ABSTRACT
Major depression disorder (MDD) has become a common life-threatening disorder. Despite the number of studies and the introduced antidepressants, MDD remains a major global health issue. Carthamus tinctorius (safflower) is traditionally used for food and medical purposes. This study investigated the chemical profile and the antidepressant-like effect of the Carthamus tincto-rius hot water extract in male mice and its mechanism using a transcriptomic analysis. The antidepressant effect of hot water extract (50 mg/kg and 150 mg/kg) was investigated in mice versus the untreated group (saline) and positive control group (fluoxetine 10 mg/kg). Hippocampus transcriptome changes were investigated to understand the Carthamus tinctorius mechanism of action. The GC-MS analysis of Carthamus tinctorius showed that hot water extract yielded the highest amount of oleamide as the most active ingredient. Neuro-behavioral tests demonstrated that the safflower treatment significantly reduced immobility time in TST and FST and improved performance in the YMSAT compared to the control group. RNA-seq analysis revealed a significant differential gene expression pattern in several genes such as Ube2j2, Ncor1, Tuba1c, Grik1, Msmo1, and Casp9 related to MDD regulation in 50 mg/kg safflower treatment as compared to untreated and fluoxetine-treated groups. Our findings demonstrated the antidepressant-like effect of safflower hot water extract and its bioactive ingredient oleamide on mice, validated by a significantly shortened immobility time in TST and FST and an increase in the percentage of spontaneous alternation.
ABSTRACT
BACKGROUND: Cytokine storm in COVID-19 patients has contributed to many morbidities and mortalities in patients. Studies have found that toll-like receptors (TLRs) and some Fc receptors play essential roles in the hyperactivation of the immune system. Up to date, researchers are still in progress to discover effective and safe drugs to alleviate the hyperinflammatory state in COVID-19. The previous studies had shown that Carthamus tinctorius and its bioactive compounds might have anti-inflammatory activities in animal models. AIM: We aimed to investigate the possible interactions of several flavonoids from C. tinctorius with several immune system components using a biocomputational approach. METHODS: Molecular docking was done using the AutoDock program based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) COVID-19 pathway. The most suitable receptors found were studied to study the interactions with several flavonoids from C. tinctorius. RESULTS: TLR4, TLR8, and FcγRIIa were found to bind with SARS CoV2 inflammatory pathway and further selected as macromolecules for potential interactions study with 22 flavonoids from C. tinctorius. Of the 22 flavonoids studied, daphnoretin showed the best binding affinity with TLR4 and Rutin was shown to attach best with FcγRIIa. Unlike its excellent binding to TLR4, daphnoretin showed weak binding to TLR8. CONCLUSION: Daphnoretin showed an excellent affinity with TLR4 and might be a good candidate as an inhibitor in hyperinflammatory reactions in COVID-19 DTLR8.