Targeting Inflammation by Flavonoids: Novel Therapeutic Strategy for Metabolic Disorders

Abstract

A balanced metabolic profile is essential for normal human physiological activities. Disproportions in nutrition give rise to imbalances in metabolism that are associated with aberrant immune function and an elevated risk for inflammatory-associated disorders. Inflammation is a complex process, and numerous mediators affect inflammation-mediated disorders. The available clinical modalities do not effectively address the underlying diseases but rather relieve the symptoms. Therefore, novel targeted agents have the potential to normalize the metabolic system and, thus, provide meaningful therapy to the underlying disorder. In this connection, polyphenols, the well-known and extensively studied phytochemical moieties, were evaluated for their effective role in the restoration of metabolism via various mechanistic signaling pathways. The various flavonoids that we observed in this comprehensive review interfere with the metabolic events that induce inflammation. The mechanisms via which the polyphenols, in particular flavonoids, act provide a promising treatment option for inflammatory disorders. However, detailed clinical studies of such molecules are required to decide their clinical fate.

Keywords: flavonoids; inflammation; inflammatory mediators; metabolic disorders; nuclear factor-κB; oxidative stress.

Figure 1

Inflammation and metabolic disorders.

Figure 2

Chemical structure of most relevant flavonoids with therapeutic effects in metabolic syndrome by targeting inflammatory pathways.

Figure 3

Underlying anti-inflammatory pathways involved in therapeutic effects of flavonoids in metabolic syndrome. NF-κB, nuclear factor-κB; IκB, inhibitor of κB; AMPK, activated protein kinase; SIRT1, Sirtuin 1; JNK, c-Jun N-terminal kinase; KLF2, Kruppel-like factor 2; AP-1, activator protein 1; Nrf2, nuclear factor erythroid 2-related factor 2; PLA2, phospholipase A2; COX, cyclooxygenase; eNOS, endothelial nitric oxide synthase; TNF-α; tumor necrosis factor-α; IL, interleukin, ROS, reactive oxygen species; red↓, decrease; all other ↓, direction of events.