Therapeutic Effect Of Bee Venom Research Articles

Possible curative effect of venom collected from Algerian bees (Apis mellifera intermissa) on adenine-induced chronic kidney damage in mice

ABSTRACT Chronic kidney disease (CKD) is a world-wide health concern, and thus curative approach becomes highly valuable. Herein, we examined the possible therapeutic effect of bee venom collected from Algeria (Apis mellifera intermissa) on adenine-induced chronic kidney damage. Mice received intraperitoneal injection of adenine at a dose of 50 mg/kg for four weeks to induce CKD. After that, bee venom was administered intraperitoneally (i.p) to mice at a dose of 0.76 mg/kg BW for a week. Adenine-treated mice decreased the body weight evolution, and significantly increased the kidney weight, water intake, and urine output compared with controls. In addition, serum and urine urea and creatinine levels, and serum albumin concentrations were significantly increased, while serum creatinine clearance level was significantly decreased in adenine-treated mice compared with controls. Adenine-induced oxidative stress was evidenced by increased MDA content, and decreased catalase and GST activity, and GSH content in renal tissue. Meanwhile, the administration of bee venom to adenine-treated mice markedly recovered kidney function via improvement of the altered physiological and biochemical parameters. These were confirmed by the morphological and histopathological results. In conclusion, bee venom is a prising therapeutic natural agent for improving kidney function in adenine-induced CKD.

Изменение ИК-спектров метаболитов энергетического обмена в крови крыс с гепатоцеллюлярной карциномой при воздействии гипертермии и апитоксина

There is a need to develop and improve conservative treatment methods for malignant liver tumours, since only in a small percentage of cases (10–30 %) radical treatments can be applied. Therefore, of relevance are studies into the effect of hyperthermia on the absorption of antitumour drugs and the effect of bee venom as a physiological therapeutic agent on the energy metabolism of tumour cells. Infrared spectroscopy could potentially be used to study changes in energy metabolism parameters in the blood plasma. The purpose of this article is to assess changes in the concentrations of energy metabolism metabolites in the blood of tumour-bearing animals during hyperthermia under the action of apitoxin using infrared spectroscopy. Materials and methods. The research involved 50 white non-linear female rats, divided into an intact, control and three experimental groups. The control and experimental groups were inoculated with hepatocellular carcinoma. The experimental groups were injected intraperitoneally with honey bee venom followed by hyperthermia sessions at different temperatures (42.5; 43.5 and 44.5 °С). Blood plasma was studied using a spectrophotometer in the wavenumber range of 1170–1025 cm–1. Results. We found a statistically significant increase in adenosine triphosphate concentrations (by 54 %) and a decrease in adenosine monophosphate (by 54 %), adenosine diphosphate (by 18 %) and glucose (by 87 %) levels compared to the control at 42.5 °C hyperthermia under the action of bee venom by the 7th day; however, on the 28th day the opposite effect was observed: an increase in adenosine monophosphate, adenosine diphosphate and glucose concentrations and a decrease in adenosine triphosphate levels. No positive dynamic was detected at other hyperthermia regimens. It is concluded that infrared spectroscopy can be used to assess energy changes in animals with hepatocellular carcinoma at different hyperthermia regimens under the therapeutic effect of bee venom. The optimal conditions for bee venom effects on the body are achieved at 42.5 °C.

Therapeutic Effect of Bee Venom and Melittin on Skin Infection Caused by Streptococcus pyogenes.

Streptococcus pyogenes (S. pyogenes) bacteria cause almost all primary skin infections in humans. Bee venom (BV) and melittin (Mel) have multiple effects, including antibacterial and anti-inflammatory activities. This study aims to demonstrate their effects on bacterial mouse skin infection using S. pyogenes. The dorsal skin was tape-stripped, then S. pyogenes was topically applied. BV or Mel were topically applied to the lesion. The tissues were stained with hematoxylin and eosin, while immunohistochemical staining was performed with anti-neutrophil. S. pyogenes-infected skin revealed increased epidermal and dermal layers, but it was reduced in the BV and Mel groups. Finding increased neutrophils in the mice infected with S. pyogenes, but the BV and Mel mice showed decreased expression. These results suggest that BV and Mel treatments could reduce the inflammatory reactions and help improve lesions induced by S. pyogenes skin infection. This study provides additional assessment of the potential therapeutic effects of BV and Mel in managing skin infection caused by S. pyogenes, further suggesting that it could be a candidate for developing novel treatment alternative for streptococcal skin infections.

Photoprotective and therapeutic effects of Apamin, Melittin and Phospholipase A2 on human keratinocyte cell line

The aim of this study is to determine the protective and therapeutic properties of bee venom components Apamin, Melittin and Phospholipase A2 against UV damage on the human keratinocyte cell line. Cosmetic and therapeutic effects of bee venom have been reported in previous studies, but it is not known which components of the venom have the most effect. For this purpose, firstly, an in vitro UV damage model was designed. Components of bee venom were tested at a different concentration. Cell viability, cytotoxicity and apoptotic processes were analyzed on the designed model. As a result, it has been observed that Apamin demonstrated a significant protective effect against UV-induced cell death at all concentrations. Photoprotective effects of Melittin were observed in all concentration time periods and its photoprotective effects were increased as the concentration increased. Our results were indicated that Phospholipase A2 could be used as a photoprotective and phototherapy agent. This study is the first to show the protective and therapeutic properties of bee venom components against UV damage. As a result, it has been shown that these components can be successful photoprotective and phototherapeutic agents against UV-induced damage, but more detailed studies should be conducted to minimize their toxic effects on cells.

Therapeutic Effects of Bee Venom

Bee venom (BV) has a long history of use in Korea for the relief of pain symptoms and for the treatment of various inflammatory diseases, including rheumatoid arthritis. There is some evidence for the underlying mechanisms involved in the venom’s anti-inflammatory and analgesic activities. Recent clinical and experimental reearch has confirmed that the venom and its active components can be applied to a broad spectrum of immunological and neurodegenerative diseases, including autoimmune diseases and Parkinson’s disease. BV has been shown to exhibit these effects by modulating immune cells in the periphery, together with glial cells and neurons in the central nervous system. This review sets out the latest scientific evidence concerning the therapeutic effects of BV and various components thereof in the context of a number of diseases, and provides a detailed description of the mechanisms.

Therapeutic effects of bee venom and its major component, melittin, on atopic dermatitis in vivo and in vitro.

Background and PurposeAtopic dermatitis (AD) is a multifactorial skin condition with complex interactions of innate and adaptive immune responses. There are several existing therapies for AD, including topical glucocorticosteroids, emollients, phototherapies, calcineurin inhibitors and immunosuppressants, such as cyclosporine A. Although these therapies reduce inflammation, they also cause serious side effects. Therefore, it is necessary to develop new therapeutic approaches for AD treatment without side effects. There are several studies on natural materials or toxins, such as herbs, ginseng extract and snake venom, for AD treatment. However, treatment of AD with bee venom and its major component, melittin has rarely been studied.Experimental ApproachEffects of bee venom and melittin were studied in a model of AD in vivo induced by 1‐chloro‐2,4‐dinitrobenzene (DNCB) in female Balb/c mice and in cultures of human keratinocytes, stimulated by TNF‐α/IFN‐γ. The potential pharmacological effects of bee venom and melittin on these in vivo and in vitro AD‐like skin disease models were studied.Key ResultsBee venom and melittin exhibited potent anti‐atopic activities, shown by decreased AD‐like skin lesions, induced by DNCB in mice. In vitro studies using TNF‐α/IFN‐γ‐stimulated human keratinocytes showed that bee venom and melittin inhibited the increased expression of chemokines, such as CCL17 and CCL22, and pro‐inflammatory cytokines, including IL‐1β, IL‐6 and IFN‐γ, through the blockade of the NF‐κB and STAT signalling pathways.Conclusions and ImplicationsOur results suggest that bee venom and melittin would be suitable for epicutaneous application, as topical administration is often appropriate for the treatment of AD.

Therapeutic effects of bee venom on experimental atopic dermatitis.

Atopic dermatitis (AD) is a chronic skin inflammatory disease characterized by recurrent eczema and itching. It is caused by a poorly controlled immune response and damage to the skin barrier. Purified bee venom (BV) is a natural toxin produced by honeybees (Apis mellifera L.), and is well known for its anti-inflammatory, analgesic and anti-cancer effects against various types of disease. However, treatment strategies based on anti-inflammatory properties have not been adequately studied in AD. Thus, the present study examined the progression of AD-like skin lesions induced by ovalbumin (OVA) and the mechanism of action of BV. BV, administered by intraperitoneal inoculation, was observed to reduce the symptoms of AD, in addition to the serum immunoglobulin E levels, according to dorsal skin thickness and histopathologic analysis. The treatment also inhibited the infiltration of eosinophils and mast cells. These results suggested that it is possible to develop novel AD alternative therapy using BV by effectively suppressing allergic skin inflammation in AD.

The therapeutic effects of bee venom on some metabolic and antioxidant parameters associated with HFD-induced non-alcoholic fatty liver in rats.

The present study was designed to investigate the therapeutic effects of bee venom (BV) on high-fat diet (HFD)-induced non-alcoholic fatty liver (NAFL) in rats at different levels. Histological manifestations, hepatic lipid content, liver function tests, glucose homeostasis, lipid abnormalities, adipocytokines, lipid peroxidation, disturbed glutathione and antioxidant enzymes systems and dysregulation of Nrf2 transcription factor were assessed. In the present study, the NAFL rats were subcutaneously treated with BV with different doses (0.01, 0.05, 0.1 mg/kg). The results indicated that BV treatment completely normalized the lipid profile values of NAFL rats. Fasting blood sugar, insulin level and homeostatic model assessment of insulin resistance significantly decreased. BV treated rats showed a significantly lower level of all liver enzymes and bilirubin. Moreover, BV treatment significantly increased the levels of active nuclear erythroid factor 2 like 2, glutathione (GSH) (total and reduced), GSH/glutathione disulphide ratio and activities of glutathione reductase, glutathione-S-transferase and glutathione peroxidase (total and Se-dependent). The level of tumor necrosis factor-α was reduced. Treatment showed correction of adiponectin level, and significant downregulation of hepatic triglycerides and cholesterol. At the histological level, BV improved the architecture of liver cells showing normal sinusoids. It may be concluded that BV may represent an interesting therapeutic alternative for the treatment of NAFL disease.

Anti-bacterial and Anti-inflammatory Effect of Melittin on Propionibacterium acnes-induced Inflammatory Skin Disease in vivo

최근 봉독의 여드름 치료에 대한 효과가 알려지면서 봉독의 주성분인 멜리틴의 항 여드름 작용이 관심을 받게되었다. 본 연구에서는 여드름 유발균으로 알려진 P. acnes를 이용해서 실험동물에 여드름을 유발한 뒤 멜리틴을 투여하여, 여드름 균에 의한 염증반응을 억제하는 효과와 억제기전의 일부를 관찰하고자 하였다. 항균효과를 측정하기 위해 agar well diffusion array 기법을 사용하였다. 마우스의 양쪽 귀에 P. acnes를 피내 주사한 후 오른쪽 귀에만 각 1, 10, 100μg의 멜리틴을 바셀린에 섞어 귀에 도포하였다. 여드름균에 의해 유도된 피부염증반응에 대한 멜리틴의 항염증작용을 확인하기 위해 실험쥐의 귀 조직에 hematoxylin and eosin 염색과 대식 세포 표면 발현물질인 F4/80의 면역화학염색을 시행하였다. 멜리틴 처리 후 짧은 시간 내에 즉각적인 항균 효과를 나타내었으며, 처리시간이 증가함에 따라 그 효과가 증가함을 관찰하였다. P. acnes로 유발된 염증성 피부질환 동물모델에서도 멜리틴을 투여한 조직에서 염증 반응이 억제되는 것을 광학 현미경 검사 및 면역조직화학염색을 통해 확인할 수 있었다. 본 연구를 통하여 봉독의 주성분인 멜리틴은 여드름 유발균인 P. acnes의 활성과 이로 유도된 염증반응을 억제시킴으로써 염증성 여드름에 대한 치료효과가 있음을 확인하여 향후 치료 약제 개발 가능성이 높을 것으로 생각된다.

The Effect of Bee Venom on Animal Model of Unilateral Ureteral Obstruction

Progressive renal fibrosis is the final common pathway for kidney diseases leading to chronic renal failure. Epithelial-mesenchymal transition (EMT) is known to be the critical mechanisms of the development and aggravation of chronic kidney injury. In this study, we examined the therapeutic effects of bee venom (BV) on the progression of renal fibrosis using the unilateral ureteral obstruction (UUO) model. UUO group increased the expression of fibrosis-related genes including FSP-1, PAI-1 and Vimentin, whereas these expressions were significantly decreased by BV treatment. The number of cells positive for ILK was increased in UUO mice, but decreased by BV treatment. In addition, β-catenin, and Snail1 expression was increased in UUO mice, while this effect was significantly decreased with BV treatment. The UUO operation significantly induced expression of Vimentin, and inhibited expression of E-cadherin compared to normal kidney. However, BV treatment markedly decreases Vimentin expression, and increases E-cadherin expression. In summary, these findings suggest that BV attenuate renal fibrosis and reduce EMT responses by suppression of pro-fibrotic genes, and EMT-related genes.

Effects of bee venom against Propionibacterium acnes-induced inflammation in human keratinocytes and monocytes.

Propionibacterium acnes (P. acnes) cause inflammatory acne and play an important role in the pathogenesis of acne by inducing inflammatory mediators. P. acnes contributes to the inflammatory responses of acne by activating inflammatory cells, keratinocytes and sebocytes to secrete pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-8. Bee venom has traditionally been used in the treatment of certain immune-related diseases. However, there has not yet been a robust trial to prove the therapeutic effect of bee venom in skin inflammation. The aim of the present study was to investigate anti-inflammatory properties of bee venom in skin inflammation induced by P. acnes using keratinocytes (HaCaT) and monocytes (THP-1). P. acnes is known to stimulate the production of pro-inflammatory cytokines such as IL-1, IL-8, IL-12 and TNF-α. In the present study, the production of interferon-γ (IFN-γ), IL-1β, IL-8 and TNF-α was increased by P. acnes treatment in HaCaT and THP-1 cells. By contrast, bee venom effectively inhibited the secretion of IFN-γ, IL-1β, IL-8 and TNF-α. Furthermore, P. acnes treatment activated the expression of IL-8 and toll-like receptor 2 (TLR2) in HaCaT cells. However, bee venom inhibited the expression of IL-8 and TLR2 in heat-killed P. acnes. Based on these results, it is concluded that bee venom has an effective anti-inflammatory activity against P. acnes in HaCaT and THP-1 cells. Therefore, we suggest that bee venom is an alternative treatment to antibiotic therapy of acne.

Bee Venom Attenuates Experimental Autoimmune Encephalomyelitis through Direct Effets on CD4+CD25+FOXP3+ T Cells

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that leads to substantial disability through deficits of sensation and of motor, autonomic, and neuro-cognitive function. Many clinical and pathological features of experimental autoimmune encephalomyelitis (EAE) show close similarity to MS. Bee venom (BV) has been used in the practice of oriental medicine and evidence from the literature indicates that BV plays an anti-inflammatory or anti-nociceptive role against inflammatory reactions associated with arthritis and other inflammatory diseases. The purpose of the present study was to determine whether BV could suppress immune cell differentiation and infiltration into spinal cord on EAE mice commonly used as a model for MS. BV treatment increased the population of CD4+CD25+Foxp3+ T cells and inhibited CD4+ T-cell proliferation in vitro. In vivo, BV treatment increased the population of CD4+CD25+Foxp3+ T cells. Furthermore, BV administration reduced the severity of EAE while concurrently decreasing INF-γ producing CD4+T cells, IL-17A producing CD4+T cells and inflammatory cytokine production including INF-γ, IL-17A, TNF and IL-6. BV-treated animals exhibited less infiltration and preserved morphology compared to saline-treated animals. Interestingly, the therapeutic effects of BV on EAE disappeared when CD4+CD25+Foxp3+ T cells were depleted by using anti-CD25 antibody. Our research suggests that BV could be a potential therapeutic agent for antiinflammatory effects in an animal model of EAE.

The assessment of bee venom responses in an experimental model of mono-arthritis using Tc-99m DPD bone scintigraphy

Several recent studies have shown that bee venom (BV) has an anti-nociceptive and anti-inflammatory effect on arthritis. However, objective methods for evaluation of the therapeutic effect of BV is insufficient in animal studies and clinical trials. Our purpose was to determine the usefulness of bone scintigraphy using Tc-99m DPD (3,3-diphosphono-1,2-propan-dicarbonacid) about effects of BV applied to carrageenan-induced mono-arthritis (CIA) model. Mono-arthritis was induced by an intra-articular injection of carrageenan in Sprague-Dawley rats. Administration of BV (0.8 mg/kg) was performed at 30 min before and at 4 h after the induction of mono-arthritis. We assigned rats to BV-before, BV-after, control-before and control-after groups and compared the results of each group by the weight-loading test and bone scintigraphy. The rats received an intravenous injection of 37 MBq of Tc-99m DPD by the tail vein and then scanning was performed at 4 and 24 h after the injection. Visual assessment and quantitative analysis were performed for both knees. The BV-before and BV-after groups were more improved than the control groups on the weight load test (p < 0.05). Bone scintigraphy showed lower activity in the BV-before group than in the control-before group (p < 0.05) on the 4 h imaging. However, a significant difference in the BV-before and BV-after groups was not observed on the 24 h imaging. BV had therapeutic effects by anti-nociceptive and anti-inflammatory activity in the CIA and bone scintigraphy performed on 4 h imaging provided visual and quantitative information for the assessment of the therapeutic response to BV as an objective method in mono-arthritis model.

Bee venom injection into an acupuncture point reduces arthritis associated edema and nociceptive responses

Bee venom (BV) has traditionally been used in Oriental medicine to relieve pain and to treat inflammatory diseases such as rheumatoid arthritis (RA). While several investigators have evaluated the anti-inflammatory effect of BV treatment, the anti-nociceptive effect of BV treatment on inflammatory pain has not been examined. Previous studies in experimental animals suggest that the therapeutic effect of BV on arthritis is dependent on the site of administration. Because of this potential site specificity, the present study was designed to evaluate the anti-nociceptive effect of BV injections into a specific acupoint (Zusanli) compared to a non-acupoint in an animal model of chronic arthritis. Subcutaneous BV treatment (1 mg/kg per day) was found to dramatically inhibit paw edema caused by Freund's adjuvant injection. Furthermore, BV therapy significantly reduced arthritis-induced nociceptive behaviors (i.e. the nociceptive scores for mechanical hyperalgesia and thermal hyperalgesia). These anti-nociceptive/anti-inflammatory effects of BV were observed from 12 days through 21 days post-BV treatment. In addition, BV treatment significantly suppressed adjuvant-induced Fos expression in the lumbar spinal cord at 3 weeks post-adjuvant injection. Finally, injection of BV into the Zusanli acupoint resulted in a significantly greater analgesic effect on arthritic pain as compared to BV injection in to a more distant non-acupoint. The present study demonstrates that BV injection into the Zusanli acupoint has both anti-inflammatory and anti-nociceptive effects on Freund's adjuvant-induced arthritis in rats. These findings raise the possibility that BV acupuncture may be a promising alternative medicine therapy for the long-term treatment of rheumatoid arthritis.

Therapeutic effect of bee venom in sows with hypogalactia syndrome postpartum

The objective of this study was to determine the clincotherapeutic effect of whole bee venom in hypogalactic sows postpartum. Sows after parturition were assigned to treated and nontreated control groups. In the treated group, 22 sows were bee acupunctured once a day for 3 consecutive days. Honeybees (Apis mellifera L.) for bee acupuncture were about 15 days after metamorphosis. One live bee was used to sting the acupoints known as Yang-ming (ST-18, 1.5 cm lateral to the base of the last 2 pairs of teats) and Jiao-chao (GV-1, at the indentation between the base of tail and the anus). In the control group, 20 sows were intramuscularly injected with a standard dosage of penicillin G (400,000 IU/head) once a day for 3 consecutive days. At post-treatment, 85.0% of the drug-treated control and 90.9% of the bee venomtreated group recovered from hypogalactia syndrome. The advantages of apitherapy were that the patients did not have stress because they were not restrained for a long period. The result suggested that apitherapy using bee venom is an effective treatment for sows with hypogalactia syndrome postpartum.