• Journal of Pharmacopuncture
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• v.3 no.1
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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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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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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• v.17 no.2
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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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• v.22 no.1
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• pp.99-108
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• 2005

Objective : The aim of this study is to investigate the analgesic effect and its mechanism of bee venom acupuncture on collagen-induced arthritis(CIA) rats. Methods : Bee venom (1 mg/kg) was subcutaneously punctured into Choksamni (ST36) of CIA Analgesic effect was evaluated by using the tail flick latency (TFL). Opioid and ${\alpha}2$-adrenergic neurotransmitter system were examined by naloxone as an opioid receptor antagonist and yohimbine as ${\alpha}2$-adrenoceptor antagonist prior to bee venom cupuncture. Results : The results were as follows; 1. The TFL for the CIA rat was decreased as time went by. 2. The TFL in CIA rat was increased in bee venom acupuncture group compared with control group (no treatment). 3. Analgesic effect of bee venom acupuncture was not abolished by naloxone pre-treatment in the CIA rat. 4. Analgesic effect of bee venom aqua-acupuncture was abolished by yohimbine pre-treatment in the CIA rat. 5. Two weeks bee venom acupuncture had the continous analgesic effect for 4 weeks. Conclusions : Bee venom acupuncture has an analgesic effect on the CIA rat and has an antinociception mediated by ${\alpha}2$-adrenergic system.

• Advances in Traditional Medicine
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• v.6 no.4
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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.

• Journal of Pharmacopuncture
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• v.17 no.4
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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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• v.17 no.2
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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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• v.18 no.1
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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.

• Journal of the Korean Institute of Oriental Medical Informatics
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• v.14 no.1
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• pp.73-80
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• 2008

Objectives: The purpose of this study is to find clinical approachment of rheumatoid arthritis with herbal medicine Byeong-geo-tang(竝祛湯 ; bing qu tang) Methods: We provided acupuncture, bee venom aqua - acupuncture, Byeong-geo-tang(竝祛湯 ; bing qu tang) on a patient of rheumatoid arthritis. Symptoms were estimated with the visual analog scale. Results: Patients chief complaints were pain and ankylosis of her right fingers and left toes and pain of her both wrists. Symptoms were relieved from 7 to 0 VAS after treatment. Conclusions: We observed that complex therapy of acupuncture, bee venom aqua - acupuncture, Byeong-geo-tang(竝祛湯 ; bing qu tang) redused symptoms of the patient. We expect this clinical report may be helpful to rheumatoid arthritis treatment.

• Journal of Life Science
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• v.19 no.4
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• pp.502-507
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• 2009

In modern oriental medicine, bee venom therapy is being used for aqua-acupuncture to relieve pain and to cure inflammatory diseases such as rheumatoid arthritis, osteoarthritis, and gout. Bee venom therapy has been processed and reported in many experimental studies, with regard to its effects on pain alleviation, anti-inflammation, removal of fever, anti-convulsion, suppression of tumor and immunity strengthening, etc., however, its mechanism of action, molecular targeting on prostaglandin $E_2$ ($PGE_2$) production and telomere length regulation in human cancer remains unclear. In this study, we investigated the effect of bee venom on the levels of cyclooxygenases (COXs) and telomere regulatory components of A549 human lung cancer cells. Bee venom-induced anti-proliferative effects of A549 cells were associated with the inhibition of human telomerase reverse transcriptase (hTERT) as well as human telomerase RNA (hTR), transcription factor c-myc and the activity of telomerase. In addition, bee venom treatment markedly decreased the levels of COX-2 mRNA and protein expression without significant changes in the expression of COX-1, which was correlated with a decrease in $PGE_2$ synthesis. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of bee venom.