Traditionally Used Plants in the Treatment of Diabetes Mellitus: Screening for Uptake Inhibition of Glucose and Fructose in the Caco2-Cell Model

Abstract

The traditional use of plants and their preparations in the treatment of diseases as a first medication in the past centuries indicates the presence of active components for specific targets in the natural material. Many of the tested plants in this study have been traditionally used in the treatment of Diabetes mellitus type 2 and associated symptoms in different cultural areas. Additionally, hypoglycemic effects, such as a decrease in blood glucose concentration, have been demonstrated in vivo for these plants. In order to determine the mode of action, the plants were prepared as methanolic and aqueous extracts and tested for their effects on intestinal glucose and fructose absorption in Caco2 cells. The results of this screening showed significant and reproducible inhibition of glucose uptake between 40 and 80% by methanolic extracts made from the fruits of Aronia melanocarpa, Cornus officinalis, Crataegus pinnatifida, Lycium chinense, and Vaccinium myrtillus; the leaves of Brassica oleracea, Juglans regia, and Peumus boldus; and the roots of Adenophora triphylla. Furthermore, glucose uptake was inhibited between 50 and 70% by aqueous extracts made from the bark of Eucommia ulmoides and the fruit skin of Malus domestica. The methanolic extracts of Juglans regia and Peumus boldus inhibited the fructose transport between 30 and 40% in Caco2 cells as well. These findings can be considered as fundamental work for further research regarding the treatment of obesity-correlated diseases, such as Diabetes mellitus type 2.

A systematic analysis of anti-diabetic medicinal plants from cells to clinical trials

“…Also, altered muscle glycogen synthesis play a major role in insulin resistance, and glycogen synthase, hexokinase, and GLUT4 are the major culprit involved in the skeletal muscle pathogenesis of type 2 dibetes ( Petersen & Shulman, 2002 ; Saini, 2010 ). GLUT2 and GLUT5 are responsible for intestinal glucose and fructose uptake ( Schreck & Melzig, 2021 ), while GLUT1 is present ubiquitously in all the body tissues ( Galochkina et al, 2019 ). The dominant glucose transporters found in the small intestine are sodium-glucose linked transporter 1 (SGLT1) which accumulates glucose into adsorptive epithelial cells against its concentration gradient and GLUT2 which mediates movement of glucose from the epithelial cells into the blood ( Schreck & Melzig, 2021 ); inhibition reduces the amount of glucose absorbed into the body.…”

“…GLUT2 and GLUT5 are responsible for intestinal glucose and fructose uptake ( Schreck & Melzig, 2021 ), while GLUT1 is present ubiquitously in all the body tissues ( Galochkina et al, 2019 ). The dominant glucose transporters found in the small intestine are sodium-glucose linked transporter 1 (SGLT1) which accumulates glucose into adsorptive epithelial cells against its concentration gradient and GLUT2 which mediates movement of glucose from the epithelial cells into the blood ( Schreck & Melzig, 2021 ); inhibition reduces the amount of glucose absorbed into the body. The hemodynamic activities of the glucose transporters have been extensively researched ( Ogurtsova et al, 2017 ; World Health Organization, 2019 ; Singhal, Bangar & Naithani, 2012 ; Nandabalan, Sujatha & Shanmuganathan, 2010 ).…”

“…The global worsening of morbidity and mortality from diabetes ( Zheng, Ley & Hu, 2018 ; Chaudhury et al, 2017 ; Modi, 2007 ; Md Sayem et al, 2018 ; Schreck & Melzig, 2021 ; Süntar, 2020 ) justifies the need for more diversified research for new therapies. Throughout human history, medicinal plants have been used for the prevention and treatment of both human and animal diseases ( Balunas & Kinghorn, 2005 ; Majolo et al, 2019 ; Khazir et al, 2014 ; Ahmad et al, 2015 ).…”

Potentially Bio-Accessible Metabolites from an Extract of Cornus mas Fruit after Gastrointestinal Digestion In Vitro and Gut Microbiota Ex Vivo Treatment

“…Promoting healthy, plant-based diets, reducing the fat, sugar, and salt content in processed foods, as well as increasing physical activity are key support in obesity prevention. The booster of these supportive fundamentals is an increased consumption of fruit and vegetables, taking into consideration that some of them inhibit the uptake of glucose and fructose [ 3 ] or lipids [ 4 ]. Increasing attention has been paid to the significance of the gut microbiome in the development of obesity-related complications recently [ 2 ].…”

Cornus mas and Cornus officinalis—A Comparison of Antioxidant and Immunomodulatory Activities of Standardized Fruit Extracts in Human Neutrophils and Caco-2 Models

“…Therefore, the resolution of inflammation both in the innate immune system and in the intestinal epithelium seems to be a good strategy to support the control of diabetes development in addition to conventional anti-diabetic therapy lowering blood glucose. Taking into consideration that extracts from fruits of C. mas and C. officinalis inhibited digestive enzymes or glucose uptake [30,31], their anti-inflammatory potential would support their anti-diabetic properties used in the traditional therapies.…”