Wang Changbin, Jiang Xiaoli, Han Shuhua, Zang Huimei, Gao Xiaoyuan
Department of Cardiology, The First Rongjun Youfu Hospital of Shandong Province, No. 23 Jiefang Road, Jinan, 25000, China.
Station for Fengming Community Health Service, People's Hospital of Zhoucun District, No. 999 Hengxing Road, Zibo, 255300, China.
J Nat Med. 2025 May 10. doi: 10.1007/s11418-025-01911-9.
Loganin (LG), a natural compound derived from Cornus officinalis Sieb. et Zucc., possesses diverse pharmacological properties, such as anti-inflammatory, anti-hypertrophic, and antioxidant effects. However, the role of LG in the pathogenesis of Heart Failure (HF) remains unclear. The current work aimed to explore the underlying mechanism of LG in pressure overload-induced HF, both in vivo and in vitro, using transverse aortic constriction (TAC) surgery or isoproterenol (ISO) administration. Following eight weeks of TAC surgery, histological assessments, including hematoxylin and eosin staining, wheat germ agglutinin staining, TUNEL assay, and Masson's trichrome staining, were conducted to evaluate the extent of cardiomyocyte remodeling. Additionally, RT-PCR and WB analyses were performed to detect the levels of various targets. Furthermore, H9C2 cardiomyocytes were treated with ISO to induce hypertrophy, and the effects of LG on cell viability, α-smooth muscle actin (α-SMA) expression, and molecular targets were investigated. Our findings revealed that LG treatment at 40 mg/kg/day significantly attenuated cardiac dysfunction, decreased left ventricular collagen deposition in both interstitial and perivascular spaces. Mechanistically, LG mitigated ISO-induced toxicity in H9C2 cardiomyocytes, decreasing cellular hypertrophy and α-SMA expression. Moreover, we observed a downregulation of Sirtuin 1 (Sirt1) at the molecular level, accompanied by reduced phosphorylation of Akt and transforming growth factor-β1 (TGF-β1). Notably, the administration of the Sirt1 inhibitor, EX527, effectively abolished the protective effects of LG. Therefore, the cardio-protective effects of LG were mediated through the activation of the Sirt1/Akt/TGF-β1 signaling pathway, leading to reduced fibrosis and improved cardiac function.
马钱苷（LG）是一种从山茱萸中提取的天然化合物，具有多种药理特性，如抗炎、抗肥大和抗氧化作用。然而，LG在心力衰竭（HF）发病机制中的作用仍不清楚。目前的研究旨在通过横向主动脉缩窄（TAC）手术或给予异丙肾上腺素（ISO），在体内和体外探索LG在压力超负荷诱导的HF中的潜在机制。在TAC手术八周后，进行了组织学评估，包括苏木精和伊红染色、麦胚凝集素染色、TUNEL检测和Masson三色染色，以评估心肌细胞重塑的程度。此外，进行了RT-PCR和WB分析以检测各种靶点的水平。此外，用ISO处理H9C2心肌细胞以诱导肥大，并研究LG对细胞活力、α-平滑肌肌动蛋白（α-SMA）表达和分子靶点的影响。我们的研究结果表明，每天40mg/kg的LG治疗可显著减轻心脏功能障碍，减少左心室间质和血管周围间隙的胶原沉积。从机制上讲，LG减轻了ISO诱导的H9C2心肌细胞毒性，减少了细胞肥大和α-SMA表达。此外，我们在分子水平上观察到沉默调节蛋白1（Sirt1）的下调，同时Akt和转化生长因子-β1（TGF-β1）的磷酸化减少。值得注意的是，给予Sirt1抑制剂EX527有效地消除了LG的保护作用。因此，LG的心脏保护作用是通过激活Sirt1/Akt/TGF-β1信号通路介导的，从而减少纤维化并改善心脏功能。
