Phytochemicals as modulators of β-cells and immunity for the therapy of type 1 diabetes: Recent discoveries in pharmacological mechanisms and clinical potential. (June 2020)

• Record Type: Journal Article
• Authors: Apaya, Maria Karmella; Kuo, Tien-Fen; Yang, Meng-Ting; Yang, Greta; Hsiao, Chiao-Ling; Chang, Song-Bin; Lin, Yenshou; Yang, Wen-Chin
• Is Part Of: Pharmacological research. Volume 156(2020)
• Publication Date: 2020-06
• Subjects: T1D type1 diabetes -- EPR enhanced permeability and retention -- IFN-γ interferonγ -- TNF-α tumor necrosis factor α -- Treg regulatory T cells -- ROS reactive oxygen species -- ER endoplasmic reticulum -- NAD nicotinamide adenine dinucleotide -- NK natural killer cells -- IL interleukin -- NOD non-obese diabetic -- COX cyclo-oxygenase -- iNOS inducible NO synthase -- NFκB nuclear factor κ light chain enhancer of activated B cells -- MOA mechanism of action -- ERK1/2 extracellular signal-related kinase 1/2 -- STZ streptozotocin -- PDX1 pancreatic duodenal hemeobox 1 -- PEPCK phosphoenolpyruvate carboxykinase -- GLUT glucose transporter -- AMPK5′ AMP-activated protein kinase -- TRPV1=transient receptor potential cation channel V1 -- VR1 vanilloid receptor 1 -- Drp1 hyperglycemia-induced dynamin-related protein 1 -- Th helper T-cells -- TGF-β transforming growth factor β -- G6Pase glucose 6-phospahatase -- DGTS 2, 5-dihydroxy-4, 3-di(-d-glucopyranosyloxy)-trans-stilbene -- NO nitric oxide -- DHAvD dihydroavenanthramide D -- PPAR-γ peroxisome proliferator-activated receptor-γ -- PKA protein kinase A -- KATP ATP-sensitive K -- C/EBPα CCAAT/enhancer-binding protein α -- GSPE grape seed procyanidin extract -- AGE advanced glycosylated end products -- SAR structure-activity relationship; Type 1 diabetes -- Phytochemicals -- Mechanism of mode -- Clinical application; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2020.104754
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Highlights: Type 1 diabetes is a lethal metabolic disease caused by autoimmune destruction of pancreatic β-cells in childhood. Autoreactive immune cells and/or failure of pancreatic β-cells are associated with type 1 diabetes. Modulators of autoimmunity and/or β-cell loss/dysfunction can be applied to modulate abnormal autoimmunity and β-cell failure. Phytochemicals are an extraordinary source of immunomodulators and β-cell modulators. Abstract: 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.