The venom of honeybees is composed of numerous peptides and proteins and has been used for decades as an anti-inflammatory and anti-cancer agent in traditional medicine. However, the bioactivity of ...specific biomolecular components has been evaluated for the predominant constituent, melittin. So far, only a few melittin-like peptides from solitary bee species have been investigated, and the molecular mechanisms of bee venoms as therapeutic agents remain largely unknown. Here, the preclinical pharmacological activities of known and proteo-transcriptomically discovered new melittin variants from the honeybee and more ancestral variants from phylogenetically older solitary bees were explored in the context of cancer and inflammation. We studied the effects of melittin peptides on cytotoxicity, second messenger release, and inflammatory markers using primary human cells, non-cancer, and cancerous cell lines. Melittin and some of its variants showed cytotoxic effects, induced Ca
signaling and inhibited cAMP production, and prevented LPS-induced NO synthesis but did not affect the IP3 signaling and pro-inflammatory activation of endothelial cells. Compared to the originally-described melittin, some phylogenetically more ancestral variants from solitary bees offer potential therapeutic modalities in modulating the in vitro inflammatory processes, and hindering cancer cell viability/proliferation, including aggressive breast cancers, and are worth further investigation.
In the present study, we examined the potential symptomatic and/or disease-modifying effects of monthly bee venom injections compared to placebo in moderatly affected Parkinson disease patients. We ...conducted a prospective, randomized double-blind study in 40 Parkinson disease patients at Hoehn & Yahr stages 1.5 to 3 who were either assigned to monthly bee venom injections or equivalent volumes of saline (treatment/placebo group: n = 20/20). The primary objective of this study was to assess a potential symptomatic effect of s.c. bee venom injections (100 μg) compared to placebo 11 months after initiation of therapy on United Parkinson’s Disease Rating Scale (UPDRS) III scores in the « off » condition pre-and post-injection at a 60 minute interval. Secondary objectives included the evolution of UPDRS III scores over the study period and 123I-FP-CIT scans to evaluate disease progression. Finally, safety was assessed by monitoring specific IgE against bee venom and skin tests when necessary. After an 11 month period of monthly administration, bee venom did not significantly decrease UPDRS III scores in the « off » condition. Also, UPDRS III scores over the study course, and nuclear imaging, did not differ significantly between treatment groups. Four patients were excluded during the trial due to positive skin tests but no systemic allergic reaction was recorded. After an initial increase, specific IgE against bee venom decreased in all patients completing the trial. This study did not evidence any clear symptomatic or disease-modifying effects of monthly bee venom injections over an 11 month period compared to placebo using a standard bee venom allergy desensitization protocol in Parkinson disease patients. However, bee venom administration appeared safe in non-allergic subjects. Thus, we suggest that higher administration frequency and possibly higher individual doses of bee venom may reveal its potency in treating Parkinson disease.
ClinicalTrials.gov NCT01341431.
Background Detection of IgE to recombinant Hymenoptera venom allergens has been suggested to improve the diagnostic precision in Hymenoptera venom allergy. However, the frequency of sensitization to ...the only available recombinant honeybee venom (HBV) allergen, rApi m 1, in patients with HBV allergy is limited, suggesting that additional HBV allergens might be of relevance. Objective We performed an analysis of sensitization profiles of patients with HBV allergy to a panel of HBV allergens. Methods Diagnosis of HBV allergy (n = 144) was based on history, skin test results, and allergen-specific IgE levels to HBV. IgE reactivity to 6 HBV allergens devoid of cross-reactive carbohydrate determinants (CCD) was analyzed by ImmunoCAP. Results IgE reactivity to rApi m 1, rApi m 2, rApi m 3, nApi m 4, rApi m 5, and rApi m 10 was detected in 72.2%, 47.9%, 50.0%, 22.9%, 58.3%, and 61.8% of the patients with HBV allergy, respectively. Positive results to at least 1 HBV allergen were detected in 94.4%. IgE reactivity to Api m 3, Api m 10, or both was detected in 68.0% and represented the only HBV allergen–specific IgE in 5% of the patients. Limited inhibition of IgE binding by therapeutic HBV and limited induction of Api m 3– and Api m 10–specific IgG4 in patients obtaining immunotherapy supports recent reports on the underrepresentation of these allergens in therapeutic HBV preparations. Conclusion Analysis of a panel of CCD-free HBV allergens improved diagnostic sensitivity compared with use of rApi m 1 alone, identified additional major allergens, and revealed sensitizations to allergens that have been reported to be absent or underrepresented in therapeutic HBV preparations.
High dose bee venom exposure in beekeepers by natural bee stings represents a model to understand mechanisms of T cell tolerance to allergens in healthy individuals. Continuous exposure of ...nonallergic beekeepers to high doses of bee venom antigens induces diminished T cell-related cutaneous late-phase swelling to bee stings in parallel with suppressed allergen-specific T cell proliferation and T helper type 1 (Th1) and Th2 cytokine secretion. After multiple bee stings, venom antigen-specific Th1 and Th2 cells show a switch toward interleukin (IL) 10-secreting type 1 T regulatory (Tr1) cells. T cell regulation continues as long as antigen exposure persists and returns to initial levels within 2 to 3 mo after bee stings. Histamine receptor 2 up-regulated on specific Th2 cells displays a dual effect by directly suppressing allergen-stimulated T cells and increasing IL-10 production. In addition, cytotoxic T lymphocyte-associated antigen 4 and programmed death 1 play roles in allergen-specific T cell suppression. In contrast to its role in mucosal allergen tolerance, transforming growth factor beta does not seem to be an essential player in skin-related allergen tolerance. Thus, rapid switch and expansion of IL-10-producing Tr1 cells and the use of multiple suppressive factors represent essential mechanisms in immune tolerance to a high dose of allergens in nonallergic individuals.
Insect stings can cause life-threatening IgE-mediated anaphylactic reactions in venom-allergic patients. Although several compounds have already been described as venom allergens, prominent allergen ...candidates especially in the higher m.w. range have still remained elusive. Tandem mass spectrometry-based sequencing assigned a candidate gene to the most prominent putative high m.w. allergen Api m 5 (allergen C) in honeybee (Apis mellifera) venom and also allowed identification of its homologue Ves v 3 in yellow jacket (Vespula vulgaris) venom. Both proteins exhibit a pronounced sequence identity to human dipeptidyl peptidase IV or CD26. Reactivity of a human IgE mAb verified the presence of these proteins in the venoms. Both proteins were produced in insect cells and characterized for their enzymatic activity as well as their allergenic potential using sera and basophils from insect venom-allergic patients. Both Api m 5 and Ves v 3 were recognized by specific IgE of the majority of patients even in the absence of cross-reactive carbohydrate determinants. Serologic IgE reactivity closely matched activation of human basophils by Api m 5 or Ves v 3, thus underlining their relevance in functional assays. With Api m 5 and Ves v 3, a new pair of homologous allergens becomes available for future clinical applications in diagnosis and therapy that may also contribute to the understanding of molecular mechanisms of insect venoms. Moreover, the patient IgE reactivity together with the cellular activation demonstrates for the first time the relevance of high m.w. allergens in the context of hymenoptera venom allergy.
This study investigated the possible beneficial role of the bee venom (BV,
Apis mellifera
L.) against zinc oxide nanoparticles (ZNPs)-induced neurobehavioral and neurotoxic impacts in rats. Fifty ...male Sprague Dawley rats were alienated into five groups. Three groups were intraperitoneally injected distilled water (C 28D group), ZNPs (100 mg/kg b.wt) (ZNPs group), or ZNPs (100 mg/kg.wt) and BV (1 mg/ kg.bwt) (ZNPs + BV group) for 28 days. One group was intraperitoneally injected with 1 mL of distilled water for 56 days (C 56D group). The last group was intraperitoneally injected with ZNPs for 28 days, then BV for another 28 days at the same earlier doses and duration (ZNPs/BV group). Depression, anxiety, locomotor activity, spatial learning, and memory were evaluated using the forced swimming test, elevated plus maze, open field test, and Morris water maze test, respectively. The brain contents of dopamine, serotonin, total antioxidant capacity (TAC), malondialdehyde (MDA), and Zn were estimated. The histopathological changes and immunoexpressions of neurofilament and GAP-43 protein in the brain tissues were followed. The results displayed that BV significantly decreased the ZNPs-induced depression, anxiety, memory impairment, and spatial learning disorders. Moreover, the ZNPs-induced increment in serotonin and dopamine levels and Zn content was significantly suppressed by BV. Besides, BV significantly restored the depleted TAC but minimized the augmented MDA brain content associated with ZNPs exposure. Likewise, the neurodegenerative changes induced by ZNPs were significantly abolished by BV. Also, the increased neurofilament and GAP-43 immunoexpression due to ZNPs exposure were alleviated with BV. Of note, BV achieved better results in the ZNPs + BV group than in the ZNPs/BV group. Conclusively, these results demonstrated that BV could be employed as a biologically effective therapy to mitigate the neurotoxic and neurobehavioral effects of ZNPs, particularly when used during ZNPs exposure.
Cosmetic Applications of Bee Venom El-Wahed, Aida A Abd; Khalifa, Shaden A M; Elashal, Mohamed H ...
Toxins,
11/2021, Letnik:
13, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Bee venom (BV) is a typical toxin secreted by stingers of honeybee workers. BV and BV therapy have long been attractive to different cultures, with extensive studies during recent decades. Nowadays, ...BV is applied to combat several skin diseases, such as atopic dermatitis, acne vulgaris, alopecia, vitiligo, and psoriasis. BV is used extensively in topical preparations as cosmetics and used as dressing for wound healing, as well as in facemasks. Nevertheless, the safety of BV as a therapeutic choice has always been a concern due to the immune system reaction in some people due to BV use. The documented unfavorable impact is explained by the fact that the skin reactions to BV might expand to excessive immunological responses, including anaphylaxis, that typically resolve over numerous days. This review aims to address bee venom therapeutic uses in skin cosmetics.
This study aims to fully exploit the natural compound; bee venom (BV) as a substance that can kill and inhibit the growth of microbes and viruses. For this target, BV was loaded onto a safe, natural, ...and economically inexpensive polymer; chitosan (Ch) in its nano-size form prepared using ionic gelation method in the presence of chemical crosslinking agent (sodium tripolyphosphate; TPP). The findings illustrated that chitosan nanoparticles (ChNPs) were prepared thru this method and exhibited spherical shape and average hydrodynamic size of 202 nm with a polydispersity index (PDI = 0.44). However, the size was increased to 221 nm with PDI (0.37) when chitosan nanoparticles were loaded with BV (ChNC). In addition, the particles of BV appeared as a core and chitosan nanoparticles as a shell implying the successful preparation of nanocomposite (ChNC). Encapsulation of BV into ChNPs with significantly small size distribution and good stability that protect these formed nanocomposites from agglomeration. The cytopathic effect (CPE) inhibition assay was used to identify potential antivirals for Middle East respiratory syndrome coronavirus (MERS-CoV). The response of the dose study was designed to influence the range of effectiveness for the chosen antiviral, i.e., the 50 % inhibitory concentration (IC50), as well as the range of cytotoxicity (CC50). However, our results indicated that crude BV had mild anti-MERS-COV with selective index (SI = 4.6), followed by ChNPs that exhibited moderate anti-MERS-COV with SI = 8.6. Meanwhile. The nanocomposite of ChNC displayed a promising anti-MERS-COV with SI = 12.1. Additionally, the synthesized nanocomposite (ChNC) had greater antimicrobial activity against both Gram-positive and Gram-negative bacteria when compared with ChNPs, BV or the utilized model drug.
•Bee venom (BV) loaded chitosan nanoparticles (ChNPs) were prepared and fully characterized.•The findings illustrated that BV appeared as a core and ChNPs as a shell.•BV loaded ChNPs (ChNC) displayed anti-MERS-COV with SI = 12.1.•ChNC exhibited greater antimicrobial activity against different pathogenic species.
Allergen-specific immunotherapy is the only curative treatment of honeybee venom (HBV) allergy, which is able to protect against further anaphylactic sting reactions. Recent analyses on a molecular ...level have demonstrated that HBV represents a complex allergen source that contains more relevant major allergens than formerly anticipated. Moreover, allergic patients show very diverse sensitization profiles with the different allergens. HBV-specific immunotherapy is conducted with HBV extracts which are derived from pure venom. The allergen content of these therapeutic extracts might differ due to natural variations of the source material or different down-stream processing strategies of the manufacturers. Since variations of the allergen content of therapeutic HBV extracts might be associated with therapeutic failure, we adressed the component-resolved allergen composition of different therapeutic grade HBV extracts which are approved for immunotherapy in numerous countries. The extracts were analyzed for their content of the major allergens Api m 1, Api m 2, Api m 3, Api m 5 and Api m 10. Using allergen-specific antibodies we were able to demonstrate the underrepresentation of relevant major allergens such as Api m 3, Api m 5 and Api m 10 in particular therapeutic extracts. Taken together, standardization of therapeutic extracts by determination of the total allergenic potency might imply the intrinsic pitfall of losing information about particular major allergens. Moreover, the variable allergen composition of different therapeutic HBV extracts might have an impact on therapy outcome and the clinical management of HBV-allergic patients with specific IgE to particular allergens.
In clinical practice, bee venom injection into acupuncture points is used to relieve various types of musculoskeletal pain. In the current study, we describe a patient who had persistent severe ...muscle pain caused by mistakenly injected high-dose bee venom.
A 63-year-old woman mistakenly received an injection of high-dose (2 mL; standard dose, 0.1 mL) bee venom (diluted in saline at a 1:2000 ratio). Immediately after the injection, extreme burning pain developed at the injection site, which persisted for 1 month with a mean pain score of 9 on the numeric rating scale. T1-weighted gadolinium-enhanced axial lumbar magnetic resonance imaging revealed increased intensity in the medial part of the left psoas muscle around the L4-5 intervertebral disc level.
This finding indicated the presence of inflammation in the left psoas muscle, which was thought to be associated with pain.
A buprenorphine transdermal patch (releasing 5 mcg/hours) was applied to alleviate the pain.
Six months after the bee venom injection, the pain completely resolved.
Bee venom has a strong toxic effect; therefore, only a minimal dose of diluted bee venom should be administered for musculoskeletal pain control. Special caution is required during bee venom injection to avoid excessive doses of bee venom.
PDF
