Identification of cyclooxygenase-II inhibitory saponins from fenugreek wastes: Insights from liquid chromatography-tandem mass spectrometry metabolomics, molecular networking, and molecular docking

Asmaa M Khalil; Omar M Sabry; Hesham I El-Askary; Soheir M El Zalabani; Basma M Eltanany; Laura Pont; Fernando Benavente; Ahmed Elshewy; Nesrin M Fayek

doi:10.1002/pca.3322

Identification of cyclooxygenase-II inhibitory saponins from fenugreek wastes: Insights from liquid chromatography-tandem mass spectrometry metabolomics, molecular networking, and molecular docking

Phytochem Anal. 2024 Jan 11. doi: 10.1002/pca.3322. Online ahead of print.

Authors

Asmaa M Khalil¹, Omar M Sabry^{1

2}, Hesham I El-Askary¹, Soheir M El Zalabani¹, Basma M Eltanany³, Laura Pont^{4

5}, Fernando Benavente⁴, Ahmed Elshewy^{6

7}, Nesrin M Fayek¹

Affiliations

¹ Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
² Department of Pharmacognosy, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt.
³ Department of Analytical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
⁴ Department of Chemical Engineering and Analytical Chemistry, Institute for Research on Nutrition and Food Safety (INSA-UB), University of Barcelona, Barcelona, Spain.
⁵ Serra Húnter Program, Generalitat de Catalunya, Barcelona, Spain.
⁶ Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
⁷ Department of Medicinal Chemistry, Faculty of Pharmacy, Galala University, New Galala, Egypt.

PMID: 38212263
DOI: 10.1002/pca.3322

Abstract

Introduction: This research explores sustainable applications for waste generated from fenugreek (Trigonella foenum-graecum), a plant with both nutritional and medicinal uses. The study specifically targets waste components as potential sources of nutrients and bioactive compounds.

Objectives: The focus is to conduct detailed metabolic profiling of fenugreek waste, assess its anti-inflammatory properties by studying its cyclooxygenase (COX) inhibitory effect, and correlate this effect to the metabolite fingerprint.

Materials and methods: Ethanolic extracts of fenugreek fruit pericarp and a combination of leaves and stems were subjected to untargeted metabolic profiling using liquid chromatography-mass spectrometry integrated with online database searches and molecular networking as an effective dereplication strategy. The study also scrutinized the COX inhibitory capabilities of these extracts and saponin-rich fractions prepared therefrom. Molecular docking was employed to investigate the specific interactions between the identified saponins and COX enzymes.

Results: The analysis led to the annotation of 81 metabolites, among which saponins were predominant. The saponin-rich fraction of the fruit pericarp extract displayed the strongest COX-II inhibitory activity in the in vitro inhibition assay (IC₅₀ value of 81.64 ± 3.98 μg/mL). The molecular docking study supported the selectivity of the identified saponins towards COX-II. The two major identified saponins, namely, proto-yamogenin 3-O-[deoxyhexosyl (1 → 2)] [hexosyl (1 → 4)] hexoside 26-O-hexoside and trigofenoside A, were predicted to have the highest affinity to the COX-II receptor site.

Conclusion: In the present study, we focused on the identification of COX-II inhibitory saponins in fenugreek waste through an integrated approach. The findings offer valuable insights into potential anti-inflammatory and cancer chemoprotective applications of fenugreek waste.

Keywords: COX inhibitors; Trigonella foenum-graecum; metabolomics; molecular docking; saponins.

Grants and funding

Egyptian Ministry of Higher Education