Xanthones show promise in diabetes with antioxidant and anti-inflammatory properties

In a review article published in the European Journal of Medicinal Chemistry Reports, the authors provide an in-depth overview of the antidiabetic potential and mode of action of xanthones, natural polyphenolic compounds found in various plants.

Review: Exploring the Therapeutic Potential of Xanthones in Diabetes Management: Current Insights and Future Directions. Image Credit: PhilipYb Studio / ShutterstockReview: Exploring the Therapeutic Potential of Xanthones in Diabetes Management: Current Insights and Future Directions. Image Credit: PhilipYb Studio / Shutterstock

Background

Diabetes is a chronic metabolic disease characterized by reduced insulin secretion, reduced glucose utilization, and increased glucose production. These factors collectively lead to the development of hyperglycemia or high blood glucose. Diabetes is divided into two main categories, i.e., type 1 and type 2 diabetes.

The primary hallmark of type 1 diabetes is the depletion of pancreatic beta-cell mass and subsequent insulin insufficiency. A complex interaction between specific genetic factors, autoimmune response, and specific environmental factors is responsible for the pathogenesis of type 1 diabetes. 

Type 2 diabetes is more prevalent than type 1 diabetes. The pathogenesis of type 2 diabetes can be attributed to a complex interaction between genetic predisposition and certain inherent factors (hypertension, obesity, physical inactivity), which can collectively lead to reduced insulin secretion or insulin resistance and subsequent induction in hepatic glucose synthesis. All these factors collectively result in increased blood glucose levels.

Graphical abstract indicating the effectiveness of xanthones in the treatment of diabetes.

Graphical abstract indicating the effectiveness of xanthones in the treatment of diabetes.

Xanthones

Xanthones are natural polyphenolic compounds with diverse biological activities, including antioxidant, anti-inflammatory, and anticancer properties. Garcinia mangostana, commonly known as mangosteen, is the most enriched source of xanthones. Two most prominent xanthones found in mangosteen are α-mangostin and γ-mangostin. 

Hypericum perforatum, Polygala species, Swertia chirayita, and Morus alba are other potential sources of xanthones, including hyperforin (polyprenylated acylphloroglucinol), 1,3,7-trihydroxyxanthone, swerchirin, morusin (prenylated flavonoids), and albanol A (benzofuran derivatives).

Xanthones in diabetes management

Several studies have identified strong antidiabetic effects of some xanthones, including gambogic acid, α-mangostin, γ-mangostin, mangiferin, hypericin, swerchirin, and chebulagic acid. These compounds have been found to increase insulin sensitivity, modulate glucose metabolism, and prevent oxidative stress and inflammation through various pathways.

The major molecular targets of xanthones in diabetes management include AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptors (PPARs), α-amylase, and α-glucosidase.

Xanthones as adjuvants

Chronic inflammation and oxidative stress are significant hallmarks of diabetes. The antidiabetic potency of xanthones can be attributed to their potent antioxidant and anti-inflammatory properties.

The integration of xanthones as adjuncts to existing diabetes medications represents a compelling avenue for enhancing the management of diabetes and related metabolic disorders.

Evidence indicates that xanthones can maintain glucose homeostasis by improving insulin sensitivity and facilitating cellular glucose uptake. The insulin-sensitizing activity of xanthones can be attributed to their ability to improve pancreatic beta-cell functions.

Dyslipidemia, characterized by irregular blood lipid levels, frequently occurs alongside diabetes. Xanthones have shown efficacy in maintaining normal blood lipid profile by regulating lipid metabolism, effectively preventing cardiovascular complications.

Moreover, xanthones can be useful in ameliorating diabetes neuropathy and diabetes-related kidney complications because of their neuroprotective and kidney-protective activities.

These observations highlight that combining xanthones with traditional diabetic therapies, such as insulin or oral antidiabetic drugs, may lead to better glycemic control and improved management of diabetes-related secondary complications.

Antidiabetic mode of action of xanthones

Xanthones exert antidiabetic effects through robust antioxidant and anti-inflammatory properties.

Xanthone derivatives that have shown strong anti-inflammatory activities include magniferin, β-mangostin, inophinnin, cudratricus xanthone A, dulxisxanthone F, ellidifolin, swerchirin, 2,8-dihydroxy-1,6-dimethoxyxanthone, cowaxanthone B, and γ-mangostin.   

Evidence indicates that xanthones inhibit the release of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha) and interleukins] and COX-2 enzyme, which is responsible for mediating inflammation. Moreover, xanthones can inhibit inflammation-inducing signaling pathways, including the nuclear factor kappa B (NF-κB) pathway.    

Regarding antioxidant properties, evidence indicates that xanthones can suppress oxidative stress by donating electron and neutralizing reactive oxygen species (ROS). By counteracting oxidative stress, xanthones can preserve beta-cell functions, improve insulin secretion, and inhibit the production of advanced glycation end products (AGEs).   

Both natural and synthetic xanthones have shown efficacy in improving beta-cell viability and functionality.

Among naturally occurring xanthones, mangiferin has shown efficacy in increasing beta-cell mass by inhibiting apoptosis. Alpha-mangostin and cudratricusxanthone A have been found to protect beta-cells from cytokine-induced apoptosis.

Among synthetic xanthones, hydroxyxanthone, xanthone-triazole derivatives, and xanthone amine derivatives have shown beta-cell protective activities.

Xanthone-mediated preservation of beta-cell viability and functionality is associated with improved insulin secretion. Xanthones can also influence protein kinase C (PKC) pathways, regulating ion channel activities on beta-cell membrane and subsequent insulin release.

Xanthones in the management of diabetic complications

Diabetic nephropathy

Diabetic nephropathy is a serious kidney complication that can potentially lead to end-stage renal failure. Mangiferin has been found to ameliorate diabetic nephropathy in rats by suppressing AGEs and oxidative stress through the induction of glyoxalase1 (Glo-1) activity.

Alpha-mangostin protects against diabetic nephropathy by mitigating endoplasmic reticulum (ER) stress-induced renal cell apoptosis in diabetic rats.

The phenolic aqueous extract of mangosteen has also shown significant efficacy in mitigating glucose intolerance, metabolic disturbances, oxidative stress-related kidney damage, and cellular apoptosis in diabetic mice.

Diabetic retinopathy

Diabetic retinopathy is a serious eye complication and a leading cause of newly-onset blindness in diabetic patients.

Alpha-mangostin supplementation has been found to reduce retinal oxidative stress, inflammation, and glycation-related factors and improve blood flow and barrier function in diabetic rats, suggesting its potency in ameliorating diabetic retinopathy.      

Mangostin has been found to prevent retinal neovascularization by reducing angiogenic sprouting and vascular endothelial growth factor (VEGF)-induced increases in bovine retinal endothelial cell permeability, proliferation, migration, and tube formation.

Mangiferin has been found to prevent retinopathy by altering the PI3K/AKT/mTOR signaling pathway and subsequently reducing retinal capillary endothelial cell angiogenesis in rats.  

Diabetic neuropathy

Diabetic neuropathy is characterized by sensory loss and pain in the lower extremities, which eventually occurs in 50% of diabetic patients.

Xanthones isolated from G. mangostana Linn.'s root bark, including α-mangostin, β-mangostin, and 3-isomangostin, have shown a strong ability to inhibit aldose reductase, which may have beneficial impact on diabetic neuropathy.    

Journal reference:

Article Revisions

  • Jul 30 2024 - Inclusion of graphical abstract indicating the effectiveness of xanthones in the treatment of diabetes.
Dr. Sanchari Sinha Dutta

Written by

Dr. Sanchari Sinha Dutta

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.

Citations

Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Dutta, Sanchari Sinha Dutta. (2024, July 29). Xanthones show promise in diabetes with antioxidant and anti-inflammatory properties. News-Medical. Retrieved on December 14, 2024 from https://www.news-medical.net/news/20240729/Xanthones-show-promise-in-diabetes-with-antioxidant-and-anti-inflammatory-properties.aspx.

  • MLA

    Dutta, Sanchari Sinha Dutta. "Xanthones show promise in diabetes with antioxidant and anti-inflammatory properties". News-Medical. 14 December 2024. <https://www.news-medical.net/news/20240729/Xanthones-show-promise-in-diabetes-with-antioxidant-and-anti-inflammatory-properties.aspx>.

  • Chicago

    Dutta, Sanchari Sinha Dutta. "Xanthones show promise in diabetes with antioxidant and anti-inflammatory properties". News-Medical. https://www.news-medical.net/news/20240729/Xanthones-show-promise-in-diabetes-with-antioxidant-and-anti-inflammatory-properties.aspx. (accessed December 14, 2024).

  • Harvard

    Dutta, Sanchari Sinha Dutta. 2024. Xanthones show promise in diabetes with antioxidant and anti-inflammatory properties. News-Medical, viewed 14 December 2024, https://www.news-medical.net/news/20240729/Xanthones-show-promise-in-diabetes-with-antioxidant-and-anti-inflammatory-properties.aspx.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Eating breakfast later lowers blood sugar spikes in type 2 diabetes patients