Understanding glycaemic control and current approaches for screening antidiabetic natural products from evidence-based medicinal plants

Abstract

Type 2 Diabetes Mellitus has reached epidemic proportions as a result of over-nutrition and increasingly sedentary lifestyles. Current therapies, although effective, are not without limitations. These limitations, the alarming increase in the prevalence of diabetes, and the soaring cost of managing diabetes and its complications underscores an urgent need for safer, more efficient and affordable alternative treatments. Over 1200 plant species are reported in ethnomedicine for treating diabetes and these represents an important and promising source for the identification of novel antidiabetic compounds. Evaluating medicinal plants for desirable bioactivity goes hand-in-hand with methods in analytical biochemistry for separating and identifying lead compounds. This review aims to provide a comprehensive summary of current methods used in antidiabetic plant research to form a useful resource for researchers beginning in the field. The review summarises the current understanding of blood glucose regulation and the general mechanisms of action of current antidiabetic medications, and combines knowledge on common experimental approaches for screening plant extracts for antidiabetic activity and currently available analytical methods and technologies for the separation and identification of bioactive natural products. Common in vivo animal models, in vitro models, in silico methods and biochemical assays used for testing the antidiabetic effects of plants are discussed with a particular emphasis on in vitro methods such as cell-based bioassays for screening insulin secretagogues and insulinomimetics. Enzyme inhibition assays and molecular docking are also highlighted. The role of metabolomics, metabolite profiling, and dereplication of data for the high-throughput discovery of novel antidiabetic agents is reviewed. Finally, this review also summarises sample preparation techniques such as liquid–liquid extraction, solid phase extraction, and supercritical fluid extraction, and the critical function of nuclear magnetic resonance and high resolution liquid chromatography–mass spectrometry for the dereplication, putative identification and structure elucidation of natural compounds from evidence-based medicinal plants.

Comparison of Phenolic Compounds, Carotenoids, Amino Acid Composition, In Vitro Antioxidant and Anti-Diabetic Activities in the Leaves of Seven Cowpea (Vigna unguiculata) Cultivars

“…Inclusion of higher dietary fibre and low glycaemic index foods in daily meals has been proved to reduce blood glucose levels, thereby reducing the risk of type 2 diabetes mellitus [ 9 ]. Indigenous edible plant extracts demonstrated anti-diabetic effects [ 10 ], such as insulin (diabetic drug), by executing the vital regulatory mechanism transporting the glucose uptake into skeletal muscle and adipose tissue by facilitating glucose transporter protein type-4 (GLUT4), playing a major role in the management of type 2 diabetes [ 11 ]. GLUT4 therefore plays a vital role in glucose homeostasis of skeletal muscle cells and the removal of glucose from blood circulation [ 11 ].…”

Improvements in HOMA indices and pancreatic endocrinal tissues in type 2-diabetic rats by DPP-4 inhibition and antioxidant potential of an ethanol fruit extract of Withania coagulans 

“…In same context, it is illustrated that the phytocompounds have the ability to inhibit speci c enzymes by binding to the active site within the enzyme molecule or a related mode of action [56,57]. Ideal inhibitors have a low molecular weight that can reduce or completely inhibit enzyme activity at low concentrations [55].…”

Potential Antidiabetic Activity of Extracts and Isolated Compound from Adenosma bracteosum (Bonati)

“…Phytochemical analysis of the samples was used for the identification of constituents, using procedures previously described [9]. The presence of alkaloids was tested by Mayer, Dragendorff, and Bouchardat's reagent; phenolics and tannin were tested with 2% FeCl 2 and 1% gelatine in 10% NaCl; the flavonoids were tested with a Shinoda test and alkaline reagent; triterpenoids were tested with the Liebermann-Burchard test; steroids were tested with a Salkowski test; and saponins were tested by a foam test with distilled water.…”

“…Medicinal plants continue to contribute significantly to developing modern prescription drugs by providing lead compounds upon which the synthesis of new drugs can be made. Therefore, the hypoglycemic activity of a number of plant extracts has been evaluated and confirmed in animal models [8][9][10]. Many recent studies have revealed that plant-based formulations can contribute to a better management of diabetes, as certain phytochemicals exert antioxidant, anti-inflammatory, and glucose-lowering effects [10][11][12][13].…”