Exploring the sedative properties of natural molecules from hop cones (Humulus lupulus) as promising natural anxiolytics through GABA receptors and the human serotonin transporter

Amany Belal; Mohammed S Elballal; Ahmed A Al-Karmalawy; Ahmed H E Hassan; Eun Joo Roh; Mohammed M Ghoneim; Mohamed A M Ali; Ahmad J Obaidullah; Jawaher M Alotaibi; Salwa Shaaban; Mohamed A Elanany

doi:10.3389/fchem.2024.1425485

Exploring the sedative properties of natural molecules from hop cones (Humulus lupulus) as promising natural anxiolytics through GABA receptors and the human serotonin transporter

Front Chem. 2024 Jul 10:12:1425485. doi: 10.3389/fchem.2024.1425485. eCollection 2024.

Authors

Amany Belal¹, Mohammed S Elballal², Ahmed A Al-Karmalawy^{3

4}, Ahmed H E Hassan⁵, Eun Joo Roh^{6

7}, Mohammed M Ghoneim⁸, Mohamed A M Ali^{9

10}, Ahmad J Obaidullah¹¹, Jawaher M Alotaibi¹¹, Salwa Shaaban^{12

13}, Mohamed A Elanany¹⁴

Affiliations

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, Taif, Saudi Arabia.
² Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Cairo, Egypt.
³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta, Egypt.
⁴ Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt.
⁵ Deparment of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
⁶ Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.
⁷ Division of Bio-Medical Science and Technology, University of Science and Technology, Daejeon, Republic of Korea.
⁸ Department of Pharmacy Practice, College of Pharmacy, Almaarefa University, Ad Diriyah, Saudi Arabia.
⁹ Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia.
¹⁰ Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
¹¹ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
¹² Department of Microbiology and Immunology, Faculty of Pharmacy, Suef University, Beni-Suef, Egypt.
¹³ Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.
¹⁴ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Cairo, Egypt.

Abstract

This research work aimed to identify the main components that are responsible for the sedative properties of hop cones and allocate their targets. This investigation was performed through molecular docking, molecular dynamic simulations, root mean square fluctuation (RMSF) analysis, and DFT calculation techniques. The tested compounds from Humulus lupulus were compared to diazepam and paroxetine. Molecular docking showed that two-thirds of the compounds had a good affinity to gamma-aminobutyric acid (GABA), outperforming diazepam, while only three surpassed paroxetine on the SERT. Compounds 3,5-dihydroxy-4,6,6-tris(3-methylbut-2-en-1-yl)-2-(3-methylbutanoyl)cyclohexa-2,4-dien-1-one (5) and (S,E)-8-(3,7-dimethylocta-2,6-dien-1-yl)-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one (15) showed stable binding and favorable energy parameters, indicating their potential for targeting GABA receptors and the SERT. This study provides a basis for future clinical research on these promising compounds.

Keywords: DFT; RMSF analysis; hop cones; molecular docking; molecular dynamics; natural anxiolytics; natural molecules.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research work was supported by Taif University, Saudi Arabia through the project number (TU-DSPP-2024-64). This research was also supported by the National Research Council of Science and Technology (NST) grant by the Korea government (MSIT) (No. CAP23011-100), KIST Institutional programs (2E33133) from Korea Institute of Science and Technology (KIST).