ABSTRACT
Insulin resistance (IR) is a main etiology of various metabolic diseases
such as type 2 diabetes mellitus (T2DM), hypertension, hyperlipidemia
and coronary heart disease. IR is a multi-factorial etiology disease
regulated by various mechanisms. Obesity, a significant public health
problem worldwide, is considered as a high-risk factor to induce IR and
T2DM. Thus, inhibiting obesity-induced IR is one of the key therapeutic
strategies to improve T2DM. Natural products from herbs and
nutraceuticals have shown promising efficacy on obesity-induced IR and
T2DM owing to its multi-component and multi-target characteristics.
However, the active constituents and the action mechanisms are still not
yet well elucidated. In this review,
the natural constituents with protective capacities against IR were
summarized. The active constituents include crude extracts such as
polyphenols, saponins, alkaloids, terpenoids, phenylpropanoids, as well
as monomeric compounds such as curcumin, berberine, capsaicin,
naringenin, quercetin, betaine and isoliquiritigenin. The action
mechanisms of these active constituents could be mainly divided into 4
categories: ameliorating metabolic
abnormality, inhibiting
inflammation, reversing gut
microbiota dysbiosis, regulating micro RNAs (miRNAs). Their precise
roles in regulating PI3K/AKT, AMPK, PPARs, SIRT1 and NF-κB pathways,
brown adipose tissue activity and white adipose tissue browning, NLRP3
inflammasome activity, gut microbiota structure and composition and
miRNA expression were discussed. The sources, chemical structures,
experimental models, pharmacological effects and action targets of these
active constituents were also summarized. This review provides new
active constituents, therapeutic targets and reasoning for the clinical
application of herbs and nutraceuticals in the treatment of IR and T2DM.
Keywords: insulin resistance, obesity, type 2 diabetes
mellitus, traditional Chinese medicine