Potential Therapeutic Efficacy of Berberine and Crocin Combination Through Targeting Multiple Pathways: An in-silico,...

Berberine and crocin, two valuable bioactive compounds in Traditional Chinese Medicine (TCM), are known for their diverse pharmacological properties and have gained attention for their potential therapeutic effects in neurological disorders.

This study investigates the potential synergistic efficacy of a berberine and crocin combination by targeting multiple molecular pathways implicated in neuroprotection, using both in-silico and in-vivo approaches.

The in-silico docking analysis demonstrated favourable binding affinities for both compounds, indicating their preference to interact with these receptors effectively in a synergistic manner. Behavioural studies, along with biochemical assays for oxidative stress markers and inflammatory cytokines, indicated significant improvements in cognitive function and reductions in neuroinflammatory markers. The combination of berberine and crocin demonstrated a significant decline in cytokine levels (TNF-α, IL-6) and oxidative markers (MDA, NO). A rise in oxidative markers (GSH, SOD, and Catalase), IL-10 cytokine levels, and neuroprotective markers (BDNF, CREB) was also observed. A marked improvement in mitochondrial function was observed in the treatment groups. Moreover, histological analysis revealed decreased neuroinflammation in the brain.

In-silico docking studies performed evaluated the interaction of berberine and crocin with key targets, viz. histone deacetylase 2 (HDAC2), nuclear factor kappa B (NF-κB), Nrf2/Keap1, Calcium channel and NMDA pathway. This interaction plays a significant role in neuroinflammation, oxidative stress response, and excitotoxicity during neurodevelopment. Invivo assessments further explored the neuroprotective and anti-inflammatory potential of the berberine-crocin combination in a rodent model of neuroinflammation.

The findings highlight the therapeutic potential of the combination therapy (berberine and crocin) in treating neurodevelopmental conditions through multi-target modulation. Further clinical studies are warranted to explore their combination as a novel therapeutic approach.