Protective Effects of Caesalpinia sappan Linn. and Its Bioactive Compounds on Cardiovascular Organs

Abstract

Cardiovascular diseases are the leading cause of death worldwide. The long-term aim of cardiovascular disease therapy is to reduce the mortality rate and decelerate the progression of cardiovascular organ damage. Current therapies focus on recovering heart function and reducing risk factors such as hyperglycemia and dyslipidemia. However, oxidative stress and inflammation are important causes of further damage to cardiovascular organs. Caesalpinia sappan Linn. (Fabaceae), a flowering tree native to tropical Asia, has antioxidant and anti-inflammatory properties. It is used as a natural dye to color food and beverages and as a traditional treatment for diarrhea, diabetes, and blood stasis. The phytochemical compounds in C. sappan, mainly the homoisoflavonoids brazilin, sappanone A, protosappanin, and hematoxylin, can potentially be used to protect cardiovascular organs. This review aims to provide updates on recent developments in research on C. sappan in relation to treatment of cardiovascular diseases. Many studies have reported protective effects of the plant's bioactive compounds that reduce cardiac damage and enhance vasorelaxation. For example, brazilin and sappanone A have an impact on molecular and cellular changes in cardiovascular disease pathogenesis, mainly by modulating oxidative, inflammatory, and apoptotic signaling pathways. Therefore, bioactive compounds of C. sappan have the potential to be developed as therapeutic agents to combat cardiovascular diseases like myocardial infarction and vascular disease. This review could help further the understanding of the possible modulatory role of the compounds in cardiovascular diseases, thereby facilitating future studies.

Keywords: Caesalpinia sappan; brazilein; brazilin; heart; ischemia/reperfusion injury; sappanone A; vascular; vasorelaxation.

FIGURE 1

Chemical structures of major metabolites isolated from Caesalpinia sappan.

FIGURE 2

Possible sites of action of Caesalpinia sappan bioactive compounds in myocardial injury. Akt, protein kinase B; AMP, adenosine monophosphate; ARE, antioxidant responsive element; AST, aspartate transaminase; ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; CK-MB, creatin kinase MB; GSK-3β, glycogen synthase kinase-3β; HO, heme oxygenase; JAK, Janus kinase; Keap1, Kelch-like ECH-associated protein 1; LDH, lactate dehydrogenase; mPTP, mitochondrial permeability transition pore; Na⁺/K⁺-ATPase, sodium potassium ATPase; NCX, sodium-calcium exchanger; Nrf2, nuclear factor erythroid 2-related factor 2; NQO1, NAD(P)H quinone oxidoreductase 1; PDE, phosphodiesterase; PI3K, phosphatidylinositol 3-kinase; PKA, protein kinase A; PKC, protein kinase C; ROS, reactive oxygen species; RyR, ryanodine receptor; SERCA, sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase; STAT3, signal transducer and activator of transcription 3; XO, xanthine oxidase; ⊥, suppression; +, stimulates; −, inhibits.

FIGURE 3

Possible sites of action of Caesalpinia sappan bioactive compounds in vascular.AA, arachidonic acid; ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; COX, cyclooxygenase; eNOS, endothelial nitric oxide synthase; ER, endoplasmic reticulum; ERK, extracellular signal-regulated kinase; GTP, guanosine-5′-triphosphate; ICAM, intercellular adhesion molecule; IP3, inositol trisphosphate; K_ATP channel, ATP-sensitive potassium channel; L-Arg, l-arginine; MAPK, mitogen activated protein kinase; MLC, myosin light chain kinase; pMLC, phosphorylated myosin light chain; NF-κB, nuclear factor-κB; NO, nitric oxide; PGH₂, prostaglandin H₂; PGI₂, prostacyclin; PKC, protein kinase C; PLC, phospholipase C; ROCK, Rho kinase; ROS, reactive oxygen species; RyR, ryanodine receptor; SERCA, sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase; sGC, soluble guanylate cyclase; SR, sarcoplasmic reticulum; TXA₂, thromboxane A₂; VCAM, vascular cell adhesion molecule; ⊥, suppression; +, stimulates; −, inhibits.