Screening of α‐Glucosidase Inhibitors from Houttuynia cordata and Evaluation of the Binding Mechanisms

Abstract

α‐glucosidase inhibitors have been used to treat diabetes for many years. Recently, natural products have attracted much attention, because they are kinds of safety source to screen α‐glucosidase inhibitor. In this study, we separated two monomers (quercitrin and afzelin) from Houttuynia cordata with notable inhibitory activity against α‐glucosidase, and evaluated inhibitory kinetics and the binding mechanisms. The 50% inhibitory concentration (IC50) of the quercitrin and afzelin were 0.231±0.033 mg/mL and 0.215±0.004 mg/mL, which were lower than the IC50 of acarbose. The inhibitory type between α‐glucosidase and the two monomers was a competitive inhibition, which is similar to acarbose and could compete binding sites. The fluorescence spectroscopy showed that quercitrin and afzelin statically quenched the fluorescence of α‐glucosidase. Circular dichroism and molecular docking analyses indicated that quercitrin and afzelin changed the alpha‐helix structure of α‐glucosidase and bound with the key amino acids through hydrophobic interactions, hydrogen bonds and salt bridge interaction. This study is the first time to clarify the inhibitory kinetics and binding mechanisms of quercitrin and afzelin on α‐glucosidase.

α‐Glucosidase Inhibition Action of Major Flavonoids Identified from Hypericum Attenuatum Choisy and Their Synergistic Effects

“…The values of horizontal axis (−1/ K m ) remained unaltered and the values of vertical axis (1/ V max ) increased with increasing the concentrations of the detected compounds, which indicated that all the three compounds caused a non‐competitive inhibition. Other flavonols such as kaempferol, quercetin 3‐ O ‐(3′′‐ O ‐galloyl)‐ β ‐galactopyranoside, quercetin 3‐ O ‐(6′′‐ O ‐galloyl)‐ β ‐glucopyranoside, quercetin 3‐ O ‐ β ‐glucopyranoside and quercetin 3‐ O ‐ β ‐galactopyranoside also demonstrated non‐competitive inhibition [5,19,21] . For non‐competitive inhibition, inhibitors bind to other site of the enzyme‐substrate complex instead of competing with pNPG for active sites.…”

Stevia Genus: Phytochemistry and Biological Activities Update

“…The flavonoid heteroside quercitrin (quercetin-3-O-ramnoside) ( 94 ) was isolated from S. rebaudiana as documented in the Stevia genus [ 1 ]. The biological activity of this compound has been extensively studied through the years, involving anti-inflammatory activity determined by Camuesco et al [ 235 ], antiproliferative and proapoptotic effects by Cincin et al [ 236 ], anti-Dengue virus 2 [ 237 ], osteoporosis attenuation [ 238 ], hair growth stimulation [ 239 ], improvement of hyperlipidemia and hepatic steatosis in ovariectomized mice [ 240 ], and inhibition of α-glicosidase [ 241 ]. Like other flavonoids discussed in this update, quercitrin was reviewed by Boniface and Ferreira et al [ 176 ], showing antiprotozoal activity against P. falciparum (43.4% inhibition after 48 h), inhibitory effects on L. amazonensis arginase (IC 50 = 10.0 µM), and activity against Dengue virus 2 (DENV-2 NS2B) (IC 50 = 43.6 µM) and Dengue virus 3 (DENV-3 NS2B) (IC 50 = 32.0 µM).…”

Phytochemicals with Added Value from Morella and Myrica Species

“…Killick leaves [55] Methanol extract of Myrica gale L. seeds [54] Cryptostrobin (31) Dichloromethane extract of Morella serrata (Lam.) Killick leaves [55] Demethoximatteucinol-7methoxy (32) Methanol extract of Myrica gale L. seeds [54] Methanol extract of Myrica gale L. seeds [54] Gallocatechin-4-α-8epicatechin (34) Aerial parts of Myrica gale L. [80] Gallocatechin-4-α-8epigallocatechin (35) Aerial parts of Myrica gale L. [80] Adenodimerin B (36) Methanol extract of Morella adenophora (Hance) J. Herb. roots [19] Adenodimerin C (37) Methanol extract of Morella adenophora (Hance) J. Herb.…”

“…roots [19] Adenodimerin C (37) Methanol extract of Morella adenophora (Hance) J. Herb. roots [19] Methanol extract of Myrica gale L. (Myrica gale var tormentosa L.) branches [24] Gallocatechin-4-α-8-epicatechin (34) Gallocatechin-4-α-8epicatechin (34) Aerial parts of Myrica gale L. [80] Gallocatechin-4-α-8epigallocatechin (35) Aerial parts of Myrica gale L. [80] Adenodimerin B (36) Methanol extract of Morella adenophora (Hance) J. Herb. roots [19] Adenodimerin C (37) Methanol extract of Morella adenophora (Hance) J. Herb.…”

“…Compound 9 is a potent α-glucosidase inhibitor, an enzymatic target used to evaluate antidiabetic effect. It has an IC 50 four times lower than acarbose, a commercial inhibitor, which indicates the great potential of quercitrin as a hypoglycemic agent for diabetes treatment [ 36 ]. Mercury and lead are considered as threats to human organisms, due to their low elimination rate and high accumulation, which have nefarious effects in several physiological functions, especially of liver and nervous system [ 67 , 68 ].…”