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

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

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

OBJECTIVEScorpion (Hemiscorpius lepturus) stings are a public health concern in Iran, particularly in south and southwestern regions of Iran. The gold standard for the treatment of a scorpion sting is anti-venom therapy. However, immunotherapy can have serious side effects, such as anaphylactic shock (which can sometimes even lead to death). The aim of the current study was to demonstrate the protective effect of ozone against toxicity induced by Hemiscorpius lepturus (H. lepturus) venom in mice.

METHODSEight hours after the injection of ozone to the experimental design groups, the male mice were decapitated and mitochondria were isolated from five different tissues (liver, kidney, heart, brain, and spinal cord) using differential ultracentrifugation. Then, assessment of mitochondrial parameters including mitochondrial reactive oxidative species (ROS) production, mitochondrial membrane potential (MMP), ATP level, and the release of cytochrome c from the mitochondria was performed.

RESULTSOur results showed that H. lepturus venom-induced oxidative stress is related to ROS production and MMP collapse, which is correlated with cytochrome c release and ATP depletion, indicating the predisposition to the cell death signaling.

CONCLUSIONIn general, ozone therapy in moderate dose can be considered as clinically effective for the treatment of H. lepturus sting as a protective and antioxidant agent.

Animals ; Brain ; drug effects ; metabolism ; Cytochromes c ; metabolism ; Heart ; drug effects ; Kidney ; drug effects ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Membrane Potential, Mitochondrial ; drug effects ; Mice ; Mice, Inbred BALB C ; Muscle, Skeletal ; drug effects ; metabolism ; Myocardium ; metabolism ; Ozone ; pharmacology ; Scorpion Venoms ; toxicity ; Scorpions ; physiology ; Spinal Cord ; drug effects ; metabolism

The present study evaluated the effects of Androctonus amoreuxi scorpion venom, Cerastes cerastes snake venom and their mixture on prostate cancer cells (PC3). An MTT assay was used to determine the anti-proliferative effect of the venoms, while quantitative real time PCR was used to evaluate the expression of apoptosis-related genes (Bax and Bcl-2). Furthermore, colorimetric assays were used to measure the levels of malondialdehyde (MDA) and antioxidant enzymes. Our results show that the venoms significantly reduced PC3 cell viability in a dose-dependent manner. On the other hand, these venoms significantly decreased Bcl-2 gene expression. Additionally, C. cerastes venom significantly reduced Bax gene expression, while A. amoreuxi venom and a mixture of A. amoreuxi & C. cerastes venoms did not alter Bax expression. Consequently, these venoms significantly increased the Bax/Bcl-2 ratio and the oxidative stress biomarker MDA. Furthermore, these venoms also increased the activity levels of the antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase. Overall, the venoms have cytotoxic and anti-proliferative effects on PC3 cells.
Apoptosis ; Catalase ; Cell Survival ; Gene Expression ; Genes, bcl-2 ; Glutathione Peroxidase ; Glutathione Reductase ; Hand ; Humans* ; Malondialdehyde ; Oxidative Stress ; Prostate* ; Prostatic Neoplasms* ; Real-Time Polymerase Chain Reaction ; Scorpion Venoms ; Scorpions* ; Snake Venoms* ; Snakes* ; Superoxide Dismutase ; Venoms ; Viper Venoms ; Viperidae*

Specific anti-venom used to treat scorpion envenomation is usually obtained from horses after hyperimmunization with crude scorpion venom. However, immunized animals often become ill because of the toxic effects of the immunogens used. This study was conducted to evaluate the toxic and immunogenic activities of crude and detoxified Tityus serrulatus (Ts) venom in sheep during the production of anti-scorpionic anti-venom. Sheep were categorized into three groups: G1, control, immunized with buffer only; G2, immunized with crude Ts venom; and G3, immunized with glutaraldehyde-detoxified Ts venom. All animals were subjected to clinical exams and supplementary tests. G2 sheep showed mild clinical changes, but the other groups tolerated the immunization program well. Specific antibodies generated in animals immunized with either Ts crude venom or glutaraldehyde-detoxified Ts venom recognized the crude Ts venom in both assays. To evaluate the lethality neutralization potential of the produced sera, individual serum samples were pre-incubated with Ts crude venom, then subcutaneously injected into mice. Efficient immune protection of 56.3% and 43.8% against Ts crude venom was observed in G2 and G3, respectively. Overall, the results of this study support the use of sheep and glutaraldehyde-detoxified Ts venom for alternative production of specific anti-venom.
Animals ; Antibodies ; Horses ; Immunization Programs ; Mice ; Scorpion Venoms ; Scorpions ; Sheep* ; Venoms*

It is hypothesized that protease inhibitors play an essential role in survival of venomous animals through protecting peptide/protein toxins from degradation by proteases in their prey or predators. However, the biological function of protease inhibitors in scorpion venoms remains unknown. In the present study, a trypsin inhibitor was purified and characterized from the venom of scorpion Mesobuthus eupeus, which enhanced the biological activities of crude venom components in mice when injected in combination with crude venom. This protease inhibitor, named MeKTT-1, belonged to Kunitz-type toxins subfamily. Native MeKTT-1 selectively inhibited trypsin with a Kivalue of 130 nmol·L(-1). Furthermore, MeKTT-1 was shown to be a thermo-stable peptide. In animal behavioral tests, MeKTT-1 prolonged the pain behavior induced by scorpion crude venom, suggesting that protease inhibitors in scorpion venom inhibited proteases and protect the functionally important peptide/protein toxins from degradation, consequently keeping them active longer. In conclusion, this was the first experimental evidence about the natural existence of serine protease inhibitor in the venom of scorpion Mesobuthus eupeus, which preserved the activity of venom components, suggests that scorpions may use protease inhibitors for survival.
Amino Acid Sequence ; Animals ; Base Sequence ; Female ; Kinetics ; Male ; Mice ; Molecular Sequence Data ; Protease Inhibitors ; chemistry ; toxicity ; Scorpion Venoms ; chemistry ; genetics ; toxicity ; Scorpions ; chemistry ; genetics ; Trypsin ; chemistry

OBJECTIVETo explore the alterations of apoptosis factor Bcl-2/Bax in the early Parkinson's disease (PD) rats and the protective effect of scorpion venom derived bioactive peptide.

METHODSHealthy male SD rats (180-220 g) were randomly divided into 4 groups (n = 10): early PD model group, sham operation group, scorpion venom derived bioactive peptide control group, scorpion venom derived bioactive peptide therapy group. 6-hydroxydopamine (6-OHDA) was used to prepare the early PD rat model. The immunohistochemistry was used to detect the expression of Bax and Bcl-2 and further explore the mechanism of anti-apoptosis regarding the neuroprotective effect of scorpion venom derived bioactive peptide.

RESULTSThe results indicated that compared with the control rats, the immunostaining of Bax in the brain increased significantly while that of Bcl-2 decreased significantly in the lesion side of 6-OHDA treated rats. Interestingly, scorpion venom derived bioactive peptide could attenuate the above abnormal changes.

CONCLUSIONUp-regulation of Bax and down-regulation of Bcl-2 could participate in the early stage of PD and the anti-apoptotic mechanism could be involved in the neuroprotective effect exerted by scorpion venom derived activity peptide regarding the dopaminergic neuron in the early stage.

Animals ; Apoptosis ; Disease Models, Animal ; Down-Regulation ; Male ; Neuroprotective Agents ; chemistry ; Oxidopamine ; Parkinson Disease ; metabolism ; Peptides ; chemistry ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Scorpion Venoms ; chemistry ; Up-Regulation ; bcl-2-Associated X Protein ; metabolism

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

Chinese scorpion Buthus martensii Karsch (BmK) venom is a rich source of neurotoxins which bind to various ion channels with high affinity and specificity and thus widely used as compounds to modulate channel gating or channel currents. To promote the insecticidal effects of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV), the gene encoding an excitatory insect toxin, BmK IT, was inserted into the genome of AcMNPV to construct a recombinant baculovirus, AcMNPV-BmK IT. Spodopter frugiperda 9 (Sf9) cells were infected with AcMNPV and AcMNPV-BmK IT respectively for 24 h. Results from the MTT assay, TUNEL assay, analysis of the expression level of apoptosis-related proteins (c-Myc, cleaved-Caspase3, Bcl-2 and Bax) of Sf9 cells, the transcription level of key genes (38K, C42, P78, F) of AcMNPV, and viral propagation assay demonstrated that AcMNPV-mediated expression of BmK IT promoted the apoptosis of Sf9 cells and replication of AcMNPV. The results laid a foundation for further structural and functional analysis of BmK IT.
Animals ; Apoptosis ; Cell Line ; Nucleopolyhedrovirus ; metabolism ; physiology ; Scorpion Venoms ; biosynthesis ; Sf9 Cells ; drug effects ; Virus Replication