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

This study aims to validate our hypothesis that acid-sensing ion channels (ASICs) may contribute to the symptom of pain in patients with chronic prostatitis (CP). We first established a CP rat model, then isolated the L5-S2 spinal dorsal horn neurons for further studies. ASIC1a was knocked down and its effects on the expression of neurogenic inflammation-related factors in the dorsal horn neurons of rat spinal cord were evaluated. The effect of ASIC1a on the Ca²⁺ ion concentration in the dorsal horn neurons of rat spinal cord was measured by the intracellular calcium ([Ca²⁺]i) intensity. The effect of ASIC1a on the p38/mitogen-activated protein kinase (MAPK) signaling pathway was also determined. ASIC1a was significantly upregulated in the CP rat model as compared with control rats. Acid-induced ASIC1a expression increased [Ca²⁺]i intensity in the dorsal horn neurons of rat spinal cord. ASIC1a also increased the levels of neurogenic inflammation-related factors and p-p38 expression in the acid-treated dorsal horn neurons. Notably, ASIC1a knockdown significantly decreased the expression of pro-inflammatory cytokines. Furthermore, the levels of p-p38 and pro-inflammatory cytokines in acid-treated dorsal horn neurons were significantly decreased in the presence of PcTx-1, BAPTA-AM, or SB203580. Our results showed that ASIC1a may contribute to the symptom of pain in patients with CP, at least partially, by regulating the p38/MAPK signaling pathway.
Acid Sensing Ion Channel Blockers/pharmacology* ; Acid Sensing Ion Channels/genetics* ; Animals ; Calcium/metabolism* ; Chelating Agents/pharmacology* ; Chronic Disease ; Cytokines/metabolism* ; Disease Models, Animal ; Egtazic Acid/pharmacology* ; Gene Knockdown Techniques ; Imidazoles/pharmacology* ; Inflammation/metabolism* ; MAP Kinase Signaling System/genetics* ; Male ; Pain/genetics* ; Peptides/pharmacology* ; Phosphorylation/drug effects* ; Posterior Horn Cells/metabolism* ; Prostatitis/complications* ; Protein Kinase Inhibitors/pharmacology* ; Pyridines/pharmacology* ; Rats ; Spider Venoms/pharmacology* ; Up-Regulation ; p38 Mitogen-Activated Protein Kinases/metabolism*

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 investigate the effect of exenatide on chemotactic migration of adipose-derived stem cells (ADSCs) and confirm that Rho GTPase is the downstream effector protein of SDF-1/CXCR-4 migration pathway.

METHODSADSCs were isolated, cultured, identified by flow cytometry, and induced to differentiate in vitro. RTCA xCELLigence system was used to analyze the effect of exenatide on ADSC proliferation. The effects of exenatide at different concentrations, AMD3100 (CXCR-4 antagonist), and CCG-1423 (Rho GTPase antagonist) on chemotactic migration of ADSCs were tested using Transwell assay. The expression of CXCR-4 in exenatide-treated ADSCs was measured by flow cytometry and Western blotting. Active Rho pull-down detection kit was used to detect the expression of Rho GTPase. Laser confocal microscopy was used to observe the formation of stress fibers in ADSCs with different treatments.

RESULTSExenatide treatment for 24 h had no significant effect on ADSC proliferation. Exenatide obviously promoted chemotactic migration of ADSCs in a concentration-dependent manner, and this effect was blocked by either AMD3100 or CCG-1423. Both flow cytometry and Western blotting showed that exenatide dose-dependently up-regulated CXCR-4 expression in ADSCs. Western blotting showed that the expression of Rho GTPase was related to SDF-1/CXCR-4 pathway, and laser confocal microscopy revealed that the formation of stress fibers in ADSCs was related to SDF-1/CXCR-4/ Rho GTPase pathway.

CONCLUSIONExenatide promotes chemotactic migration of ADSCs, and Rho GTPase is the downstream effector protein of SDF-1/CXCR-4 pathway.

Adipose Tissue ; cytology ; Anilides ; pharmacology ; Benzamides ; pharmacology ; Cells, Cultured ; Chemokine CXCL12 ; metabolism ; Chemotaxis ; Heterocyclic Compounds ; pharmacology ; Humans ; Peptides ; pharmacology ; Receptors, CXCR4 ; antagonists & inhibitors ; metabolism ; Signal Transduction ; Stem Cells ; cytology ; Venoms ; pharmacology ; rho GTP-Binding Proteins ; antagonists & inhibitors ; metabolism

OBJECTIVETo investigate the therapeutic effect of acupoint injection of bee venom on collagen-induced arthritis (CIA) in rats and explore the mechanism of bee venom therapy in the treatment of rheumatoid arthritis.

METHODSFifteen male Wistar rats were randomly divided into bee venom treatment group (BV group), CIA model group, and control group. In the former two groups, CIA was induced by injections of collagen II+IFA (0.2 mL) via the tail vein, and in the control group, normal saline was injected instead. The rats in BV group received daily injection of 0.1 mL (3 mg/mL) bee venom for 7 consecutive days. All the rats were assessed for paw thickness and arthritis index from days 14 to 21, and the pain threshold was determined on day 21. The expressions of TRPV1 and TrkA in the dorsal root ganglion at the level of L4-6 were detected using immunohistochemistry and Western blotting, respectively.

RESULTSThe rats in CIA model group started to show paw swelling on day 10, and by day 14, all the rats in this group showed typical signs of CIA. In BV group, the rats receiving been venom therapy for 7 days showed a significantly smaller paw thickness and a low arthritis index than those in the model group. The pain threshold was the highest in the control group and the lowest in the model group. TRPV1-positive cells and TrkA expression in the dorsal root ganglion was significantly reduced in BV group as compared with that in the model group.

CONCLUSIONs Injection of bee venom can decrease expression of TRPV1 and TrkA in the dorsal root ganglion to produce anti-inflammatory and analgesic effects, suggesting the potential value of bee venom in the treatment of rheumatoid arthritis.

Analgesics ; pharmacology ; Animals ; Anti-Inflammatory Agents ; pharmacology ; Arthritis, Experimental ; chemically induced ; drug therapy ; Arthritis, Rheumatoid ; drug therapy ; Bee Venoms ; pharmacology ; Collagen ; Edema ; Ganglia, Spinal ; drug effects ; metabolism ; Injections ; Male ; Pain Threshold ; Random Allocation ; Rats ; Rats, Wistar ; Receptor, trkA ; metabolism ; TRPV Cation Channels ; metabolism

OBJECTIVETo explore effects of exendin-4 on the metabolism of extracellular matrix (ECM) in human mesangial cells (HMC) cultured in the presence of high glucose and explore the possible mechanism.

METHODSHuman mesangial cells (HMC) were treated with exendin-4 under high glucose conditions. The cell proliferation was observed using CCK8 assay, and the expressions of collagen type I, fibronectin, transforming growth factor-β1 (TGFβ1) expression and extracellular signal- regulated kinase (ERK) signaling pathway activity were assessed using Western blotting.

RESULTSExendin-4 inhibited cell proliferation and the expressions of collagen type I, fibronectin and TGFβ1 and reversed ERK phosphorylation in high glucose-induced HMC.

CONCLUSIONExendin-4 can regulate ECM metabolism in HMC cultured in high glucose by inhibiting TGFβ1/ERK pathway, suggesting the beneficial effects of exendin-4 in preventing and treating diabetic nephropathy.

Cell Proliferation ; Cells, Cultured ; Collagen Type I ; metabolism ; Culture Media ; chemistry ; Diabetic Nephropathies ; Extracellular Matrix ; metabolism ; Fibronectins ; metabolism ; Glucose ; chemistry ; Humans ; MAP Kinase Signaling System ; Mesangial Cells ; drug effects ; Peptides ; pharmacology ; Phosphorylation ; Signal Transduction ; Transforming Growth Factor beta1 ; metabolism ; Venoms ; pharmacology

BACKGROUNDTumor necrosis factor-α (TNF-α) plays an important role in progressive contractile dysfunction in several cardiac diseases. The cytotoxic effects of TNF-α are suggested to be partly mediated by reactive oxygen species (ROS)- and mitochondria-dependent apoptosis. Glucagon-like peptide-1 (GLP-1) or its analogue exhibits protective effects on the cardiovascular system. The objective of the study was to assess the effects of exenatide, a GLP-1 analogue, on oxidative stress, and apoptosis in TNF-α-treated cardiomyocytes in vitro.

METHODSIsolated neonatal rat cardiomyocytes were divided into three groups: Control group, with cells cultured in normal conditions without intervention; TNF-α group, with cells incubated with TNF-α (40 ng/ml) for 6, 12, or 24 h without pretreatment with exenatide; and exenatide group, with cells pretreated with exenatide (100 nmol/L) 30 mins before TNF-α (40 ng/ml) stimulation. We evaluated apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry, measured ROS production and mitochondrial membrane potential (MMP) by specific the fluorescent probes, and assessed the levels of proteins by Western blotting for all the groups.

RESULTSExenatide pretreatment significantly reduced cardiomyocyte apoptosis as measured by flow cytometry and TUNEL assay at 12 h and 24 h. Also, exenatide inhibited excessive ROS production and maintained MMP. Furthermore, declined cytochrome-c release and cleaved caspase-3 expression and increased bcl-2 expression with concomitantly decreased Bax activation were observed in exenatide-pretreated cultures.

CONCLUSIONThese results suggested that exenatide exerts a protective effect on cardiomyocytes, preventing TNF-α-induced apoptosis; the anti-apoptotic effects may be associated with protection of mitochondrial function.

Animals ; Apoptosis ; drug effects ; Cells, Cultured ; In Situ Nick-End Labeling ; Membrane Potential, Mitochondrial ; drug effects ; Mitochondria ; drug effects ; Myocytes, Cardiac ; cytology ; drug effects ; Oxidative Stress ; drug effects ; Peptides ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Tumor Necrosis Factor-alpha ; pharmacology ; Venoms ; pharmacology

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