Zhong Wanru, Li Yihua, Zhong Haixiang, Cheng Yuanyuan, Chen Qi, Zhao Xinjun, Liu Zhongqiu, Li Rong, Zhang Rong
Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, School of Pharmaceutical Sciences, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
The first clinical medical college, Guangzhou University of Chinese Medicine, Guangzhou, China.
Front Pharmacol. 2023 Feb 13;14:1111007. doi: 10.3389/fphar.2023.1111007. eCollection 2023.
Qiweiqiangxin І granules (QWQX І) is a traditional Chinese medicine preparation based on the basic theory of traditional Chinese medicine, which produces a good curative effect in treating chronic heart failure (CHF). However, its pharmacological effect and potential mechanism for CHF remain unknown. The purpose of this study is to clarify the efficacy of QWQX І and its possible mechanisms. A total of 66 patients with CHF were recruited and randomly assigned to the control or QWQX І groups. The primary endpoint was the effect of left ventricular ejection fraction (LVEF) after 4 weeks of treatment. The LAD artery of rats was occluded to establish the model of CHF. Echocardiography, HE and Masson staining were performed to evaluate the pharmacological effect of QWQX І against CHF. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) untargeted metabolomics was to screen endogenous metabolites in rat plasma and heart and elucidate the mechanism of QWQX І against CHF. Results: In the clinical study, a total of 63 heart failure patients completed the 4-week follow-up, including 32 in the control group and 31 in QWQX І group. After 4 weeks of treatment, LVEF was significantly improved in QWQX І group compared with the control group. In addition, the patients in QWQX І group had better quality of life than the control group. In animal studies, QWQX І significantly improved cardiac function, decreased B-type natriuretic peptide (BNP) levels, reduced inflammatory cell infiltration, and inhibited collagen fibril rate. Untargeted metabolomic analysis revealed that 23 and 34 differential metabolites were screened in the plasma and heart of chronic heart failure rats, respectively. 17 and 32 differential metabolites appeared in plasma and heart tissue after QWQX І treatment, which were enriched to taurine and hypotaurine metabolism, glycerophospholipid metabolism and linolenic acid metabolism by KEGG analysis. LysoPC (16:1 (9Z)) is a common differential metabolite in plasma and heart, which is produced by lipoprotein-associated phospholipase A2 (Lp-PLA2), hydrolyzes oxidized linoleic acid to produce pro-inflammatory substances. QWQX І regulates the level of LysoPC (16:1 (9Z)) and Lp-PLA2 to normal. QWQX І combined with western medicine can improve the cardiac function of patients with CHF. QWQX І can effectively improve the cardiac function of LAD-induced CHF rats through regulating glycerophospholipid metabolism and linolenic acid metabolism-mediated inflammatory response. Thus, QWQX I might provide a potential strategy for CHF therapy.
芪苈强心Ⅰ号颗粒（QWQXⅠ）是一种基于中医基础理论的中药制剂，在治疗慢性心力衰竭（CHF）方面产生了良好的疗效。然而，其对CHF的药理作用和潜在机制仍不清楚。本研究的目的是阐明QWQXⅠ的疗效及其可能的机制。共招募了66例CHF患者，并随机分为对照组或QWQXⅠ组。主要终点是治疗4周后左心室射血分数（LVEF）的变化。通过结扎大鼠左前降支动脉建立CHF模型。采用超声心动图、HE和Masson染色来评估QWQXⅠ对CHF的药理作用。运用超高效液相色谱-四极杆飞行时间质谱（UPLC-QTOF/MS）非靶向代谢组学技术筛选大鼠血浆和心脏中的内源性代谢物，并阐明QWQXⅠ抗CHF的机制。结果：在临床研究中，共有63例心力衰竭患者完成了4周的随访，其中对照组32例，QWQXⅠ组31例。治疗4周后，QWQXⅠ组的LVEF较对照组显著改善。此外，QWQXⅠ组患者的生活质量优于对照组。在动物研究中，QWQXⅠ显著改善了心脏功能，降低了B型利钠肽（BNP）水平，减少了炎性细胞浸润，并抑制了胶原纤维率。非靶向代谢组学分析显示，在慢性心力衰竭大鼠的血浆和心脏中分别筛选出23种和34种差异代谢物。QWQXⅠ治疗后，血浆和心脏组织中分别出现17种和32种差异代谢物，经KEGG分析这些差异代谢物富集于牛磺酸和低牛磺酸代谢、甘油磷脂代谢和亚麻酸代谢。溶血磷脂酰胆碱（LysoPC，16:1（9Z））是血浆和心脏中常见的差异代谢物，由脂蛋白相关磷脂酶A2（Lp-PLA2）产生，可水解氧化型亚油酸产生促炎物质。QWQXⅠ将LysoPC（16:1（9Z））和Lp-PLA2的水平调节至正常。QWQXⅠ联合西药可改善CHF患者的心脏功能。QWQXⅠ可通过调节甘油磷脂代谢和亚麻酸代谢介导的炎症反应有效改善左前降支诱导的CHF大鼠的心脏功能。因此，QWQXⅠ可能为CHF治疗提供一种潜在策略。
