Animals ; Dynorphins ; metabolism ; Parkinson Disease ; drug therapy ; metabolism ; Peptides ; pharmacology ; Rats ; Scorpion Venoms ; pharmacology

The East Asian scorpion Buthus martensii Karsch (BmK) is one of the classical traditional Chinese medicines for treating epilepsy for over a thousand years. Neurotoxins purified from BmK venom are considered as the main active ingredients, acting on membrane ion channels. Voltage-gated sodium channels (VGSCs) play a crucial role in the occurrence of epilepsy, which make them become important drug targets for epilepsy. Long chain toxins of BmK, composed of 60-70 amino acid residues, could specifically recognize VGSCs. Among them, α-like neurotoxins, binding to the receptor site-3 of VGSC, induce epilepsy in rodents and can be used to establish seizure models. The β or β-like neurotoxins, binding to the receptor site-4 of VGSC, have significant anticonvulsant effects in epileptic models. This review aims to illuminate the anticonvulsant/convulsant effects of BmK polypeptides by acting on VGSCs, and provide potential frameworks for the anti-epileptic drug-design.
Animals ; Anticonvulsants/therapeutic use* ; Neurotoxins/pharmacology* ; Scorpion Venoms/pharmacology* ; Scorpions/chemistry* ; Voltage-Gated Sodium Channels

Evolution and natural selection have endowed animal venoms, including scorpion venoms, with a wide range of pharmacological properties. Consequently, scorpions, their venoms, and/or their body parts have been used since time immemorial in traditional medicines, especially in Africa and Asia. With respect to their pharmacological potential, bioactive peptides from scorpion venoms have become an important source of scientific research. With the rapid increase in the characterization of various components from scorpion venoms, a large number of peptides are identified with an aim of combating a myriad of emerging global health problems. Moreover, some scorpion venom-derived peptides have been established as potential scaffolds helpful for drug development. In this review, we summarize the promising scorpion venoms-derived peptides as drug candidates. Accordingly, we highlight the data and knowledge needed for continuous characterization and development of additional natural peptides from scorpion venoms, as potential drugs that can treat related diseases.
Animals ; Scorpion Venoms/pharmacology* ; Peptides/pharmacology* ; Scorpions ; Drug Development ; Medicine, Traditional

OBJECTIVETo investigate the effects of BmkTXK(beta), a newly purified 'long chain' peptide inhibitor of K(+) channels from the Chinese scorpion Buthus martensi Karsch (BmK), on the electrophysiological properties of isolated rabbit atrial myocytes.

METHODSThe standard whole-cell patch-clamp technique was used to study the effects of multiple concentrations of BmkTXK(beta) on potassium currents and action potentials.

RESULTSBmkTXK(beta) produced concentration-dependent prolongation of action potential duration at 20%, 50%, and 90% repolarization (APD(20,50,90)) without any use-dependence. Meanwhile, it had no significant effect on RMP, APA, or V(max) (n = 9). At a dose of 1 micro mol/L, BmkTXK(beta) decreased I(to) by 41.4% (n = 10, P < 0.01) at a membrane potential of +50 mV [from (13.63 +/- 0.87) pA/pF to (7.98 +/- 0.78) pA/pF]. I(to) was reduced significantly with an IC(50) value of 1.82 micromol/L (95% confidence interval: 1.47 - 2.17 micro mol/L), in a clear concentration-dependent manner. BmkTXK(beta) blocked I(Ks) and I(Ks),tail with an IC(50) of 20.15 micromol/L and a 95% confidence interval of 16.93 - 23.37 micromol/L. At a concentration of 10 micromol/L, BmkTXK(beta) blocked both I(Ks) (mean reduction 37.3% +/- 4.2%, P < 0.01, n = 7) and I(Ks), tail (mean reduction 35.8% +/- 4.1%, P < 0.01, n = 7). At 0 mV, 10 micromol/L BmkTXK(beta) inhibited both I(Kr) (mean reduction 40.5% +/- 2.6%, P < 0.01, n = 6) and I(Kr), tail (mean reduction 42.3% +/- 2.9%, P < 0.01, n = 6). Blocking of I(Kr) by BmkTXK(beta) occurred in a concentration-dependent manner, with an IC(50) of 17.21 micromol/L (95% confidence interval: 14.76-19.66 micromol/L). An absence of effects on I(K1) was observed for BmkTXK(beta), with no change in reversal-potential (n = 6, P > 0.05).

CONCLUSIONSBmkTXK(beta) exerts direct blocking effects on several potassium channels involved in cardiac repolarization, and has a strong effect on prolonging the repolarization of rabbit cardiomyocytes without reverse frequency dependence. This finding suggests that BmkTXK(beta) could be a promising class III drug for anti-arrhythmic therapy without the risk of proarrhythmia.

Action Potentials ; drug effects ; Animals ; Cells, Cultured ; Heart Atria ; Myocardium ; cytology ; Patch-Clamp Techniques ; Rabbits ; Scorpion Venoms ; pharmacology

AIMTo investigate the effects of scorpion venom heat-resistant protein (SVHRP) on kainic acid induced-damage of cultured primitive rat hippocampal neuropeptide Y-nergic neurons.

METHODSWe observed morphological changes, celluar vigor, NPY-immunoreactivity and NPY mRNA expression by means of Thionine staining, MTT assay, immunocytochemistry and RT-PCR, respectively, on the primitively cultured Sprague-Dawley rat hippocampal neuron treated with KA and SVHRP for 24 h.

RESULTSMTT assay and morphologic analysis showed that SVHRP markedly increased neuron survival-rate, and protected them from kA-induced damage. The expression of NPY-immunoreactivity and NPY mRNA in SVHRP group increased obviously compared with other groups.

CONCLUSIONSVHRP protected the primitively cultured hippocampal neurons from KA-induced neuroexcitotoxicity and promoted the expression of NPY.

Animals ; Cell Death ; Cells, Cultured ; Hippocampus ; cytology ; metabolism ; Kainic Acid ; pharmacology ; Male ; Neurons ; drug effects ; metabolism ; pathology ; Neuropeptide Y ; metabolism ; Rats ; Rats, Sprague-Dawley ; Scorpion Venoms ; pharmacology

This study was aimed to investigate the effect of polypeptide extract from scorpion venom (PESV) on PI3K, p-Akt signal protein regulating K562 cell apoptosis and its mechanism. The K562 cells were cultured with PESV for different time, the cell growth curve was determined by MTT method, the levels of PI3K and p-Akt proteins were detected by Western blot. The results showed that as compared with control group, the apoptosis rate of K562 cells treated with PESV increased, the levels of PI3K and p-Akt expression decreased. It is concluded that the PESV inhibits the proliferation and promotes the apoptosis of K562 cells probably through suppressing the expression of PI3K and p-Akt signal proteins.
Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Humans ; K562 Cells ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Scorpion Venoms ; pharmacology ; Signal Transduction ; drug effects

Being a biologic toxin, scorpion toxins have complicate physiologic and pharmalogic actions because of its intricate components. This text reviewed the effect of scorpion toxins on endothelial cell function, platelet function, microcirculation, atherosclerosis, ironic channel, and cardiac function.
Animals ; Endothelial Cells ; metabolism ; Epoprostenol ; metabolism ; Ion Channels ; drug effects ; Microcirculation ; drug effects ; Myocardial Contraction ; drug effects ; Platelet Aggregation ; drug effects ; Scorpion Venoms ; pharmacology ; Tissue Plasminogen Activator ; metabolism

According to the reported sequence of Buthus martensii Karsch scorpion toxin gene (BmK IT3), we synthesized two primers, which were complementary in a region. By the means of PCR, we got the gene. The gene was fused in expression vector pET-28a, which gave rise to a recombinant plasmid pET(IT3R). Then it was transformed into E. coli BL21 (DE3). With IPTG induction, the gene was efficiently expressed. And the fusion product was soluble.
Animals ; Cloning, Molecular ; Escherichia coli ; genetics ; Gene Expression ; drug effects ; Isopropyl Thiogalactoside ; pharmacology ; Recombinant Proteins ; biosynthesis ; genetics ; Scorpion Venoms ; biosynthesis ; chemistry ; genetics ; Scorpions ; chemistry ; genetics

Animals ; Epilepsy ; genetics ; Gene Expression Regulation ; drug effects ; Glial Fibrillary Acidic Protein ; genetics ; metabolism ; Hippocampus ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Scorpion Venoms ; pharmacology

Animals ; Cells, Cultured ; NAV1.8 Voltage-Gated Sodium Channel ; metabolism ; Pain ; chemically induced ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Scorpion Venoms ; pharmacology ; Up-Regulation