Comparative Chemical Profiling, Antioxidant Activity, and Antidiabetic Potential of Four Whole-Grain Red Rice...

Background/Objectives: Pigmented rice is increasingly recognized as a functional food because of its rich phytochemical composition and health-promoting potential. However, local red rice cultivars from the three southern border provinces of Thailand remain insufficiently characterized. This study comparatively evaluated four whole-grain red rice cultivars-Hawm Gra Dang Ngah 59 (HGDN 59), Hawm Mue Lau (HML), Lued Pla Lai (LPL), and Se Bu Kan Tang (SBKT)-for their chemical composition, antioxidant activities, and antidiabetic potential. Methods: Whole-grain rice samples were extracted with 95% ethanol and assessed for extraction yield, total phenolic content, and total flavonoid content. Antioxidant activity was measured using DPPH^•, FRAP, and anti-lipid peroxidation assays, while antidiabetic activity was measured using α-amylase and α-glucosidase inhibition assays. LC-MS/MS-based chemical profiling, pathway classification, PCA-based chemical space analysis, molecular docking against α-glucosidase, and physicochemical/ADMET prediction were also performed. Results: Among the tested cultivars, HGDN 59 showed the most favorable overall profile, with the highest phenolic content, strongest antioxidant activity, and marked α-glucosidase inhibitory activity. LC-MS/MS analysis combined with docking-based screening revealed that HGDN 59 contained several abundant compounds, including ent-Epicatechin-(4α→6)-ent-epicatechin, cinnamtannin A1, apiin, and α-tocotrienol. These compounds exhibited strong binding affinities toward α-glucosidase (-10.7 to -9.6 kcal/mol), comparable to or slightly more favorable than acarbose. ADMET prediction indicated that most polyphenolic compounds exceeded Lipinski's rule of five, while α-tocotrienol demonstrated favorable absorption property. Conclusions: This is the first study to suggest that HGDN 59 exhibits potential α-glucosidase inhibitory activity in vitro and may serve as a promising functional food candidate for the dietary management of postprandial glycemic response.