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Hyunsu Bae - One of the best experts on this subject based on the ideXlab platform.

  • Bee Venom Phospholipase A2 Alleviate House Dust Mite-Induced Atopic Dermatitis-Like Skin Lesions by the CD206 Mannose Receptor
    MDPI AG, 2018
    Co-Authors: Dasom Shin, Won Choi, Hyunsu Bae
    Abstract:

    Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by highly pruritic, erythematous, and eczematous skin plaques. We previously reported that phospholipase A2 (PLA2) derived from Bee Venom alleviates AD-like skin lesions induced by 2,4-dinitrochlorobenzene (DNCB) and house dust mite extract (Dermatophagoides farinae extract, DFE) in a murine model. However, the underlying mechanisms of PLA2 action in actopic dermatitis remain unclear. In this study, we showed that PLA2 treatment inhibited epidermal thickness, serum immunoglobulin E (IgE) and cytokine levels, macrophage and mast cell infiltration in the ear of an AD model induced by DFE and DNCB. In contrast, these effects were abrogated in CD206 mannose receptor-deficient mice exposed to DFE and DNCB in the ear. These data suggest that bvPLA2 alleviates atopic skin inflammation via interaction with CD206

  • anti inflammatory applications of melittin a major component of Bee Venom detailed mechanism of action and adverse effects
    Molecules, 2016
    Co-Authors: Gihyun Lee, Hyunsu Bae
    Abstract:

    Inflammation is a pervasive phenomenon triggered by the innate and adaptive immune systems to maintain homeostasis. The phenomenon normally leads to recovery from infection and healing, but when not properly phased, inflammation may cause immune disorders. Bee Venom is a toxin that Bees use for their protection from enemies. However, for centuries it has Been used in the Orient as an anti-inflammatory medicine for the treatment of chronic inflammatory diseases. Bee Venom and its major component, melittin, are potential means of reducing excessive immune responses and provide new alternatives for the control of inflammatory diseases. Recent experimental studies show that the biological functions of melittin could be applied for therapeutic use in vitro and in vivo. Reports verifying the therapeutic effects of melittin are accumulating in the literature, but the cellular mechanism(s) of the anti-inflammatory effects of melittin are not fully elucidated. In the present study, we review the current knowledge on the therapeutic effects of melittin and its detailed mechanisms of action against several inflammatory diseases including skin inflammation, neuroinflammation, atherosclerosis, arthritis and liver inflammation, its adverse effects as well as future prospects regarding the use of melittin.

  • Bee Venom Phospholipase A2: Yesterday's Enemy Becomes Today's Friend.
    Toxins, 2016
    Co-Authors: Gihyun Lee, Hyunsu Bae
    Abstract:

    Bee Venom therapy has Been used to treat immune-related diseases such as arthritis for a long time. Recently, it has revealed that group III secretory phospholipase A2 from Bee Venom (Bee Venom group III sPLA2) has in vitro and in vivo immunomodulatory effects. A growing number of reports have demonstrated the therapeutic effects of Bee Venom group III sPLA2. Notably, new experimental data have shown protective immune responses of Bee Venom group III sPLA2 against a wide range of diseases including asthma, Parkinson's disease, and drug-induced organ inflammation. It is critical to evaluate the beneficial and adverse effects of Bee Venom group III sPLA2 because this enzyme is known to be the major allergen of Bee Venom that can cause anaphylactic shock. For many decades, efforts have Been made to avoid its adverse effects. At high concentrations, exposure to Bee Venom group III sPLA2 can result in damage to cellular membranes and necrotic cell death. In this review, we summarized the current knowledge about the therapeutic effects of Bee Venom group III sPLA2 on several immunological diseases and described the detailed mechanisms of Bee Venom group III sPLA2 in regulating various immune responses and physiopathological changes.

  • Bee Venom phospholipase a2 suppresses allergic airway inflammation in an ovalbumin induced asthma model through the induction of regulatory t cells
    Immunity inflammation and disease, 2015
    Co-Authors: Soojin Park, Gihyun Lee, Hyunjung Baek, Kyunghwa Jung, Hyeonhoon Lee, Geunhyung Kang, Gyeseok Lee, Hyunsu Bae
    Abstract:

    Bee Venom (BV) is one of the alternative medicines that have Been widely used in the treatment of chronic inflammatory diseases. We previously demonstrated that BV induces immune tolerance by increasing the population of regulatory T cells (Tregs) in immune disorders. However, the major component and how it regulates the immune response have not Been elucidated. We investigated whether Bee Venom phospholipase A2 (bvPLA2) exerts protective effects that are mediated via Tregs in OVA-induced asthma model. bvPLA2 was administered by intraperitoneal injection into control and OVA-challenged mice. The Treg population, total and differential bronchoalveolar lavage fluid (BALF) cell count, Th2 cytokines, and lung histological features were assessed. Treg depletion was used to determine the involvement of Treg migration and the reduction of asthmatic symptoms. The CD206-dependence of bvPLA2-treated suppression of airway inflammation was evaluated in OVA-challenged CD206(-/-) mice. The bvPLA2 treatment induced the Tregs and reduced the infiltration of inflammatory cells into the lung in the OVA-challenged mice. Th2 cytokines in the bronchoalveolar lavage fluid (BALF) were reduced in bvPLA2-treated mice. Although bvPLA2 suppressed the number of inflammatory cells after OVA challenge, these effects were not observed in Treg-depleted mice. In addition, we investigated the involvement of CD206 in bvPLA2-mediated immune tolerance in OVA-induced asthma model. We observed a significant reduction in the levels of Th2 cytokines and inflammatory cells in the BALF of bvPLA2-treated OVA-induced mice but not in bvPLA2-treated OVA-induced CD206(-/-) mice. These results demonstrated that bvPLA2 can mitigate airway inflammation by the induction of Tregs in an OVA-induced asthma model.

  • Bee Venom phospholipase a2 protects against acetaminophen induced acute liver injury by modulating regulatory t cells and il 10 in mice
    PLOS ONE, 2014
    Co-Authors: Hyunseong Kim, Dong June Keum, Jung Won Kwak, Hwansuck Chung, Hyunsu Bae
    Abstract:

    The aim of this study was to investigate the protective effects of phospholipase A2 (PLA2) from Bee Venom against acetaminophen-induced hepatotoxicity through CD4+CD25+Foxp3+ T cells (Treg) in mice. Acetaminophen (APAP) is a widely used antipyretic and analgesic, but an acute or cumulative overdose of acetaminophen can cause severe hepatic failure. Tregs have Been reported to possess protective effects in various liver diseases and kidney toxicity. We previously found that Bee Venom strongly increased the Treg population in splenocytes and subsequently suppressed immune disorders. More recently, we found that the effective component of Bee Venom is PLA2. Thus, we hypothesized that PLA2 could protect against liver injury induced by acetaminophen. To evaluate the hepatoprotective effects of PLA2, C57BL/6 mice or interleukin-10-deficient (IL-10−/−) mice were injected with PLA2 once a day for five days and sacrificed 24 h (h) after acetaminophen injection. The blood sera were collected 0, 6, and 24 h after acetaminophen injection for the analysis of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). PLA2-injected mice showed reduced levels of serum AST, ALT, proinflammatory cytokines, and nitric oxide (NO) compared with the PBS-injected control mice. However, IL-10 was significantly increased in the PLA2-injected mice. These hepatic protective effects were abolished in Treg-depleted mice by antibody treatment and in IL-10−/− mice. Based on these findings, it can be concluded that the protective effects of PLA2 against acetaminophen-induced hepatotoxicity can be mediated by modulating the Treg and IL-10 production.

Jun Chen - One of the best experts on this subject based on the ideXlab platform.

  • melittin the major pain producing substance of Bee Venom
    Neuroscience Bulletin, 2016
    Co-Authors: Jun Chen, Sumin Guan, Wei Sun
    Abstract:

    Melittin is a basic 26-amino-acid polypeptide that constitutes 40–60% of dry honeyBee (Apis mellifera) Venom. Although much is known about its strong surface activity on lipid membranes, less is known about its pain-producing effects in the nervous system. In this review, we provide lines of accumulating evidence to support the hypothesis that melittin is the major pain-producing substance of Bee Venom. At the psychophysical and behavioral levels, subcutaneous injection of melittin causes tonic pain sensation and pain-related behaviors in both humans and animals. At the cellular level, melittin activates primary nociceptor cells through direct and indirect effects. On one hand, melittin can selectively open thermal nociceptor transient receptor potential vanilloid receptor channels via phospholipase A2-lipoxygenase/cyclooxygenase metabolites, leading to depolarization of primary nociceptor cells. On the other hand, algogens and inflammatory/pro-inflammatory mediators released from the tissue matrix by melittin’s pore-forming effects can activate primary nociceptor cells through both ligand-gated receptor channels and the G-protein-coupled receptor-mediated opening of transient receptor potential canonical channels. Moreover, subcutaneous melittin up-regulates Nav1.8 and Nav1.9 subunits, resulting in the enhancement of tetrodotoxin-resistant Na+ currents and the generation of long-term action potential firing. These nociceptive responses in the periphery finally activate and sensitize the spinal dorsal horn pain-signaling neurons, resulting in spontaneous nociceptive paw flinches and pain hypersensitivity to thermal and mechanical stimuli. Taken together, it is concluded that melittin is the major pain-producing substance of Bee Venom, by which peripheral persistent pain and hyperalgesia (or allodynia), primary nociceptive neuronal sensitization, and CNS synaptic plasticity (or metaplasticity) can be readily induced and the molecular and cellular mechanisms underlying naturally-occurring Venomous biotoxins can be experimentally unraveled.

  • characterization of nociceptive responses to Bee Venom induced inflammation in neonatal rats
    Brain Research, 2012
    Co-Authors: Hui-sheng Chen, Jun Chen, Jiaguang Tang, Jianhua Hao, Jianren Mao
    Abstract:

    Abstract To assess developmental characteristics of nociceptive responses induced by Bee Venom (BV) injection in neonatal rats, we exposed pups to intra-plantar injection of various BV concentrations given at different time points between postnatal day 1 and day 28 (P1–P28). Persistent spontaneous nociception (PSN) as well as thermal and mechanical nociceptive response was compared before and after a BV injection. There were distinct age-related changes in the baseline paw withdrawal thermal latency (PWTL) and paw withdrawal mechanical threshold (PWMT) when examined on P1, P4, P7, P14, P21, and P28. The lowest and highest baseline PWTL was shown on P1 and P7, respectively, and PWTL was unchanged from P7 to P28. In contrast, the baseline PWMT remained low before P21 but increased dramatically afterward. Neonatal rats receiving intra-plantar BV injection showed a time-dependent change in nociceptive responses, including (1) a dose-related increase in PSN from P1 to P28; (2) a non-specific decrease (indistinguishable between saline and BV injection) in PWTL and PWMT up to P14 and P21, respectively; and (3) a specific decrease (in response to BV injection only) in PWTL and PWMT after P14 and P21, respectively. These findings indicate that characteristic changes in the baseline and BV-induced nociceptive response are both time-dependent and modality-specific in neonatal rats. The data reveal a critical postnatal period during which nociceptive stimulation could have a significant influence on nociceptive behavior in adult rats and suggest that preclinical models of neonatal nociception should be evaluated according to different postnatal time points.

  • The nociceptive and anti-nociceptive effects of Bee Venom injection and therapy: A double-edged sword
    Progress in neurobiology, 2010
    Co-Authors: Jun Chen, William R. Lariviere
    Abstract:

    Bee Venom injection as a therapy, like many other complementary and alternative medicine approaches, has Been used for thousands of years to attempt to alleviate a range of diseases including arthritis. More recently, additional theraupeutic goals have Been added to the list of diseases making this a critical time to evaluate the evidence for the beneficial and adverse effects of Bee Venom injection. Although reports of pain reduction (analgesic and antinociceptive) and anti-inflammatory effects of Bee Venom injection are accumulating in the literature, it is common knowledge that Bee Venom stings are painful and produce inflammation. In addition, a significant number of studies have Been performed in the past decade highlighting that injection of Bee Venom and components of Bee Venom produce significant signs of pain or nociception, inflammation and many effects at multiple levels of immediate, acute and prolonged pain processes. This report reviews the extensive new data regarding the deleterious effects of Bee Venom injection in people and animals, our current understanding of the responsible underlying mechanisms and critical Venom components, and provides a critical evaluation of reports of the beneficial effects of Bee Venom injection in people and animals and the proposed underlying mechanisms. Although further studies are required to make firm conclusions, therapeutic Bee Venom injection may be beneficial for some patients, but may also be harmful. This report highlights key patterns of results, critical shortcomings, and essential areas requiring further study.

  • Secondary heat, but not mechanical, hyperalgesia induced by subcutaneous injection of Bee Venom in the conscious rat: effect of systemic MK-801, a non-competitive NMDA receptor antagonist
    European journal of pain (London England), 2000
    Co-Authors: Hui-sheng Chen, Jun Chen
    Abstract:

    Subcutaneous (s.c.) administration of Bee Venom into the plantar surface of one hind paw in rats has Been found to produce an immediate single phase of persistent spontaneous nociceptive responses (continuously flinching, licking or lifting the injected paw) for 1–2 h accompanied by a 72–96 hour period of primary heat and mechanical hyperalgesia in the injection site and a spread of heat, but not mechanical, hyperalgesia in the non-injected hind paw (Chen et al., 1999b). To gain insight into the underlying mechanisms of the Bee Venom-induced hyperalgesia in particular, we further identified a heat, but not mechanical, hyperalgesia in an area (paw pad) distant from the injection site induced by s.c. injection of Bee Venom into the posterior leg 0.8–1.2 cm proximal to the heel measured by paw withdrawal reflex to radiant heat or von Frey monofilament stimuli in conscious rats. In the Bee Venom-treated hind limb, however, significant reduction in both thermal latency and mechanical threshold of withdrawal reflex was identified for a period of more than 96 h in the heel with a similar characteristic to the primary heat and mechanical hyperalgesia identified in the injection site previously. The time course of the heat hyperalgesia identified in the paw pad of the Bee Venom-treated side was shorter and lasted for less than 48 h, which was in parallel with the reduction in thermal latency of the withdrawal reflex identified in the non-injected hind paw. Moreover, pre- or post-treatment with a single dose of MK-801 (0.01 mg/kg, i.p.), a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, completely blocked the occurrence, and reversed the established process of the heat hyperalgesia identified in either the Bee Venom-treated or non-treated paw pads, while the same treatments with the drug did not produce any influence upon the development and maintaining of the heat and mechanical hyperalgesia identified in the heel of the injected hind limb. Taken together with our previous results following s.c. intraplantar Bee Venom injection, we conclude that: (1) in addition to the well-identified primary heat and mechanical hyperalgesia in the injection site and its adjacent area, s.c. Bee Venom is also able to produce a secondary heat hyperalgesia in a region distant from the injection site which has a similar characteristic to the contralateral heat hyperalgesia; (2) NMDA receptors are involved in either development or maintenance of the secondary and the contralateral heat hyperalgesia, but without any role in those processes of the primary heat and mechanical hyperalgesia; (3) the secondary heat hyperalgesia seen in the injected hind limb is likely to share the same neural mechanisms with that identified in the non-injected side via co-activation of NMDA receptors.

  • involvement of peripheral nmda and non nmda receptors in development of persistent firing of spinal wide dynamic range neurons induced by subcutaneous Bee Venom injection in the cat
    Brain Research, 1999
    Co-Authors: Jun Chen, Ceng Luo, Jihong Zheng
    Abstract:

    To study the roles of peripheral excitatory amino acids receptor subtypes N-methyl-D-aspartate (NMDA) and non-NMDA receptors in persistent nociception, extracellular single unit recording technique was used to assess the effects of a single dose NMDA and non-NMDA receptor antagonists, AP(5) (5-aminophosphonovaleric acid) and CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) or DNQX (6,7-dinitroquinoxaline-2,3-dione), on s.c. Bee Venom-induced increase in firing of wide-dynamic-range (WDR) neurons in the spinal dorsal horn of the urethane-chloralose anesthetized cats. Subcutaneous Bee Venom injection into the cutaneous receptive field resulted in a single phase of increased firing of WDR neurons over the background activity for more than 1 h. Local pre-administration of AP(5) (200 microg/100 microl) or CNQX (8.3 microg/100 microl) into the Bee Venom injection site produced 94% (1.01+/-0.96 spikes/s, n=5) or 76% (2.97+/-0.58 spikes/s, n=4) suppression of the increased neuronal firing when compared with local saline (16.32+/-4.55 spikes/s, n=10) or dimethyl sulfoxide (DMSO) (12.37+/-6.36 spikes/s, n=4) pre-treated group, respectively. Local post-administration of the same dose of AP(5) produced a similar result to the pre-treatment group with a 67% inhibition of the mean firing rate, however, the same treatment with CNQX and even a higher dose of DNQX (100 microg/100 microl) did not produce any inhibition of the neuronal firing induced by s.c. Bee Venom injection (DNQX vs. DMSO: 23.91+/-0. 25 vs. 22.14+/-0.04 spikes/s, P=0.0298, n=5). In the control experiments, local pre-administration of the same dose of AP(5) or CNQX into a region on the contralateral hindpaw symmetrical to the Bee Venom injection site produced no significant influence on the increased firing of the WDR neurons [contralateral AP(5) vs. saline: 14.17+/-6.27 spikes/s (n=5) vs. 16.32+/-4.55 spikes/s (n=10), P0.05; contralateral CNQX vs. DMSO: 12.85+/-6.38 spikes/s (n=4) vs. 12. 37+/-6.36 spikes/s (n=4), P0.05], implicating that the suppressive action of local AP(5) or CNQX was not the result of systemic effects. The present results suggest that activation of the peripheral NMDA receptors is involved in both induction and maintenance, while activation of non-NMDA receptors is only involved in induction, but not in the maintenance of persistent firing of the dorsal horn WDR neurons induced by s.c. Bee Venom injection.

Hung Dae Sohn - One of the best experts on this subject based on the ideXlab platform.

  • antifibrinolytic role of a Bee Venom serine protease inhibitor that acts as a plasmin inhibitor
    PLOS ONE, 2012
    Co-Authors: Young Moo Choo, Hyung Joo Yoon, Hu Wan, Kwang Sik Lee, Yuling Qiu, Mi Ri Sohn, Hung Dae Sohn, Byung Rae Jin
    Abstract:

    Bee Venom is a rich source of pharmacologically active substances. In this study, we identified a bumbleBee (Bombus ignitus) Venom Kunitz-type serine protease inhibitor (Bi-KTI) that acts as a plasmin inhibitor. Bi-KTI showed no detectable inhibitory effect on factor Xa, thrombin, or tissue plasminogen activator. In contrast, Bi-KTI strongly inhibited plasmin, indicating that it acts as an antifibrinolytic agent; however, this inhibitory ability was two-fold weaker than that of aprotinin. The fibrin(ogen)olytic activities of B. ignitus Venom serine protease (Bi-VSP) and plasmin in the presence of Bi-KTI indicate that Bi-KTI targets plasmin more specifically than Bi-VSP. These findings demonstrate a novel mechanism by which bumbleBee Venom affects the hemostatic system through the antifibrinolytic activity of Bi-KTI and through Bi-VSP-mediated fibrin(ogen)olytic activities, raising interest in Bi-KTI and Bi-VSP as potential clinical agents.

  • dual function of a Bee Venom serine protease prophenoloxidase activating factor in arthropods and fibrin ogen olytic enzyme in mammals
    PLOS ONE, 2010
    Co-Authors: Young Moo Choo, Hyung Joo Yoon, Kwang Sik Lee, Mi Ri Sohn, Bo Yeon Kim, Jong Yul Roh, Namjung Kim, Iksoo Kim, Soo Dong Woo, Hung Dae Sohn
    Abstract:

    Bee Venom contains a variety of peptides and enzymes, including serine proteases. While the presence of serine proteases in Bee Venom has Been demonstrated, the role of these proteins in Bee Venom has not Been elucidated. Furthermore, there is currently no information available regarding the melanization response or the fibrin(ogen)olytic activity of Bee Venom serine protease, and the molecular mechanism of its action remains unknown. Here we show that Bee Venom serine protease (Bi-VSP) is a multifunctional enzyme. In insects, Bi-VSP acts as an arthropod prophenoloxidase (proPO)-activating factor (PPAF), thereby triggering the phenoloxidase (PO) cascade. Bi-VSP injected through the stinger induces a lethal melanization response in target insects by modulating the innate immune response. In mammals, Bi-VSP acts similarly to snake Venom serine protease, which exhibits fibrin(ogen)olytic activity. Bi-VSP activates prothrombin and directly degrades fibrinogen into fibrin degradation products, defining roles for Bi-VSP as a prothrombin activator, a thrombin-like protease, and a plasmin-like protease. These findings provide a novel view of the mechanism of Bee Venom in which the Bee Venom serine protease kills target insects via a melanization strategy and exhibits fibrin(ogen)olytic activity.

Kirok Kwon - One of the best experts on this subject based on the ideXlab platform.

  • study of four weeks repeated dose toxic test of sweet Bee Venom in rats original articles
    Journal of Pharmacopuncture, 2011
    Co-Authors: Haeyon Kwon, Kirok Kwon
    Abstract:

    Objective: This study was performed to analyse four weeks repeated -dose toxicity of Sweet Bee Venom (SBV-pure melittin, the major component of honey Bee Venom) in rats. Methods: All experiments were conducted under the regulations of Good Laboratory Practice (GLP) at Biotoxtech Company, a non-clinical study authorized institution. Male and female rats of 5 weeks old were chosen for the pilot study of four weeks repeated-dose toxicity and was injected at the level of 0.56 mg/kg body weight (eighty times higher than the clinical application dosage as the high dosage), followed by 0.28 and 0.14 mg/kg as midium and low dosage, respectively. Equal amount of normal saline was injected as the control group every day for four weeks. Results: 1. No mortality was witnessed in all of the experiment groups. 2. All experiment groups appealed pain sense in the treating time compared to the control group, and side effects such as hyperemia and movement disorder were observed around the area of injection in all experiment groups, and the higher dosage in treatment, the higher occurrence in side effects. 3. Concerning weight measurement, neither male nor female groups showed significant changes compared to the control group. 4. Concerning to the CBC and biochemistry, all experiment groups didn`t show any significant changes compared to the control group. 5. Concerning weight measurement of organs, experiment groups didn`t show any significant changes compared to the control group. 6. To verify abnormalities of organs and tissues, those such as cerebellum, cerebrum, liver, lung, kidney, and spinal cords were removed and we conducted histologocal observation with H-E staining. Concerning the histologocal observation of liver tissues, some fatty changes were observed around portal vein in 0.56 mg/kg experiment group. But another organs were not detected in any abnormalities. 7. The proper high dosage of SBV for the thirteen weeks repeated test in rats may be 0.28 mg/kg in one time. Conclusion: Above findings suggest that SBV is relatively safe treatment medium. Further studies on the subject should be conducted to yield more concrete evidences.

  • study of single dose toxic test of sweet Bee Venom in beagle dogs
    Journal of Pharmacopuncture, 2010
    Co-Authors: Hyechul Yoon, Kwangho Lee, Kirok Kwon
    Abstract:

    Objectives : This study was performed to analyse single dose toxicity of Sweet Bee Venom(Sweet BV) extracted from the Bee Venom in Beagle dogs. Methods : All experiments were conducted under the regulations of Good Laboratory Practice (GLP) at Biotoxtech Company, a non-clinical study authorized institution. Male and female Beagle dogs of 5-6 months old were chosen for the pilot study of single dose toxicity of Sweet BV which was administered at the level of 9.0 mg/kg body weight which is 1300 times higher than the clinical application dosage as the high dosage, followed by 3.0 and 1.0 mg/kg as midium and low dosage, respectively. Equal amount of excipient(normal saline) 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 the experiment groups, and higher occurrence in the higher dosage treatment. 3. For weight measurement, Neither male nor female groups showed significant changes. 4. To verify abnormalities of organs and tissues, thigh muscle which treated with Sweet BV, brain, liver, lung, kidney, and spinal cords were removed and histologocal observation using H-E staining was conducted. In the histologocal observation of thigh muscle, cell infiltration, inflammation, degeneration, necrosis of muscle fiber, and fibrosis were found in both thigh tissue. And the changes depend on the dose of Sweet BV. But the other organs did not showed in any abnormality. 5. The maximum dose of Sweet BV in Beagle dogs were over 9 mg/kg in this study. Conclusions : The above findings of this study suggest that Sweet BV is a relatively safe treatment medium. Further studies on the toxicity of Sweet BV should be conducted to yield more concrete evidences.

  • study of four week repeated dose toxic test of sweet Bee Venom in beagle dogs
    Journal of Pharmacopuncture, 2010
    Co-Authors: Jaeseuk Park, Kwangho Lee, Kirok Kwon
    Abstract:

    Objectives: This study was performed to analyse four week repeated dose toxicity of Sweet Bee Venom(Sweet BV) extracted from the Bee Venom in Beagle dogs. Methods: All experiments were conducted under the regulations of Good Laboratory Practice (GLP) at Biotoxtech Company, a non-clinical study authorized institution. Male and female Beagle dogs of 5-6 months old were chosen for the pilot study of four week repeated dose toxicity of Sweet BV which was administered at the level of 0.56mg/kg body weight which is eighty times higher than the clinical application dosage as the high dosage, followed by 0.28 and 0.14mg/kg as midium and low dosage, respectively. Equal amount of excipient(normal saline) to the Sweet BV experiment groups was administered as the control group every day for four weeks. Results: 1. No mortality was witnessed in all of the experiment groups. 2. All experiment groups were appealed pain sense in the treating time compared to the control group, and hyperemia and movement disorder were observed around the area of administration in all experiment groups, and higher occurrence in the higher dosage treatment. 3. For weight measurement, Neither male nor female groups showed significant changes. 4. In the urine analysis, CBC and biochemistry didn`t show any significant changes in the experiment groups compared with control group. 5. For weight measurement of organs, experiment groups didn`t show any significant changes compared with control group. 6. To verify abnormalities of organs and tissues, thigh muscle which treated with Sweet BV, cerebrum, liver, lung, kidney, and spinal cords were removed and conducted histologocal observation with H-E staining. In the histologocal observation of thigh muscle, cell infiltration, inflammatory, degeneration, necrosis of muscle fiber, and fibrosis were found in both thigh tissue. And the changes were depend on the dose of Sweet BV. But another organs were not detected in any abnormalities. 7. The proper high dosage of Sweet BV for the thirteen week repeated test in Beagle dogs may be 0.28mg/kg in one time. Conclusion: Above findings suggest that Sweet BV is relatively safe treatment medium. Further studies on the subject should be conducted to yield more concrete evidences.

  • study of single dose test of sweet Bee Venom in rats
    Journal of Pharmacopuncture, 2009
    Co-Authors: Young Jin Kim, Chungsan Lim, Kirok Kwon
    Abstract:

    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.

  • purification of peptide components including melittin from Bee Venom using gel filtration chromatography and propionic acid urea polyacrylamide gel electrophoresis
    Journal of Pharmacopuncture, 2006
    Co-Authors: Youngchon Choi, Sukho Choi, Kirok Kwon
    Abstract:

    Objectives : This study was conducted to carry out Purification of Melittin and other peptide components from Bee Venom using gel filtration chromatography and propionic acid/urea polyacrylamide gel electrophoresis Methods : Melittin and other peptide components were separated from Bee Venom by using gel filtration chromatography on Sephadex G-50 column in 0.05M ammonium acetate buffer. Results : Melittin and other peptide components were separated from Bee Venom by using gel filtration chromatography on Sephadex G-50 column in 0.05M ammonium acetate buffer. The fractions obtained from gel filtration chromatography was analyzed by using SDS-PAGE and propionic acid/urea polyacrylamide gel electrophoresis. The melittin obtained from the gel filtration contained residual amount of phospholipase and a protein with molecular weight of 6,000. The contaminating proteins were removed by the second gel filtration chromatography. Conclusion : Gel filtration chromatography and propionic acid/urea polyacrylamide gel electrophoresis are useful to separate peptide components including melittin from Bee Venom.

Kwang Sik Lee - One of the best experts on this subject based on the ideXlab platform.

  • secapin a Bee Venom peptide exhibits anti fibrinolytic anti elastolytic and anti microbial activities
    Developmental and Comparative Immunology, 2016
    Co-Authors: Kwang Sik Lee, Hyung Joo Yoon, Bo Yeon Kim, Yongsoo Choi, Byung Rae Jin
    Abstract:

    Bee Venom contains a variety of peptide constituents that have various biological, toxicological, and pharmacological actions. However, the biological actions of secapin, a Venom peptide in Bee Venom, remain largely unknown. Here, we provide the evidence that Asiatic honeyBee (Apis cerana) secapin (AcSecapin-1) exhibits anti-fibrinolytic, anti-elastolytic, and anti-microbial activities. The recombinant mature AcSecapin-1 peptide was expressed in baculovirus-infected insect cells. AcSecapin-1 functions as a serine protease inhibitor-like peptide that has inhibitory effects against plasmin, elastases, microbial serine proteases, trypsin, and chymotrypsin. Consistent with these functions, AcSecapin-1 inhibited the plasmin-mediated degradation of fibrin to fibrin degradation products, thus indicating the role of AcSecapin-1 as an anti-fibrinolytic agent. AcSecapin-1 also inhibited both human neutrophil and porcine pancreatic elastases. Furthermore, AcSecapin-1 bound to bacterial and fungal surfaces and exhibited anti-microbial activity against fungi and gram-positive and gram-negative bacteria. Taken together, our data demonstrated that the Bee Venom peptide secapin has multifunctional roles as an anti-fibrinolytic agent during fibrinolysis and an anti-microbial agent in the innate immune response.

  • antifibrinolytic role of a Bee Venom serine protease inhibitor that acts as a plasmin inhibitor
    PLOS ONE, 2012
    Co-Authors: Young Moo Choo, Hyung Joo Yoon, Hu Wan, Kwang Sik Lee, Yuling Qiu, Mi Ri Sohn, Hung Dae Sohn, Byung Rae Jin
    Abstract:

    Bee Venom is a rich source of pharmacologically active substances. In this study, we identified a bumbleBee (Bombus ignitus) Venom Kunitz-type serine protease inhibitor (Bi-KTI) that acts as a plasmin inhibitor. Bi-KTI showed no detectable inhibitory effect on factor Xa, thrombin, or tissue plasminogen activator. In contrast, Bi-KTI strongly inhibited plasmin, indicating that it acts as an antifibrinolytic agent; however, this inhibitory ability was two-fold weaker than that of aprotinin. The fibrin(ogen)olytic activities of B. ignitus Venom serine protease (Bi-VSP) and plasmin in the presence of Bi-KTI indicate that Bi-KTI targets plasmin more specifically than Bi-VSP. These findings demonstrate a novel mechanism by which bumbleBee Venom affects the hemostatic system through the antifibrinolytic activity of Bi-KTI and through Bi-VSP-mediated fibrin(ogen)olytic activities, raising interest in Bi-KTI and Bi-VSP as potential clinical agents.

  • dual function of a Bee Venom serine protease prophenoloxidase activating factor in arthropods and fibrin ogen olytic enzyme in mammals
    PLOS ONE, 2010
    Co-Authors: Young Moo Choo, Hyung Joo Yoon, Kwang Sik Lee, Mi Ri Sohn, Bo Yeon Kim, Jong Yul Roh, Namjung Kim, Iksoo Kim, Soo Dong Woo, Hung Dae Sohn
    Abstract:

    Bee Venom contains a variety of peptides and enzymes, including serine proteases. While the presence of serine proteases in Bee Venom has Been demonstrated, the role of these proteins in Bee Venom has not Been elucidated. Furthermore, there is currently no information available regarding the melanization response or the fibrin(ogen)olytic activity of Bee Venom serine protease, and the molecular mechanism of its action remains unknown. Here we show that Bee Venom serine protease (Bi-VSP) is a multifunctional enzyme. In insects, Bi-VSP acts as an arthropod prophenoloxidase (proPO)-activating factor (PPAF), thereby triggering the phenoloxidase (PO) cascade. Bi-VSP injected through the stinger induces a lethal melanization response in target insects by modulating the innate immune response. In mammals, Bi-VSP acts similarly to snake Venom serine protease, which exhibits fibrin(ogen)olytic activity. Bi-VSP activates prothrombin and directly degrades fibrinogen into fibrin degradation products, defining roles for Bi-VSP as a prothrombin activator, a thrombin-like protease, and a plasmin-like protease. These findings provide a novel view of the mechanism of Bee Venom in which the Bee Venom serine protease kills target insects via a melanization strategy and exhibits fibrin(ogen)olytic activity.