Theranekron attenuates lipopolysaccharide-induced neuroinflammation via NLRP3 inflammasome modulation

Acute neuroinflammation plays a critical role in the pathogenesis of various central nervous system (CNS) disorders. Theranekron (TH), a homeopathic preparation derived from Tarantula cubensis venom, has demonstrated anti-inflammatory potential in several experimental models. This study aimed to evaluate the therapeutic efficacy of TH in a lipopolysaccharide (LPS) induced acute neuroinflammation model, focusing on oxidative stress parameters, histopathological changes, immunohistochemical markers, and key neuroinflammatory pathways involving the NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome.

Thirty-two Wistar Albino rats were randomly divided into four groups: control, LPS (5 mg/kg, intraperitoneally), TH (0.2 ml, single dose, subcutaneously), and LPS + TH. Theranekron (0.2 mL, s.c.) was administered 30 min after LPS injection. Six hours after LPS administration, brain tissues were collected for the biochemical analyses of total antioxidant species (TAS), total oxidant species (TOS), and oxidative stress index (OSI)with histopathological and immunohistochemical analyses of tyrosine hydroxylase (TyrH) caspase-3 (Cas-3), tumor necrosis factor-alpha (TNF-α); and gene expression analyses of NLRP3, caspase 1 (Cas-1), interleukin-1 beta (IL-1β), and interleukin 18 (IL-18). LPS administration significantly increased Cas-3, TNF-α immunoexpression, TOS, OSI, and the expression of NLRP3, Cas-1, IL-1β, and IL-18 genes, while reducing TyrH immunoexpression and TAS levels. TH treatment reversed these alterations; demonstrating strong anti-inflammatory, antioxidant, and neuroprotective effects in the cerebral cortex, hippocampus and cerebellum.

This study provides compelling evidence that TH exerts potent neuroprotective effects by suppressing NLRP3 inflammasome activation, reducing oxidative stress, and restoring neurochemical homeostasis in an LPS-induced neuroinflammation model. These findings highlight TH as a promising therapeutic candidate for CNS inflammatory disorders, warranting further molecular and clinical investigation.