Possible Mechanisms Underlying the Antispasmodic, Bronchodilator, and Antidiarrheal Activities of Polarity-Based Extracts of Cucumis sativus L. Seeds in In Silico, In Vitro, and In Vivo Studies

Muqeet Wahid; Fatima Saqib; Saeed Akhtar; Anam Ali; Polrat Wilairatana; Mohammad S Mubarak

doi:10.3390/ph15050641

Possible Mechanisms Underlying the Antispasmodic, Bronchodilator, and Antidiarrheal Activities of Polarity-Based Extracts of Cucumis sativus L. Seeds in In Silico, In Vitro, and In Vivo Studies

Pharmaceuticals (Basel). 2022 May 23;15(5):641. doi: 10.3390/ph15050641.

Authors

Muqeet Wahid¹, Fatima Saqib¹, Saeed Akhtar², Anam Ali¹, Polrat Wilairatana³, Mohammad S Mubarak⁴

Affiliations

¹ Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60000, Pakistan.
² Institute of Food Science and Nutrition, Bahauddin Zakariya University, Multan 60000, Pakistan.
³ Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
⁴ Department of Chemistry, The University of Jordan, Amman 11942, Jordan.

Abstract

Apart from the nutritional value, Cucumis sativus L. has also been used in the traditional medicine of Iran, Pakistan, and India. Its seeds are used by herbalists to treat gastrointestinal, respiratory, and urinary problems. However, more investigations are required to explain its mechanisms for treating GI, respiratory, and urinary diseases. Accordingly, the aim of the present work was to investigate the antispasmodic, bronchodilator, and antidiarrheal activities of C. sativus seeds extracts and the underlying mechanisms of action. For this purpose, sequential extracts of C. sativus seeds were prepared in n-hexane, dichloromethane, ethanol, and water. Bioactive compounds in C. sativus seed extracts were identified and quantified by utilizing LC ESI-MS/MS and HPLC. Moreover, network pharmacology and molecular docking were employed to examine the antispasmodic and bronchodilator effects of the bioactive substances in the extracts. In vitro and in vivo experiments were also conducted to validate the mechanistic insights gained from the in silico analysis. Results indicated the presence of kaempferol with a concentration of 813.74 µg/g (highest concentration) in the seed extract of C. sativus, followed by quercetin (713.83 µg/g), narcissin (681.87 µg/g), and orientin (676.19 µg/g). In silico investigations demonstrated that the bioactive chemicals in C. sativus seeds inhibited the expression of the target genes involved in smooth muscle contraction and calcium-mediated signaling. Sequential seed extracts of C. sativus caused a dose-dependent relaxant response for spasmolytic reaction and resulted in a relaxation of K⁺ (80 mM) spastic contraction. In animal models, C. sativus seed extracts exhibited partial or complete antiperistalsis, antidiarrheal, and antisecretory actions. By modulating the contractile response through calcium-mediated signaling target proteins, C. sativus seeds generated bronchodilator, antispasmodic, and antidiarrheal therapeutic effects.

Keywords: Cucumis sativus; LC ESI–MS/MS; antidiarrheal effects; antispasmodic; bronchodilator; cucumber; mechanism of action.

Grants and funding

This research received no external funding.