Advances in research on the protective mechanisms of traditional Chinese medicine (TCM) in myocardial ischaemia-reperfusion injury

Abstract

Context: Developing effective drugs to treat myocardial ischaemia-reperfusion (MI/R) injury is imperative. Traditional Chinese medicines (TCMs) have had considerable success in the treatment of cardiovascular diseases. Elucidating the mechanisms by which TCMs improve MI/R injury can supplement the literature on MI/R prevention and treatment.

Objective: To summarise TCMs and their main protective mechanisms against MI/R injury reported over the past 40 years.

Methods: Relevant literature published between 1980 and 2020 in Chinese and English was retrieved from the Web of Science, PubMed, SpringerLink, PubMed Central, Scopus, and Chinese National Knowledge Infrastructure (CNKI) databases. Search terms included 'medicinal plants', 'myocardial ischaemia reperfusion injury', 'Chinese medicine prescriptions', 'mechanisms', 'prevention', 'treatment' and 'protection'. For inclusion in the analysis, medicinal plants had to be searchable in the China Medical Information Platform and Plant Database.

Results: We found 71 medicinal species (from 40 families) that have been used to prevent MI/R injury, of which Compositae species (8 species) and Leguminosae species (7 species) made up the majority. Most of the effects associated with these plants are described as antioxidant and anti-inflammatory. Furthermore, we summarised 18 kinds of Chinese compound prescriptions, including the compound Danshen tablet and Baoxin pill, which mainly reduce oxidative stress and regulate mitochondrial energy metabolism.

Discussion and conclusions: We summarised TCMs that protect against MI/R injury and their pharmacological mechanisms. This in-depth explanation of the roles of TCMs in MI/R injury protection provides a theoretical basis for the research and development of TCM-based treatment drugs.

Keywords: Chinese compound prescriptions; Compositae; anti-inflammatory; antioxidative; flavonoids.

Figure 1.

Overview of the pathophysiological mechanisms in MI/R injury affected by TCMs. ① Inhibit the NLRP3 inflammasome: Carthamus tinctorius L., Erigeron breviscapus (Vant.) Hand.-Mazz., Artemisia annua L. ② Reduce production of inflammatory cytokines, such as TNF-α, IL-6, IL-8: Eclipta prostrata L., Bidens Pilosa L., Pueraria lobata (Willd.) Ohwi, Glycyrrhiza uralensis Fisch., Plumbago zeylanica L., Rosa rugosa Thunb., Dioscorea zingiberensis C. H. Wright, Valeriana officinalis L., Tribulus terrestris L. ③ Regulate the release of NO: Eclipta prostrata L., Rubiayunnanensis (Franch.) Diels, Fagopyrum tataricum (L.), Rhododendron simsii Planch. ④ Block NF-κB activation pathway: Erigeron multiradiatus (Lindl.) Benth., Bacopa monnieri (Linn.) Wettst., Gynostemma pentaphyllum (Thunb.) Makino, Cyperus rotundus L., Sinomenium acutum (Thunb.) Rehd. et Wils., Astragalus membranaceus (Fish.) Bge., Abelmoschus manihot L. ⑤ Through PI3K/Akt signalling pathways: Salvia miltiorrhiza Bge., Fibraurea recisa Pierre., Citrus reticulata blanco, Cyperus rotundus L., Myrica rubra (Lour.) Sieb.et Zucc., Ginkgo biloba L., Ilex pubescens Hook.et Arn. ⑥ Block p38/ERK MAPK pathway: Bacopa monnieri (Linn.) Wettst., Fibraurea recisa Pierre., Gynostemma pentaphyllum (Thunb.) Makino, Cyperus rotundus L., Draba nemorosa L., Gastrodia elata Bl., Diospyros kaki Thunb. ⑦ Activate AMPK/GSK-3β signalling pathway: Carthamus tinctorius L., Aloe barbadensis Miller. ⑧ Regulate RhoA signalling pathway: Panax ginseng C. A. Mey. ⑨ Activate the Nrf2/ARE/HO-1 signal pathway: Dalbergia odorifera T. Chen., Rheum palmatum L. ⑩ Scavenging ROS: Cassia mimosoides L., Bidens pilosa L., Arctium lappa L., Fagopyrum tataricum (L.), Panax notoginseng (Burk.) F. H. Chen, Plumbago zeylanica L., Magnolia officinalis Rehd.et Wils., Acanthopanax senticosus (Rupr.et maxim) Harms, Lentinus edodes (Berk.) Sing., Cuscuta chinensis Lam., Bombax malabaricum L., Tribulus terrestris L., Rhododendron simsii Planch. ⑪ Enhance the activity of antioxidant enzymes, such as SOD, CAT, glutathione peroxidase: Diospyros kaki Thunb., Glycyrrhiza uralensis Fisch., Sophora japonica L., Bauhinia championii (Benth.) Benth., Eclipta prostrata L., Silybum marianum (Linn.) Gaertn., Polygonum multiflorum Thunb., Citrus maxima (Burm.) Merr., Panax notoginseng (Burk.) F. H. Chen, Rosa rugosa Thunb., Schisandra chinensis (Turcz.) Ball, Galium verum L., Andrographis paniculata (Burm.F.) nees, Valeriana officinalis L., Cinnamomum cassia Presl, Malva sinensis Cav. ⑫ Reduce Ca²⁺ overload: Mollugo pentaphylla L. ⑬ Activate the mitoKATP channel: Citrus maxima (Burm.) Merr., Dioscorea zingiberensis C. H. Wright, Hypericum monogynum L. ⑭ Improve mitochondrial energy metabolism: Crataegus pinnatifida Bge., Dracocephalum moldavica L., Polygonatum odoratum (Mill.) Druce, Rubiayunnanensis (Franch.) Diels. ⑮ Activate ALDH2 to protect mitochondrial function: Piper longum Linn. ⑯ Prevent the apoptotic cascade: Cassia mimosoides L., Astragalus membranaceus (Fish.) Bge., Pueraria lobata (Willd.) Ohwi, Curcuma longa L., Tribulus terrestris L., Morus alba L. ⑰ Activate sirtuin-1/FOXO1 signal: Epimedium brevicornu Maxim., Paeonia veitchii Lynch. ⑱ Inhibit ATF6 and PERK pathways to attenuate ERS: Dracaena cochinchinensis (Lour.) S. C. Chen, Allium fistulosum L., Schisandra chinensis (Turcz.) Ball, Paeonia lactiflora Pall. ⑲ Inhibit autophagy: Coptis chinensis Franch., Magnolia officinalis Rehd.et Wils., Gardenia jasminoides Ellis. ⑳ Inhibit necrosis: Scutellaria baicalensis Ceorgi, Arctium lappa L., Bauhinia championii (Benth.) Benth.