Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jan 9;23(2):704.
doi: 10.3390/ijms23020704.

Effects of Isorhamnetin on Diabetes and Its Associated Complications: A Review of In Vitro and In Vivo Studies and a Post Hoc Transcriptome Analysis of Involved Molecular Pathways

Feten Zar Kalai  1   2 , Mondher Boulaaba  1   2 , Farhana Ferdousi  1   3 , Hiroko Isoda  1   3
Affiliations
Review

Effects of Isorhamnetin on Diabetes and Its Associated Complications: A Review of In Vitro and In Vivo Studies and a Post Hoc Transcriptome Analysis of Involved Molecular Pathways

Feten Zar Kalai et al. Int J Mol Sci. .

Abstract

Diabetes mellitus, especially type 2 (T2DM), is a major public health problem globally. DM is characterized by high levels of glycemia and insulinemia due to impaired insulin secretion and insulin sensitivity of the cells, known as insulin resistance. T2DM causes multiple and severe complications such as nephropathy, neuropathy, and retinopathy causing cell oxidative damages in different internal tissues, particularly the pancreas, heart, adipose tissue, liver, and kidneys. Plant extracts and their bioactive phytochemicals are gaining interest as new therapeutic and preventive alternatives for T2DM and its associated complications. In this regard, isorhamnetin, a plant flavonoid, has long been studied for its potential anti-diabetic effects. This review describes its impact on reducing diabetes-related disorders by decreasing glucose levels, ameliorating the oxidative status, alleviating inflammation, and modulating lipid metabolism and adipocyte differentiation by regulating involved signaling pathways reported in the in vitro and in vivo studies. Additionally, we include a post hoc whole-genome transcriptome analysis of biological activities of isorhamnetin using a stem cell-based tool.

Keywords: biological activities; diabetes; isorhamnetin; microarray; molecular pathways; quercetin.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funder had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Simplified biosynthetic of isorhamnetin by (A) the shikimic and (B) the phenylpropanoid pathways. PAL: phenylalanine ammonia lyase, C4H: cinnamate 4-hydroxylase, 4CL: 4-coumaroyl-coenzyme A ligase, CHS: chalcone synthase, CHI: chalcone-flavanone isomerase, FNS: flavone synthase, F3D: flavanone 3-dioxygenase, FS: flavonol synthase, FMT: flavone 3′-O-methyltransferase.
Figure 2
Figure 2
(A): Basic skeleton of flavonoids, (B): Isorhamnetin.
Figure 3
Figure 3
Overview of biological activities of isorhamnetin. NB. Circles do not represent any hierarchical relationship.
Figure 4
Figure 4
Whole-genome microarray analysis predicts the potential effect of the isorhamnetin on diabetes in a stem cell-based tool of hAEC. (A) Significantly enriched cell type signature gene sets (MSigDB of GSEA; https://www.gsea-msigdb.org/gsea/index.jsp, accessed on 26 November 2021); (B) significantly enriched hallmark gene sets (GSEA); (C) significantly enriched pathways (CTD; http://ctdbase.org/, accessed on 29 November 2021); (D) significantly enriched metabolic diseases (CTD); (E) heatmap for DM-associated gene expression. All data are available at Gene Expression Omnibus (GEO) under accession number: GSE153149 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE153149, accessed on 24 November 2021).
Figure 5
Figure 5
Anti-diabetic effects of isorhamnetin (NF-κβ and PPARS images were downloaded from Protein Data Bank (https://www.rcsb.org/, accessed on 10 November 2021), other images were freely downloaded from free picture database (https://fr.freepik.com/, accessed on 10 November 2021).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Gill S.S., Tuteja N. Reactive oxygen species and antioxidant machinery in abiotic stress tolerance in crop plants. Plant Physiol. Biochem. 2010;48:909–930. doi: 10.1016/j.plaphy.2010.08.016. - DOI - PubMed
    1. Corpas F.J., Gupta D.K., Palma J.M. Reactive Oxygen Species and Oxidative Damage in Plants under Stress. Springer; Berlin/Heidelberg, Germany: 2015. Production sites of reactive oxygen species (ROS) in organelles from plant cells; pp. 1–22.
    1. Falleh H., Oueslati S., Guyot S., Dali A.B., Magné C., Abdelly C., Ksouri R. LC/ESI-MS/MS characterisation of procyanidins and propelargonidins responsible for the strong antioxidant activity of the edible halophyte Mesembryanthemum edule L. Food Chem. 2011;127:1732–1738. doi: 10.1016/j.foodchem.2011.02.049. - DOI
    1. Trabelsi N., Oueslati S., Falleh H., Waffo-Téguo P., Papastamoulis Y., Mérillon J.-M., Abdelly C., Ksouri R. Isolation of powerful antioxidants from the medicinal halophyte Limoniastrum guyonianum. Food Chem. 2012;135:1419–1424. doi: 10.1016/j.foodchem.2012.05.120. - DOI - PubMed
    1. Boulaaba M., Mkadmini K., Tsolmon S., Han J., Smaoui A., Kawada K., Ksouri R., Isoda H., Abdelly C. In vitro antiproliferative effect of Arthrocnemum indicum extracts on Caco-2 cancer cells through cell cycle control and related phenol LC-TOF-MS identification. Evid.-Based Complement. Altern. Med. 2013;2013:529375. doi: 10.1155/2013/529375. - DOI - PMC - PubMed