Behavioural brain research · 2024
Anxiogenic-like effects of coumarin, possibly through the GABAkine interaction pathway: Animal studies with in silico approaches.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Prottay Abdullah Al Shamsh, Emamuzzaman, Ripu Tawfik Rakaiyat, Sarwar Md Nazim, Rahman Towfiqur, Ahmmed Md Shakil, Bappi Mehedi Hasan, Emon Md, Ansari Siddique Akber, Coutinho Henrique D M, Islam Muhammad Torequl
Аннотация
BACKGROUND: Anxiety disorder is the most common mental illness and a major contributor to impairment. Thus, there is an urgent need to find novel lead compounds to mitigate anxiety. It is widely recognized that the neurobiology of anxiety-related behavior involves GABAergic systems.
OBJECTIVES: This research aimed to examine the anxiogenic action of coumarin (CMN), a natural benzopyrone derived from plants, and determine its underlying mechanism through in vivo and in silico investigations.
METHODS: This was accomplished by using a variety of behavioral procedures, including open field, swing, hole cross, and light-dark tests, on male and female Swiss albino mice that had been orally administered three experimental doses of CMN (1, 2, and 4 mg/kg). The CMN group was also examined with the GABAA receptor agonist diazepam (DZP, 2 mg/kg) and flumazenil antagonist (FLU, 0.1 mg/kg). Furthermore, CMN and standards were subjected to a molecular docking analysis to determine their binding affinities for the GABAA receptor subunits (α1, α4, β2, γ2, and δ). Several software programs were used to visualize the ligand-receptor interaction and analyze the pharmacokinetic profile.
RESULTS: Compared to typical treatments, our results show that CMN (1 mg/kg) significantly (p < 0.05) increases the locomotor activity of animals. Furthermore, CMN exerted the highest binding affinity (-6.5 kcal/mol) with the GABA-α1 receptor compared to conventional DZP. Along with FLU, CMN displayed several hydrophobic and hydrogen bonds with GABAA receptor subunits. The pharmacokinetic and drug-like properties of CMN are also remarkable. In animal studies, CMN worked synergistically with FLU to provide anxiogenic-like effects.
CONCLUSION: We conclude that, based on in vivo and in silico data, CMN, alone or in combination with FLU, may be employed in future neurological clinical studies. However, further research is needed to confirm this behavioral activity and elucidate the possible mechanism of action.
OBJECTIVES: This research aimed to examine the anxiogenic action of coumarin (CMN), a natural benzopyrone derived from plants, and determine its underlying mechanism through in vivo and in silico investigations.
METHODS: This was accomplished by using a variety of behavioral procedures, including open field, swing, hole cross, and light-dark tests, on male and female Swiss albino mice that had been orally administered three experimental doses of CMN (1, 2, and 4 mg/kg). The CMN group was also examined with the GABAA receptor agonist diazepam (DZP, 2 mg/kg) and flumazenil antagonist (FLU, 0.1 mg/kg). Furthermore, CMN and standards were subjected to a molecular docking analysis to determine their binding affinities for the GABAA receptor subunits (α1, α4, β2, γ2, and δ). Several software programs were used to visualize the ligand-receptor interaction and analyze the pharmacokinetic profile.
RESULTS: Compared to typical treatments, our results show that CMN (1 mg/kg) significantly (p < 0.05) increases the locomotor activity of animals. Furthermore, CMN exerted the highest binding affinity (-6.5 kcal/mol) with the GABA-α1 receptor compared to conventional DZP. Along with FLU, CMN displayed several hydrophobic and hydrogen bonds with GABAA receptor subunits. The pharmacokinetic and drug-like properties of CMN are also remarkable. In animal studies, CMN worked synergistically with FLU to provide anxiogenic-like effects.
CONCLUSION: We conclude that, based on in vivo and in silico data, CMN, alone or in combination with FLU, may be employed in future neurological clinical studies. However, further research is needed to confirm this behavioral activity and elucidate the possible mechanism of action.