Effect of tetramethylpyrazine and hyperlipidemia on hepcidin homeostasis in mice

Abstract

Iron homeostasis is strictly regulated in mammals, and disordered iron metabolism is recognized as a risk factor for various diseases, including cardiovascular disease. The hepcidin-ferroportin axis is the key signaling mechanism that controls systemic iron homeostasis. Increased serum hepcidin is associated with multiple types of cancer and atherosclerosis (AS), and therapeutics that decrease hepcidin levels have been proposed to treat these diseases. However, the effects of abnormal circulating hepcidin on hyperlipidemia remain unexploited. The natural compound tetramethylpyrazine (TMP) has been reported to have therapeutic effects on cardiovascular diseases, whereas the mechanisms involved remain incompletely understood. Thus, the effects of TMP on the expression of hepcidin in hyperlipidemic mice were investigated and the mechanisms involved were explored. Hyperlipidemia increased serum hepcidin, which was inhibited by TMP intervention. The results also indicated that TMP may decrease hepcidin expression via inhibition of Stat3 signaling. These findings suggest a promising rationale to prevent and hyperlidemia by targeting hepcidin or its upstream regulators, and highlight the potential application of natural compounds in treating hepcidin disorder-associated diseases.

Ferroptosis and metabolic syndrome and complications: association, mechanism, and translational applications

“…Moreover, hepcidin is a hormonal regulator of iron homeostasis. Zhang et al ( 135 ). found that the serum hepcidin was elevated in a hyperlipidemia model, which suggests the iron burden in hyperlipidemia may be connected to an unbalanced hepcidin-FPN axis.…”