Apteranthes tuberculata's Antidiabetic Potential: Exploring Phytochemicals, Screening Antioxidant Activity, and Validating DPP‐4 Inhibition Using In Vitro and In Silico Approaches

TL;DR

This study explores the antidiabetic potential of Apteranthes tuberculata, finding it has strong antioxidant and DPP-4 inhibitory properties that could help manage diabetes.

Contribution

The study is the first to scientifically validate the antidiabetic potential of Apteranthes tuberculata using in vitro and in silico methods.

Findings

The plant extract showed 70% DPP-4 inhibitory activity, comparable to the drug Sitagliptin.

LC–MS identified 24 bioactive compounds, including flavonoids and glycosides, with strong DPP-4 binding.

Five compounds showed no PAINS alerts, indicating good drug-likeness.

Abstract

Diabetes is a chronic metabolic disorder that affects an increasing number of people worldwide, frequently managed with synthetic drugs that have side effects and can be costly. Apteranthes tuberculata (N.E.Br.) Meve & Liede, a plant with traditional medicinal use in Pakistan to treat diabetes, but its antidiabetic potential has not been scientifically validated. This research assessed the phytochemicals, antioxidant properties, and dipeptidyl peptidase‐4 (DPP‐4) inhibitory activity of
A. tuberculata
's methanolic extract. The extract was assessed through in vitro antioxidant assays, DPP‐4 inhibition test, and metabolomic analysis via Fourier‐transform infrared (FTIR) spectroscopy and liquid chromatography–mass spectrometry (LC–MS). The study used computational tools to visualize compound structures, protein‐ligand interactions, and to measure pharmacokinetic parameters. Phytochemical analysis revealed significant levels of total phenols (71.991 ± 0.78 mg/g gallic acid equivalents) and flavonoids (66.216 ± 0.09 mg/g quercetin equivalents). Results showed a robust total antioxidant capacity (70.900 ± 2 mg/g ascorbic acid), total reducing power (72.000 ± 2.00 mg/g gallic acid equivalents), and DPPH IC50 value of 96.54 μg/mL. FTIR spectra showed the presence of carbohydrates and glycosides. The extract exhibited 70% DPP‐4 inhibitory activity (IC50 value = 46.761 ± 0.043 μg/mL), comparable to Sitagliptin at 78% (IC50 value = 20.474 ± 0.407 μg/mL). LC–MS identified 24 bioactive compounds, including flavonoids and glycosides, with compounds like Kaempferol‐3‐O‐rutinoside‐7‐O‐glucoside and Kaempferol‐7‐O‐rutinoside showing strong binding interactions with DPP‐4. These results underscore the therapeutic potential of
A. tuberculata
as a natural source of DPP‐4 inhibitors for managing diabetes.

Metabolomics revealed 24 major compounds, mainly glycosides, flavonoids, and triterpenes. Antidiabetic compounds Kaempferol‐7‐O‐rutinoside and Kaempferol‐3‐O‐rutinoside‐7‐O‐glucoside show maximum inhibiting activity for DPP4 protein (in vitro and in silico). Out of 24 compounds, 5 demonstrate no PAINS and break alerts.

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