Kai‑Xin‑San suppresses matrix metalloproteinases and myocardial apoptosis in rats with myocardial infarction and depression

Abstract

depression is often triggered by prolonged exposure to psychosocial stressors and associated with coronary heart disease (cHd). Matrix metalloproteinases (MMPs) are involved in the pathogenesis of various emotional and cardiovascular disorders. The purpose of this study was to investigate whether Kai-Xin-San (KXS), which may terminate the signaling of MMPs, exerts antidepressant-like and cardioprotective effects in a myocardial infarction (Mi) plus depression rat model. Rats were randomly assigned to five groups: a normal control (control group), a celisc-injection of isopropyl adrenaline group (iSo group), depression (depression group), an iSo + depression (depression + iSo group), and an iSo + depression group treated with intragastric administration of 1,785 mg/kg KXS (KXS group). Behavioral changes, echocardiography, biochemical index, matrix metalloproteinase (MMP) and apoptosis-related proteins were assessed. compared with the depression + iSo group, KXS significantly improved stress-induced alterations of behavioral parameters and protected the heart by enlarging the left ventricular (lV) fractional shortening (FS) and lV ejection fraction (EF). Moreover, KXS significantly attenuated iSo + depression-induced MMP-2 and MMP-9 expression at the mrna and protein level and decreased TiMP in the heart compared to the complex model group. Myocardial apoptosis was significantly attenuated by KXS by regulating the Bcl-2/Bax axis. These results indicated that Mi comorbid with depression may damage the MMP balance in the central and peripheral system, and KXS may have a direct anti-depressive and cardio-protective effect by regulating the level of MMPs and associated myocardial apoptosis. it is promising to further explore the clinical potential of KXS for the therapy or prevention of Mi plus depression comorbidity disease.

Kai-Xin-San Attenuates Doxorubicin-Induced Cognitive Impairment by Reducing Inflammation, Oxidative Stress, and Neural Degeneration in 4T1 Breast Cancer Mice

“…And the removal of these productions of oxidative stress depends on the activity of antioxidant defensive systems including SOD, CAT, and GPx [ 43 ]. There has been increasing evidence that KXS has beneficial activities as antioxidants by increasing the activity or expression of endogenous antioxidant enzymes and reducing the apoptosis of neurons in the brain [ 20 , 23 , 44 ]. In this study, the degree of oxidative stress in the hippocampus was determined by measuring the levels of MDA and GSH and the activities of SOD, CAT, and GPx enzymes.…”

Exploration of the molecular targets and mechanisms of suxiao xintong dropping pills for myocardial infarction by network pharmacology method

“…Many studies report that MMPs exert a main role in atherosclerotic plaque disruption and result in myocardial infarction. Study finds that Kai-Xin-San can protect cardiomyocytes effect via regulating MMPs [ 30 ]. NFKB inhibitor alpha (also named as NFKBIA) participates in inflammatory responses.…”

Pathophysiological Mechanisms and Pharmaceutical Interventions of Myocardial Infarction with Depression

“…Kai-xin-san reduced depression-induced matrix metalloproteinases (MMPs) expression at mRNA and protein levels; the inhibition of MMPs signaling pathway plays an antidepressant and cardiac protective role [65]. In addition, ginsenosides (GFS) have been shown to inhibit 5-HT transporters, thereby inhibiting 5-HT reuptake and improving post-MI depressive behavior [66].…”