Abstract
The current study accentuates the significance of performing the multiplex approach of LC-HRESIMS, biological activity, and docking studies in drug discovery, taking into consideration a review of the literature. In this regard, the investigation of antioxidant and cytotoxic activities of Trigonella stellata collected from the Egyptian desert revealed a significant antioxidant capacity using DPPH with IC50 = 656.9 µg/mL and a moderate cytotoxicity against HepG2, MCF7, and CACO2, with IC50 values of 53.3, 48.3, and 55.8 µg/mL, respectively. The evaluation of total phenolic and flavonoid contents resulted in 32.8 mg GAE/g calculated as gallic acid equivalent and 5.6 mg RE/g calculated as rutin equivalent, respectively. Chemical profiling of T. stellata extract, using LC-HRESIMS analysis, revealed the presence of 15 metabolites, among which eleven compounds were detected for the first time in this species. Interestingly, in vitro testing of the antidiabetic activity of the alcoholic extract noted an α-glucosidase enzyme inhibitory activity (IC50 = 559.4 µg/mL) better than that of the standard Acarbose (IC50 = 799.9 µg/mL), in addition to a moderate inhibition of the α-amylase enzyme (IC50 = 0.77 µg/mL) compared to Acarbose (IC50 = 0.21 µg/mL). α-Glucosidase inhibition was also virtualized by binding interactions through the molecular docking study, presenting a high binding activity of six flavonoid glycosides, as well as the diterpenoid compound graecumoside A and the alkaloid fenugreekine. Taken together, the conglomeration of LC-HRESIMS, antidiabetic activity, and molecular docking studies shed light on T. stellata as a promising antidiabetic herb.
Highlights
Diabetes mellitus (DM) is a chronic disorder marked by raised blood glucose levels due to disruption in the secretion of insulin, or its utilization or both [1]
The current study is the first report for the estimation of the total phenolic (TPC) and TFC of T. stellata, where their TPC was estimated as 32.8 ± 1.57 mg GAE/g and their TFC was 5.6 ± 0.14 mg RE/g
The molecular ion peaks at m/z 538.8999, 147.0239, 256.1580, 663.3963, 414.2121, 258.1368, and 171.0821, corresponding to the suggested molecular formulas C27H38O11, C6H13NO3, C15H12O4, C21H27N7O14P2, C27H42O3, C15H14O4, and C7H6O5, respectively, were detected. These peaks were dereplicated as the kaurene diterpenoid glycoside 1 [42], amino acid (4-hydroxyisoleucine) 2 [43], pterocarpan 3 [44], alkaloid 4 [45], phytosteroid sapogenin 5 [46], stilbene 6 [47], and gallic acid 7 [45], which were previously isolated from T. foenum-graecum
Summary
Diabetes mellitus (DM) is a chronic disorder marked by raised blood glucose levels due to disruption in the secretion of insulin, or its utilization or both [1]. Dereplication plays a crucial role in the drug discovery process as it is a fast and reliable approach, allowing scientists to focus on novel bioactive natural products It helps to confront the significant challenges in drug discovery procedures, including the difficulty to interpret biological activities of crude extracts due to the presence of numerous metabolites with a great variation in their physicochemical properties and abundance levels [10,11,12]. Our approach taken together is as follows: a review of the literature, biological activity, chemical profiling, and computational studies to point out T. stellata as a promising bioactive candidate Acting on this premise, we examined the antioxidant, cytotoxic, and antidiabetic potential of the plant, followed by identification of phytochemicals in T. stellata. We explored the compounds expected to be responsible for the antidiabetic activity through molecular docking of the identified compounds toward the α-glucosidase enzyme
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