Key Laboratory of Hunan Forest Products and Chemical Industry Engineering, Jishou University, Jishou, PR China; Key Laboratory of Plant Resource Conservation and Utilization, Jishou University, Jishou, PR China; Department of Pharmacology, School of Medicine, Jishou University, Jishou, PR China.
Department of Pharmacy, Zhaoqing Medical College, Zhaoqing, PR China.
Mol Cell Endocrinol. 2018 Jul 15;470:259-268. doi: 10.1016/j.mce.2017.11.007. Epub 2017 Nov 11.
It has been reported that inflammation is closely related with cardiac hypertrophy. Some inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interleukin-6 directly induce cardiac hypertrophy, which is associated with the activation of nuclear factorkappa B (NF-κB). Thus, NF-κB is an attractive target for cardiac hypertrophy. In the present study, oleanonic acid inhibited the elevation of transcriptional activity of NF-κB and reduced the mRNA expressions of hypertrophic genes such as atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) in a concentration-dependent manner in phenylephrine (PE)-treated cardiomyocytes. Furthermore, we found that oleanonic acid inhibited the phosphorylation of protein kinase C ζ (PKCζ) at Thr410 site and then reduced the activation of NF-κB using gain- and loss-of-function approaches in PE-treated cardiomyocytes. In vivo, similar results were observed in abdominal aortic constriction (AAC) rats that were intragastrically administered with oleanonic acid, and the pathological changes accompanying cardiac hypertrophy were relieved. In conclusion, oleanonic acid can effectively ameliorate cardiac hypertrophy by inhibiting PKCζ-NF-κB signaling pathway.
据报道，炎症与心肌肥厚密切相关。一些炎症细胞因子，如肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6，直接诱导心肌肥厚，这与核因子-κB（NF-κB）的激活有关。因此，NF-κB 是心肌肥厚的一个有吸引力的靶点。在本研究中，齐墩果酸以浓度依赖的方式抑制了去甲肾上腺素（PE）处理的心肌细胞中 NF-κB 的转录活性升高，并降低了心房利钠肽（ANF）和脑利钠肽（BNP）等肥大基因的 mRNA 表达。此外，我们发现齐墩果酸通过在 PE 处理的心肌细胞中使用增益和失能方法，抑制了蛋白激酶 C ζ（PKCζ）在 Thr410 位点的磷酸化，从而减少了 NF-κB 的激活。在体内，给予齐墩果酸的腹主动脉缩窄（AAC）大鼠也观察到了类似的结果，伴随心肌肥厚的病理变化得到缓解。总之，齐墩果酸通过抑制 PKCζ-NF-κB 信号通路，可有效改善心肌肥厚。
