Insights into one drug, multi-target aspects of polyphenols for diabetes management: in vitro, in vivo, and clinical evidence

A myriad of in vitro, in vivo, and clinical data provide compelling evidence for the antidiabetic potential of plant polyphenols. One of the primary explanations for this is the ability of polyphenols to target multiple factors that contribute to diabetes. Insulin resistance, insulin signaling, oxidative stress, obesity, hypertension, and inflammation play critical roles in the onset and progression of diabetes. Being a multifactorial disease, diabetes, therefore, requires therapeutic molecules with multi-targeting capabilities. This makes us recognize the importance of polyphenols in the treatment of diabetes. Several polyphenols are known to inhibit alpha-amylase and alpha-glucosidase, ameliorate insulin resistance, increase glucose uptake, protect the beta-cells, increase antioxidant properties of blood plasma, inhibit pro-inflammatory agents, possess cardioprotective and neuroprotective activities in complications of diabetes mellitus. This review highlights the 'one drug, multi-target and multi-therapeutic' aspects of polyphenols for diabetes treatment with recent in vitro, in vivo, and clinical evidence. We aim to unveil the diverse molecular targets of polyphenols in the context of diabetes management, showcasing their potential as a safe and natural alternative to conventional diabetes medications, making them a promising candidate for holistic and integrative diabetes treatment, and exemplifying the paradigm shift from one drug, one target to one drug, multi-target.