Scorpion venom peptides: Novel therapeutic approaches for inflammatory and hepatic disorders

Chronic hepatic disorders, such as metabolic dysfunction associated steatohepatitis (MASH), alcohol associated liver disease (ALD), and viral hepatitis (Hepatitis B virus [HBV]/Hepatitis C virus [HCV]), are primarily driven by persistent immune-mediated inflammation and hepatic stellate cell activation leading to fibrosis, yet conventional therapies lack tissue and molecular specificity. Scorpion venom peptides, refined through evolutionary selection, provide highly potent, target specific scaffolds capable of modulating intrahepatic inflammatory networks. Recent in vivo preclinical studies indicate that voltage gated potassium (Kv1.3) channel blocking peptides, such as BmKK2, significantly reduce macrophage activation and inhibit downstream cytokine production, effectively ameliorating diet-induced steatohepatitis and tissue scarring in murine models. Engineered hepatotropic candidates, such as Smp76 and Mucroporin-M1, demonstrate dual therapeutic functions: they neutralize extracellular Hepatitis C particles and suppress key host transcription factors necessary for Hepatitis B replication. This review systematically examines scorpion venom peptides organized by disease category, covering their historical development, structural classification into disulfide-bridged and non-disulfide-bridged families, ion channel specificity, hepatic anti-inflammatory and antiviral mechanisms, and translational challenges including nano-formulation delivery strategies and computational drug design. These target-specific peptides are ultimately positioned as promising molecular leads that may bridge targeted immunomodulation with the resolution of chronic, progressive liver injury.