Hemiscorpius Lepturus Research Articles

Cutaneous Manifestations of the Hemiscorpius lepturus Stings

Cutaneous Manifestations of the Hemiscorpius lepturus Stings

In silico Discovery of Leptukalins, The New Potassium Channel Blockers from the Iranian Scorpion, Hemiscorpius Lepturus.

Blocking Kv 1.2 and Kv 1.3 potassium channels using scorpion venom- derived toxins holds potential therapeutic value. These channels are implicated in autoimmune diseases such as neurodegenerative diseases, multiple sclerosis, rheumatoid arthritis, and type 1 diabetes. The present work aims at the discovery and in silico activity analysis of potassium channel blockers (KTxs) from the cDNA library derived from the venom gland of Iranian scorpion Hemiscorpius lepturus (H. lepturus). The sequence regarding potassium channel blockers were extracted based on Gene Ontology for H. lepturus venom gland. Homology analyses, superfamily, family, and evolutionary signatures of H. lepturus KTxs (H.L KTxs) were determined by using BLASTP, COBALT, PROSITE, and InterPro servers. The predicted 3D structures of H.L KTxs were superimposed against their homologs to predict structure activity relationship. Molecular docking analysis was also performed to predict the binding affinity of H.L KTxs to Kv 1.2 and Kv 1.3 channels. Finally, the toxicity was predicted. Seven H.L KTxs, designated as Leptukalin, were extracted from the cDNA library of H. lepturus venom gland. Homology analyses proved that they can act as potassium channel blockers and they belong to the superfamily and family of Scorpion Toxin-like and Short-chain scorpion toxins, respectively. Structural alignment results confirmed the activity of H.L KTxs. Binding affinity of all H.L KTxs to Kv 1.2 and Kv 1.3 channels ranged from -4.4 to -5.5 and -4 to -5.7 Kcal/mol, respectively. In silico toxicity assay showed that Leptukalin 3, Leptukalin 5, and Leptukalin 7 were non-toxic. Three non-toxic KTxs, Leptukalin 3, 5, and 7, were successfully discovered from the cDNA library of H. lepturus venom gland. Gathering all data together, the discovered peptides are promising potassium channel blockers. Accordingly, Leptukalin 3, 5, and 7 could be suggested for complementary in vitro studies and mouse model of autoimmune diseases.

Insights into the Evolutionary Dynamics: Characterization of Disintegrin and Metalloproteinase Proteins in the Venom Gland Transcriptome of the Hemiscorpius lepturus Scorpion.

The Disintegrin and Metalloproteinase (ADAM) family, also known as the metalloproteinase/disintegrin/cysteine-rich (MDC) proteins, includes both secreted and transmembrane molecules involved in critical biological processes, such as cell migration, adhesion, and signaling. This study aimed to investigate the evolutionary relationships and structural characteristics of disintegrin and metalloproteinase proteins identified in the venom gland transcriptome of the scorpion Hemiscorpius lepturus. Using bioinformatics tools, we analyzed the open reading frame, conserved motifs, and primary, secondary, and tertiary structures of these proteins. Five proteins, named HLDis- Met1, HLDisMet2, HLDisMet3, HLDisMet4, and HLDisMet5, were identified. Their predicted 3- D structures were within normal ranges (Z-score between -4 to -9). Phylogenetic analysis revealed that HLDisMet1 shares similarities with proteins from various spider species (Nephila pilipes, Argiope bruennichi, Araneus ventricosus, and Trichonephila inaurata madagascariensis), HLDisMet2 with the scorpion Centruroides sculpturatus, HLDis- Met4 with the scorpion Tityus serrulatus, and HLDisMet5 with several snake species (Python bivittatus, Vipera anatolica senliki, Protobothrops mucrosquamatus, and Naja naja). These findings highlight the significant similarities between HLDisMet proteins and those found in other venomous species, suggesting a complex and diverse evolutionary pathway for venom components. The cross-species conservation observed may indicate a convergent evolutionary strategy, where different species independently develop similar venom components to adapt to similar ecological niches or prey types. This study highlights the evolutionary significance of venom diversification and its potential applications in understanding venom biology across different species.

Corneal ulceration following periocular scorpion sting: a case report

BackgroundScorpion envenomation, a prevalent medical emergency in rural areas, demands immediate attention due to its potential severity. While ocular manifestations are uncommon, they can lead to significant complications such as corneal ulceration. We present a unique case of corneal ulceration subsequent to a yellow scorpion (Hemiscorpius lepturus) sting near the eye, a scenario not previously documented.Case presentationA 34-year-old male sought medical care following a scorpion sting despite prior anti-venom treatment. Clinical examination revealed pronounced ocular inflammation, corneal stromal melting, and anterior chamber inflammation, with microbiological confirmation of Pseudomonas spp infection. Treatment comprised fortified ceftazidime and vancomycin eye drops, alongside topical corticosteroids, leading to visual and corneal healing.ConclusionThis case highlights the urgency of addressing scorpion envenomation and its potential for severe ocular complications, including corneal ulceration. Prompt diagnosis and targeted therapy with antibiotics and corticosteroids are crucial for favorable outcomes. A comprehensive understanding and timely intervention in scorpion sting-induced ocular manifestations are essential for optimal patient management and outcomes in such cases.

Protective Effects of the Aqueous Extract of Malva sylvestris Plant against the Lethality and Histopathological Damage in Experimental Envenoming of Hemiscorpius lepturus Venom in Balb/c Mice.

Hemiscorpius lepturus envenomation is a serious health problem in the southern provinces of Iran. The antiserum produced in Iran to counteract this scorpion venom is not entirely effective due to the risk of anaphylactic shock and other adverse effects. Therefore, more efficient alternatives to treat patients deserve attention, and plants are extensively good candidates to be studied. This study aimed to assess the potential of the aqueous fraction of Malva sylvestris in inhibiting the toxic effects of H. lepturus venom. Injection of sub-lethal dose of H. lepturus venom leads to severe tissue damage in vital organs including the kidney, liver, heart and intestine, after 24 hours. By injecting 80 mg of the aqueous extract of M. sylvestris into the peritoneum helped treat the damaged tissues caused by H. lepturus venom in mice. Thus, Malva sylvestris could serve as an alternative treatment for scorpion sting envenomation and may be used as a drug to neutralize relevant toxic effects in patients stung by H. lepturus.

Identification and Phylogenetic Analysis of Venom Allergens from Transcriptome of Hemiscorpius lepturus Scorpion

Introduction: Venom allergens have been identified in the venom of scorpion, snake, bee, wasp, etc. Some allergy reactions in humans may refer to the venom allergens. Aim: Phylogenetic analysis of venom allergens from the transcriptome of Hemiscorpius lepturus scorpion was the main aim of the study. Methods: Seven venom allergens: HLAllergen1, HLAllergen2, HLAllergen3, HLAllergen4, HLAllergen5, HLAllergen6, and HLAllergen7 have been identified in the venom of Hemiscorpius lepturus scorpion using venom gland transcriptome analysis. Primary, secondary and tertiary structures of the identified venom allergens were predicted using ExPASy ProtParam, PSIPRED, and SWISS MODEL servers. Phylogenetic tree was constructed using MEGA 11 software through neighbor-joining method with 1000 bootstraps. Results: Structure analysis of identified venom allergens showed a molecular weight of between 46 to 52 kDa. Tertiary structure results showed that all predicted 3-D structures were in a normal range. Phylogenetic tree analysis showed that HLAllergen 3, 4 and 5 were formed single clades and HLAllergen 1, 2, 7, and 6 other clades Conclusion: However, further studies using proteomic analysis of H. lepturus are needed to confirm and compare with transcriptome data.

The Anti-cancer Effect of Two Extract Fractions from the Hemiscorpius lepturus Scorpion Venom

The Anti-cancer Effect of Two Extract Fractions from the Hemiscorpius lepturus Scorpion Venom

Identification of several coding sequences of phospholipase A2 protein in the venom gland of the scorpion of Hemiscorpius lepturus using RNA-sequencing

Identification of several coding sequences of phospholipase A2 protein in the venom gland of the scorpion of Hemiscorpius lepturus using RNA-sequencing

Molecular study of Hemiscorpius Peters (Scorpiones: Hemiscorpiidae) in Hormozgan province, South of Iran.

Three species of Hemiscorpius were identified in Hormozgan province, for which the available antivenoms lack the efficacy required for treating patients. Consequently, an exact identification of the existing species was deemed necessary as the first step in managing treatment procedures. Considering the morphological similarities among the species, the aim of this research was the molecular study of the samples to accurately identify the species. Hemiscorpius specimens were collected from various locations in Hormozgan province between 2021 to 2023. The Cytochrome c oxidase subunit I gene was amplified and sequenced. Four sequences were obtained from Hemiscorpius specimens collected from Hormozgan province, and three sequences were sourced from the NCBI for analysis. Bayesian inference and Maximum likelihood phylogenetic trees showed similar results, positioning the base of Hemiscorpius enischnochela tree as an older species and Hemiscorpius lepturus adjacent to Hemiscorpius acanthocercus, identified as the newest species at the tree's tip. The results confirmed the validity of three species, namely H. acanthocercus, H. enischnochela, and H. lepturus. Hemiscorpius acanthocercus and H. lepturus are known for having dangerous venom for humans with reported deaths due to their stings. Considering the importance of the members of this genus from the medical point of view, a comprehensive examination of all species is imperative.

Faunistic Study of Scorpions in Lendeh County in 2020

Background: Given the importance of scorpion stings and poisonous creatures that cause casualties and fatality to humans and located in the city of Lendeh (in Kohgiluyeh and Boyer-Ahmad province) in the tropical zone, this study has been conducted. Objectives: The results can be used in the prevention, control, and treatment programs and for research purposes in the country. Methods: In this cross-sectional study, 59 samples were collected from five rural areas of Lendeh county in the summer of 2020. The samples were transferred to the entomology and parasitology laboratory of the Behbahan Faculty of Medical Sciences. They were identified using stereomicroscope-based diagnostic key scorpions in Iran. Results: In this study, 59 samples from five villages in the summer 2020 collection, including 5 species of 2 families, were identified Buthidae and Liochelidae. Mesobuthus eupeus with 30 samples (50.8%), the dominant species and species Hemiscorpios lepturus with 16 samples (27.1%), Compsobuthus matthiesseni with 10 samples (16.9%), Simonoides farzanpay with 2 cases (3.3%) and any Hottentata schach 1 sample (1.6%) had the lowest reported among the species identified. Conclusions: Considering the importance of scorpion stings in Iran, identifying the fauna of Scorpions seemed necessary. Observation of Hemiscorpius lepturus species in this area as the main cause of death due to scorpion stings in Iran; it can be dangerous for the residents of these areas. Therefore, the present research can be an introduction to continue the work and complete the research on the scorpions of this region.

Analysis of Some Putative Novel Peptides from Iranian Scorpion Venom Glands, Hemiscorpius lepturus, Using cDNA Library Construction

Background: To date, more than 300,000 distinct peptides have been identified in scorpion venom. However, only a limited number of these peptides have been described. Objectives: We characterized some putative peptides from the venom gland cDNA library of the Iranian yellow scorpion Hemiscorpius lepturus. Methods: Total RNA was extracted from yellow Iranian scorpion glands. Single-stranded cDNA (sscDNA) and double-stranded cDNA (dscDNA) were synthesized by polymerase chain reaction (PCR). A cDNA library was achieved by inserting dscDNA into a special vector and subsequently transformed to chemically competent Escherichia coli as a host. The library was screened by culturing the liquid library on Lysogeny broth (LB)-agar plates. Analysis of positive clones was performed by plasmid extraction and the sequencing of the inserts. Finally, all cDNA sequences were analyzed and characterized by bioinformatics software. Results: One hundred colonies were randomly analyzed. Eighty-nine cDNA sequences had acceptable quality for bioinformatics analysis. Five sequences were selected for further analysis. The peptides related to these sequences were divided into two groups, non-disulfide bridge peptides (NDBP) and disulfide bridge peptides (DBP), the application of which in health and medical issues has been suggested. Conclusions: The data obtained in this study may be an important resource for further in vivo and in vitro functional assays to identify valuable therapeutic peptides.

Cellular Immunity in Mice Vaccinated with Recombinant Phospholipase D Toxoid of Hemiscorpius lepturus Scorpion.

Hemiscorpius lepturus is one of the most dangerous scorpions in Iran and the world. Numerous studies have been conducted on phospholipases, especially phospholipase D, in this scorpion's venom, and the results have shown this protein to be the main cause of death. Therefore, one of the most effective ways of preventing fatalities is to produce a toxoid vaccine from the deadly toxin of the venom. The present study was conducted to assess the non-toxicity of this toxoid and the safety of the vaccine candidate in BALB/c mice. The production of interferon-gamma and interleukin-4 cytokines in the spleen cells of the mice was measured using ELISpot assay 28 days following immunization with rPLD toxoid. The unpaired t-test results showed a significant increase in the concentration of IFN-γ cytokine in the vaccinated mice (P= 0.001), indicating that the immune system is directed toward the Th1 pattern, while no significant difference was observed in the levels of IL-4 (P= 0.16) despite an increase in this cytokine. The in-vivo tests showed that the mice immunized with interval doses of 80µg of toxoid were completely protected against 10 × the LD100 of the venom. Moreover, the toxoid had no dermonecrotic effects and caused no necrotic and inflammatory complications in the rabbit skin. As a vaccine, the toxoid has the potential to increase the Th1 cytokine response and, subsequently, increase acquired cellular immunity. Thus, this toxoid appears to be able to provide an effective vaccine against the venom of Hemiscorpius lepturus.

Correlation between coenzyme Q10 content and the nutrient sensors in AKI induced by Hemiscorpius lepturus envenomation.

Introduction: Acute kidney injury (AKI) may have a negative effect on mitochondrial hemostasis and bioenergetics as well as coenzyme Q10 (CoQ10) content. PGC-1α, AMPK, sirtuin 1 (Sirt1), and Sirt3, as the key metabolic regulators under nutritional stress, stimulate energy production via mitochondrial biogenesis during AKI. However, no report is available on the relationship between CoQ10 level and nutrient sensors in the pathophysiology of AKI caused by Hemiscorpius lepturus scorpion envenomation. Methods: Three doses of venoms (1, 5, and 10 mg/kg) were administered by subcutaneous (SC) injection to male albino mice. The animals were sacrificed 1 day or 7 days after administration of venom and their kidneys were collected to analyze gene expression involved in AKI, nutrient sensors, and apoptosis signaling activation by real-time polymerase chain reaction (PCR) and the measurement of CoQ10 level using the High-performance liquid chromatography (HPLC) method. Results: The data indicated a significant decrease in CoQ10 level after the administration of venom in 5 and 10 mg/kg. In addition, 1 day after the treatment, a significant over-expression of Sirt1 (5 and 10 mg/kg) was observed compared with normal mice. Overexpression of Sirt3 occurred 1 day and 7 days after treatment only at the dose of 5.0 mg/kg of venom. Furthermore, over-expression of AMPK as an important mitochondrial energetic sensor happened 1 day and 7 days after the injection of venom (5 mg/kg) (P < 0.01). The significant increase in the gene expression of caspase-9 and 3 after the injection of venom (5 and 10 mg/kg) confirmed the role of cell death signaling. Conclusion: The venom-induced energy-sensing pathways have a key role in gene expression of PGC-1α, AMPK, Sirt3, and CoQ10 content after venom-induced AKI.

Identification, characterization, and molecular phylogeny of scorpion enolase (Androctonus crassicauda and Hemiscorpius lepturus)

Scorpions are the oldest terrestrial fauna with an ancient evolutionary history. To study the origins of scorpions, we conducted a molecular phylogenetic study of the arthropod using slowly evolving enolase sequences. In this study, we used deep RNA-seq technology to identify the enolase sequences of Androctonus crassicauda and Hemiscorpius lepturus scorpions. The scorpion’s enolase sequences were in silico analyzed to predict the protein structures, physicochemical characterization, and exon-intron organization. The enolase of the scorpion was found to be a protein of 433 amino acids with a molecular mass of ∼47 kDa and an acidic isoelectric point. Here, we reported the existence of 8 exons and an inner GC/AG intron for scorpion enolase. Using homology modeling, the enolase of the scorpions was found to be very conservative during the evolution process. Furthermore, our phylogenetic analysis indicated the independent evolution of the Buthidae family from other scorpions and also the sister group relationship of Hemiscorpionidae with the Caraboctonidae families. The scorpions’ enolase sequences demonstrated a close fit to those of spiders, followed by mite counterparts. This strongly supports our phylogeny analysis, which indicates a sister-group relationship between scorpions and spiders and their common ancestors with mites. This study provided support for the pairing of scorpions with spiders, mites, etc. using enolase as a nuclear gene. Our molecular clock analyzes of the arthropod show that the most recent common ancestor of arachnids and insects were diversified in the Cryogenian period of Neoproterozoic era, earlier than dates reported from fossil records.

Beneficial effect of fresh frozen plasma in reducing renal complications in Hemiscorpius lepturus scorpion envenomated children with severe hemoglobinuria: an open label randomized clinical trial

Acute kidney injury is a common complication of Hemiscorpius lepturus (HL) scorpion envenomation, via several mechanisms including pigment nephropathy, direct nephrotoxic effects of scorpion venom, hemolytic uremic syndrome (HUS), and acute interstitial nephritis. ADAMTS13 deficiency is highly prevalent in patients with severe HL scorpion envenomation and is effective in the development of HUS. Fresh frozen plasma (FFP), by replacing ADAMTS13, has proven effects on HL scorpion envenomated patients with HUS. This study evaluated the role of FFP in reducing of kidney injuries in complicated cases. In this open label randomized clinical trial, a total of 98 patients with massive hemoglobinuria following HL scorpion envenomation were included in the intervention and control groups (49 patients per group). The intervention group received FFP (10 cc/kg every 12 hours for three days) in addition to the anti-venom and other current therapies. Laboratory findings of renal activity, hemolysis, and urinalysis were evaluated in both groups, and maximum changes were compared. Comparison of maximum changes in laboratory findings between the two groups showed that administration of FFP can significantly reduce the deterioration of Blood Urea Nitrogen (BUN) and Creatinine (Cr) levels in the intervention group (p < 0.001 and p = 0.003, respectively). In comparison with the control group, the incidence of proteinuria was significantly lower (p = 0.012), reduction of platelet count was significantly less (p = 0.044), and increase of lactate dehydrogenase (LDH) and leukocytosis was lower in the intervention group (p = 0.037 and p = 0.007, respectively). The mean length of hospital stay was 5.44 days in the intervention group and 5.933 days in the control group (p = 0.149). According to the present findings, FFP can significantly reduce the development of kidney damage after HL scorpion envenomation and can be safely used against the fatal progression of venom complications in severe cases, along with other common treatments.

Acute Venom Toxicity Determinations for Five Iranian Vipers and a Scorpion

Background: Poisoning due to the bites and stings of venomous snakes and scorpions is a neglected public health problem, particularly in rural areas. Poor health facilities and inadequate knowledge of health care personnel are the major factors that result in envenomated human victims not receiving adequate care and medical attention. There is a great need for up-to-date and effective healthcare knowledge and awareness of the potency and lethality of venomous creatures in Iran. Assessment of the potency, acute toxicity, and lethal effects of venomous creatures come from a variety of specific tests, such as the 50% median lethal dose (LD50) and ample animal experimentations. Methods: In the present study, using modified Reed-Muench method, the LD0, LD50, and LD100 values of the venoms from five Iranian vipers and one scorpion were determined. The studied venomous creatures were: Macrovipera lebetina, Vipera albicornuta, Vipera raddei, Caucasicus intemedius agkistrodon, Montivipera latifii, and one scorpion Hemiscorpius lepturus. The venoms were injected in Albino mice (n=204) intraperitoneally, and their toxicities determined. Results: The results revealed that the LD50 values of the above-mentioned creatures were 3.87, 2.05, 1.63, 1.45, 0.84, and 6.33 mg/kg, respectively. Among the vipers, M. latifii had the most potent venom while M. lebetina’s venom had the lowest toxicity. Conclusion: Theoretically, the determined LD50 values provide for objective comparisons of the toxicity among of the venoms. However, comparison becomes complicated due to variations in the venoms’ LD50. Further, based on the venoms’ toxicity levels, H. lepturus’ venom caused the lowest toxicity in the Albino mice.

Discovery of Leptulipin, a New Anticancer Protein from theIranian Scorpion, Hemiscorpius lepturus.

Cancer is one of the leading causes of mortality in the world. Unfortunately, the present anticancer chemotherapeutics display high cytotoxicity. Accordingly, the discovery of new anticancer agents with lower side effects is highly necessitated. This study aimed to discover an anticancer compound from Hemiscorpius lepturus scorpion venom. Bioactivity-guided chromatography was performed to isolate an active compound against colon and breast cancer cell lines. 2D electrophoresis and MALDI-TOF were performed to identify the molecule. A partial protein sequence was obtained by mass spectrometry, while the full-length was deciphered using a cDNA library of the venom gland by bioinformatics analyses and was designated as leptulipin. The gene was cloned in pET-26b, expressed, and purified. The anticancer effect and mechanism action of leptulipin were evaluated by MTT, apoptosis, and cell cycle assays, as well as by gene expression analysis of apoptosis-related genes. The treated cells displayed inhibition of cell proliferation, altered morphology, DNA fragmentation, and cell cycle arrest. Furthermore, the treated cells showed a decrease in BCL-2 expression and an increase in Bax and Caspase 9 genes. In this study, we discovered a new anticancer protein from H. lepturus scorpion venom. Leptulipin showed significant anticancer activity against breast and colon cancer cell lines.

The First Data on the BioEcology of Scorpions (Arachnida: Scorpiones) in Bavi County, Southwestern Iran (2016–2017)

Aims: The purpose of this study was to determine the scorpion species, abundance, distribution, monthly activity, comparisons between different scorpion collecting methods, and sex ratio in Bavi County, during 2016–2017. Materials and Methods: Collection of scorpions was made during the night examinations using the ultraviolet (UV) light and ordinary flashlight. Meanwhile, during the day, scorpions were gathered through rock rolling and pouring water in-ground holes. Scorpions were hunted using a long forceps and then transferred to the laboratory in separate glass containers containing alcohol 75%. All the specimens were identified based on valid taxonomic keys. Results: A total of nine species in nine genera from three families were identified. Androctunus crassicauda, Hemiscorpius lepturus, and Mesobuthus phillipsii were the most abundant in the investigated areas. The most scorpion activity was recorded in the summer. The most of the specimens were collected through UV light. The sex ratio was 1: 1.2 in favor of females. Conclusion: There are three medically major scorpion species including H. lepturus, A. crassicauda, and M. philipsi in Bavi County. Among them, H. lepturus is the most venomous scorpion in the investigated region. Therefore, inhabitants must be careful of its sting, in particular in children.

Inhibitory Effect of Hemiscorpius lepturus Scorpion Venom Fractions on Tachyzoites of Toxoplasma gondii.

Background:The present study determined the effect of the fractions obtained from Hemiscorpius lepturus scorpion venom on the tachyzoite of Toxoplasma gondii.Methods:The fractions of dried venom of He. lepturus scorpion of Khuzestan Province, southern Iran in 2019 were isolated through gel filtration chromatography, and then tachyzoites were exposed to fractions of venom at different concentrations. Trypan blue counting and MTT were applied to assay tachyzoite viability, and the inhibition of the cellular growth of fractions in Vero cells was evaluated.Results:The maximum effect on tachyzoite was observed in fraction 5 of venom. To further separate the protein, fraction 5 was used in high-performance liquid chromatography assay to purify its proteins. Based on the results of HPLC of fraction 5, among which the second peak, a peptide with <10 KDa representing a more potent effect in eliminating the tachyzoite of T. gondii.Conclusion:The scorpion venom-purified fractions possess anti-parasitic activity against the tachyzoite of T. gondii and can be used in parasite-controlling studies.

Discovery of a New Analgesic Peptide, Leptucin, from the Iranian Scorpion, Hemiscorpius lepturus.

Hemiscorpius lepturus scorpion stings do not induce considerable pain based on epidemiological surveys conducted in the southwest part of Iran. Accordingly, this study was aimed to identify the analgesic molecule in H. lepturus venom by analyzing a cDNA library of the scorpion venom gland looking for sequences having homology with known animal venom analgesic peptides. The analgesic molecule is a cysteine rich peptide of 55 amino acids. the synthetic peptide was deprotected and refolded. RP-HPLC, Ellman’s, and DLS assays confirmed the refolding accuracy. Circular dichroism (CD) showed helix and beta sheet contents. This peptide, called leptucin, demonstrated 95% analgesic activity at the dose of 0.48 mg/kg in hot plate assay. Leptucin at the doses of 0.32, 0.48, and 0.64 mg/kg showed 100% activity in thermal tail flick test. No hemolysis or cytotoxicity was observed at 8 and 16 μg. Histopathology evaluations indicated no hepatotoxicity, nephrotoxicity, and cardiotoxicity. We thus report that leptucin is the analgesic agent of H. lepturus venom. Regarding the high in vivo efficacy of leptucin and the fact it shows no observable toxicity, it could be suggested as a drug lead in a preclinical study of acute pain as well as the study of its mechanism of action.