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Review
. 2024 Jan 30;12(5):3025-3045.
doi: 10.1002/fsn3.3983. eCollection 2024 May.

Dietary phenolic compounds as promising therapeutic agents for diabetes and its complications: A comprehensive review

Dipa Aryal  1 , Soniya Joshi  1 , Nabin Kumar Thapa  1 , Pratiksha Chaudhary  1 , Sirjana Basaula  1 , Usha Joshi  1 , Damodar Bhandari  1 , Hannah M Rogers  2 , Salyan Bhattarai  3 , Khaga Raj Sharma  1 , Bishnu P Regmi  2 , Niranjan Parajuli  1
Affiliations
Review

Dietary phenolic compounds as promising therapeutic agents for diabetes and its complications: A comprehensive review

Dipa Aryal et al. Food Sci Nutr. .

Abstract

In the middle of an ever-changing landscape of diabetes care, precision medicine, and lifestyle therapies are becoming increasingly important. Dietary polyphenols are like hidden allies found in our everyday meals. These biomolecules, found commonly in fruits, vegetables, and various plant-based sources, hold revolutionary potential within their molecular structure in the way we approach diabetes and its intimidating consequences. There are currently numerous types of diabetes medications, but they are not appropriate for all patients due to limitations in dosages, side effects, drug resistance, a lack of efficacy, and ethnicity. Currently, there has been increased interest in practicing herbal remedies to manage diabetes and its related complications. This article aims to summarize the potential of dietary polyphenols as a foundation in the treatment of diabetes and its associated consequences. We found that most polyphenols inhibit enzymes linked to diabetes. This review outlines the potential benefits of selected molecules, including kaempferol, catechins, rosmarinic acid, apigenin, chlorogenic acid, and caffeic acid, in managing diabetes mellitus as these compounds have exhibited promising results in in vitro, in vivo, in silico, and some preclinical trials study. This encompassing exploration reveals the multifaceted impact of polyphenols not only in mitigating diabetes but also in addressing associated conditions like inflammation, obesity, and even cancer. Their mechanisms involve antioxidant functions, immune modulation, and proinflammatory enzyme regulation. Furthermore, these molecules exhibit anti-tumor activities, influence cellular pathways, and activate AMPK pathways, offering a less toxic, cost-effective, and sustainable approach to addressing diabetes and its complications.

Keywords: Anti‐obesity; Enzyme Inhibition; Medicinal Plants; α‐Amylase; α‐Glucosidase.

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Conflict of interest statement

There is no conflict of interest between authors.

Figures

FIGURE 1
FIGURE 1
A schematic representation of three biosynthetic pathways of polyphenolic compounds. A solid arrow indicates a single‐step reaction, while a broken arrow indicates multi‐step reactions.
FIGURE 2
FIGURE 2
Phenolic compounds on starch digestion by hydrolysis of 1,4‐glycosidic bond.
FIGURE 3
FIGURE 3
Chemical structures of phenolic compounds exhibiting inhibition α‐amylase and α‐glucosidase.
FIGURE 4
FIGURE 4
Mechanism of action of antioxidants from phytochemicals on diabetes mellitus. The excess production of reactive free radicals through different processes induces oxidative stress, which disrupts the pancreatic β‐cells and develops insulin resistance. Antioxidants stabilize free radicals by donating electrons, increasing glucose uptake, and recovering endothelial dysfunction, thereby reducing oxidative stress.
FIGURE 5
FIGURE 5
Mechanism of action of polyphenols on diabetes and obesity. Polyphenols reduce oxidative stress by decreasing adipocyte levels and increasing hormone‐sensitive lipase, thereby decreasing adipogenesis and increasing lipolysis resulting in the low accumulation of lipids reflecting its anti‐obesity ability. Low lipid accumulation results in less glucagon secretion and low blood glucose levels, showing its antidiabetic ability.
FIGURE 6
FIGURE 6
Anti‐inflammatory actions of phytochemicals derived from natural products on diabetes. Phytochemicals like flavonoids, stilbenes, and alkaloids inhibit the inflammatory cytokines produced by macrophage and dendritic cells through different mechanisms, including the modulation of mast cells, macrophages, neutrophils, and proinflammatory enzyme activities like nitric acid synthase, COX, PLA2, and LOX The release of cytokines increases insulin demand leading to T2DM.
FIGURE 7
FIGURE 7
Mechanism of diabetes‐related anti‐cancer efficacy. T2DM contributes to the emergence of insulin resistance, thereby decreasing the adiponectin hormone, connecting with obesity and coronary artery disease, and inhibits the AMPK pathway. The inhibition of the AMPK pathway increases glucose uptake, which causes cells to expand out of control and also activates the ERK (MAPK) and AKT pathways, which in turn results in the metastasis of tumor cells leading to carcinogenesis.
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