Therapeutic evaluation of artocarpin-enriched extract from Artocarpus heterophyllus heartwood in multiple sclerosis rat model.

Neuro-inflammation leads to the development of neurological disorders such as multiple sclerosis (MS) by promoting demyelination in Central nervous system (CNS). Due to limitations in the efficacy and side effects of the currently available treatments of MS this study is designed to explore neuroprotective role of artocarpin enriched extract (AEE) of Artocarpus heterophyllus heartwood as a favorable natural therapeutic substitute in MS. AEE was prepared from the heartwood of A. heterophyllus using a green microwave-assisted extraction technique. To assess the safety profile of AEE acute toxicity assessment was performed in accordance with OECD guidelines. Molecular docking analysis was performed to analyze the binding affinity and interaction behavior of artocarpin against multiple therapeutic targets S1PR1, MMP-9, BTK, IL-17, TNF-α and NLRP3. For the therapeutic evaluation of AEE, in cuprizone (CPZ) induced demyelination, forty-two Wistar albino rats were selected and evenly distributed into seven groups: Normal control (NC), disease control (DC), standard treatment drug (fingolimod, 15 mg/kg, pure artocarpin (AC) 100 mg/kg and three treatment groups receiving AEE at dose of 200 mg, 400 mg, and 800 mg/kg. Neuroinflammation was induced in all groups except NC by administering 0.2% w/w 450 mg/kg cuprizone for 42 days. Behavioral assessments, biochemical analyses, histopathological examinations, gene expression and neurotransmitter level were observed to explore the meyelin protection effects of AEE. Results demonstrated that pure artocarpin and AEE produced significant effects in the protection of neuron myelin sheath and can be considered as a suitable therapeutic agent for further study in MS.