Herbal therapies for type 2 diabetes mellitus: chemistry, biology, and potential application of selected plants and compounds

Abstract

Diabetes mellitus has been recognized since antiquity. It currently affects as many as 285 million people worldwide and results in heavy personal and national economic burdens. Considerable progress has been made in orthodox antidiabetic drugs. However, new remedies are still in great demand because of the limited efficacy and undesirable side effects of current orthodox drugs. Nature is an extraordinary source of antidiabetic medicines. To date, more than 1200 flowering plants have been claimed to have antidiabetic properties. Among them, one-third have been scientifically studied and documented in around 460 publications. In this review, we select and discuss blood glucose-lowering medicinal herbs that have the ability to modulate one or more of the pathways that regulate insulin resistance, β-cell function, GLP-1 homeostasis, and glucose (re)absorption. Emphasis is placed on phytochemistry, anti-diabetic bioactivities, and likely mechanism(s). Recent progress in the understanding of the biological actions, mechanisms, and therapeutic potential of compounds and extracts of plant origin in type 2 diabetes is summarized. This review provides a source of up-to-date information for further basic and clinical research into herbal therapy for type 2 diabetes. Emerging views on therapeutic strategies for type 2 diabetes are also discussed.

Figure 1

Etiology, development, and current therapies for T2D. (a) Genetic and environmental factors are the main contributors to the development of insulin resistance and impaired glucose tolerance. Under normal glucose tolerance conditions, β cells secrete insulin in response to a surge in glucose after a meal. At the initial stage, β cells overwork to compensate for the development of insulin resistance. Later on, β cells are no longer able to secrete enough insulin to overcome insulin resistance. As a result, glucose tolerance is impaired and the disease progresses from prediabetes to diabetes. Diabetes is characterized as a loss of blood glucose homeostasis, a condition termed hyperglycemia, in the patients. Glucotoxicity, lipotoxicity, ER/oxidative stress, inflammation, and incretin impairment are risk factors for β-cell dysfunction. Besides insulin, insulin releasers, insulin sensitizers, GLP-1 analogues/DDP-4 inhibitors, and a-glucosidase inhibitors and Sglt 2 inhibitors are common antidiabetic drugs. (b) Insulin releasers (e.g., sulfonylureas such as glibenclamide and glimepiride) can stimulate pancreatic β cells to secrete insulin. Insulin sensitizers (TZDs (e.g., rosiglitazone and pioglitazone) and biguanide (metformin)) reduce insulin resistance in the peripheral tissues. GLP-1 has multiple direct actions on pancreas (insulin and glucagon production) and gastric emptying. Injection of exogenous GLP-1 (e.g., exenatide and liraglutide) or inhibition of endogenous GLP-1 degradation by DPP-4 inhibitors (e.g., sitagliptin, vildagliptin, saxagliptin, and linagliptin) can maintain GLP-1 levels. Inhibitors of α-glucosidases (acarbose) and Sglt 2 (e.g., dapagliflozin and empagliflozin) reduce glucose absorption in guts and glucose reabsorption in kidney, respectively. All the drugs can diminish hyperglycemia. *Sglt 2 inhibitors were disproved by the FDA because of a safety issue.

Figure 2

Mechanisms underlying herbal therapies using antidiabetic plants and phytocompounds. (a) Different types of medicinal herbs can be classified based on their modes of action such as insulin resistance (type 1 herbs), β-cell function (type 2 herbs), and GLP-1 (type 3 herbs) and glucose (re)absorption (type 4 herbs). (b) The selected plants and compounds exert their antihyperglycemic effect through targeting one single mechanism (insulin resistance (type 1 herbs), β-cell function (type 2 herbs), GLP-1 (type 3 herbs), or glucose (re)absorption (type 4 herbs)) or multiple mechanisms.