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

OBJECTIVETo observe enhanced effects of polypeptide extract from scorpion venom (PESV) combined Rapamycin on autophagy of H22 hepatoma cells in mice and to explore its possible mechanism.

METHODSThe H22 hepatocarcinoma cell suspension was subcutaneously inoculated into 40 Kunming mice. Then tumor-bearing mice were randomly divided into four groups, i.e., the control group,the high dose PESV group, the low dose PESV group, and the combination group (high dose PESV + Rapamycin), 10 in each group. Mice in high and dose PESV groups were administered with 20 mg/kg and 10 mg/kg PESV respectively by gastrogavage. Mice in the combination group were administered with 2 mg/kg rapamycin and 20 mg/kg PESV by gastrogavage. The intervention lasted for 14 successive days. The tumor volume was measured once every other day, the tumor growth curve was drawn, and then the tumor inhibitory rate calculated. Pathological changes of the tumor tissue were observed by HE staining. Protein expression levels of mammal target of rapamycin (mTOR), UNC-51-like kinase-1 (ULK1), microtubule-associated protein1 light chain3 (MAPILC3A), and Beclin1 were detected by immunohistochemical assay.

RESULTSThe growth of H22 hepatoma transplantation tumor was inhibited in high and low dose PESV groups and the combination group (P < 0.05). And there was statistical difference in tumor weight and tumor volume between the combination group and high and low dose PESV groups (P < 0.05). There was no statistical difference in tumor weight or tumor volume between the high dose PESV group and the low dose PESV group (P > 0.05). lmmunohistochemical assay showed that the protein expression of mTOR was higher, but protein expressions of ULK1, MAP1LC3A, Beclin1 were lower in the control group than in the rest 3 groups (P < 0.05, P < 0.01). Compared with the high dose PESV group, protein expressions of ULK1, MAP1LC3A, and Beclin1 were obviously lower (P < 0.05).

CONCLUSIONPESV combined Rapamycin might inhibit the development of H22 hepatoma transplantation tumor in mice possibly through inhibiting the activity of mTOR, enhancing expressions of ULK1, MAP1LC3A, and Beclin1.

Animals ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; therapeutic use ; Autophagy ; drug effects ; Carcinoma, Hepatocellular ; Cell Line, Tumor ; Liver Neoplasms ; Mice ; Neoplasm Transplantation ; Peptides ; Scorpion Venoms ; pharmacology ; therapeutic use ; Sirolimus ; pharmacology ; therapeutic use

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

Voltage-gated sodium channels (VGSCs) in primary sensory neurons play a key role in transmitting pain signals to the central nervous system. BmK I, a site-3 sodium channel-specific toxin from scorpion Buthus martensi Karsch, induces pain behaviors in rats. However, the subtypes of VGSCs targeted by BmK I were not entirely clear. We therefore investigated the effects of BmK I on the current amplitude, gating and kinetic properties of Nav1.8, which is associated with neuronal hyperexcitability in DRG neurons. It was found that BmK I dose-dependently increased Nav1.8 current in small-sized (<25 μm) acutely dissociated DRG neurons, which correlated with its inhibition on both fast and slow inactivation. Moreover, voltage-dependent activation and steady-state inactivation curves of Nav1.8 were shifted in a hyperpolarized direction. Thus, BmK I reduced the threshold of neuronal excitability and increased action potential firing in DRG neurons. In conclusion, our data clearly demonstrated that BmK I modulated Nav1.8 remarkably, suggesting BmK I as a valuable probe for studying Nav1.8. And Nav1.8 is an important target related to BmK I-evoked pain.
Aniline Compounds ; pharmacology ; Animals ; Cell Size ; Cells, Cultured ; Electrophysiological Phenomena ; drug effects ; Furans ; pharmacology ; Ganglia, Spinal ; cytology ; Kinetics ; Male ; NAV1.8 Voltage-Gated Sodium Channel ; metabolism ; Rats ; Rats, Sprague-Dawley ; Scorpion Venoms ; antagonists & inhibitors ; pharmacology ; Scorpions ; Sensory Receptor Cells ; drug effects ; metabolism ; physiology ; Sodium Channel Blockers ; pharmacology ; Voltage-Gated Sodium Channel Agonists ; pharmacology

Neuroprotective effect of scorpion venom on Parkinson's disease (PD) has already been reported. The present study was aimed to investigate whether scorpion venom heat resistant peptide (SVHRP) could attenuate ultrastructural abnormalities in mitochondria and oxidative stress in midbrain neurons of early-stage PD model. The early-stage PD model was established by injecting 6-hydroxydopamine (6-OHDA) (20 μg/3 μL normal saline with 0.1% ascorbic acid) into the striatum of Sprague Dawley (SD) rats unilaterally. The rats were intraperitoneally administered with SVHRP (0.05 mg/kg per day) or vehicle (saline) for 1 week. Two weeks after 6-OHDA treatment, the rats received behavior tests for validation of model. Three weeks after 6-OHDA injection, the immunoreactivity of dopaminergic neurons were detected by immunohistochemistry staining, and the ultrastructure of neuronal mitochondria in midbrain was observed by electron microscope. In the meantime, the activities of monoamine oxidase-B (MAO-B), superoxide dismutase (SOD) and content of malondialdehyde (MDA) in the mitochondria of the midbrain neurons, as well as the inhibitory ability of hydroxyl free radical and the antioxidant ability in the serum, were measured by corresponding kits. The results showed that 6-OHDA reduced the optical density of dopaminergic neurons, induced damage of mitochondrial ultrastructure of midbrain neurons, decreased SOD activity, increased MAO-B activity and MDA content, and reduced the antioxidant ability of the serum. SVHRP significantly reversed the previous harmful effects of 6-OHDA in early-stage PD model. These findings indicate that SVHRP may contribute to neuroprotection by preventing biochemical and ultrastructure damage changes which occur during early-stage PD.
Animals ; Antioxidants ; metabolism ; Corpus Striatum ; Disease Models, Animal ; Dopaminergic Neurons ; drug effects ; Malondialdehyde ; metabolism ; Mesencephalon ; cytology ; Mitochondria ; metabolism ; ultrastructure ; Neuroprotective Agents ; pharmacology ; Oxidative Stress ; Oxidopamine ; Parkinson Disease ; drug therapy ; Peptides ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Scorpion Venoms ; pharmacology ; Superoxide Dismutase ; metabolism

OBJECTIVETo explore the mechanism of polypeptide extract from scorpion venom (PESV) on inhibiting angiogenesis.

METHODSThe H22 hepatoma tumor model was established by subcutaneously implanting H22 hepatoma cells into mice. The tumor-bearing mice were randomly divided into 4 groups, i.e., the control group, the high dose PESV group, the low dose PESV group, and the 5-fluorouracil (5-Fu) group, 10 mice in each group. The intervention was lasted for 14 days. The growth curve of the tumor volume was drawn and the inhibition rate calculated. Pathological changes of the tumors were observed by HE staining. The microvessel density (MVD) was detected using SP method. The protein expression levels of phosphatidylinositol 3-kinase (P13K), phosphoprotein kinase B (P-Akt), hypoxia-inducible factor-1 alpha (HIF-1 )alpha, and vascular endothelial growth factor-A (VEGF-A) were detected by immunohistochemical assay and Western blot.

RESULTSThe tumor inhibitory rate was 64.8%, 43.7%, and 32.4% in the 5-Fu group, the high dose PESV group, and the low dose PESV group. Compared with the control group, the protein expression of PI3K, P-Akt, HIF-1alpha, and VEGF-A were obviously inhibited by PESV and 5-Fu (P <0. 05,P <0. 01). The MVD also decreased in the high and low dose PESV groups (P < 0.05).

CONCLUSIONSPESV could inhibit the angiogenesis of H22 hepatoma. The mechanisms might be associated with suppressing the expression of PI3K, P-Akt, HIF-1 alpha, and VEGF-A.

Angiogenesis Inhibitors ; pharmacology ; Animals ; Cell Line, Tumor ; Fluorouracil ; pharmacology ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Liver Neoplasms ; Male ; Mice ; Peptides ; pharmacology ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Scorpion Venoms ; pharmacology ; Vascular Endothelial Growth Factor A

OBJECTIVETo investigate the mechanisms for inhibition effects of PESV on proliferation of non-small cell lung cancer cell line A549.

METHODMTT was used to observe cell growth and proliferation of A549 at different concentrations of PESV. Flow cytometry (FCM) was applied to analyze cell cycle distribution. Immunocytochemistry and western blot assay was recruited to detect the expression of VEGF, HIF-1alpha, PTEN after the intervention of PESV.

RESULTA549 cells may be arrested mainly in G0/G1 phase and cell proliferation was significantly inhibited (P < 0.01) after PESV intervention in a certain range of concentration. PESV can significantly reduce the expression of HIF-1alpha,VEGF and increase the expression of PTEN.

CONCLUSIONPESV can block cell cycle and inhibit angiogenesis directly to inhibit cell proliferation of non-small cell lung cancer cell line A549 mainly through reducing the expression of HIF-1alpha, VEGF and increasing the expression of PTEN.

Antineoplastic Agents ; isolation & purification ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; PTEN Phosphohydrolase ; metabolism ; Peptides ; isolation & purification ; pharmacology ; Scorpion Venoms ; chemistry ; Vascular Endothelial Growth Factor A ; metabolism