Scorpion Venom Peptides as a Potential Source for Human Drug Candidates

Uzair, Bushra; Bint-E-Irshad, Sarah; Khan, Barkat Ali; Azad, Beenish; Mahmood, Tariq; Rehman, Mujaddad Ur; Braga, Valdir de Andrade

doi:10.2174/0929866525666180614114307

Cited by 29 publications

(12 citation statements)

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“…Actually, venoms from a diverse range of venomous animals have become valuable source for drug development as they are very rich in peptide toxins with high specificity and potency for particular molecular targets (Undheim et al, 2016). Quite a few peptide toxins from BmK venom have been shown to affect ion channel functions, and have anticonvulsant, anti-tumor, and analgesic activities (Uzair et al, 2018). However, no component with anti-inflammatory property has been identified from BmK or scorpion venom (SV) of any scorpion species.…”

Section: Introductionmentioning

confidence: 99%

Scorpion Venom Heat-Resistant Peptide Attenuates Microglia Activation and Neuroinflammation

Yang

et al. 2021

Front. Pharmacol.

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Background: Intervention of neuroinflammation in central nervous system (CNS) represents a potential therapeutic strategy for a host of brain disorders. The scorpion Buthus martensii Karsch (BmK) and its venom have long been used in the Orient to treat inflammation-related diseases such as rhumatoid arthritis and chronic pain. Scorpion venom heat-resistant peptide (SVHRP), a component from BmK venom, has been shown to reduce seizure susceptibility in a rat epileptic model and protect against cerebral ischemia-reperfusion injury. As neuroinflammation has been implicated in chronic neuronal hyperexcitability, epileptogenesis and cerebral ischemia-reperfusion injury, the present study aimed to investigate whether SVHRP has anti-inflammatory property in brain.Methods: An animal model of neuroinflammation induced by lipopolysacchride (LPS) injection was employed to investigate the effect of SVHRP (125 µg/kg, intraperitoneal injection) on inflammagen-induced expression of pro-inflammatory factors and microglia activation. The effect of SVHRP (2–20 μg/ml) on neuroinflammation was further investigated in primary brain cell cultures containing microglia as well as the immortalized BV2 microglia culture stimulated with LPS. Real-time quantitative PCR were used to measure mRNA levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in hippocampus of animals. Protein levels of TNF-α, iNOS, P65 subunit of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) were examined by ELISA or western blot. Microglia morphology in animal hippocampus or cell cultures and cellular distribution of p65 were shown by immunostaining.Results: Morphological study demonstrated that activation of microglia, the main component that mediates the neuroinflammatory process, was inhibited by SVHRP in both LPS mouse and cellular model. Our results also showed dramatic increases in the expression of iNOS and TNF-α in hippocampus of LPS-injected mice, which was significantly attenuated by SVHRP treatment. In vitro results showed that SVHRP attenuated LPS-elicited expression of iNOS and TNF-α in different cultures without cell toxicity, which might be attributed to suppression of NF-κB and MAPK pathways by SVHRP.Conclusion: Our study demonstrates that SVHRP is able to inhibit neuroinflammation and microglia activation, which may underlie the therapeutic effects of BmK-derived materials, suggesting that BmK venom could be a potential source for CNS drug development.

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Section: Introductionmentioning

confidence: 99%

Scorpion Venom Heat-Resistant Peptide Attenuates Microglia Activation and Neuroinflammation

Yang

et al. 2021

Front. Pharmacol.

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“…It also exhibited the advantage of being able to penetrate deep into tumor tissue [217,218]. Since the discovery of CTx, the list of scorpion crude venoms and isolated toxins with anticancer activity has been growing rapidly, hence a comprehensive review of all reported compounds exceeds the scope of this review, but can be found elsewhere [216][217][218][219]. Here, we present a few cherry-picked recent studies with the most significant findings.…”

Section: Anticancer Effectsmentioning

confidence: 99%

Scorpion Venom: Detriments and Benefits

et al. 2020

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Scorpion venom may cause severe medical complications and untimely death if injected into the human body. Neurotoxins are the main components of scorpion venom that are known to be responsible for the pathological manifestations of envenoming. Besides neurotoxins, a wide range of other bioactive molecules can be found in scorpion venoms. Advances in separation, characterization, and biotechnological approaches have enabled not only the development of more effective treatments against scorpion envenomings, but have also led to the discovery of several scorpion venom peptides with interesting therapeutic properties. Thus, scorpion venom may not only be a medical threat to human health, but could prove to be a valuable source of bioactive molecules that may serve as leads for the development of new therapies against current and emerging diseases. This review presents both the detrimental and beneficial properties of scorpion venom toxins and discusses the newest advances within the development of novel therapies against scorpion envenoming and the therapeutic perspectives for scorpion toxins in drug discovery.

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“…Therefore, additional –omic analyses, such as genomics and transcriptomics ( Zhijian et al, 2006 ; Ma et al, 2009 ; Rokyta and Ward, 2017 ; Ward et al, 2018 ), are encouraged to promote the discovery of novel scorpion venom toxins. This research will increase our understanding of Indian red scorpion venom ( Schendel et al, 2019 ), its toxicity mechanism, and identify novel drug prototypes from this venom ( Uzair et al, 2018 ).…”

Section: Conclusion On Future Directions For Research and Augmentation Of Clinical Treatment On Scorpion Stingmentioning

confidence: 99%

Biochemical and Proteomic Characterization, and Pharmacological Insights of Indian Red Scorpion Venom Toxins

2021

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The Indian red scorpion (Mesobuthus tamulus) is one of the world’s deadliest scorpions, with stings representing a life-threatening medical emergency. This species is distributed throughout the Indian sub-continent, including eastern Pakistan, eastern Nepal, and Sri Lanka. In India, Indian red scorpions are broadly distributed in western Maharashtra, Saurashtra, Kerala, Andhra Pradesh, Tamil Nadu, and Karnataka; however, fatal envenomations have been recorded primarily in the Konkan region of Maharashtra. The Indian red scorpion venom proteome comprises 110 proteins belonging to 13 venom protein families. The significant pharmacological activity is predominantly caused by the low molecular mass non-enzymatic Na+ and K+ ion channel toxins. Other minor toxins comprise 15.6% of the total venom proteome. Indian red scorpion stings induce the release of catecholamine, which leads to pathophysiological abnormalities in the victim. A strong correlation has been observed between venom proteome composition and local (swelling, redness, heat, and regional lymph node involvement) and systemic (tachycardia, mydriasis, hyperglycemia, hypertension, toxic myocarditis, cardiac failure, and pulmonary edema) manifestations. Immediate administration of antivenom is the preferred treatment for Indian red scorpion stings. However, scorpion-specific antivenoms have exhibited poor immunorecognition and neutralization of the low molecular mass toxins. The proteomic analysis also suggests that Indian red scorpion venom is a rich source of pharmacologically active molecules that may be envisaged as drug prototypes. The following review summarizes the progress made towards understanding the venom proteome of the Indian red scorpion and addresses the current understanding of the pathophysiology associated with its sting.

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Scorpion Venom Peptides as a Potential Source for Human Drug Candidates

Cited by 29 publications

References 0 publications

Scorpion Venom Heat-Resistant Peptide Attenuates Microglia Activation and Neuroinflammation

Scorpion Venom Heat-Resistant Peptide Attenuates Microglia Activation and Neuroinflammation

Scorpion Venom: Detriments and Benefits

Biochemical and Proteomic Characterization, and Pharmacological Insights of Indian Red Scorpion Venom Toxins

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