Abstract

Holigarna caustica (Dennst.), a popular plant used in folk medicine in Bangladesh, is often used by the local folk practitioner to treat a variety of chronic diseases. The present research is an attempt to find out an innovative therapeutic prospect for the management of neuropsychiatric disorders. The methanol extract of H. caustica leaves (MEHC) were utilized on various behavioral tests for assessing anxiolytic, anti-depressant, and anti-inflammatory activities. The antioxidant potentials and quantitative phytochemicals were evaluated through spectrophotometric methods. Results revealed that treatment of MEHC (200 and 400 mg/kg) significantly reduced anxiety like behaviors in mice, particularly, 400 mg/kg efficiently improved % of entries and time spent (p < 0.05) in the open arms in elevated plus maze test, whereas, superior head dipping tendency (p < 0.05) was observed in hole-board test. In contrast, mice treated with 200 mg/kg revealed better anxiolytic effect in both open field and hole-cross tests. During antidepressant evaluation, mice administrated with MEHC exhibited active behaviors (swimming and struggling) in forced swimming and tail suspension tests. In parallel, MEHC manifested a noteworthy (p < 0.001) suppression of inflammatory response induced by histamine. The MEHC also showed strong antioxidant activities in 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) (IC50: 57.64 μg/mL) scavenging, H2O2 (IC50: 51.60 μg/mL) scavenging, and ferric reducing power assay. The levels of total phenol, flavonoid, flavonol, condensed tannin, and antioxidant were estimated as higher in MEHC. Moreover, 11 compounds were documented as bioactive, displayed good binding affinities to potassium channel receptor, human serotonin receptor, cyclooxygenase (COX-1 and 2), and xanthine oxidoreductase enzyme targets in molecular docking experiments. Furthermore, ADME/T and Prediction of Activity Spectra for Substances (PASS) analyses exposed their drug-likeness, nontoxic upon consumption, and likely pharmacological actions. Overall, the H. caustica is potentially bioactive as evident by in vivo, in vitro, and computational analysis. Our findings support the folkloric value of this plant, which may provide a potential source towards developing drug leads.

Highlights

  • In recent years, mental and behavioral disarrays are among the vital principle of disability due to the interference of affected people’s mood and emotion [1]

  • We revealed that MEHC can effectively suppress in both central and peripheral nociception pathways, which prove that the bioactive compounds of MEHC can act on the central nervous system by crossing the blood brain barrier (BBB)

  • The accumulating pharmacological evidences propose that MEHC may provide novel healing insights in neuropsychiatric disorders, anxiety and depression

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Summary

Introduction

Mental and behavioral disarrays are among the vital principle of disability due to the interference of affected people’s mood and emotion [1]. According to the Study highlight (2017) of The Global Burden of Disease, Injuries, and Risk Factors (GBD), neuropsychiatric disorders are ranked as the third leading cause of disability, where the suffering rate are higher in the case of females [2]. Depression is a persistent and multiplex disorder with an expansive impact on the community and is connected with functional disablement and elevated morbidity and mortality; in contrast, anxiety is another frequent psychiatric disorder globally [4]. It is suggested by different corroboration that depressive and anxiety disorders coincide and do not constitute discrete disease entities. The existence of anxiety in accord with depression leads into complications of symptoms, less authentic prognosis, worsened response for treatment or treatment dropout, and a higher risk of suicidal tendency [5]

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