Protein tyrosine phosphatase 1B (PTP1B) inhibitory activity and glucosidase inhibitory activity of compounds isolated from Agrimonia pilosa

Figures & data

Figure 1. Extraction and isolation scheme of compounds (1–11) from A. pilosa Ledeb.

Figure 2. Chemical structures of compounds 1–11 isolated from A. pilosa Ledeb.

Figure 3. Graphical determination of inhibition type for the isolated compounds 1, 4, 6, 8, 9, and 11. Lineweaver–Burk plots for the inhibition of compounds 1, 4, 6, 8, 9, and 11 on the PTP1B-catalyzed hydrolysis of p-NPP. Data are expressed as the mean reciprocal of initial velocity for n = 3 replicates at each substrate concentration.

Figure 4. Graphical determination of inhibition type for the isolated compounds 1, 4, 6, 8, 9, and 11. Dixon plots for compounds 1, 4, 6, 8, 9, and 11 used for determining the inhibition constant K_i. K_i values were determined from the negative x-axis value at the point of the intersection of the three lines.

Table 1. Inhibitory effects of isolated compounds (1–11) on the PTP1B and α-glucosidase enzyme activities.

	PTP1B inhibitory activity			α-Glucosidase
Compound	IC50 (μM)^a	Ki value	Inhibition type	IC50 (μM)^a
1	14.35 ± 0.76	14.02 ± 0.83	Mixed-competitive	103.3 ± 1.1
2	>50	–^b	–	44.8 ± 0.9
3	>50	–	–	11.2 ± 0.2
4	27.73 ± 1.54	6.98 ± 2.23	Uncompetitive	29.6 ± 0.9
5	42.93 ± 2.36	–	–	>150
6	12.16 ± 0.02	33.86 ± 3.79	Non-competitive	28.5 ± 0.1
7	49.78 ± 1.42	–	–	>150
8	3.47 ± 0.02	6.46 ± 0.15	Mixed-competitive	42.4 ± 0.7
9	0.50 ± 0.06	16.36 ± 0.26	Mixed-competitive	23.8 ± 0.4
10	36.39 ± 1.72	–	–	112.8 ± 1.7
11	0.10 ± 0.03	9.20 ± 0.76	Competitive	45.5 ± 1.5
RK-682^c	4.47 ± 0.03	–	–	–
Acarbose^b	–	–	–	124.2 ± 0.4

^aIC₅₀ values (μM) were determined by regression analysis and expressed as the means ± SD of three replicates. The inhibition types for the isolated compounds 1, 4, 6, 8, 9, and 11 were tested using Lineweaver–Burk plots on the PTP1B-catalyzed hydrolysis of p-NPP and Dixon plots for determining the inhibition constant K_i. K_i values were determined from the negative x-axis value at the point of the intersection of the three lines. Data are expressed as the mean reciprocal of initial velocity for n = 3 replicates at each substrate concentration.

^bThe compounds were used as positive control.

^cData not identified.