Orthopedics Department, Xixi Hospital of Hangzhou, Hangzhou, 310023, China.
Department of Bone Surgery, Yinchuan Second People's Hospital, Yinchuan, 750011, China.
Inflammation. 2022 Apr;45(2):851-862. doi: 10.1007/s10753-021-01590-0. Epub 2021 Nov 5.
Intervertebral disc (IVD) degeneration is a major cause of low back pain associated with several pathological changes in the IVD, including dysfunction of nucleus pulposus (NP) cells. Ganoderic Acid A (GAA), one of triterpenoid extracts of Ganoderma lucidum (G. lucidum), has been reported to possess anti-inflammatory effect. In the current study, we aimed to evaluate the effect of Ganoderic Acid A (GAA) on the interleukin-1β (IL-1β)-induced inflammation in human NP cells. Our results showed that the IL-1β-stimulated production of inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were suppressed by GAA. In addition, treatment of NP cells with GAA significantly inhibited the production of inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in IL-1β-stimulated human NP cells. GAA improved the reduced expression levels of extracellular matrix (ECM) proteins, collagen II and aggrecan in IL-1β-stimulated human NP cells. GAA also alleviated IL-1β-induced the levels of matrix metalloproteinase (MMP)-3 and MMP-13. Furthermore, GAA inhibited the IL-1β-induced upregulation of the phosphorylation of p65 and downregulation of IκBα. Taken together, these findings indicated that GAA alleviated IL-1β-induced inflammation and ECM degradation in NP cells through regulating NF-κB pathway.
椎间盘（IVD）退变是导致腰痛的主要原因，与 IVD 的几种病理变化有关，包括髓核（NP）细胞功能障碍。Ganoderic Acid A（GAA）是灵芝（G. lucidum）的三萜类提取物之一，据报道具有抗炎作用。在本研究中，我们旨在评估 Ganoderic Acid A（GAA）对人 NP 细胞中白细胞介素-1β（IL-1β）诱导的炎症的影响。我们的结果表明，GAA 抑制了 IL-1β刺激产生的炎症介质，包括一氧化氮（NO）、前列腺素 E2（PGE2）、诱导型一氧化氮合酶（iNOS）和环氧化酶（COX）-2。此外，GAA 处理 NP 细胞可显著抑制炎症细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）在 IL-1β刺激的人 NP 细胞中的产生。GAA 改善了 IL-1β刺激的人 NP 细胞中细胞外基质（ECM）蛋白、胶原 II 和聚集蛋白聚糖的表达水平降低。GAA 还减轻了 IL-1β诱导的基质金属蛋白酶（MMP）-3 和 MMP-13 水平升高。此外，GAA 抑制了 IL-1β诱导的 p65 磷酸化上调和 IκBα下调。综上所述，这些发现表明，GAA 通过调节 NF-κB 通路减轻了 IL-1β诱导的 NP 细胞炎症和 ECM 降解。
