Computational and experimental evidence supports the modulation of inflammaging-related pathways by Sorghum bicolor 3-deoxyanthocyanidins

Abstract Objectives Chronic inflammation, oxidative stress, and metabolic dysfunction are central drivers of biological aging. Polyphenolics from Sorghum bicolor , particularly 3-deoxyanthocyanidins, have the potential to modulate biological aging. Methods We investigated Sorghum bicolor through integrative evidence synthesis. Then, utilised an integrated computational framework comprising network pharmacology, and molecular docking to identify key molecular targets of Sorghum bicolor polyphenols. The findings were validated by aligning findings with the data from Sorghum bicolor on high-fat diet/streptozotocin (HFD-STZ) induced type 2 diabetes with chronic stress using a polyphenol-rich Sorghum bicolor extract as treatment. Results We observed a dose-dependent efficacy pattern that was strongly associated with anti-oxidant and anti-inflammation in Sorghum bicolor (Jobelyn ® ). Computational analyses identified NF-κB, Keap1–Nrf2, and PPAR-γ as predicted high-confidence targets. The molecular docking suggests plausible interactions with the targets with the 3-deoxyanthocyanidins (Apigeninidin and Luteolinidin). The in vivo validation demonstrated the activation of Nrf2-mediated antioxidant pathway. These biological effects aligned with computational predictions and were achieved using the whole extract. Conclusions The findings from this study supports the mechanistic plausibility of Sorghum bicolor polyphenols as modulators of inflammaging and metabolic dysfunction. This integrative framework provides the background for further translational and clinical investigation in aging-associated chronic diseases and treatments.