A Comprehensive Review and Perspective on Natural Sources as Dipeptidyl Peptidase-4 Inhibitors for Management of Diabetes

Abstract

Type 2 diabetes mellitus (T2DM) is an increasing global public health problem, and its prevalence is expected to rise in coming decades. Dipeptidyl peptidase-4 (DPP-4) is a therapeutic target for the management of T2DM, and its inhibitors prevent the degradation of glucose-dependent insulinotropic peptide and glucagon-like peptide 1, and thus, maintain their endogenous levels and lower blood glucose levels. Various medicinal plant extracts and isolated bioactive compounds exhibit DPP-4 inhibitory activity. In this review, we discussed different natural sources that have been shown to have anti-diabetic efficacy with a particular emphasis on DPP-4 inhibition. Furthermore, the effect of DPP-4 inhibition on pancreatic beta cell function, skeletal muscle function, and the glucose-lowering mechanisms were also discussed. We believe that scientists looking for novel compounds with therapeutic promise against T2DM will be able to develop antidiabetic drugs using these natural sources.

Dipeptidyl peptidase-4 inhibitory potentials of Glycyrrhiza uralensis and its bioactive compounds licochalcone A and licochalcone B: An in silico and in vitro study

“…Given the various side effects of currently available DPP-4 inhibitors (or 'gliptins'), which include hypersensitivity reactions, gastrointestinal discomfort, pancreatitis, diarrhea, urinary tract infections, arthritis, and congestive heart failure (Chen et al, 2015;Mascolo et al, 2016;Packer, 2018), the development of natural product-like DPP-4 inhibitors with fewer adverse effects is of considerable importance. Natural products are well-known for providing new molecular entities for treating many diseases (Patridge et al, 2016;Shaikh et al, 2021a;Shaikh et al, 2021b). In addition, phenolics are well known for their ability to alleviate diabetes by lowering blood glucose levels (Rauter et al, 2010).…”

An anti-aging dietary supplement inhibits dipeptidyl peptidase-4 (DPP-4) and arginase in vitro and improves quality of life factors of middle-aged adults

“…DPP4 inhibition had been previously reported for some of these ingredients (Shaikh et al 2021). But this is the first time that synergistic effects have been demonstrated for the combination of these ingredients.…”

Decoding the chemical composition and pharmacological mechanisms of Jiedu Tongluo Tiaogan Formula using high-performance liquid chromatography coupled with network pharmacology-based investigation

“…To determine whether JDTL activated the PI3K-Akt signaling pathway, levels of p-Akt and p-PI3K were assayed, since results of a literature search conducted here indicated that PI3K-Akt pathway core proteins Akt, TNF, and IL6 were closely related to glucometabolic processes, including T2DM. T2DM is a metabolic disease characterized by long-term hyperglycemia caused by potential metabolic dysfunctions, such as IR of muscle and liver tissues and decreased insulin secretion by pancreatic β-cells [ 46 ]. Normally β-cells can increase insulin release to maintain normal glucose tolerance.…”