Study on the protective effects of danshen-honghua herb pair (DHHP) on myocardial ischaemia/reperfusion injury (MIRI) and potential mechanisms based on apoptosis and mitochondria

Pharm Biol. 2021 Dec;59(1):335-346. doi: 10.1080/13880209.2021.1893346.

Abstract

Context: Danshen, the dried root and rhizome of Salvia miltiorrhiza Bunge (Labiatae) and honghua, the dried flower of Carthamus tinctorius L. (Compositae) as the herb pair was used to treat cardiovascular diseases (CVD).

Objective: To study the effects of DHHP on MIRI and mechanisms based on apoptosis and mitochondria.

Materials and methods: 36 SD rats (n = 6) were randomly divided into control group (Con), the ischaemia-reperfusion group (IR), positive control (Xinning tablets, XNT, 1 g/kg/d) and DHHP (1.2, 2.4, and 4.8 g/kg/d). Except for Con, the other groups were intragastrically administrated for 5 d, the rat hearts were isolated to establish the MIRI model in vitro for evaluating the effects of DHHP on MIRI. 24 SD rats (n = 6) were randomly divided into Con, IR, DPPH2.4 (2.4 g/kg/d) and DPPH 2.4 + Atractyloside (ATR) (2.4 + 5 mg/kg/d), administered intragastrically for 5 d, then treated with ATR (5 mg/kg/d) by intraperitoneal injection in DPPH2.4 + ATR group, took rat hearts to establish MIRI model in vitro for revealing mechanism.

Results: Myocardial infarct sizes were, respectively, 0.35%, 40.09%, 15.84%, 30.13%, concentrations of NAD+ (nmol/gw/w) were 144, 83, 119, and 88, respectively, in Con, IR, DHHP2.4, DHHP2.4 + ATR group. Cleaved caspase-3 were 0.3, 1.6, 0.5 and 1.3% and cleaved caspase-9 were 0.2, 1.1, 0.4 and 0.8%, respectively, in Con, IR, DHHP2.4 and DHHP2.4 + ATR group. The beneficial effects of DHHP on MIRI were reversed by ATR.

Conclusions: The improvement of MIRI by DHHP may be involved in inhibiting MPTP opening, decreasing oxidative damage, alleviating ischaemic injury and inhibiting cardiomyocyte apoptosis.

Keywords: Extracts of Chinese medicine; cardiomyocyte apoptosis; myocardial injury; myocardial mitochondria.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Carthamus tinctorius
  • Cell Line
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / pharmacology*
  • Male
  • Mitochondria / drug effects
  • Mitochondrial Permeability Transition Pore / metabolism
  • Myocardial Infarction / prevention & control*
  • Myocardial Reperfusion Injury / drug therapy*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / pathology
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Salvia miltiorrhiza

Substances

  • Drugs, Chinese Herbal
  • Mitochondrial Permeability Transition Pore
  • dan-shen root extract
  • Honghua extract, Carthamus tinctorius

Grants and funding

This work was supported by the National Natural Science Foundation of China (CN) [81974544; 81573624], the Project on Social Development of Shaanxi Provincial Science and Technology Department [2019SF-286], the Key Laboratory Project of Shaanxi Provincial Department of Education [18JS025].