Salvia miltiorrhiza (Danshen) Injection Ameliorates Iron Overload-Induced Cardiac Damage in Mice

Abstract

The traditional Chinese medicinal herb Danshen (Salvia miltiorrhiza), first recorded in the "Shen Nong's Herbal Classic", has long been used to treat cardiovascular conditions, although the mechanism(s) underlying its effects remain unclear. Here, an iron dextran injection (50 mg · kg⁻¹ per day) was delivered intraperitoneally to establish a mouse model for investigating the ameliorative effects of Danshen injection (low dose at 3 g · kg⁻¹ per day or high dose at 6 g · kg⁻¹ per day) on iron overload-induced cardiac damage. The iron-chelating agent deferoxamine (100 mg · kg⁻¹ per day) was administered as a positive control. The main constituents of Danshen injection, salvianic acid A (danshensu), protocatechuic aldehyde, and salvianolic acid B, were quantified at concentrations of 2.15, 0.44, and 1.01 mg · mL⁻¹, respectively, using HPLC with UV detection. Danshen injection significantly lowered cardiac iron deposition and the concentration of the lipid oxidation product malondialdehyde, as well as improved cardiac superoxide dismutase and glutathione peroxidase levels in iron-overloaded mice. Serum levels of creatine kinase, creatine kinase isoenzyme, and lactate dehydrogenase in the iron-overloaded mice were significantly elevated (up to ~ 160 %), whereas their activities were downregulated by Danshen injection by 25 ~ 35 % at the high dose and by ~ 20 % at the low dose. Morphological changes of cardiac tissue analyzed by hematoxylin and eosin staining indicated that lesions induced by iron overload could be ameliorated by Danshen injection dose-dependently. Altogether, these results illustrated that the protective effects of Danshen injection were at least in part due to decreased iron deposition and inhibition of lipid peroxidation.

Magnesium isoglycyrrhizinate ameliorates doxorubicin‑induced acute cardiac and hepatic toxicity via anti‑oxidant and anti‑apoptotic mechanisms in mice

“…The serum levels of AST and ALT increase rapidly when liver cells are damaged by inflammation, necrosis or poisoning (26). It was demonstrated that serum levels of AST and ALT in the MgIG-treatment groups were significantly lower than in the DOX group, indicating that MgIG exerts its protective effects in the liver by regulating the activity of AST and ALT.…”

Current and future treatment strategies for iron overload cardiomyopathy

“…1. Many novel studies have shown that antioxidant compounds decrease cardiac oxidative stress (Zhang et al, 2013), increase cardiac antioxidant levels (Zhang et al, 2013), decrease cardiac iron deposition (Kramer et al, 2012;Lin et al, 2013;Thephinlap et al, 2011;Zhang et al, 2013) and improve cardiac dysfunction in iron-overload induced cardiomyopathy in animal models (Kramer et al, 2012;Lin et al, 2013;Thephinlap et al, 2011;Zhang et al, 2013). Table 4 summarizes the therapeutic agents with antioxidative effect which have been shown to provide cardioprotection under iron overload condition.…”

“…For example, Danshen is known to exert potent antioxidative effects in treating diabetes and cardiovascular disease especially chronic heart failure (Cheng, 2007;Liu et al, 2015;Wang et al, 2006). Danshen injection has been shown to exert as effectively as DFO in reducing cardiac iron deposition, leading to the reduction of iron overload-induced cardiac damage in mice (Zhang et al, 2013). This benefit could be due partly to its antioxidative effects.…”

“…The possible mechanisms of the antioxidant therapies that enable them to improve heart dysfunction induced by conditions of iron overload are probably due to their antioxidative effects (Kramer et al, 2012;Lin et al, 2013;Musumeci et al, 2013;Thephinlap et al, 2011;Zhang et al, 2013) and ability to chelate free iron in cells, such as NAC (Banner et al, 1986;Flora, 2009) and curcumin (Nazari et al, 2013). However, further large clinical 13 trials are needed to elucidate the protective effects of antioxidant therapy, particularly in patients with iron overload in heart tissue.…”

Salvia miltiorrhizaInjection Ameliorates Renal Damage Induced by Lead Exposure in Mice

“…Recent studies have highlighted the diversity of potential effects of SM in attenuating microcirculatory disturbances, including antioxidation, inhibition of apoptosis, and amelioration of injury to target organs such as the kidney [4]. And our recent studies have found that SM injection could protect against cardiac damage, liver injury, hepatic fibrosis, and kidney injury induced by acute or chronic iron overload [5–8]. So we deduced that SM may have a protective effect on the renal damage induced by divalent heavy metal poisoning.…”