Dual Enzyme Inhibition Strategy for Type 2 Diabetes: Targeting LDH-A and α-Amylase with Flavonoid-Acarbose Combinations

Abstract

Diabetes mellitus is a complex and widespread disease affecting over 100 million people globally. It increases the risk of severe complications such as heart attack, neuropathy, and retinopathy. While various therapies aim to manage the disease, one effective approach involves reducing the activity of starch-degrading enzymes, such as -amylase, to limit the amount of free glucose in the body. Another target is lactate dehydrogenase-A (LDH-A), an enzyme involved in gluconeogenesis through its role in generating pyruvate. In recent years, flavonoids have gained significant attention for their potential to inhibit both -amylase and LDH-A. This study investigates the flavonoids present in green and black tea for their ability to inhibit porcine pancreatic amylase (PPA) and LDH-A, comparing their efficacy to established anti-diabetic drugs such as Acarbose and Metformin using computational methods. In vitro experiments demonstrated that Quercetin shows potent anti-LDHA-A activity with an IC50 of 4.161 {micro}M. Quercetin inhibits PPA with an IC50 value of 20 {micro}M, while eriodyctiol and myricetin exhibit IC50 values of 22 {micro}M and 24 {micro}M, respectively. Additionally, quercetin was found to synergistically enhance the inhibitory effects of the commonly used -amylase inhibitor, Acarbose.