Journal of Traditional Chinese Medicine ›› 2023, Vol. 43 ›› Issue (5): 915-924.DOI: 10.19852/j.cnki.jtcm.20230802.006
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HAN Shuai1,2, MAO Hua3, JIN Tingting4, YAN Rubing4, WANG Ziyi4, ZHANG Jie5, SHI Jianwen6(), LIANG Yongxin6()
Received:
2022-06-11
Accepted:
2022-10-12
Online:
2023-10-15
Published:
2023-08-02
Contact:
Prof. LIANG Yongxin, Department of Anesthesiology, Women’s and Children’s Hospital Affiliated to Qingdao University, Qingdao 266034, China. Supported by:
HAN Shuai, MAO Hua, JIN Tingting, YAN Rubing, WANG Ziyi, ZHANG Jie, SHI Jianwen, LIANG Yongxin. Inhibitory effect of berberine on morphine tolerance and hyperalgesia in mice[J]. Journal of Traditional Chinese Medicine, 2023, 43(5): 915-924.
Figure 1 Analgesic effect of BBR in the hot-plate test A: analgesic effect of BBR detected by the hot-plate test. B: effect of BBR on morphine analgesia detected by the hot-plate test. Animals were treated with intraperitoneal BBR 30 min prior to the subcutaneous administration of 5 mg/kg Mor. BBR: berberine, Mor: morphine, % MPAE: the percentage of maximal possible analgesic effect. All values are expressed as the mean ± standard deviation; n = 8 for each group; one-way analysis of variance followed by Dunnett's multiple comparison. aP < 0.01 compared with the control group, bP < 0.01 compared with the morphine group.
Figure 2 Effect of BBR on morphine-induced acute/ chronic tolerance and hyperalgesia A: the inhibitory effect of BBR on acute morphine-induced tolerance. B: the inhibitory effect of BBR on acute morphine-induced hyperalgesia. C: the inhibitory effect of BBR on morphine-induced chronic tolerance. D: the inhibitory effect of BBR on chronic morphine-induced hyperalgesia. M: morphine 10 mg/kg, L-Ber: berberine 2.5 mg/kg, M-Ber: berberine 5.0 mg/kg, H-Ber: berberine 10 mg/kg, MPAE: maximum possible analgesic effect, BBR: berberine. Data are presented as mean ± standard deviation; n = 8 for each group; one-way analysis of variance followed by Dunnett's multiple comparison (A, B, and C); (D)Two-tailed unpaired student’s t test. aP < 0.01 compared with the control group, bP < 0.01 compared with the morphine group, cP < 0.01 compared with each corresponding group at the 0 h time point, dP < 0.01 compared with each corresponding group on day 1.
Figure 3 Effect of BBR (2.5 mg/kg) on morphine-induced established tolerance and hyperalgesia A: the inhibitory effect of BBR on morphine-induced established tolerance. B: the inhibitory effect of BBR on established morphine-induced hyperalgesia. Mice were given morphine for 8 days; BBR was co-administered on days 1, 4, and 7. BBR: berberine. All values are expressed as the mean ± standard deviation; n = 8 for each group. For Figure A, aP < 0.01 compared with the control group, bP < 0.01 compared with the morphine group, one-way analysis of variance followed by Dunnett's multiple comparison; for Figure B, cP < 0.01 compared with each corresponding group on day 1, two-tailed unpaired student’s t test.
Group | n | NOS activity (kU/g protein) | NO content (μmol/g protein) | |
---|---|---|---|---|
Normal control | 8 | 6.98±0.27 | 1.22±0.13 | |
BBR | 8 | 6.78±0.38a | 1.24±0.21a | |
Mor | 8 | 7.96±0.43b | 1.87±0.17a | |
Mor+BBR | Day 1 | 8 | 7.18±0.32a | 1.39±0.14a |
Day 4 | 8 | 7.67±0.31 | 1.47±0.23a,b | |
Day 7 | 8 | 7.81±0.26b | 1.68±0.14b,c |
Table 1 Effect of Berberine on NOS activity and NO content in the spinal cord of morphine-induced established tolerance mice
Group | n | NOS activity (kU/g protein) | NO content (μmol/g protein) | |
---|---|---|---|---|
Normal control | 8 | 6.98±0.27 | 1.22±0.13 | |
BBR | 8 | 6.78±0.38a | 1.24±0.21a | |
Mor | 8 | 7.96±0.43b | 1.87±0.17a | |
Mor+BBR | Day 1 | 8 | 7.18±0.32a | 1.39±0.14a |
Day 4 | 8 | 7.67±0.31 | 1.47±0.23a,b | |
Day 7 | 8 | 7.81±0.26b | 1.68±0.14b,c |
Figure 4 Molecular docking of berberine with the human GluN1-GluN2A, GluN1-GluN2B NMDAR A: crystal structure of the human GluN1-GluN2A NMDAR. B: the binding pocket for BBR in the central vestibule between the GluN1-GluN2A channel gate and selectivity filter. C: BBR binds to the human GluN1-GluN2A NMDAR, two-dimensional pattern diagram. D: crystal structure of the human GluN1-GluN2B NMDAR. E: the binding pocket for BBR in the central vestibule between the GluN1-GluN2B channel gate and selectivity filter. F: BBR binds to the human GluN1-GluN2B NMDAR, two-dimensional pattern diagram. NMDAR: N-methyl-D-aspartate receptor; BBR: berberine.
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