Anticonvulsive Effects of Chondroitin Sulfate on Pilocarpine and Pentylenetetrazole Induced Epileptogenesis in Mice

Abstract

Chondroitin sulfate is a proteoglycan component of the extracellular matrix (ECM) that supports neuronal and non-neuronal cell activity, provides a negative domain to the extracellular matrix, regulates the intracellular positive ion concentration, and maintains the hypersynchronous epileptiform activity. Therefore, the present study hypothesized an antiepileptic potential of chondroitin sulfate (CS) in pentylenetetrazole-induced kindled epilepsy and pilocarpine-induced status epilepticus in mice. Levels of various oxidative stress markers and inflammatory mediators were estimated in the brain tissue homogenate of mice, and histopathological changes were evaluated. Treatment with valproate (110 mg/kg; i.p.) as a standard drug and chondroitin sulfate (100 & 200 mg/kg, p.o.) significantly (p < 0.01) and dose-dependently prevented the severity of kindled and spontaneous recurrent seizures in mice. Additionally, chondroitin sulfate showed its antioxidant potential by restoring the various biochemical levels and anti-inflammatory properties by reducing NF-kB levels and pro-inflammatory mediators like TNF-alpha, IL-1β, and IL-6, indicating the neuroprotective effect as well as the suppressed levels of caspase-3, which indicated a neuroprotective treatment strategy in epilepsy. The proteoglycan chondroitin sulfate restores the normal physiology and configuration of the neuronal tissue. Further, the molecular docking of chondroitin sulfate at the active pockets of TNF-alpha, IL-1β, and IL-6 showed excellent interactions with critical amino acid residues. In conclusion, the present work provides preclinical evidence of chondroitin sulfate as a new therapeutic approach in attenuating and preventing seizures with a better understanding of the mechanism of alteration in ECM changes influencing abnormal neuronal activities.

Chondroitin Sulfate from Oreochromis niloticus Waste Reduces Leukocyte Influx in an Acute Peritonitis Model

“…In vivo studies have shown the potential of CS to reduce the severity of arthritis in rats [ 14 , 38 ]. Several studies show that CS may interfere with inflammatory processes by inhibition of the expression of pro-inflammatory molecules, such as interleukin- 1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and nuclear factor-κB (NF-kB) [ 39 , 40 ]. Based on these data, the isolated compound (CST) was tested in a peritoneal inflammatory model induced by sodium thioglycolate.…”

Chondroitin sulfate supplementation improves clinical outcomes in a murine model of necrotizing enterocolitis

“…Each day, formula was made based on daily weights and the caloric needs of the pups from the batch stock and supplemented with 0.008 mg/g of Lipopolysaccharide (LPS) isolated from Escherichia Coli O111:B4 (cat # L4391, Sigma‐Aldrich Company, St. Louis, MO). Those in the group to receive chondroitin sulfate, had their formula supplemented to receive 0.2 mg/g chondroitin sulfate daily (Cimini et al, 2022 ; Gao et al, 2022 ; Qi et al, 2021 ; Singh et al, 2021 ; Song et al, 2017 ). Experimental pups were gavage fed a hyper‐concentrated formula (300 kcal/kg/day) three times per day using a 1.9 French catheter.…”

“…A certificate of analysis was provided by the company for the lot number used in these experiments. The dose of chondroitin sulfate was determined by a literature search of chondroitin sulfate doses in different rodent models of disease that all used a dose of 200 mg/kg for beneficial therapeutic effects (Cimini et al, 2022 ; Gao et al, 2022 ; Qi et al, 2021 ; Singh et al, 2021 ; Song et al, 2017 ).…”

Unveiling the neuroprotective potential of dietary polysaccharides: a systematic review

“…Dietary polysaccharides have shown potential in reducing inflammatory responses, inhibiting the expression of neurotransmission-related genes, and improving hippocampal tissue damage in epilepsy models. Due to the antioxidant and antiinflammatory properties of chondroitin sulfate, a significant reduction in seizure mice induced by pentylenetetrazole and pilocarpine was observed (105). Fructus corni polysaccharide treatment (106) decreased levels of ROS and malondialdehyde (MDA), increased superoxide dismutase (SOD) activity, and inhibited expressions of phosphorylated-Jun N-terminal Kinase (p-JNK), cytochrome C, and caspase-3 in an epileptic rat model.…”