Pharmacological Effects of Salvianolic Acid B Against Oxidative Damage

Abstract

Salvianolic acid B (Sal B) is one of the main active ingredients of Salvia miltiorrhiza, with strong antioxidant effects. Recent findings have shown that Sal B has anti-inflammatory, anti-apoptotic, anti-fibrotic effects and can promote stem cell proliferation and differentiation, and has a beneficial effect on cardiovascular and cerebrovascular diseases, aging, and liver fibrosis. Reactive oxygen species (ROS) include oxygen free radicals and oxygen-containing non-free radicals. ROS can regulate cell proliferation, survival, death and differentiation to regulate inflammation, and immunity, while Sal B can scavenge oxygen free radicals by providing hydrogen atoms and reduce the production of oxygen free radicals and oxygen-containing non-radicals by regulating the expression of antioxidant enzymes. The many pharmacological effects of Sal B may be closely related to its elimination and inhibition of ROS generation, and Nuclear factor E2-related factor 2/Kelch-like ECH-related protein 1 may be the core link in its regulation of the expression of antioxidant enzyme to exert its antioxidant effect. What is confusing and interesting is that Sal B exhibits the opposite mechanisms in tumors. To clarify the specific target of Sal B and the correlation between its regulation of oxidative stress and energy metabolism homeostasis will help to further understand its role in different pathological conditions, and provide a scientific basis for its further clinical application and new drug development. Although Sal B has broad prospects in clinical application due to its extensive pharmacological effects, the low bioavailability is a serious obstacle to further improving its efficacy in vivo and promoting clinical application. Therefore, how to improve the availability of Sal B in vivo requires the joint efforts of many interdisciplinary subjects.

Keywords: Keap1; Nrf2; ROS; oxidative damage; salvianolic acid B.

FIGURE 1

The molecular structural of salvianolic acid B (Sal B) and magnesium tanshinoate B (MTB). (A) Sal B, PubChem substance SID: 6451084; (B) MTB, PubChem substance SID: 13507533.

FIGURE 2

Pharmacological effects of salvianolic acid B (Sal B) and magnesium tanshinoate B (MTB).

FIGURE 3

Reactive oxygen species (ROS) and Peroxidation Damage. Tumor necrosis factor (TNF)-α and EGF can regulate ROS production of mitochondria and NADPH oxidase (NOX)-catalyze by binding the corresponding membrane receptors. Under physiological conditions, ROS can also regulate Nuclear factor E2-related factor 2/Kelch-like ECH-related protein 1 through the phosphatidylinositol 3-kinase pathway to increase the expression of antioxidant enzymes, inhibit ROS accumulation, and maintain redox balance. Under pathological conditions, excess ROS can regulate cell survival, growth, metabolism, differentiation, proliferation, and apoptosis by Nuclear factor κB (NF-κB), HIF1α, Mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase and other pathways.

FIGURE 4

Pharmacological mechanisms of Salvianolic acid B (Sal B) based on antioxidant effect. Sal B can inhibit the expressions of Tumor necrosis factor (TNF)-α, Cyclooxygenase (COX2) and NADPH oxidase (NOS) by inhibiting TNF-α/Nuclear factor κB (NF-κB) and Toll-like receptor (TLR4)/NF-κ-B pathways, and promote the expression of antioxidant enzymes such as Heme oxygenase-1 (HO-1), NQOD, Superoxide dismutase (SOD) and inhibit the expression of oxidases such as NOX-2, NOX-4, Poly (ADP-ribozyme) polymerase 1 (PARP-1) by the Nuclear factor E2-related factor 2/Kelch-like ECH-related protein 1 pathway, and then inhibit Reactive oxygen species (ROS) generation, improve inflammation, cell apoptosis, autophagy, fibrosis, microcirculation disorders, and stem cell proliferation and differentiation.

FIGURE 5

Mechanisms of Salvianolic acid B (Sal B) in different chronic inflammatory diseases. In addition to increasing the expression of antioxidant enzymes such as Superoxide dismutase (SOD), CAT, GSH, and reducing the expression of oxidative enzymes such as Cyclooxygenase (COX-2), NADPH oxidase (NOX)-4, iNOS to inhibit the generation of Reactive oxygen species (ROS) and malondialdehyde (MDA), Sal B has been shown to improve chronic inflammation in a variety of disease models, suggesting that its anti-inflammatory and antioxidant effects are closely related.