Journal of Traditional Chinese Medicine ›› 2025, Vol. 45 ›› Issue (2): 376-384.DOI: 10.19852/j.cnki.jtcm.2025.02.012
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Network pharmacology approach to unveiling the mechanism of berberine in the amelioration of morphine tolerance
HAN Shuai1,2,3, Du Zhikang1,2, WANG Zirui1,2, HUANG Tianfeng3, GE Yali3, SHI Jianwen4,5(
), GAO Ju3()
- 1 Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225009, China
2 Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou 225009, China
3 Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225009, China
4 Peking University People's Hospital, Qingdao 266111, China
5 Women and Children's Hospital, Qingdao University, Qingdao 266034, China
-
Received:2023-12-15Accepted:2024-05-23Online:2025-04-15Published:2025-03-10 -
Contact:Prof. GAO Ju, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225009, China. doctor2227@163.com; Prof. SHI Jianwen, Peking University People's Hospital, Qingdao; Women and Children's Hospital, Qingdao University, Qingdao 266034, China. javen0523@163.com, Telephone: +86-15618135070; +86-18553263171 -
Supported by:Natural Science Foundation-funded Project: Study on the Mechanism of Mechanical Stress Sensing Element Piezo Type Mechanosensitive Ion Channel Component 2 Interacting with Nuclear Receptor Subfamily 4 Group A Member 2 Mediating Traumatic Brain Injury(82172190)
Cite this article
HAN Shuai, Du Zhikang, WANG Zirui, HUANG Tianfeng, GE Yali, SHI Jianwen, GAO Ju. Network pharmacology approach to unveiling the mechanism of berberine in the amelioration of morphine tolerance[J]. Journal of Traditional Chinese Medicine, 2025, 45(2): 376-384.
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Figure 1 Inhibitory effect of berberine on spinal dorsal horn microglial activation and inflammatory factors in morphine-tolerant mice A: the protein expression of CD86 was detected by western blot; B: the relative expression of CD86 level was quantified; C: the production of TNF-α was detected by ELISA assays; D: the production of IL-1β was detected by ELISA assays. Mice were pretreated with BBR (5.0 mg/kg) i.p. and then injected with morphine (10.0 mg/kg) s.c. 30 min later, this was performed once per day for eight consecutive days. On day nine, except for the control group, each group was injected with morphine 10.0 mg/kg. i.p.: intraperitoneal, s.c.: subcutaneous, BBR: berberine; Mor: morphine; TNF-α: tumor necrosis factor-alpha; IL-β: Interleukin-β; ELISA: enzymelinked immunosorbent assay. All values are expressed as the mean ± standard deviation (n = 6). One-way analysis of variance followed by Dunnett's multiple comparison for (B, C, D). aP < 0.01 compared with the control group; bP < 0.01 compared with the morphine group.
Figure 1 Inhibitory effect of berberine on spinal dorsal horn microglial activation and inflammatory factors in morphine-tolerant mice A: the protein expression of CD86 was detected by western blot; B: the relative expression of CD86 level was quantified; C: the production of TNF-α was detected by ELISA assays; D: the production of IL-1β was detected by ELISA assays. Mice were pretreated with BBR (5.0 mg/kg) i.p. and then injected with morphine (10.0 mg/kg) s.c. 30 min later, this was performed once per day for eight consecutive days. On day nine, except for the control group, each group was injected with morphine 10.0 mg/kg. i.p.: intraperitoneal, s.c.: subcutaneous, BBR: berberine; Mor: morphine; TNF-α: tumor necrosis factor-alpha; IL-β: Interleukin-β; ELISA: enzymelinked immunosorbent assay. All values are expressed as the mean ± standard deviation (n = 6). One-way analysis of variance followed by Dunnett's multiple comparison for (B, C, D). aP < 0.01 compared with the control group; bP < 0.01 compared with the morphine group.
Figure 2 Inhibitory effect of berberine on morphine-mediated the activation of brain vascular 2 (BV2) cells A: effect of BBR on morphine-induced proliferation of BV2 cells (× 200). Scale bar: 50 μm. For A1: control group, A2: morphine group (200 μmol/L), and morphine (200 μmol/L) combined with BBR groups based on BBR dose (A3: 5.0, A4: 10.0, and A5: 20.0 μmol/L); B: the cell viability was evaluated by Cell Counting Kit-8 assay. BV2 cells were treated with BBR (5, 10, and 20 μmol/L) 2 h prior to morphine (200 μmol/L) induction. BBR: berberine; Mor: morphine; L-BBR: BBR dose 5.0 μmol/L; M-BBR: BBR dose 10.0 μmol/L; H-BBR: BBR dose 20.0 μmol/L. All values are expressed as the mean ± standard deviation (n = 6). One-way analysis of variance followed by Dunnett's multiple comparison for B. aP < 0.001 compared with the control group; bP < 0.01 compared with the morphine group.
Figure 2 Inhibitory effect of berberine on morphine-mediated the activation of brain vascular 2 (BV2) cells A: effect of BBR on morphine-induced proliferation of BV2 cells (× 200). Scale bar: 50 μm. For A1: control group, A2: morphine group (200 μmol/L), and morphine (200 μmol/L) combined with BBR groups based on BBR dose (A3: 5.0, A4: 10.0, and A5: 20.0 μmol/L); B: the cell viability was evaluated by Cell Counting Kit-8 assay. BV2 cells were treated with BBR (5, 10, and 20 μmol/L) 2 h prior to morphine (200 μmol/L) induction. BBR: berberine; Mor: morphine; L-BBR: BBR dose 5.0 μmol/L; M-BBR: BBR dose 10.0 μmol/L; H-BBR: BBR dose 20.0 μmol/L. All values are expressed as the mean ± standard deviation (n = 6). One-way analysis of variance followed by Dunnett's multiple comparison for B. aP < 0.001 compared with the control group; bP < 0.01 compared with the morphine group.
Figure 3 Inhibitory effect of berberine on morphine induced activation of brain vascular 2 (BV2) cells A: the protein expression of CD86 was detected by western blot; B: the relative expression of CD86 level was quantified; C: the protein expression of NF-κB p65 was detected by Western blot; D: the relative expression of NF-κB p65 level was quantified. BV2 cells were treated with BBR (20 μmol/L) prior to morphine (200 μmol/L) induction. BBR: berberine dose 20 μmol/L; Mor: morphine dose 200 μmol/L; CD86: Cluster of Differentiation 86; NF-κB: nuclear factor kappa B. All values are expressed as the mean ± standard deviation (n = 6). One-way analysis of variance followed by Dunnett's multiple comparison for (B, D). aP < 0.05 compared with the control group; bP < 0.05 compared with the morphine group.
Figure 3 Inhibitory effect of berberine on morphine induced activation of brain vascular 2 (BV2) cells A: the protein expression of CD86 was detected by western blot; B: the relative expression of CD86 level was quantified; C: the protein expression of NF-κB p65 was detected by Western blot; D: the relative expression of NF-κB p65 level was quantified. BV2 cells were treated with BBR (20 μmol/L) prior to morphine (200 μmol/L) induction. BBR: berberine dose 20 μmol/L; Mor: morphine dose 200 μmol/L; CD86: Cluster of Differentiation 86; NF-κB: nuclear factor kappa B. All values are expressed as the mean ± standard deviation (n = 6). One-way analysis of variance followed by Dunnett's multiple comparison for (B, D). aP < 0.05 compared with the control group; bP < 0.05 compared with the morphine group.
Figure 4 Inhibitory effect of berberine on morphine-mediated apoptosis and oxidative stress in brain vascular 2 (BV2) cells A: effect of BBR on apoptosis in BV2 cells induced by morphine (× 200). Scale bar: 50 μm. A1: control group, A2: morphine group (200 μmol/L), and morphine (200 μmol/L) combined with BBR groups based on BBR dose (A3: 5.0, A4: 10.0, and A5: 20.0 μmol/L). B: effect of BBR on ROS in BV2 cells induced by morphine (× 200). Scale bar: 50 μm. B1: control group, B2: morphine group (200 μmol/L), and morphine (200 μmol/L) combined with BBR groups based on BBR dose (B3: 5.0, B4: 10.0, and B5: 20.0 μmol/L). C: BV2 cells were treated with BBR (20 μmol/L) prior to morphine (200 μmol/L) induction. The protein expression of Caspase-3, Bax and Bcl-2 were detected by Western blot; D: the relative expression of Caspase-3 level was quantified; E: the relative expression of Bax level was quantified; F: the relative expression of Bcl-2 level was quantified. BBR: berberine dose 20 μmol/L; Mor: morphine dose 200 μmol/L; ROS: reactive oxygen species; Bcl-2: B-cell lymphoma 2. All values are expressed as the mean ± standard deviation (n = 6). One-way analysis of variance followed by Dunnett's multiple comparison for (D, E, F). aP < 0.05, cP < 0.01 compared with the control group; bP < 0.05 compared with the morphine group.
Figure 4 Inhibitory effect of berberine on morphine-mediated apoptosis and oxidative stress in brain vascular 2 (BV2) cells A: effect of BBR on apoptosis in BV2 cells induced by morphine (× 200). Scale bar: 50 μm. A1: control group, A2: morphine group (200 μmol/L), and morphine (200 μmol/L) combined with BBR groups based on BBR dose (A3: 5.0, A4: 10.0, and A5: 20.0 μmol/L). B: effect of BBR on ROS in BV2 cells induced by morphine (× 200). Scale bar: 50 μm. B1: control group, B2: morphine group (200 μmol/L), and morphine (200 μmol/L) combined with BBR groups based on BBR dose (B3: 5.0, B4: 10.0, and B5: 20.0 μmol/L). C: BV2 cells were treated with BBR (20 μmol/L) prior to morphine (200 μmol/L) induction. The protein expression of Caspase-3, Bax and Bcl-2 were detected by Western blot; D: the relative expression of Caspase-3 level was quantified; E: the relative expression of Bax level was quantified; F: the relative expression of Bcl-2 level was quantified. BBR: berberine dose 20 μmol/L; Mor: morphine dose 200 μmol/L; ROS: reactive oxygen species; Bcl-2: B-cell lymphoma 2. All values are expressed as the mean ± standard deviation (n = 6). One-way analysis of variance followed by Dunnett's multiple comparison for (D, E, F). aP < 0.05, cP < 0.01 compared with the control group; bP < 0.05 compared with the morphine group.
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