Secondary Metabolites in the Treatment of Diabetes Mellitus: A Paradigm Shift

Abstract

: Diabetes mellitus (DM) is a chronic, polygenic and non-infectious group of diseases that occurs due to insulin resistance or its low production by pancreas and is also associated with lifelong damage, dysfunction and collapse of various organs. Management of diabetes is quite complex having many bodily and emotional complications and warrants efficient measures for prevention and control of the same. As per the estimates of current and future diabetes prevalence around 425 million people were diabetic in 2017 which is anticipated to rise upto 629 million by 2045. Various studies have vaguely proven the fact that several vitamins, minerals, botanicals and secondary metabolites demonstrate hypoglycemic activity in vivo as well as in vitro. Flavonoids, anthocyanin, catechin, lipoic acid, coumarin metabolites etc. derived from herbs were found to elicit significant influence on diabetes. However, the prescription of herbal compounds depends on various factors, including the degree of diabetes progression, comorbidities, feasibility, economics as well as their ADR profile. For instance, cinnamon could be a more favorable choice for diabetic hypertensive patients. Diabecon®, Glyoherb® and Diabeta Plus® are some of the herbal products that had been launched in the market for the favorable or adjuvant therapy of diabetes. Moreover, Aloe vera leaf gel extract demonstrates significant activity in diabetes. The goal of this review was to inscribe various classes of secondary metabolites in particular those obtained from plants, and their role in the treatment of DM. Recent advancements for recognizing the markers which can be employed for identifying altered metabolic pathways, biomarker discovery, limitations, metabolic markers of drug potency and off-label effects are also reviewed.

Plants Secondary Metabolites as Blood Glucose-Lowering Molecules

“…Akt activates the glucose transporter translocation to the cellular membrane (GLUT-4) and triggers the phosphorylation of glycogen synthase kinase 3 (GSK3), which leads to stimulation of glycogen synthesis in liver and skeletal muscle and downregulation of PEPCK (phosphoenolpyruvate carboxykinase) and G6Pase (glucose-6- phosphatase) gene expression [ 24 ]. However, in a diabetic state, these pathways are not blocked because insulin is unable to adequately regulate the gene expression and function of PEPCK and G6Pase, leading to excessive hepatic glucose production through gluconeogenesis and glycogenolysis [ 9 , 16 ]. In addition, the activation of the Akt system leads to protein synthesis through the activation of the mechanistic target of rapamycin complex 1 (mTORC1), cell survival by the suppression of various pro-apoptotic molecules, mainly of the FOXO (forkhead box O) family of transcription factors ( Figure 4 ) [ 27 ].…”

“…Published research has proven that several secondary metabolites demonstrate hypoglycemic activity in vivo and in vitro, and usually, they affect multiple targets, proteins and enzymes. Alkaloids, phenols, anthocyanin, flavonoids, saponins, tannins, terpenes and coumarins were found to elicit a significant influence on diabetes [ 9 , 10 ].…”

Small molecule metabolites: discovery of biomarkers and therapeutic targets

“…Research has shown that small molecule metabolite-based metabolomics can be further used to identify the active compounds and targets, which develop new therapies. 712 – 715 …”

The INHIBITORY EFFECT OF DOUM PALM (HYPHAENE THEBAICA L. MART.) LEAVES EXTRACT ON Α-Glucosidase ACTIVITY

“…Polyphenols can modulate carbohydrate metabolism, decrease hyperglycemia and control insulin resistance, increase lipid metabolism, optimize oxidative stress and inflammatory processes, inhibit α-glucosidase and α-amylase in the digestive tract. Also, polyphenols may modulate glucose uptake and expression of glucose transporters; stimulate insulin secretion and pancreatic β-cell proliferation [44][45][46][47] . Although pancreatic αamylase is an important enzyme that breaks down dietary long chain carbohydrates, still αglucosidase is a concluding enzyme that acts on shorter starch chains and disaccharides to produce glucose.…”