Apitherapy is an alternate therapy that relies on the usage of honeybee products, most importantly bee venom for the treatment of many human diseases. The venom can be introduced into the human body ...by manual injection or by direct bee stings. Bee venom contains several active molecules such as peptides and enzymes that have advantageous potential in treating inflammation and central nervous system diseases, such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. Moreover, bee venom has shown promising benefits against different types of cancer as well as anti-viral activity, even against the challenging human immunodeficiency virus (HIV). Many studies described biological activities of bee venom components and launched preclinical trials to improve the potential use of apitoxin and its constituents as the next generation of drugs. The aim of this review is to summarize the main compounds of bee venom, their primary biological properties, mechanisms of action, and their therapeutic values in alternative therapy strategies.
Cardiovascular diseases (CVDs) are considered as a major cause of death worldwide. Therefore, identifying and developing therapeutic strategies to treat and reduce the prevalence of CVDs is a major ...medical challenge. Several drugs used for the treatment of CVDs, such as captopril, emerged from natural products, namely snake venoms. These venoms are complex mixtures of bioactive molecules, which, among other physiological networks, target the cardiovascular system, leading to them being considered in the development and design of new drugs. In this review, we describe some snake venom molecules targeting the cardiovascular system such as phospholipase A2 (PLA2), natriuretic peptides (NPs), bradykinin-potentiating peptides (BPPs), cysteine-rich secretory proteins (CRISPs), disintegrins, fibrinolytic enzymes, and three-finger toxins (3FTXs). In addition, their molecular targets, and mechanisms of action-vasorelaxation, inhibition of platelet aggregation, cardioprotective activities-are discussed. The dissection of their biological effects at the molecular scale give insights for the development of future snake venom-derived drugs.
Bee venom is a mixture of several components with proven therapeutic benefits, among which are anti-inflammatory, analgesic, and various cardiovascular conditions. In this work, we analyzed for the ...first time the proteomic content and biological properties of the crude venom from
, a honeybee from the Middle East region. Using high-performance liquid chromatography-tandem mass spectrometry, we evidence the venom contains phospholipase A2, hyaluronidase, mast cell-degranulating peptide, adolapin, apamin, and melittin. The latter was purified by solid phase extraction method (SPE) and tested in parallel with crude venom for biological activities. Precisely, crude venom-but not melittin-exhibited antibacterial activity against
and
strains. Alongside, hemolytic activity was observed in human blood subjected to the venom at high doses.
venom displayed antioxidant activities, and not surprisingly, PLA2 catalytic activity. Eventually, the venom proved to exert antiproliferative effects against MCF-7 and 3T3 cancer cells lines. This first report of a new bee venom opens new avenues for therapeutic uses of bee venoms.
Voltage-gated Na+ (NaV) channels are significant therapeutic targets for the treatment of cardiac and neurological disorders, thus promoting the search for novel NaV channel ligands. With the ...objective of discovering new blockers of NaV channel ligands, we screened an In-House vegetal alkaloid library using fluorescence cell-based assays. We screened 62 isoquinoline alkaloids (IA) for their ability to decrease the FRET signal of voltage sensor probes (VSP), which were induced by the activation of NaV channels with batrachotoxin (BTX) in GH3b6 cells. This led to the selection of five IA: liriodenine, oxostephanine, thalmiculine, protopine, and bebeerine, inhibiting the BTX-induced VSP signal with micromolar IC50. These five alkaloids were then assayed using the Na+ fluorescent probe ANG-2 and the patch-clamp technique. Only oxostephanine and liriodenine were able to inhibit the BTX-induced ANG-2 signal in HEK293-hNaV1.3 cells. Indeed, liriodenine and oxostephanine decreased the effects of BTX on Na+ currents elicited by the hNaV1.3 channel, suggesting that conformation change induced by BTX binding could induce a bias in fluorescent assays. However, among the five IA selected in the VSP assay, only bebeerine exhibited strong inhibitory effects against Na+ currents elicited by the hNav1.2 and hNav1.6 channels, with IC50 values below 10 µM. So far, bebeerine is the first BBIQ to have been reported to block NaV channels, with promising therapeutical applications.
The isoquinoline alkaloids (IAs) represent a large and diverse subfamily of phytochemicals in terms of structures and pharmacological activities, including ion channel inhibition. Several IAs, such ...as liriodenine (an oxoaporphine) and curine (a bisbenzylisoquinoline (BBIQ), inhibit the L-type voltage-gated Ca2+ channels (LTCC). In this study, we aimed to search for new blockers of LTCC, which are therapeutic targets in neurological and cardiovascular diseases. We set up a screening assay using the rat pituitary GH3b6 cell line, which expresses two LTCC isoforms, CaV1.2 and CaV1.3. Both LTCC subtypes can be indirectly activated by KCl concentration elevation or directly by the dihydropyridine (DHP), BAY K8644, leading to an increase in the intracellular Ca2+ concentration (Ca2+i). These Ca2+ responses were completely blocked by the selective LTCC DHP inhibitor, nifedipine. Thereby, 16 selected IAs were tested for their ability to inhibit KCl and BAY K8644-induced Ca2+ responses. We then identified three new potent LTCC blockers, namely, oxostephanine, thaliphyline, and thalmiculine. They inhibited LTCC with IC50 values in the micromolar range through interaction to a binding site different to that of dihydropyridines. The two subfamilies of IAs, oxoaporphine with oxostephanine, and BBIQs with both thalyphilline and thalmiculine, constitute interesting pharmacophores for the development of future therapeutic leads for neurological and cardiovascular diseases.
Cardiovascular diseases (CVDs) are considered as a major cause of death worldwide. Therefore, identifying and developing therapeutic strategies to treat and reduce the prevalence of CVDs is a major ...medical challenge. Several drugs used for the treatment of CVDs, such as captopril, emerged from natural products, namely snake venoms. These venoms are complex mixtures of bioactive molecules, which, among other physiological networks, target the cardiovascular system, leading to them being considered in the development and design of new drugs. In this review, we describe some snake venom molecules targeting the cardiovascular system such as phospholipase A2 (PLA2), natriuretic peptides (NPs), bradykinin-potentiating peptides (BPPs), cysteine-rich secretory proteins (CRISPs), disintegrins, fibrinolytic enzymes, and three-finger toxins (3FTXs). In addition, their molecular targets, and mechanisms of action—vasorelaxation, inhibition of platelet aggregation, cardioprotective activities—are discussed. The dissection of their biological effects at the molecular scale give insights for the development of future snake venom-derived drugs.
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