Chinese herbal medicine Xinji pill protects the heart from ischemia/reperfusion injury through the Akt/Nrf2 pathway

Abstract

The cardioprotective drugs used for treatment against ischemia/reperfusion (MI/R) injury have been well evaluated and are considered inadequate. The Chinese herbal medicine formula, Xinji pill (XJP) has been used traditionally for the prevention and treatment of ischemic heart diseases for decades. In the present study, the cardioprotective effects of XJP against MI/R injury were assessed in vivo and its possible mechanism was examined. Male Sprague‑Dawley rats were selected for establishing an MI/R model, which was induced by ischemia for 30 min followed by 24 h reperfusion. Drugs and saline were administered intragastrically from day 14 prior to MI/R. Blood samples were collected for biochemical detection. The rats were then sacrificed and cardiac muscle tissues were harvested. The mRNA expression levels of antioxidant genes were measured by reverse transcription‑quantitative polymerase chain reaction and the protein levels were measured by western blotting. Pretreatment with XJP for 14 days protected the heart against I/R‑induced myocardial function disorder, protected against heart injury, as demonstrated by normalized serum levels of lactate dehydrogenase and creatine kinase, and suppressed oxidative stress. XJP markedly upregulated the expression of antioxidant genes, including superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase, and promoted the protein expression of heme oxygenase‑1 and NFE2‑related factor 2 (Nrf2) in the heart tissues. Furthermore, Akt kinase was confirmed to be upstream of Nrf2 in the XJP treatment. LY294002, a specific inhibitor of Akt, significantly eliminated the cardioprotective effects of XJP. In conclusion, these results demonstrated that XJP exhibited notable cardioprotective properties, in which the Akt/Nrf2 signaling pathway may be involved.

Vincamine Modulates the Effect of Pantoprazole in Renal Ischemia/Reperfusion Injury by Attenuating MAPK and Apoptosis Signaling Pathways

“…It is essential to develop new therapeutic modalities for the existed candidates [18][19][20][21][22]. A major source of novel agents with different pharmaceutical activities is herbal medicine, such as vincamine (VINCA) [23,24]. It is an indole alkaloid of clinical use against brain sclerosis and postoperative conditions [25].…”

Cardioprotective effect of isorhamnetin against myocardial ischemia reperfusion (I/R) injury in isolated rat heart through attenuation of apoptosis

“…This increase was effectively suppressed in isolated rat hearts suffering isorhamnetin treatment in a dose‐dependent manner. In line with this result, decreased LDH and CK levels were adopted as the important benchmarks for evaluating the cardioprotective effect of potential drug in many literatures 30,36 …”

“…When the cell membrane becomes permeable or destroyed during myocardial IR injury, CK and LDH can easily transit through cytoplasmic membrane and released into the blood. Thus, their activity indirectly represents the extent of myocardial damage 36 . Next, we measured the release of LDH and CK to evaluate the degree of myocardial injury.…”

“…Thus, their activity indirectly represents the extent of myocardial damage. 36 Next, we measured the release of LDH and CK to evaluate the degree of myocardial injury. Compared with sham-operated hearts, LDH and CK levels significantly increased in serum of different groups in response to I/R treatment.…”

“…In line with this result, decreased LDH and CK levels were adopted as the important benchmarks for evaluating the cardioprotective effect of potential drug in many literatures. 30,36 As we know, for ischaemic heart diseases, reperfusion of the ischaemic myocardium may lead to cardiac dysfunction and eventually cardiomyocyte apoptosis. 37,38 Hence, improving cardiac function and inhibiting apoptosis is crucial for treating ischaemic heart diseases.…”