Department of Orthopedics, Dongying People's Hospital, Dongying, PR China.
Department of Joint Surgery, Dongying People's Hospital, Dongying, PR China.
Pharm Biol. 2022 Dec;60(1):535-542. doi: 10.1080/13880209.2022.2042327.
Osteoarthritis (OA) is a degenerative disease. Senkyunolide A (SenA) is an important phthalide from Hort (Umbelliferae) with anti-spasmodic and neuroprotective effects.
We explored the effect of SenA on IL-1β-stimulated chondrocytes and OA mice.
Chondrocytes were stimulated by IL-1β (10 ng/mL) to establish an OA model . Cells were treated with SenA (20, 40, 80 and 160 μg/mL) for 48 h. The OA model was established by cutting off the medial meniscus tibial ligament (MMTL) at right knee incision of male C57BL/6 mice. One week after surgery, mice were injected with SenA (intraperitoneally one week) and divided into four groups ( = 6 per group): Sham, OA, OA + SenA 20 mg/kg and OA + SenA 40 mg/kg. The OA progression was examined by haematoxylin and eosin (H&E) staining.
SenA treatment increased cell viability (33%), proliferation (71%), inhibited apoptosis (21%), decreased levels of catabolic marker proteins (MMP13, 23%; ADAMTS4, 31%; ADAMTS5, 19%), increased levels of anabolic marker proteins (IGF-1, 57%; aggrecan, 75%; Col2a1, 48%), reduced levels of inflammation cytokines (TNF-α, 31%; IL-6, 19%; IL-18, 20%) and decreased levels of NLRP3 (21%), ASC (20%) and caspase-1 (29%) of chondrocytes. However, NLRP3 agonist nigericin increased levels of MMP13 (55%), ADAMTS4 (70%), ADAMTS5 (53%), decreased levels of IGF-1 (36%), aggrecan (26%), Col2a1 (25%), inhibited proliferation (61%) and promoted apoptosis (76%).
SenA alleviates OA progression by inhibiting NLRP3 signalling pathways. These findings provide an experimental basis for the clinical application of drugs in the treatment of OA.
骨关节炎（OA）是一种退行性疾病。Senkyunolide A（SenA）是一种重要的苯酞类化合物，具有抗痉挛和神经保护作用。
探讨 SenA 对 IL-1β刺激的软骨细胞和 OA 小鼠的作用。
用 IL-1β（10ng/mL）刺激软骨细胞建立 OA 模型。用 SenA（20、40、80 和 160μg/mL）处理细胞 48h。通过在右膝切口处切断内侧半月板胫骨韧带（MMTL）建立雄性 C57BL/6 小鼠的 OA 模型。手术后 1 周，通过腹腔注射 SenA（每周 1 次）将小鼠分为 4 组（每组 6 只）：Sham、OA、OA+SenA 20mg/kg 和 OA+SenA 40mg/kg。通过苏木精和伊红（H&E）染色检查 OA 进展。
SenA 处理增加了细胞活力（33%）、增殖（71%）、抑制了细胞凋亡（21%）、降低了分解代谢标志物蛋白（MMP13，23%；ADAMTS4，31%；ADAMTS5，19%）、增加了合成代谢标志物蛋白（IGF-1，57%；聚集蛋白，75%；Col2a1，48%）、降低了炎症细胞因子（TNF-α，31%；IL-6，19%；IL-18，20%）和 NLRP3（21%）、ASC（20%）和 caspase-1（29%）的水平。然而，NLRP3 激动剂 Nigericin 增加了 MMP13（55%）、ADAMTS4（70%）、ADAMTS5（53%）、降低了 IGF-1（36%）、聚集蛋白（26%）、Col2a1（25%）的水平，抑制了增殖（61%），促进了细胞凋亡（76%）。
SenA 通过抑制 NLRP3 信号通路缓解 OA 进展。这些发现为药物在 OA 治疗中的临床应用提供了实验依据。
