• Journal of Acupuncture Research
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• 제40권4호
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• pp.368-376
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• 2023

Background: Although bee venom (BV) has clinical benefits in osteoarthritis and rheumatoid arthritis, it has not been tested as treatment for gouty arthritis. Moreover, in vitro, BV has been proven to exhibit anti-inflammatory and positive effects on osteoarthritis, but only limited evidence can confirm its beneficial effects on gout. Thus, this study aims to assess the anti-inflammatory effects of BV on monosodium urate (MSU)-induced THP-1 monocytes. Methods: THP-1 monocytes were differentiated into mature macrophages using phorbol 12-myristate 13-acetate (PMA) and pretreated for 6 hours with BV and a Caspase-1 inhibitor in a physiologically achievable range of concentrations (BV, 0.1-1 ㎍/mL; Caspase-1 inhibitor, 1-10 μM), followed by MSU crystal stimulation for 24 hours. The secretions of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6, IL-8, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and nitric oxide (NO) were increased in the MSU crystal-stimulated THP-1 cells. Results: Caspase-1 inhibitors suppressed the production of all mediators in a dose-dependent manner. BV worked on equal terms with Caspase-1 inhibitors and showed more satisfactory effects on TNF-α, PGE2, COX-2, and inducible nitric oxide synthase (iNOS). Moreover, the western blot analysis revealed that BV regulated the transcriptional levels of these mediators via the suppression of extracellular signal-regulated kinase (ERK) pathway activation. Conclusion: The results of the present study clearly suggest that BV inhibits MSU-induced inflammation in vitro, suggesting a possible role for BV in gout treatment.

• Journal of Microbiology and Biotechnology
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• 제27권10호
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• pp.1827-1836
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• 2017

The world dairy industry has long been challenged by bovine mastitis, an inflammatory disease, which causes economic loss due to decreased milk production and quality. Attempts have been made to prevent or treat this disease with multiple approaches, primarily through increased abuse of antibiotics, but effective natural solutions remain elusive. Bee venom (BV) contains a variety of peptides (e.g., melittin) and shows multiple bioactivities, including prevention of inflammation. Thus, in the current study, it was hypothesized that BV can reduce inflammation in bovine mammary epithelial cells (MAC-T). To examine the hypothesis, cells were treated with LPS ($1{\mu}g/ml$) to induce an inflammatory response and the anti-inflammatory effects of BV (2.5 and $5{\mu}g/ml$) were investigated. The cellular mechanisms of BV against LPS-induced inflammation were also investigated. Results showed that BV can attenuate expression of an inflammatory protein, COX2, and pro-inflammatory cytokines such as IL-6 and TNF-${\alpha}$. Activation of NF-${\kappa}B$, an inflammatory transcription factor, was significantly downregulated by BV in cells treated with LPS, through dephosphorylation of ERK1/2. Moreover, pretreatment of cells with BV attenuated LPS-induced production of intracellular reactive oxygen species (e.g., superoxide anion). These results support our hypothesis that BV can decrease LPS-induced inflammatory responses in bovine mammary epithelial cells through inhibition of oxidative stress, NF-${\kappa}B$, ERK1/2, and COX-2 signaling.

• 생약학회지
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• 제42권4호
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• pp.366-370
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• 2011

Bee venom (BV) has been used as a treatment for a wide variety of ailments such as inflammatory diseases in korean traditional medicine. Despite its well documented anti-inflammatory property, it has not been fully demonstrated regarding the influence of BV against Propionibactierium acnes (P. acnes), which promotes follicular inflammation (inflammatory acne). This study evaluated the anti-inflammatory property of BV against P. acnes in vivo. To induce inflammation in vivo using P. acnes, $1{\times}10^7$ CFU of living P. acnes were intradermally injected into the ear of mice. BV (1, 10, 100 ${\mu}g$) in vaseline was applied epicutaneously on the ear resulting in P. acnes-induced ear swelling and inflammation. Epicutaneous administration of BV with P. acnes decreased the number of infiltrated inflammatory cells and inflammatory cytokines in the ear, thereby relieving P. acnes-induced ear swelling and granulomatous inflammation, especially at the dose of 1 ${\mu}g$ of BV. In this report, we demonstrated the therapeutic effects of BV on P. acnes-induced inflammation in vivo using the mouse model. These data highlight the potential of using BV as an alternative treatment to the antibiotic therapy of acne vulgaris.

• Journal of Acupuncture Research
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• 제34권1호
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• pp.1-9
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• 2017

Objectives : We investigated the synergistic effects of bee venom (BV) and natural killer (NK) cells on B16F10 melanoma cell apoptosis mediated by IL-4. Methods : We performed a cell viability assay to determine whether BV can enhance the inhibitory effect of NK-92MI cells on the growth of B16F10 melanoma cells, and western blot analysis to detect changes in the expression of IL-4, $IL-4R{\alpha}$, and other apoptosis-related proteins. EMSA was performed to observe the activity of STAT6. To confirm that the inhibitory effect of BV and NK cells was mediated by IL-4, the above tests were repeated after IL-4 silencing by siRNA (50 nM). Results : B16F10 melanoma cells co-cultured with NK-92MI cells and simultaneously treated by BV ($5{\mu}g/ml$) showed a higher degree of proliferation inhibition than when treated by BV ($5{\mu}g/ml$) alone or co-cultured with NK-92MI cells alone. Expression of IL-4, $IL-4R{\alpha}$, and that of other pro-apoptotic proteins was also enhanced after co-culture with NK-92MI cells and simultaneous treatment with BV ($5{\mu}g/ml$). Furthermore, the expression of anti-apoptotic bcl-2 decreased, and the activity of STAT6, as well as the expression of STAT6 and p-STAT6 were enhanced. IL-4 silencing siRNA (50 nM) in B16F10 cells, the effects of BV treatment and NK-92MI co-culture were reversed. Conclusion : These results suggest that BV could be an effective alternative therapy for malignant melanoma by enhancing the cytotoxic and apoptotic effect of NK cells through an IL-4-mediated pathway.

• 한국동물위생학회지
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• 제39권2호
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• pp.81-86
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• 2016

Honeybee venom (BV) from Apis mellifera L. has been used as natural antimicrobial compounds in pigs, cows, dairy cattle and chicken farms in Korea. The purpose of this study was conducted to confirm homogeneity and stability of BV dissolved with distilled water or saline solution. Melittin was analyzed with ultra-high performance liquid chromatography (UPLC) for BV to secure the validation of analysis. BV at concentration of 1 mg/mL was dissolved with distilled water or saline solution at room temperature. Homogeneity of BV dissolved with distilled water or saline solution at upper, milddle, and lower layers all satisfied the accuracy and precision criteria. Stability of BV dissolved with distilled water or saline solution for 7 days all satisfied the criterion both light and dark storage condition. BV has satisfied with homogeneity and stability in distilled water or saline solution at room temperature under light or dark condition. The results of this study suggest that BV has a possibility as the substitute of natural antimicrobial agents for the animal drugs and feed additives.

• 대한약침학회지
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• 제10권2호통권23호
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• pp.47-55
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• 2007

Objectives : To verify pain relief effects and allergy inhibitory action for the osteoarthritis of the knee joint in Sweet Bee Venom in which allergy causing enzyme is removed. Methods : We randomly allocated 36 participants to treatment group Sweet Bee Venom and Bee Venom. Outcomes on pain reduction were measured by 100mm VAS(Visual Analog Scale). And we recorded into details allergic responses during Pharmacopuncture treatment. Results : Whole body condition and pain rate through VAS measurement were improved significantly in 2 weeks. We could get difference in pain score of two Pharmacopuncture groups significantly in 2 weeks. BV group showed superior reduction in pain compared to the Sweet BV group. But we could not get difference in whole score of two pharmacopuncture groups significantly. On the other hand other allergic responses such as edema, itchiness, pain were significantly lower in the Sweet BV group.

• 한국임상수의학회지
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• 제24권4호
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• pp.499-502
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• 2007

본 연구는 전기충격 요법으로 얻은 한국산 건조봉독을 랫드의 포르말린 시험으로 항통각 효능을 관찰하였다. 실험동물로 수컷 Spraque-Dawley 랫드(평균 체중 265.38g, 6주령) 56마리를 각 군당 8마리씩 4개군으로 분류하였다. 봉독 투여군은 6 mg/kg 투여군과 0.6 mg/kg 투여군, 0.06 mg/kg 투여군으로 분류하였고, 대조군에는 생리식염수를 투여하였다. 건조 봉독은 포르말린을 투여하기 15분 전에 족삼리(ST-36)에 피하로 투여하였다. 통증은 1%포르말린 $50{\mu}l$을 랫드의 우측 뒷발바닥의 피하에 투여하여 유발하였다. 랫드가 포르말린을 투여한 후 우측 후지를 입으로 핥거나 깨무는 등의 행동을 포르말린 유발 통증행동으로 평가하였으며, 포르말린 투여 후 60분간 랫드의 통증 반응을 관찰하였다. 랫드의 통증반응은 첫 10분간은 5분 간격으로 관찰하였고, 10분 후부터 60분까지 10분 간격으로 관찰하였다. 한국산 건조 봉독은 봉독 투여 후 10분 이내에는 통증 억제 반응을 나타내지 않았으나, 봉독 투여 10분 후에 용량 의존적인 통증 억제 반응을 보였다. 이상의 결과에서 랫드의 포르말린 시험에서 한국산 건조봉독의 통증 억제 반응은 봉독량에 의존성을 보였고, 통증치료에 있어 다른 약물을 대체하여 사용될 수 있을 것으로 생각된다.

• 대한약침학회지
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• 제12권4호
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• pp.5-32
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• 2009

Objectives: This study was performed to analyse single dose toxicity of pure melittin(Sweet Bee Venom-Sweet BV) extracted from the bee venom by utilizing protein isolation method of gel filtration. Methods: All experiments were conducted at Biotoxtech, a non-clinical studies authorized institution, under the regulations of Good Laboratory Practice (GLP). Six weeks old female Sprague-Dawley rats were chosen for the pilot study and determined 30㎎/㎏ which is 4285 times higher than the clinical application dosage as the high dosage, followed by 15 and 7.5㎎/㎏ as mid and lose dosage, respectively. Equal amount of excipient to the Sweet BV experiment groups was administered as the control group. Results: 1. No mortality was witnessed in all of the experiment groups. 2. Hyperemia and movement disorder were observed around the area of administration in all groups, and higher occurrence in the higher dosage groups. Hyperemia and movement disorder diminished with elapsed time. 3. For the weight measurement, male groups showed larger reduction in weight in accordance with higher dosage. Female groups didn't s how significant changes. 4. To verify abnormalities of organs and tissues, cerebellum, cerebrum, liver, lung, kidney, and spinal nerves were removed and conducted histological observation with H-E staining. No abnormalities were detected in any of organs and tissues. 5. One female rat in the 30㎎/㎏ group had amputated toe near the administered area and histopathological finding was hemorrhage with inflammation. This is presumed as a secondary infection after the administration of Sweet BV. Conclusion: Above findings suggest Sweet BV is relatively s safe treatment medium. Further studies on the subject should be conducted to yield more concrete evidences.

• Journal of Acupuncture Research
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• 제20권5호
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• pp.50-62
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• 2003

Objective: Bee Venom(BV) has been used for various kinds of inflammatory or painful conditions in Oriental Medicine clinics, and there publishes reports on its therapeutic effects and the probable mechanism of those therapeutic effects, where CDs and cytokines plays important role. This study investigated the influences of bee venom on the expressions of CDs and cytokines of HMC cell line Methods: In this study we analysed the expression profile of HMC cell line treated with BV of 10-2ug/ml in relation to that of HMC cell line treated with vehicle by way of CD/cytokine microarray hybridization with 342 genes on it. Results: There were no upregulated genes by more than 3 fold, while there showed some downregulated genes by less than 1/3 fold as follows: colony stimulating factor 2, CD122, IL-7, CD112, TNF-alpha, CD138, CD166, TGFbetaR2, CD42b, CD62L, CD111, interleukin 10 receptor alpha, colony stimulating factor 1(macrophage), CD38 antigen(p45), CD121a, CD33 antigen(gp67), colony stimulating factor 1 receptor, B cell linker protein (SLP65) mRNA, CD94, alanyl(membrane) aminopeptidase, immunoglobulin(CD79A) binding protein 1, CD205, CD241, CD207, CDw121b, integrin alpha L(CD11a), integrin beta 1(CD29), CD91, CD42b. Conclusions: Bee venom treatment induced downregulation of some CDs or cytokines including $TNF-{\alpha}$. IL-1R with its possible implication in an antiinflammatory action of BV. Further research on expression profile changes induced by BV treatment is expected.

• 대한약침학회지
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• 제18권4호
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• pp.59-62
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• 2015

Objectives: A previous study showed that bee venom (BV) could cause anaphylaxis or other hypersensitivity reactions. Although hypersensitivity reactions due to sweet bee venom (SBV) have been reported, SBV has been reported to be associated with significantly reduced sensitization compared to BV. Although no systemic immediate hypersensitive response accompanied by abnormal vital signs has been reported with respect to SBV, we report a systemic immediate hypersensitive response that we experienced while trying to use SBV clinically. Methods: The patient had undergone BV treatment several times at other Oriental medicine clinics and had experienced no adverse reactions. She came to acupuncture & moxibustion department at Semyung university hospital of Oriental medicine (Je-cheon, Korea) complaining of facial hypoesthesia and was treated using SBV injections, her first SBV treatment. SBV, 0.05 cc, was injected at each of 8 acupoints, for a total of 0.40 cc: Jichang (ST4), Daeyeong (ST5), Hyeopgeo (ST6), Hagwan (ST7), Yepung (TE17), Imun (TE21), Cheonghoe (GB2), and Gwallyeo (SI18). Results: The patient showed systemic immediate hypersensitive reactions. The main symptoms were abdominal pain, nausea and perspiration, but common symptoms associated with hypersensitivity, such as edema, were mild. Abdominal pain was the most long-lasting symptom and was accompanied by nausea. Her body temperature decreased due to sweating. Her diastolic blood pressure could not be measured on three occasions. She remained alert, though the symptoms persisted. The following treatments were conducted in sequence; intramuscular epinephrine, 1 mg/mL, injection, intramuscular dexamethasone, 5 mg/mL, injection, intramuscular buscopan, 20 mg/mL, injection, oxygen ($O_2$) inhalation therapy, 1 L/minutes, via a nasal prong, and intravascular injection of normal saline, 1 L. After 12 hours of treatment, the symptoms had completely disappeared. Conclusion: This case shows that the use of SBV does not completely eliminate the possibility of hypersensitivity and that patients who received BV treatment before may also be sensitized to SBV. Thus, a skin test should be given prior to using SBV.