• 대한약침학회지
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• 제3권1호
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• pp.65-87
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• 2000

This study was designed to evaluate the effect of the bee venom(BV) aqua-acupuncture on the neuronal activities of catecholaminergic(tyrosine hydroxylase : TH, dopamine ${\beta}$ hydroxylase : D${\beta}$H) system in the brainstem. After the BV aqua-acupuncture was applied on Chok-Samni(ST36) and the gluteal part(Blank locus) in rats. Also, the number of colocalization between catecholamine containing neurons and Fos immunoreactive neurons were analyzed by using the double immunohistochemical technique. The results of the experiments were summarized as follows : 1. In DR and LC, Chok-Samni group and the Blank locus group showed more significant increase in the number of colocalization between TH containing neurons and Fos immunoreactive neurons than the control group. Furthermore, Chok-Samni group showed more significant increase than the Blank locus group. Also, in Arc, Chok-Samni group showed more significant increase than the Blank locus group and the control group. 2. In LC, Chok-Samni group showed more significant increase in the number of colocalization between D${\beta}$H containing neurons and Fos immunoreactive neurons than the Blank locus group and the control group. Also, in A5, Chok-Samni group and the Blank locus group showed more significant increase than the control group. Chok-Samni group showed more significant increase than the Blank locus group. However, there was no significant change in A7. Consequently, the BV aqua-acupuncture increased more potent the number of Fos immunoreactive neurons and the activity of catecholaminergic neurons. Furthermore, the BV aqua-acupuncture was more effective on Chok-Samni than Blank locus group. These results indicate that the BV aqua-acupuncture is very effective therapy to control pain. The therapeutic effect of BV aqua-acupunture may associated with the endogenous modulatory system such as catecholamine. Those data from the study can be applied to establish the effective treatment of the BV for pain control in the clinical field.

• 동의생리병리학회지
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• 제20권2호
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• pp.365-371
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• 2006

Bee Venom aqua-acupuncture (BVA) simultaneously exerts pharmacological effects of biologically active compounds, existed in the whole bee venom, and medicinal effect of the stimulation of acupuncture points. BVA has been considered as a promising therapeutic method for treating various chronic diseases, mainly accompanying severe pain and inflammation. As a painless injection device, jet injectors have been commercially marketed for various clinical applications including insulin injection and vaccination. Among them, a pressure-driven jet injector system could be used for intradermal delivery of a variety of drugs. The aim of this study was to investigate the analgesic effects of the BVA using a needle-free injector (Biojector $2000^{\circledR}$, Bioject Inc., OR, USA), compared to the conventional BV aqua-acupuncture using a typical syringe. Adult Sprague-Dawley rats were injected with bee venom $(0.08mg/kg,\;50{\mu}l)$ using Biojector $2000^{\circledR}$ (BVA-B) or a syringe (BVA-5) into the Zusanli (ST36) acupoint, 30 minutes before plantar injection of 2% formalin. It was found that BVA-B-, or BVA-5-treated rats, compared to controls, exhibited significantly less licking behavior during the late phase in the rat formalin test, when compared to controls. During early phase, however, those effects were not significant but substantial. The analgesic effect of BVA-B was also compatible with that of the conventional BVA-5. In the immunohistochemical studies, BVA-B significantly suppressed the expression of formalin-evoked c-fos, a biomarker of neuronal activity, in the lumbar dorsal horn of the spinal cord. These results indicated that BVA-B waseffective in the modulation of pain in the rat formalin test, compared to BVA-5. Taken together, the needle-free jet injector system could be substituted for the conventional aqua- acupuncture with the advantage of little pain.

• Journal of Acupuncture Research
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• 제17권2호
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• pp.119-138
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• 2000

This study was designed to evaluate the effect of the bee venom(BV) aqua-acupuncture on the neuronal activities of serotonergic(5-HT) system in the brainstem. After the BV aqua-acupuncture was applied on Chok-Samni(ST36) and the gluteal part(Blank locus) in rats, the number of Fos immunoreactive neurons was counted by using computerized image analyzing system. Also, the number of colocalization between 5-HT containing neurons Fos immunoreactive neurons were analyzed by using the double immunohistochemical technique. The results of the experiments were summarized as follows : 1. In almost every neucli, the Chok-Samni group and Blank locus group showed more increase in the number of Fos immunoreactive neurons than the control group. Especially, in Arc, DR, LC, RMg, Gi, PAG Rost and PAG LV, the Chok-Samni group showed more significant increase than the control group. Also, in PAG LV Mid and Arc, Chok-Samni group showed more significant increase than the Blank locus group. 2. In DR and PAG LV Mid, Chok-Samni group and the Blank locus group showed more significant increase in the number of colocalization between 5-HT containing neurons and Fos immunoreactive neurons than the control group after the BV aqua- acupuncture. Also, the Chok-Samni group showed more significant increase than the Blank locus group. Consequently, the BV aqua-acupuncture increased more potent the number of Fos immunoreactive neurons and the activity of serotonergic neurons. Furthermore, the BV aqua-acupuncture was more effective on Chok-Samni than Blank locus group. These results indicate that the BV aqua-acupuncture is very effective therapy to control pain. The therapeutic effect of BV aqua-acupunture may associated with the endogenous modulatory system such as serotonin Those data from the study can be applied to establish the effective treatment of the BV for pain control in the clinical field.

• Journal of Acupuncture Research
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• 제22권1호
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• pp.99-108
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• 2005

Collagen 유발(誘發) 관절염(關節炎) 동물모델을 이용하여 족삼리(足三里) (ST36) 봉독약월(蜂毒藥鉞)의 진통효과(鎭痛效果)와 그 기전(機轉) 을 관찰하기 위하여 TFL을 지표로 하여 통증 역치의 변화와 naloxone 및 yohimbine으로 전처(前處) 치한(置) 후 (後) 봉독약침(蜂毒藥鍼)의 진통효과(鎭痛效果)를 관찰한 결과 다음과 같은 결론을 얻었다. 1. Collagen 유발(誘發) 관절염(關節炎)의 rat에서 TFL 통증 역치는 1, 2, 3 및 4주로 갈수록 지속적 감소를 나타내었다. 2. 1회와 2주간 봉독약철(蜂毒藥鐵)은 collagen 유발(誘發) 관절염(關節炎) rat의 통증역치를 각각 증가시켰다. 3. CIA rat에 opioid receptor antagonist인 naloxone을 투여한 후 봉독약침(蜂毒藥鍼)을 처치한 결과 진통효과(鎭痛效果)가 유지되는 것으로 보아 봉독약광(蜂毒藥鑛)의 진통기전(鎭痛機轉)은 아편양 기전(機轉)과 관련이 없는 것으로 사료된다. 4. CIA rat에 ${\alpha}2$-adrenoceptor antagonist인 ohimbine을 투여한 후 봉독약침(蜂毒藥鍼)을 처치한 결과 진통효과(鎭痛效果)가 길항(拮抗)되는 것으로 보아, 봉독약침(蜂毒藥鍼)의 기전(機轉)은 ${\alpha}2$-adrenoceptor에 의하여 매개는 것으로 사료된다.

• Advances in Traditional Medicine
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• 제6권4호
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• pp.324-329
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• 2006

Neuropathic pain syndromes resulted from peripheral nerve injury appear to be resistant to conventional analgesics like opioids. However, it has been demonstrated that acupuncture including aqua-acupuncture may be effective in managing neuropathic pain. The present study was conducted to determine if bee venom injection into acupoint ihibits neuropathic pain, which is difficult to be treated by usual analgesics. Under pentobarbital anesthesia, male Sprague-Dawley rats were subjected to neuropathic surgery. Two weeks after nerve injury, mechanical and cold allodynia were tested in order to evaluate the antiallodynic effects of bee venom injection into an acupoint. Intraperitoneal injection of morphine inhibited mechanical allodynia dose-dependently. Bee venom injected into Zusanli acupoint significantly inhibited mechanical and cold allodynia. These results suggest that bee venom-acupuncture as well as morphine is very effective to inhibit mechanical allodynia.

• 대한약침학회지
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• 제17권4호
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• pp.15-21
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• 2014

Objectives: The purpose of this study was to investigate the current trends in research on pharmacopuncture in Korea since 2007. Methods: A literature review was performed by using the search engines 'Science and Technology Society Village', 'Korean Studies Information Service System', 'National Discovery for Science Leaders', and 'Oriental Medicine Advanced Searching Integrated System' in Korea from January 2007 to December 2013. Searched key words were 'pharmacopuncture', 'herbal acupuncture', 'aqua-acupuncture', and 'bee venom'. Finally, we selected 457 papers, including Korean experimental studies and clinical studies. Selected papers were classified according to year of publication, type of pharmacopuncture, disease & topic, research type and the publishing journal. Results: One hundred fifty pharmacopunctures were studied in 457 papers. Single compound pharmacopuncture was the most studied pharmacopuncture in experimental studies while animal-based pharmacopuncture was the most studied pharmacopuncture in clinical studies. Bee venom placed first among the various pharmacopunctures, followed by placenta, sweet bee venom, mountain-ginseng, and anti-inflammatory pharmacopunctures. Experimental research on pharmacopuncture has fallen since 2007 when 55 papers were published. However, clinical research has been increasing steadily. In clinical studies, case reports were numerous than randomized clinical trials (RCTs). Musculoskeletal diseases were the most frequently-treated diseases in studies on pharmacopuncture; among the musculoskeletal diseases, rheumatoid arthritis was the most frequently-treated disease in experimental studies and low back pain was the most frequently-treated condition in clinical studies. Since 2007, 45 different journals have published studies on pharmacopuncture, with the Journal of the Korean Acupuncture and Moxibustion Medicine Society having the largest number of papers on pharmacopuncture and the Journal of Pharmacopuncture the second largest number. Conclusion: The trends in research on pharmacopuncture published in studies from 2007 to 2013 were similar to those in studies published before 2006. Many studies on pharmacopuncture focused on bee venom and musculoskeletal diseases. Additional studies on diverse types of and indications for pharmacopuncture are needed.

• Journal of Acupuncture Research
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• 제17권2호
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• pp.169-186
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• 2000

To study anti-cancer effect and molecular biological mechanism of bee venom for aqua-acupuncture, the effects of bee venom on cell viability, apoptosis, and cell cycle were analyzed using MTT assay, tryphan blue assay, [3H]thymidine release assay, flow cytometric analysis, activity of caspase-3 protease activity assay, and immunocytometric analysis of PCNA. To explore whether anti-cancer effects of bee venom are associated with the transcriptional control of gene expression, quantitative RT-PCR analysis of apoptosis- and cell cycle-related genes was performed. The obtained results are summarized as follows: 1. The MTT assay demonstrated that cell viability was decreased by bee venom in a dose-dependant manner. 2. Significant induction of apoptosis was identified using tryphan blue assay, [$^3H$]thymidine release assay, and flow cytometric analysis of sub $G_1$ fraction. 3. In analysis of caspase-3 protease activity, the activity had increased significantly, in a dose-dependant manner. 4. Quantitative RT-PCR analysis of the apoptosis-related genes showed that Bcl-2 and $Bcl-X_L$ were down-regulated whereas Bax was up-regulated by bee venom treatment. 5. In flow cytometric analysis of cell cycle and immunocytometric analysis of PCNA expression, cell numbers of $G_1$ phase was increased by a dose-dependant manner. 6. In quantitative RT-PCR analysis of the cell cycle-related genes, p21, p27, and p57 were increased, while Cyclin D1, CDK4, c-Myc, c-Fos, and Histone H3 were decreased. In contrast, there were no remarkable changes in expression levels of CDC2 and c-Jun.

• Journal of Acupuncture Research
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• 제18권1호
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• pp.129-145
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• 2001

Objectives : To characterize the antitumorigenic potential of three representative bee venom components, Melittin, Apamin, and Phospholipase A2, their effects on cell proliferation and apotosis of the human melanoma cell line SK-MEL-2 were analyzed using molecular biological approaches. Methodes & Results : To determine the doses of the drugs that do not induce cytotoxic damage to this cell line, cell viability was examined by MTT assay. While SK-MEL-2 cells treated with 0.5 - 2.0㎍/㎖ of each drug showed no recognizable cytotoxic effect, marked reductions of cell viability were detected at concentrations over 5.0㎍/㎖. [3H]thymidine incorporation assay for cell proliferation demonstrated that DNA replication of SK-MEL-2 cells is inhibited by Apamin and Phospholipase A2 in a dose-dependent manner. Consistent with this result, the cells were accumulated at the G1 phase of the cell cycle after treatment with Apamin and Phospholipase A2, whereas no detectable change in cell proliferation was identified by Melittin treatment. In addition, tryphan blue exclusion and flow cytometric analyses showed that all of these drugs can trigger apoptotic cell death of SK-MEL-2, suggesting that Melittin, Apamin, and Phospholipase A2 have antitumorigenic potential through the suppression of cell growth and/or induction of apoptosis. Qantitative RT-PCR analysis revealed that Apamin and Phospholipase A2 inhibit expression of growth-promoting genes such as c-Jun, c-Fos, and Cyciin D1. Furthermore, Phospholipase A2 induced tumor suppressors p53 and p21/Wafl. In addition, all three drugs were found to activate expression of a representative apoptosis-inducing gene Bax while expression of apoptosis-suppressing Bcl-2 and Bcl-XL genes was not changed. Taken together, this study strongly suggests that Metittin, Apamin, and Phosphalipase A2 may have antitumorigenic activities, which are associated with its growth-inhibiting and/or apoptosis-inducing potentials.

• 대한한의정보학회지
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• 제14권1호
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• pp.73-80
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• 2008

본 증례는 2005년 류마토이드 관절염 진단을 받은 우측 수지의 경직 및 통증, 양측 손목 관절의 통증 좌측 족지의 경직과 통증, 아침 기상시에 경직과 부종이 심하게 있는 환자를 대상으로 편신골통으로 진단하고 이에 따라 변증기문의 병거탕을 사용하여 치료해서 호전된 증례이다. 현재 류마티스성 관절염에 대한 한의학적 실험 연구는 매우 활발하나 임상 연구는 많지 않고 대개의 경우 약침 요법으로 치료한 보고가 많아 이에 대한 한약 치료 경험을 문헌 고찰과 함께 보고하는 바이다.

• 생명과학회지
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• 제19권4호
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• pp.502-507
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• 2009

본 연구에서는 봉독의 처리에 따른 A549 폐암세포의 증식억제에서 $PGE_2$ 생성 및 telomerase 활성의 변화 관련성을 조사하였다. A549 세포의 증식은 봉독 처리에 의하여 유의적으로 감소되었으며, 이는 apoptosis 유발과 연관성이 있음을 알 수 있었다. 봉독 처리 농도의 증가에 따라 COX-2의 발현이 전사 및 번역 수준에서 모두 감소되었으며 이에 따른 $PGE_2$의 생성이 현저하게 감소되었으나, COX-1의 발현에는 큰 변화가 없었다. 또한 봉독 처리에 따라 telomere 조절인자들 중, hTERT, hTR 및 c-myc의 발현이 억제되었으며, telomerase의 활성도 매우 감소되었다. 본 연구의 결과는 $PGE_2$ 생성과 telomerase 활성 저하가 봉독의 항암 작용 표적인자로서 작용될 수 있음을 보여준다.