Xinkeshu Improves Endothelial Function and Augments Reendothelialization Capacity in Coronary Artery Disease with Anxiety/Depression

Abstract

The disruption of endothelial homeostasis is the hallmark of coronary artery disease (CAD) and psychological disorders such as anxiety/depression. Xinkeshu (XKS), a traditional Chinese patent medicine, plays an essential role in CAD and psychological condition; however, the mechanisms underlying the effects of XKS on the endothelial function and endogenous endothelium-repair capacity in CAD patients with anxiety/depression remain elusive. In this study, endothelial function and endothelial progenitor cell- (EPC-) mediated reendothelialization capacity were compared among age-matched healthy subjects, CAD patients with or without anxiety/depression. Besides, CAD patients with anxiety/depression received 1-month XKS treatment. Anxiety/depression symptoms were evaluated by Generalized Anxiety Disorder 7-item (GAD-7)/Patient Health Questionnaire-9 (PHQ-9) score, endothelial function was tested by flow mediated dilation (FMD) measurement, and EPC-mediated reendothelialization capacity was evaluated by a carotid artery injury model in nude mouse ( n = 6 ) with the injection of XKS-incubated EPCs from CAD patients with anxiety/depression. The results showed that FMD and EPC-mediated reendothelialization capacity of CAD patients with anxiety/depression were compromised compared to healthy subjects and CAD patients without anxiety/depression. After 1 month of XKS treatment, FMD increased from 4.29 ± 1.65 to 4.87 ± 1.58 % ( P < 0.05 ) in CAD patients with anxiety/depression, whereas it remained unchanged in the controls. Moreover, XKS decreased GAD-7 and PHQ-9 scores. Meanwhile, incubating XKS enhanced in vivo reendothelialization capacity and in vitro apoptosis of EPCs from CAD patients with anxiety/depression, which was associated with the upregulation of CXC-chemokine receptor 7 (CXCR7) and inhibition of phosphorylation of p38 signaling. CXCR7 knockdown abolished the beneficial effects of XKS, which was rescued by p38 inhibitor SB203580. Our data demonstrate for the first time that XKS improves endothelial function and enhances EPC-mediated reendothelialization through CXCR7/p38/cleaved casepase-3 signaling and provides novel insight into the detailed mechanism of XKS in maintaining endothelial homeostasis in CAD patients with anxiety/depression.

Exploring global research trends in Chinese medicine for atherosclerosis: a bibliometric study 2012–2023

“…Specific mixtures of herbs, notably Ge Gen Baicalin Wan and Sheng Wei San, possess the capacity to impart vasoprotective effects by orchestrating the modulation of distinct signaling cascades, including the HMGB1/NF-κB/NLRP3 and ROCK/cofilin pathways ( 103 , 104 ). Additionally, Xinkeshu, through its enhancement of endothelial progenitor cell-facilitated endothelial regeneration, and rhodopsin, by modulating the hepatic low-density lipoprotein receptor (LDLR) and endothelial nitric oxide synthase (p-eNOS), potentially contribute positively to the improvement of endothelial functionality ( 105 , 106 ).…”

The effect of Qi‐Shao‐Tong‐Mai‐An‐Shen herbal paste on coronary heart disease patients with depression and/or anxiety: Study protocol for a randomized controlled trial

“…Thus, current guidelines recommend non-psychotropic drug intervention as the initial treatment [19]. Yet, numerous clinical and experimental studies have confirmed that Traditional Chinese medicine (TCM) has a definite effect and relatively high safety in the treatment of psycho-cardiology disease [20][21][22][23]. Qi-Shao-Tong-Mai-An-Shen (QSTMAS) herbal paste, summarized by Professor Huang Li based on 40 years of clinical experience, is used to treat CHD with qi deficiency and blood stasis symptoms.…”

The Effect of Qi-Shao-Tong-Mai-An-Shen (QSTMAS) Herbal Paste in Coronary Heart Disease Patients with Depression and/or Anxiety: A Randomized Controlled Clinical Trial Protocol

“…Thus, current guidelines recommend non-psychotropic drug intervention as the initial treatment [19]. Yet, numerous clinical and experimental studies have con rmed that Traditional Chinese medicine (TCM) has a de nite effect and relatively high safety in the treatment of psycho-cardiology disease [20][21][22][23]. QSTMAS herbal paste, one Chinese patent preparation summarized by Professor Huang Li based on 40 years of clinical experience, is used to treat coronary heart disease with qi de ciency and blood stasis symptoms.…”