State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China.
The Clinical Metabolomics Center, China Pharmaceutical University, Nanjing, Jiangsu, China.
J Ethnopharmacol. 2021 Apr 24;270:113646. doi: 10.1016/j.jep.2020.113646. Epub 2020 Nov 29.
As a classic herbal prescription, Huanglian Jiedu Decoction (HLJDD) exhibits positive effects against cardiac dysfunction. However, its cardioprotective effects and potential mechanism(s) of action still need to be systematically investigated.
This study aimed to reveal the underlying therapeutic mechanism of HLJDD on transverse aortic constriction (TAC)-induced pathological cardiac hypertrophy and remodeling.
TAC-induced cardiac hypertrophy and remodeling mice model was established to evaluate the therapeutic effects of HLJDD. Serum untargeted metabolomics and lipidomic profiling were performed using ultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry coupled with multivariate statistical analyses.
Oral administration of HLJDD (2.5 g/kg/day, 5.0 g/kg/day) significantly improved the heart morphology, enhanced the heart function, and alleviated the accumulation of fibrosis in the interstitial space and the infiltration of inflammatory cells in TAC-stimulated mice. Serum untargeted metabolomics analysis showed that significant alterations were observed in metabolic signatures between the TAC-model and sham group. Principal component analysis and orthogonal partial least-squares discriminant analysis screened 59 differential metabolic features and 13 metabolites were identified. The disturbed metabolic pathways in TAC group mainly related to lipid metabolism. Further serum lipidomic profiling showed that most lipids including cholesterol esters, ceramides, glycerides, fatty acids and phospholipids were decreased in TAC group and these alterations were reversed after HLJDD intervention.
HLJDD alleviates TAC-induced pathological cardiac hypertrophy and remodeling, and its potential therapeutic mechanism involves the regulation of lipid metabolism.
黄连解毒汤（HLJDD）作为经典的草药方剂，对心功能障碍具有积极作用。然而，其心脏保护作用及其潜在的作用机制仍需系统研究。
本研究旨在揭示 HLJDD 对主动脉缩窄（TAC）诱导的病理性心肌肥厚和重构的潜在治疗机制。
建立 TAC 诱导的心肌肥厚和重构小鼠模型，以评估 HLJDD 的治疗效果。采用超高效液相色谱-四极杆飞行时间质谱联用多变量统计分析方法进行血清非靶向代谢组学和脂质组学分析。
HLJDD（2.5 g/kg/天，5.0 g/kg/天）口服给药可显著改善心脏形态，增强心脏功能，并减轻 TAC 刺激小鼠间质纤维化的积累和炎症细胞浸润。血清非靶向代谢组学分析显示，TAC 模型组与假手术组之间的代谢特征存在显著差异。主成分分析和正交偏最小二乘判别分析筛选出 59 个差异代谢特征，鉴定出 13 种代谢物。TAC 组中受干扰的代谢途径主要与脂质代谢有关。进一步的血清脂质组学分析显示，胆固醇酯、神经酰胺、甘油酯、脂肪酸和磷脂等大多数脂质在 TAC 组中减少，而这些变化在 HLJDD 干预后得到逆转。
HLJDD 可减轻 TAC 诱导的病理性心肌肥厚和重构，其潜在的治疗机制涉及脂质代谢的调节。
