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Impact of Natural Products on Glycation Linked Metabolic Disease
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Impact of Natural Products on Glycation Linked Metabolic Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 8525

Special Issue Editor

Dr. Saheem Ahmad

E-Mail Website
Guest Editor
Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail, Saudi Arabia
Interests: glycation; advanced glycation end-products; cancer; diabetes; metabolic diseases; natural and medicinal plants

Special Issue Information

Dear Colleagues,

Glycation-induced oxidative and glycative stress results in advanced glycation end-products (AGEs), which have been implicated in the development and progression of metabolic diseases, such as cancer and diabetes.

Dicarbonyls, which are the main AGE precursors, and crosslinked forms of AGEs may directly react with proteins, lipids and nucleic acids, modify their structure, affect the tissue microenvironment and cause cancer and diabetes. They may also induce the elevation of reactive oxygen species (ROS) and enhance cellular oxidative stress, an important regulator of the hallmarks of cancer and diabetes.

In this Thematic Issue, we aim to provide evidence for the impact of glycative stress in promoting human tumorigenesis and the progression of diabetes. The proposed themes/sub-themes will be the potential application of antiglycating, antidiabetic and anticancer agents, and the use of RAGE and glyoxalase inhibitors in diabetes and cancer prevention. Natural compounds isolated from medicinally important plants have shown promising antiglycation, antidiabetic and anticancer activity both in vitro and in vivo. Despite the fact that scientists have discovered medicines with which to treat many diseases that have long been of concern to mankind, these two metabolic diseases continue to be fatal, ultimately making them a prime and serious health issue around the globe. According to the World Health report, cancer is amongst the four most prominent metabolic and chronic diseases, including cardiovascular diseases (CVDs), chronic obstructive pulmonary disease (COPD) and type 2 diabetes; these cause almost 60% of all deaths worldwide, and this is expected to increase up to 79% in 2020. Therefore, there is a continuous need for the exploration of innovative therapeutic agents and strategies that can help in treating metabolic diseases.

The themes for this issue including the following:

  • Dietary AGEs and their role in metabolic diseases, especially cancer and/or diabetes mellitus.
  • The anticancer and antidiabetic effects of polyphenols: locking horns with AGEs.
  • Do the antiglycation effects of curcumin promote the inhibition and apoptosis of cancer cells?
  • The preventive effects of natural products on cancer and diabetes via glycation inhibition: can they act as a double-edged sword?
  • Metformin: an old antidiabetic drug with new potential in cancer(s).
  • The antiglycation, antidiabetic and anticancerous potential of phenolic compounds from olive leaves: locking horns with glycation products.
  • The pharmacognosy of natural products and their therapeutic potential in the inhibition of cancer and glycation.
  • The treatment of glycation and metabolic diseases by means of natural antioxidants.

Dr. Saheem Ahmad
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • glycation
  • advanced glycation end-products
  • cancer
  • diabetes
  • metabolic diseases
  • natural and medicinal plants

Published Papers (3 papers)

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Research

22 pages, 5879 KiB  
Article
Therapeutic Efficacy of Natural Product ‘C-Phycocyanin’ in Alleviating Streptozotocin-Induced Diabetes via the Inhibition of Glycation Reaction in Rats
by Arbab Husain, Sultan Alouffi, Afreen Khanam, Rihab Akasha, Alvina Farooqui and Saheem Ahmad
Int. J. Mol. Sci. 2022, 23(22), 14235; https://doi.org/10.3390/ijms232214235 - 17 Nov 2022
Cited by 10 | Viewed by 1931
Abstract
Diabetes is a long-term metabolic disorder characterized by persistently elevated blood sugar levels. Chronic hyperglycemia enhances glucose–protein interactions, leading to the formation of advanced glycation end products (AGEs), which form irreversible cross-links with a wide variety of macromolecules, and accumulate rapidly in the [...] Read more.
Diabetes is a long-term metabolic disorder characterized by persistently elevated blood sugar levels. Chronic hyperglycemia enhances glucose–protein interactions, leading to the formation of advanced glycation end products (AGEs), which form irreversible cross-links with a wide variety of macromolecules, and accumulate rapidly in the body tissues. Thus, the objective of this study was to assess the therapeutic properties of C-phycocyanin (C-PC) obtained from Plectonema species against oxidative stress, glycation, and type 2 diabetes mellitus (T2DM) in a streptozotocin (STZ)-induced diabetic Wistar rat. Forty-five days of C-PC administration decreased levels of triglycerides (TGs), blood glucose, glycosylated hemoglobin, (HbA1c), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), liver and kidney function indices, and raised body weight in diabetic rats. C-PC suppressed biochemical glycation markers, as well as serum carboxymethyllysine (CML) and fluorescent AGEs. Additionally, C-PC maintained the redox state by lowering lipid peroxidation and protein-bound carbonyl content (CC), enhancing the activity of high-density lipoprotein cholesterol (HDL-C) and renal antioxidant enzymes, and preserving retinal and renal histopathological characteristics. Thus, we infer that C-PC possesses antidiabetic and antiglycation effects in diabetic rats. C-PC may also act as an antidiabetic and antiglycation agent in vivo that may reduce the risk of secondary diabetic complications. Full article
(This article belongs to the Special Issue Impact of Natural Products on Glycation Linked Metabolic Disease)
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16 pages, 2017 KiB  
Article
Luteolin Causes 5′CpG Demethylation of the Promoters of TSGs and Modulates the Aberrant Histone Modifications, Restoring the Expression of TSGs in Human Cancer Cells
by Sreepoorna Pramodh, Ritu Raina, Arif Hussain, Sali Abubaker Bagabir, Shafiul Haque, Syed Tasleem Raza, Mohammad Rehan Ajmal, Shalini Behl and Deepika Bhagavatula
Int. J. Mol. Sci. 2022, 23(7), 4067; https://doi.org/10.3390/ijms23074067 - 06 Apr 2022
Cited by 10 | Viewed by 2555
Abstract
Cancer progression is linked to abnormal epigenetic alterations such as DNA methylation and histone modifications. Since epigenetic alterations, unlike genetic changes, are heritable and reversible, they have been considered as interesting targets for cancer prevention and therapy by dietary compounds such as luteolin. [...] Read more.
Cancer progression is linked to abnormal epigenetic alterations such as DNA methylation and histone modifications. Since epigenetic alterations, unlike genetic changes, are heritable and reversible, they have been considered as interesting targets for cancer prevention and therapy by dietary compounds such as luteolin. In this study, epigenetic modulatory behaviour of luteolin was analysed on HeLa cells. Various assays including colony forming and migration assays, followed by biochemical assays of epigenetic enzymes including DNA methyltransferase, histone methyl transferase, histone acetyl transferase, and histone deacetylases assays were performed. Furthermore, global DNA methylation and methylation-specific PCR for examining the methylation status of CpG promoters of various tumour suppressor genes (TSGs) and the expression of these TSGs at transcript and protein level were performed. It was observed that luteolin inhibited migration and colony formation in HeLa cells. It also modulated DNA methylation at promoters of TSGs and the enzymatic activity of DNMT, HDAC, HMT, and HAT and reduced the global DNA methylation. Decrease in methylation resulted in the reactivation of silenced tumour suppressor genes including FHIT, DAPK1, PTEN, CDH1, SOCS1, TIMPS, VHL, TP53, TP73, etc. Hence, luteolin-targeted epigenetic alterations provide a promising approach for cancer prevention and intervention. Full article
(This article belongs to the Special Issue Impact of Natural Products on Glycation Linked Metabolic Disease)
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20 pages, 2391 KiB  
Article
Fisetin Deters Cell Proliferation, Induces Apoptosis, Alleviates Oxidative Stress and Inflammation in Human Cancer Cells, HeLa
by Nazia Afroze, Sreepoorna Pramodh, Jasmin Shafarin, Khuloud Bajbouj, Mawieh Hamad, Madhumitha Kedhari Sundaram, Shafiul Haque and Arif Hussain
Int. J. Mol. Sci. 2022, 23(3), 1707; https://doi.org/10.3390/ijms23031707 - 01 Feb 2022
Cited by 19 | Viewed by 2989
Abstract
Background: Fisetin, a flavonol profusely found in vegetables and fruits, exhibited a myriad of properties in preclinical studies to impede cancer growth. Purpose: This study was proposed to delineate molecular mechanisms through analysing the modulated expression of various molecular targets in HeLa cells [...] Read more.
Background: Fisetin, a flavonol profusely found in vegetables and fruits, exhibited a myriad of properties in preclinical studies to impede cancer growth. Purpose: This study was proposed to delineate molecular mechanisms through analysing the modulated expression of various molecular targets in HeLa cells involved in proliferation, apoptosis and inflammation. Methods: MTT assay, flow cytometry, nuclear morphology, DNA fragmentation and Annexin–Pi were performed to evaluate the anti-cancer potential of fisetin. Furthermore, qPCR and proteome profiler were performed to analyse the expression of variety of gene related to cell death, cell proliferation, oxidative stress and inflammation and cancer pathways. Results: Fisetin demonstrated apoptotic inducing ability in HeLa cells, which was quite evident through nuclear morphology, DNA ladder pattern, decreased TMRE fluorescent intensity, cell cycle arrest at G2/M and increased early and late apoptosis. Furthermore, fisetin treatment modulated pro-apoptotic genes such as APAF1, Bad, Bax, Bid and BIK at both transcript and protein levels and anti-apoptotic gene Bcl-2, BIRC8, MCL-1, XIAP/BIRC4, Livin/BIRC7, clap-2/BIRC3, etc. at protein levels to mitigate cell proliferation and induce apoptosis. Interestingly, the aforementioned alterations consequently led to an elevated level of Caspase-3, Caspase-8 and Caspase-9, which was found to be consistent with the transcript and protein level expression. Moreover, fisetin downregulated the expression of AKT and MAPK pathways to avert proliferation and enhance apoptosis of cancer cells. Fisetin treatment also improves oxidative stress and alleviates inflammation by regulating JAK-STAT/NF-kB pathways. Conclusion: Together, these studies established that fisetin deters human cervical cancer cell proliferation, enhances apoptosis and ameliorates inflammation through regulating various signalling pathways that may be used as a therapeutic regime for better cancer management. Full article
(This article belongs to the Special Issue Impact of Natural Products on Glycation Linked Metabolic Disease)
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