Department of Orthopaedics, Baoding NO.1 Central Hospital, Baoding, China.
Department of Spine, The Third Hospital of Hebei Medical University, Shijiazhuang, China.
Pharm Biol. 2022 Dec;60(1):427-436. doi: 10.1080/13880209.2022.2035773.
Cyanidin has been shown to have therapeutic potential in osteoarthritis. However, it is unclear whether cyanidin prevents the progression of intervertebral disc degeneration (IVDD).
This study evaluates the effects of cyanidin on IVDD and .
Nucleus pulposus cells (NPCs) isolated from lumbar IVD of 4-week-old male Sprague-Dawley (SD) rats were exposed to 20 ng/mL IL-1β, and then treated with different doses (0-120 µM) of cyanidin for 24 h. SD rats were classified into three groups ( = 8) and treated as follows: control (normal saline), IVDD (vehicle), IVDD + cyanidin (50 mg/kg). Cyanidin was administered intraperitoneally for 8 weeks.
The IC of cyanidin for NPCs was 94.78 µM, and cyanidin had no toxicity at concentrations up to 500 mg/kg in SD rats. Cyanidin inhibited the apoptosis of NPCs induced by IL-1β (12.73 ± 0.61% vs. 18.54 ± 0.60%), promoted collagen II (0.82-fold) and aggrecan (0.81-fold) expression, while reducing MMP-13 (1.02-fold) and ADAMTS-5 (1.40-fold) expression. Cyanidin increased the formation of autophagosomes in IL-1β-induced NPCs, and promoted LC3II/LC3I (0.83-fold) and beclin-1 (0.85-fold) expression, which could be reversed by chloroquine. Cyanidin inhibited the phosphorylation of JAK2 (0.47-fold) and STAT3 (0.53-fold) in IL-1β-induced NPCs. The effects of cyanidin could be enhanced by AG490. Furthermore, cyanidin mitigated disc degeneration in IVDD rats .
Cyanidin improved the function of NPCs in IVDD by regulating the JAK2/STAT3 pathway, which may provide a novel alternative strategy for IVDD. The mechanism of cyanidin improving IVDD still needs further work for in-depth investigation.
矢车菊素在骨关节炎中具有治疗潜力。然而,目前尚不清楚矢车菊素是否能预防椎间盘退行性变(IVDD)的进展。
本研究评估了矢车菊素对 IVDD 的影响。
从小鼠腰椎间盘分离出核因子培养液(NPCs),并将其暴露于 20ng/ml 的白细胞介素-1β中,然后用不同剂量(0-120μM)的矢车菊素处理 24 小时。将 SD 大鼠分为三组(每组 8 只),并分别进行如下处理:对照组(生理盐水)、IVDD 组(载体)、IVDD+矢车菊素(50mg/kg)。矢车菊素通过腹腔内给药 8 周。
矢车菊素对 NPCs 的 IC 为 94.78μM,且在 SD 大鼠中浓度高达 500mg/kg 时无毒性。矢车菊素抑制了 IL-1β诱导的 NPCs 凋亡(12.73±0.61%比 18.54±0.60%),促进了胶原蛋白 II(0.82 倍)和聚集蛋白聚糖(0.81 倍)的表达,同时降低了基质金属蛋白酶-13(1.02 倍)和 ADAMTS-5(1.40 倍)的表达。矢车菊素增加了 IL-1β诱导的 NPCs 中自噬体的形成,促进了 LC3II/LC3I(0.83 倍)和 beclin-1(0.85 倍)的表达,这一过程可被氯喹所逆转。矢车菊素抑制了 IL-1β诱导的 NPCs 中 JAK2(0.47 倍)和 STAT3(0.53 倍)的磷酸化。AG490 可增强矢车菊素的作用。此外,矢车菊素减轻了 IVDD 大鼠的椎间盘退变。
矢车菊素通过调节 JAK2/STAT3 通路改善了 NPCs 在 IVDD 中的功能,这可能为 IVDD 提供了一种新的治疗策略。矢车菊素改善 IVDD 的机制仍需要进一步深入研究。