The Roles of Flavonoids and Other Plant‐Based Phenolics in Mitigating Diabetes‐Induced Macrovascular Complications

ABSTRACT Macrovascular complications of diabetes mellitus (DM) are diseases of the peripheral and coronary arteries and the cerebrovascular system. Despite the availability of several conventional antidiabetic drugs, the macrovascular complications associated with DM remain a major health burden, partly because the focus of diabetes management has been glucocentric. Interestingly, phytochemicals, particularly flavonoids and other phenolics, were highly promising in the treatment of diabetes‐associated macrovascular complications. Herein, we reviewed the studies that reported the beneficial effects of flavonoids and other phenolics in the treatment of diabetes‐associated macrovascular complications. Quercetin, apigenin, luteolin, kaempferol, curcumin, resveratrol, and cinnamaldehyde were well studied and demonstrated profound therapeutic activities in reducing the severity of diabetes‐associated macrovascular complications through the activation of Nrf2, P13K/Akt, PPARs, and PKC expressions with the suppression of NF‐κB, TGF‐β, VCAM, and ICAM. Despite strong potential to manage diabetes‐associated macrovascular complications in in vitro and in vivo (animal trials) studies, only two studies were reported on patients with diabetes. Hence, it is recommended that further high‐quality and in‐depth studies, particularly clinical studies, be conducted to unravel the efficacy and beneficial roles of the aforementioned flavonoids and other phenolics in the management of diabetes‐associated macrovascular complications.