2. Academic Validation
  3. Tongmai Yangxin pill alleviates myocardial no-reflow by activating GPER to regulate HIF-1α signaling and downstream potassium channels

Tongmai Yangxin pill alleviates myocardial no-reflow by activating GPER to regulate HIF-1α signaling and downstream potassium channels

  • Pharm Biol. 2023 Dec;61(1):499-513. doi: 10.1080/13880209.2023.2184481.
Ting Chen 1 2 3 4 5,  Yulong Zhang 2 3 4,  Manyun Chen 2 3 4,  Pu Yang 6,  Yi Wang 5,  Wei Zhang 1,  Weihua Huang 2 3 4,  Wei Zhang 2 3 4
Affiliations

Affiliations

  • 1 Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China.
  • 2 Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, People's Republic of China.
  • 3 Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, People's Republic of China.
  • 4 Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, People's Republic of China.
  • 5 Institute of Traditional Chinese medicine, Tianjin University of Traditional Chinese medicine, Tianjin, People's Republic of China.
  • 6 Department of General Surgery, Xiangya Hospital, Central South University, Changsha, People's Republic of China.
PMID: 36896463 DOI: 10.1080/13880209.2023.2184481
Abstract

Context: The Tongmai Yangxin pill (TMYX) has potential clinical effects on no-reflow (NR); however, the effective substances and mechanisms remain unclear.

Objective: This study evaluates the cardioprotective effects and molecular mechanisms of TMYX against NR.

Materials and methods: We used a myocardial NR rat model to confirm the effect and mechanism of action of TMYX in alleviating NR. Sprague-Dawley (SD) rats were divided into Control (Con), sham, NR, TMYX (4.0 g/kg), and sodium nitroprusside (SNP, 5.0 mg/kg), and received their treatments once a day for one week. In vitro studies in isolated coronary microvasculature of NR rats and in silico network pharmacology analyses were performed to reveal the underlying mechanisms of TMYX and determine the main components, targets, and pathways of TMYX, respectively.

Results: TMYX (4.0 g/kg) showed therapeutic effects on NR by improving the cardiac structure and function, reducing NR, ischemic areas, and cardiomyocyte injury, and decreasing the expression of cardiac troponin I (cTnI). Moreover, the mechanism of TMYX predicted by network pharmacology is related to the HIF-1, NF-κB, and TNF signaling pathways. In vivo, TMYX decreased the expression of MPO, NF-κB, and TNF-α and increased the expression of GPER, p-ERK, and HIF-1α. In vitro, TMYX enhanced the diastolic function of coronary microvascular cells; however, this effect was inhibited by G-15, H-89, L-NAME, ODQ and four K+ channel inhibitors.

Conclusions: TMYX exerts its pharmacological effects in the treatment of NR via multiple targets. However, the contribution of each pathway was not detected, and the mechanisms should be further investigated.

Keywords

Cardioprotective effects; coronary microvasculature; molecular mechanisms; network pharmacology.

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