In vitro evaluation of antioxidant activity, alpha-amylase and alpha-glucosidase inhibitory potential of anthraquinone derivatives

Ee Xin Sim; Bryan Ee Pinn Chee; Harshini Velayudaraja; Ahmed Darwish Samal; Sabrina Teo Muhammad Teo; Chin Fei Chee; Theebaa Anasamy

doi:10.5455/JPPR.20250701012347

Abstract
Background: Type 2 diabetes mellitus (T2DM), a chronic metabolic disorder characterised by impaired insulin function and postprandial hyperglycaemia (PPHG), is found to be strongly affected by oxidative stress and enzyme action. Emerging evidence indicates that oxidative stress damages pancreatic β cells, disrupting insulin signalling pathways. The activity of carbohydrate-hydrolysing enzymes, α-amylase and α-glucosidase, significantly influences postprandial blood glucose levels, making them critical targets for diabetic control.
Methods: This study examined the structure-activity relationship (SAR) of five anthraquinone derivatives (AQ1 – AQ5) for their antioxidant potential using DPPH radical scavenging assay, and inhibitory activity against key enzymes (α-amylase and α-glucosidase) involved in carbohydrate digestion using standard colourimetric assays.
Results: AQ1 showed the highest α-amylase inhibition (25.0 ± 2.4%) and antioxidant activity (IC₅₀=31.8 ± 4.3μM), while in contrast, AQ3 and AQ4 showed the weakest antioxidant and enzymatic activities, respectively. Structure-activity analysis revealed that the presence and position of electron-donating or -withdrawing groups play a critical role in altering bioactivity. Chlorinated analogues exhibited less activity in general, depending on the position of the chlorine substitution.
Conclusion: These findings suggest that anthraquinone derivatives show potential in treating T2DM through both antioxidant effects and inhibition of carbohydrate-digesting enzymes. Further in vivo studies and safety tests are recommended to support their future therapeutic use.

Key words: Anthraquinone; Diabetes; Antioxidant; alpha-amylase; alpha-glucosidase