Rhein for treating diabetes mellitus: A pharmacological and mechanistic overview

Abstract

With the extension of life expectancy and changes in lifestyle, the prevalence of diabetes mellitus is increasing worldwide. Rheum palmatum L. a natural botanical medicine, has been used for thousands of years to prevent and treat diabetes mellitus in Eastern countries. Rhein, the main active component of rhubarb, is a 1, 8-dihydroxy anthraquinone derivative. Previous studies have extensively explored the clinical application of rhein. However, a comprehensive review of the antidiabetic effects of rhein has not been conducted. This review summarizes studies published over the past decade on the antidiabetic effects of rhein, covering the biological characteristics of Rheum palmatum L. and the pharmacological effects and pharmacokinetic characteristics of rhein. The review demonstrates that rhein can prevent and treat diabetes mellitus by ameliorating insulin resistance, possess anti-inflammatory and anti-oxidative stress properties, and protect islet cells, thus providing a theoretical basis for the application of rhein as an antidiabetic agent.

Keywords: Rheum palmatum L. (dahuang); blood glucose; diabetes; inflammatory; oxidative stress; rhein (PubChem CID: 10168).

FIGURE 1

Plant and Slice of root of Rheum palmatum L. The leaves of Rheum palmatum L. are palmately lobed to half-lobed, with the lobes mostly narrowly triangular; its flowers are small, purple-red or yellowish-white; its buds are inverted pyramidal; and its fruits are small. The outer skin of rhubarb is yellowish-brown or reddish-brown, with white-like reticulate texture and scattered stars, and its broken surface is light reddish-brown or yellowish-brown, showing granularity; it has a fresh aroma and a bitter and slightly astringent taste. (A) Rheum palmatum L. is a kind of herb with medicinal value. (B) prepared slices of Rhubarb, containing a variety of active pharmacological ingredients.

FIGURE 2

Chemical structures of the main active ingredients of Rhubarb. (A) chrysophanol, (B) rhein, (C) emodin, (D) aloe-emodin, (E) emodin methyl ether.

FIGURE 3

The pharmacological mechanisms of rhein in improving IR in DM by inhibiting HBP overactivity. PAGM, Phosphoacetllucosaminemutase; ATP, adenosine triphosphate; ADP, adenosine diphosphate; UDP, uridine diphosphate; UTP, uridine triphosphate.

FIGURE 4

Pharmacological mechanism of rhein in inhibition of oxidative stress in diabetes mellitus. Drpl, dynamin-relatedprotein 1; Nrf2, nuclea factor erythroid-2-related factor 2; MDA,malonaldehyde; ROS, reactive oxygen species; SOD,superoxide dismutase; HO-1, Heme Oxygenase-1; CAT,catalase; GPX, glutathione peroxidase; GSH, glutathione,reduced; GSSG glutathione,oxydized; GR, gluathione reductase; NADPH, nicotinamide adenine dinucleotide phosphate; G-6-PDH,glucose-6-phosphate dehydrogenase; G-6-P, glucose-6-phosphate; GPI, phosphohexose isomerase; F-6-P, fructose-6-phosphate; PEK, Phosphofructokinase; PGAL, glyceraldehyde-3-phosphate; 1,3 BPG, 1,3 Biphosphoglycerate; TCA cycle, tricarboxylicacidcycle.

FIGURE 5

Pharmacological mechanisms of rhein in diabetes mellitus. Rhein maintains glucose homeostasis by anti-inflammation, alleviating renal lesions, improving insulin resistance, improving lipid metabolism, anti-oxidative stress, maintaining mitochondrial respiratory function, improving gut microbiota, and improving β -cell functional. GSK-3 β, Glycogen synthase kinase 3 β; PPAR- γ ,peroxisome proliferator-activated receptor γ ; NF-κ B, nuclear factor kappa-B; HDAC3, histone deacetylase 3; NLRP3, NOD-like receptor thermal protein domain associated protein 3; IL-6, Interleukin-6; IL-1 β ,Interleukin-1 β ; TNF- α ,tumor necrosis factor α ; IKK β ,inhibitor of kappa B kinase β ;Foxo3 α, Forkhead box 03 α ; SIRT1, sirtuin 1; HBP, Hexosamine pathway; TC, Serum total cholesterol; HDL-C,High density liptein cholesterol; TG, triacylglycerol; LDL-C, Low-Density Lipoprotein Cholesterol; VLDL,very low-density lipoprotein; SOD, Superoxide dismutase; CAT,Catalase from micrococcus lysodeiktic; GSH,glutathione,reduced; GSSG, glutathione, oxydized; MDA, malonaldehyde; ROS, reactive oxygen species; Drpl,Dynamin-related protein 1; AMPK,Adenosine 5' -monophosphate (AMP)-activated protein kinase; GLP-1,glucagon-like peptide-1; Bcl-2,B-cell lymphoma-2; BAX,BCL2-Associated X.