Comparative Evaluation of the Antiglycation and Anti-α-Glucosidase Activities of Baicalein, Baicalin (Baicalein 7-O-Glucuronide) and the Antidiabetic Drug Metformin

Abstract

The discovery of new oral antidiabetic drugs remains a priority in medicine. This research aimed to evaluate the activity of the flavonoid baicalein and its natural glucuronide baicalin, compared to the antidiabetic drug metformin, as potential antiglycation, anti–radical, and anti-α–glucosidase agents, in order to assess their potential role in counteracting hyperglycemia-induced tissue damage. The study considered: (i) the BSA assay, to detect the formation of advanced glycation end products (AGEs), (ii) the GK peptide–ribose assay, which evaluates the cross–linking between the peptide and ribose, and (iii) the carbonyl content assay to detect the total carbonyl content, as a biomarker of tissue damage. In addition, to obtain a reliable picture of the antiglycation capacity of the investigated compounds, DPPH scavenging and oxygen radical absorbance capacity (ORAC) assays were performed. Furthermore, the anti–α–glucosidase activity of baicalein and baicalin was detected. Furthermore, to estimate cell permeability, preliminarily, the cytotoxicity of baicalein and baicalin was evaluated in HT–29 human colon adenocarcinoma cells using the MTT assay. Successively, the ability of the compounds to pass through the cytoplasmic membranes of HT–29 cells was detected as a permeability screen to predict in vivo absorption, showing that baicalein passes into cells even if it is quickly modified in various metabolites, being its main derivative baicalin. Otherwise, baicalin per se did not pass through cell membranes. Data show that baicalein is the most active compound in reducing glycation, α-glucosidase activity, and free radicals, while baicalin exhibited similar activities, but did not inhibit the enzyme α–glucosidase.

Evaluation of Carbonic Anhydrase, Acetylcholinesterase, Butyrylcholinesterase, and α-Glycosidase Inhibition Effects and Antioxidant Activity of Baicalin Hydrate

“…The findings exhibited that Cu 2+ reducing ability of baicalin hydrate is lower than those that used standard antioxidants. Furthermore, absorbance values for natural phenolic compound have been recorded in the previous literature, including usnic acid's absorbance values for Cu 2+ reduction as 0.277 (r 2 : 0.9836) [53], 0.468 (r 2 : 0.9729) for magnofluorine [28] 0.519 (r 2 : 0.9675) for spiraeoside [57] 0.762 for eugenol (r 2 : 0.9957) [69], 0.780 (r 2 : 0.9981) for coumestrol [16], 1.085 (r 2 : 0.8403) for resveratrol [70], 0.750 (r 2 : 0.9550) for taxifolin [71], and 1.314 (r 2 : 0.9682) for olivetol [72] at the same concentration.…”

“…The findings demonstrated that baicalin hydrate's Fe 3+ reducing capacity is lower than that of BHA and Trolox but comparable to that of BHT and α-Tocopherol. When examining the literature on this topic, it is observed that the Fe 3+ reducing absorbance for usnic acid has been determined as 0.278 (r 2 : 0.9567) [53], 2.769 for caffeic acid (r 2 : 0.9945) [54], 0.432 (r 2 : 0.9981) for uric acid [55], 0.739 (r 2 : 0.9478) for coumestrol [16], 2.428 (r 2 : 0.9474) for tannic acid [56], 1.012 (r 2 : 0.9523) for spiraeoside [57], 0.967 (r 2 : 0.9938) for magnofluorine [28] and 2.509 (r 2 : 0.9906) for caffeic acid phenethyl ester [58] at similar concentration.…”

“…Diabetes mellitus (DM) is considered an epidemic as it is the fourth great contributing factor to mortality in developed countries. The etiology of type-2 DM (T2DM), which includes lifestyle choices, dyslipidemia, and genetic susceptibility, is complicated because of the number of variables involved [16]. Inhibition of α-glycosidase, one of the most significant digestive enzymes that catalyzes the breakdown of dietary polysaccharides, is a primary target for treatment of T2DM [17].…”

Luteolin and Vernodalol as Bioactive Compounds of Leaf and Root Vernonia amygdalina Extracts: Effects on α-Glucosidase, Glycation, ROS, Cell Viability, and In Silico ADMET Parameters

“…Protein glycation was obtained in accordance with a previously described method [ 39 , 40 ]. AGEs were detected using BSA (10 mg/mL, pH 7.4) as the protein substrate, and glucose (1.0 M), fructose (0.5 M), or ribose (0.05 M) as glycation inducers.…”

Selected Plant-Derived Polyphenols as Potential Therapeutic Agents for Peripheral Artery Disease: Molecular Mechanisms, Efficacy and Safety

“…A study using three structurally related polyphenols, such as baicalin, baicalein and wogonin, showed the inhibition of endothelial cell barrier disruption, suggesting their protective activity against vascular inflammatory diseases [ 75 ]. Recently, studies have suggested that baicalein exhibits potential antidiabetic activities in metabolic syndrome [ 76 ]; the effect is related to the inhibition of α–glucosidase activity [ 77 , 78 ].…”