Phytochemicals as modulators of β-cells and immunity for the therapy of type 1 diabetes: Recent discoveries in pharmacological mechanisms and clinical potential.

Type 1 diabetes (T1D) is a lethal autoimmune disease afflicting as many as 10 million people worldwide. Considerable advances have been made in early diagnosis and understanding the cause of T1D development. However, new remedies are still in great demand as TID remains an incurable disease. Natural products, primarily phytochemicals, are an extraordinary source of discovery of drug leads for diabetes. This review covers recent findings regarding plant compounds and extracts for T1D based on a literature search of articles published between 2004-2019 in PubMed, Reaxyx, and America/European patent databases. Over this period more than 90 plant compounds and extracts were reported to have beneficial effects on T1D via multiple mechanisms involving the regulation of immunity and/or β cells. In this review, we focus on recent progress in the understanding of the chemistry (chemical structure and plant source), anti-diabetic bioactivities, and likely mechanisms of action of plant compounds for T1D. Mechanistic studies are summarized, which indicate that flavonoids, terpenoids, and anthranoids can inhibit starch-digesting enzymes, aldose reductase, MAP kinases, NFκB, and/or IκB kinases implicated in energy metabolism, β-cells, and immunity. Furthermore, human clinical trials centering on flavonoids, isoflavonoids, terpenoids, stilbenoids, and polyynes are discussed, and an overview of emerging anti-diabetic strategies using plant compounds and extracts for applications in T1D prophylaxis and therapy is also provided.