs after OVA inhalation compared with levels in the control group. After administration of the Citri Reticulatae Viride Pericarpiu, the levels of the VEGF in BAL fluids 72 hrs after OVA inhalation reduced dramatically. Western blot analysis revealed that VEGF protein levels were increased in the all mice which were challenge with OVA, without administered Citri Reticulatae Viride Pericarpium, compared the normal mouse. However, in the groups of the administered Citri Reticulatae Viride Pericarpium, the VEGF protein level markedly decreased. Conclusion: Citri Reticulatae Viride Pericarpium might affect the treatment of the bronchial ashma as a inhibition of the VEGF.

• Herbal Formula Science
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• v.18 no.2
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• pp.93-108
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• 2010

This report was studied 72 cases studies related to the use of Pericarpium Citri Reticulatae Virdie mainly blended prescriptions from Dongeuibogam. The following conclusion were reached through investigations on the prescriptions that use Pericarpium Citri Reticulatae Virdie as a key ingredient. Prescriptions that Pericarpium Citri Reticulatae Virdie was taken as a monarch drug are utilized for 25 therapeutic purposes, for example, abdominal mass, children disease, malaria and abdominal dropsy. In particular, 13.9% of prescriptions appear in the chapter of abdominal mass, and 12.5% of those appear in the chapter of children. Prescriptions that utilize Pericarpium Citri Reticulatae Virdie as the main ingredient are used in the treatment of abdominal mass, abdominal dropsy, scrotal hernia and malaria. Pericarpium Citri Reticulatae Virdie is used in pathogenic factors such as cold and used in pathology related to the spleen system. The dosage of Pericarpium Citri Reticulatae Virdie is 1bun(about 0.375 gram) to 4jeon(about 15 gram), however 5bun(about 1.875 gram) to 8bun(about 3 gram) has been taken the most for clinical application. Yukmisamleunghwan and Hyungbongjeonwon are the most useful base prescriptions which use the Pericarpium Citri Reticulatae Virdie as the main ingredient.

• The Korea Journal of Herbology
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• v.25 no.2
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• pp.117-128
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• 2010

Objectives : In this study the antidepressant effects of mixture of Citri Peticulatae Viride Pericarpium and Lycii Radicis Cortex on the change of HPA-Axis and Catecholamic system was investigated Methods : The forced swimming test(FST) was performed. The expression of corticotropin-releasing factor(CRF), c-Fos in the paraventricular nucleus(PVN), and tyrosine hydroxylase(TH) in the ventral tegmental area(VTA) and locus coeruleus(LC) was measured with immunohistochemical method and the concentration of seum adrenocorticotropic hormone(ACTH) was measured with ELISA method. And the experimental groups were divided into the extraction after mixing(A) and mixture after extraction(B). The effects of both group were compared. Results : The duration of immobility in the forced swimming test was significantly decreased in the A400 group(P<0.01). The expression of CRF in PVN were significantly reduced in the A100, A400, B100, B400groups(P<0.001). but the expression of c-fos in PVN weren't reduced in all groups. And the concentration of ACTH in Plasma were significantly reduced in the A 100 group(P<0.01). The expression of TH in LC were significantly reduced in the A 400, B 100 and B400 groups(P<0.05~P<0.01). Conclusion : Mixture of Citri Peticulatae Viride Pericarpium and Lycii Radicis Cortex has antidepressant effects. But the difference between mixing and extracting methods was not shown.

• The Journal of Korean Obstetrics and Gynecology
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• v.34 no.1
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• pp.34-47
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• 2021

Objectives: This study was designed to examine anti-inflammatory effect and mechanism of Citri Reticulatae Viride Pericarpium water extract (CRE). Methods: Cell cytotoxicity was tested with RAW 264.7 cells. To investigate anti-inflammatory effect of CRE in lipopolysaccharide (LPS)-induced RAW 264.7 cell, we measured nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10). In addition, mitrogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) were examined by western blotting in LPS-induced RAW 264.7 cell with treated CRE. Results: In cytotoxicity analysis, CRE does not affect cell cytotoxicity. As compared with the control group, the expression of NO, PGE2, TNF-α, IL-6 were significantly decreased, and IL-10 was significantly increased in LPS-induced RAW 264.7 cell with treated CRE. As a result of Western blotting, there was concentration-dependent inhibition of pp38, pERK in MAPK pathway and significant reduction of pp65 in the NF-κB pathway. Conclusions: CRE might have anti-inflammatory effect in LPS-induced macrophages by promoting the production of IL-10.

• Journal of Physiology & Pathology in Korean Medicine
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• v.38 no.1
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• pp.10-15
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• 2024

Previous studies have highlighted the pivotal role of the β-adrenergic receptor (β-AR) signaling pathway in stimulating cancer metastasis induced by chronic stress. According to the theory of traditional Korean medicine, chronic stress can induce Qi stagnation. Based on the traditional role of premature citrus unshiu peel in moving Qi, we hypothesized that an ethanol extract of premature citrus unshiu peel (EPCU) can attenuate chronic stress-induced cancer progression. In this study, we investigated the potential role of EPCU on modulating the adrenergic agonists-induced metastatic properties of liver cancer cells. Our findings revealed that adrenergic agonists, including norepinephrine (NE), epinephrine (E), and isoproterenol (ISO), augmented the migratory capacity of Hep3B human hepatocellular carcinoma cells, which was completely abrogated by EPCU treatment in a concentration-dependent manner. Consistently, EPCU inhibited the E-induced invasive property of Hep3B cells in a dose-dependent manner. These results suggest that EPCU efficiently attenuates adrenergic agonists-induced metastatic abilities of liver cancer cells. As a molecular mechanism, EPF suppressed the phosphorylation of major components of β-AR signaling pathway, including Src, signal transducer and activator of transcription 3 (STAT3) and ERK, induced by E treatment. Taken together, our results demonstrate that EPCU impedes the adrenergic agonists-driven metastatic potential of cancer cells by inhibiting β-AR signaling pathway. This study provides basic evidence supporting the probable use of premature citrus unshiu peel to prevent metastasis in liver cancer patients under chronic stress.