ABSTRACT
Genomic screened homeobox 1 (Gsx1 or Gsh1) is a neurogenic transcription factor required for the generation of excitatory and inhibitory interneurons during spinal cord development. In the adult, lentivirus (LV) mediated Gsx1 expression promotes neural regeneration and functional locomotor recovery in a mouse model of lateral hemisection spinal cord injury (SCI). The LV delivery method is clinically unsafe due to insertional mutations to the host DNA. In addition, the most common clinical case of SCI is contusion/compression. In this study, we identify that adeno-associated virus serotype 6 (AAV6) preferentially infects neural stem/progenitor cells (NSPCs) in the injured spinal cord. Using a rat model of contusion SCI, we demonstrate that AAV6 mediated Gsx1 expression promotes neurogenesis, increases the number of neuroblasts/immature neurons, restores excitatory/inhibitory neuron balance and serotonergic neuronal activity through the lesion core, and promotes locomotor functional recovery. Our findings support that AAV6 preferentially targets NSPCs for gene delivery and confirmed Gsx1 efficacy in clinically relevant rat model of contusion SCI.
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Scorpion sting is a public health concern with limited clinical symptomatic treatment. The clinical treatment uses anti-scorpion antivenom and prazosin (α-adrenergic inhibitor), often in combination with insulin, to reduce scorpion venom-induced hyperglycemia and other complications. However, these therapies also possess some limitations, necessitating urgent exploration of ethnomedicines, mainly traditional medicinal plants, to treat scorpion stings. Unfortunately, several conventional treatments are not scientifically validated, thus raising questions about their quality and utility. Therefore, pharmacological re-assessment of such medicinal plants to alleviate scorpion stings' complications is essential. AIM OF THE STUDY: The principal objectives of this study are to provide a brief overview of medically important scorpions of the world, outline the extant traditional practices, and comprehensively review plants used in conventional ethnic medicines to treat scorpion stings over time. Modern technological advances in identifying and characterizing plant bioactive molecules are also mentioned in this review. MATERIALS AND METHODS: The traditionally used medicinal plants against scorpion stings were reviewed from the available literature in the database. The Plant List (http://www.theplantlist.org/) was used to validate the scientific names of the plants mentioned in this study. The search targeted literature on conventional treatments and crude plant extracts or their bioactive components with proven neutralization capacity against scorpion stings. Search words used were 'scorpion sting,' 'treatment for a scorpion sting,' 'antivenom and scorpion sting,' 'traditional treatment for scorpion stings, and 'natural compounds against scorpion stings'. RESULTS: A list of more than 200 medicinal plants traditionally used in several countries for treating scorpion stings is presented in this review. Though some myth-based remedies are practiced to treat scorpion stings, no empirical evidence exists to validate this aspect of traditional knowledge. Only 38 traditional medicinal plant extracts have been tested under in-vivo and in-vitro conditions to determine their neutralization potency of scorpion envenomation. Although a few bioactive plant constituents showing scorpion venom neutralization potency have been characterized, they are not yet commercially available for clinical application. CONCLUSIONS: There is tremendous potential locked in medicinal plants' traditional knowledge for scorpion envenomation treatment. Translating this knowledge into the clinical application will require pharmacological reassessment, in tandem with isolation and characterization of active compounds to prove their prophylactic prowess. Almost equally important would be the formulation of stringent strategies to conserve such medicinal plants from overexploitation.
