Korean Thistle (Cirsium japonicum var. maackii (Maxim.) Matsum.): A Potential Dietary Supplement against Diabetes and Alzheimer's Disease

Abstract

In the search for natural products having a dual inhibitory action on diabetes and Alzheimer's disease, this study investigated the activity of different parts of Korean thistle (Cirsium japonicum var. maackii (Maxim.) Matsum), and its fractional constituents by in vitro enzymatic and in silico molecular docking studies. Cirsium maackii has been used as a traditional medicine for the treatment of several diseases. The ethyl acetate and dichloromethane fractions of a leaf extract showed α-glucosidase and BACE1 inhibitory activity, respectively. Furthermore, the isolated compound, luteolin, exhibited concentration-dependent non-competitive inhibition against both α-glucosidase and BACE1 (IC₅₀ = 51.27 ± 1.23 and 13.75 ± 0.26 μM; K_i value = 52.04 and 14.76 μM, respectively). Moreover, docking studies showed that luteolin formed a strong hydrogen bond with the peripheral binding amino acid residues, and hydrophobic interactions with the α-glucosidase and BACE1 enzymes. Therefore, Korean thistle may act as an important dietary supplement against diabetes and Alzheimer's disease, especially the leaves, because of the preponderance of the active component, luteolin, making Korean thistle a promising candidate for more detailed in vitro and in vivo studies.

Keywords: BACE1; Cirsium maackii; Korean thistle; luteolin; supplements; α-Glucosidase.

Figure 1

Structures of different isolated compounds from C. maackii.

Figure 2

Concentration-dependent (A) α-glucosidase and (B) BACE1 inhibitory activity of MeOH extract of leaves of C. maackii along with the standards, acarbose and quercetin, respectively. Error bars indicate standard deviation (SD).

Figure 3

Pro-oxidant activity of different isolated compounds from C. maackii as measured from Fenton reaction using ascorbic acid as positive control. Data are represented as mean ± SD of triplicate experiments.

Figure 4

Lineweaver-Burk plot (A,C,E) and Dixon plot (B,D,F) for the inhibition of α-glucosidase by luteolin (A,B), luteolin 5-O-β-d-glucopyranoside (C,D), and luteolin 7-O-β-d-glucopyranoside (E,F), respectively.

Figure 5

Lineweaver-Burk plot (A) and Dixon plot (B) for the inhibition of BACE1 by luteolin.

Figure 6

2D (A,C,E,G) and 3D (B,D,F,H) diagrams of α-glucosidase inhibition by luteolin (allosteric inhibition, A,B), luteolin 5-O-β-d-glucopyranoside (catalytic inhibition, C,D), luteolin 5-O-β-d-glucopyranoside (allosteric inhibition, E,F), and luteolin 7-O-β-d glucopyranoside (catalytic inhibition, G,H). Luteolin, luteolin 5-O-β-d glucopyranoside, luteolin 7-O-β-d-glucopyranoside, acarbose, and BIP are represented by yellow, bold red, blue, black, and red colored structures, respectively.

Figure 7

2D (A,C,E) and 3D (B,D,F) diagrams of BACE1 inhibition by luteolin (allosteric inhibition, A,B), luteolin 5-O-β-d-glucopyranoside (catalytic inhibition, C,D), and luteolin 7-O-β-d-glucopyranoside (catalytic inhibition, E,F). Luteolin, luteolin 5-O-β-d-glucopyranoside, luteolin 7-O-β-d-glucopyranoside, QUD, and PMF are represented by yellow, bold red, blue, black, and red colored structures, respectively.