Tang Jiayang, Li Xiang, Yu Xue, Wang Dong, Huang Kai, Pu Haiyin, Yu Jiang, Li Shuai, Wang Wei, Liu Bin, Guo Shuzhen
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
Phytomedicine. 2025 Jan;136:156326. doi: 10.1016/j.phymed.2024.156326. Epub 2024 Dec 12.
Inflammation serves an essential function in the occurrence and progression of heart failure (HF), especially in the early stage. Lonicerae japonicae Flos (LJF), Angelicae sinensis Radix (ASR), and their compatibility (LJF+ASR) can inhibit excessive inflammation and have significant cardioprotective effects. However, the primary active ingredients and mechanism of LJF and ASR in anti-inflammatory and anti-HF effect remain to be elucidated.
This study aimed to evaluate the influence of LJF, ASR, and LJF+ASR on early inflammation and subsequent cardiac function in HF mice and to identify the primary pharmacologically active components of these compounds.
LJF, ASR, and LJF+ASR components entering the plasma and heart were identified via UPLC-LTQ-Orbitlaps-MS. The cardioprotective effects of LJF, ASR, and LJF+ASR after 8 weeks of treatment were validated in transverse aortic constriction (TAC)-induced HF mice via echocardiography, HE staining, and cardiac indices. The anti-inflammatory effects of these treatments after 1 week of TAC induction, as well as the cardioprotective and anti-inflammatory effects of the primary component chlorogenic acid (CGA), were confirmed in H9c2 cardiomyocytes through flow cytometry, Western blot, and siRNA transfection.
LJF, ASR and LJF+ASR enhanced cardiac contractile function and ameliorated cardiac pathological remodeling induced by TAC. Moreover, these compounds inhibited platelet-granulocyte aggregation, platelet-monocyte aggregation, the calmodulin-dependent protein kinase II delta (CaMKII δ)/nuclear factor-kappaB (NF-κB) signaling pathway and proinflammatory factor levels in early-stage HF to different extents. Moreover, 9 potentially effective components were identified in the aqueous extract and blood-absorbed components of LJF+ASR, and CGA inhibited the CaMKII δ/NF-κB signaling pathway and decreased proinflammatory factor levels in vitro.
LJF, ASR, LJF+ASR and CGA inhibit the CaMKII δ/NF-κB signaling pathway and are potentially novel therapeutics for mitigating early inflammation and improving late cardiac function of HF.
炎症在心力衰竭（HF）的发生和发展中起着至关重要的作用，尤其是在早期阶段。金银花（LJF）、当归（ASR）及其配伍（LJF+ASR）可抑制过度炎症反应并具有显著的心脏保护作用。然而，LJF和ASR在抗炎和抗HF作用中的主要活性成分及机制仍有待阐明。
本研究旨在评估LJF、ASR和LJF+ASR对HF小鼠早期炎症和随后心脏功能的影响，并确定这些化合物的主要药理活性成分。
通过超高效液相色谱-线性离子阱-轨道阱质谱法（UPLC-LTQ-Orbitlaps-MS）鉴定进入血浆和心脏的LJF、ASR和LJF+ASR成分。通过超声心动图、苏木精-伊红（HE）染色和心脏指数，在经主动脉缩窄（TAC）诱导的HF小鼠中验证治疗8周后LJF、ASR和LJF+ASR的心脏保护作用。通过流式细胞术、蛋白质免疫印迹法和小干扰RNA（siRNA）转染，在H9c2心肌细胞中证实TAC诱导1周后这些治疗的抗炎作用，以及主要成分绿原酸（CGA）的心脏保护和抗炎作用。
LJF、ASR和LJF+ASR增强了心脏收缩功能，改善了TAC诱导的心脏病理重塑。此外，这些化合物在不同程度上抑制了早期HF中的血小板-粒细胞聚集、血小板-单核细胞聚集、钙调蛋白依赖性蛋白激酶IIδ（CaMKIIδ）/核因子-κB（NF-κB）信号通路和促炎因子水平。此外，在LJF+ASR的水提取物和吸收入血成分中鉴定出9种潜在有效成分，并且CGA在体外抑制CaMKIIδ/NF-κB信号通路并降低促炎因子水平。
LJF、ASR、LJF+ASR和CGA抑制CaMKIIδ/NF-κB信号通路，可能是减轻HF早期炎症和改善晚期心脏功能的新型治疗药物。
