Ligusticum chuanxiong Hort (known as Chuanxiong in China, CX) is one of the most widely used and long-standing medicinal herbs in China. Tetramethylpyrazine (TMP) is an alkaloid and one of the active components of CX. Over the past few decades, TMP has been proven to possess several pharmacological properties. It has been used to treat a variety of diseases with excellent therapeutic effects. Here, the pharmacological characteristics and molecular mechanism of TMP in recent years are reviewed, with an emphasis on the signal-regulation mechanism of TMP. This review shows that TMP has many physiological functions, including anti-oxidant, anti-inflammatory, and anti-apoptosis properties; autophagy regulation; vasodilation; angiogenesis regulation; mitochondrial damage suppression; endothelial protection; reduction of proliferation and migration of vascular smooth muscle cells; and neuroprotection. At present, TMP is used in treating cardiovascular, nervous, and digestive system conditions, cancer, and other conditions and has achieved good curative effects. The therapeutic mechanism of TMP involves multiple targets, multiple pathways, and bidirectional regulation. TMP is, thus, a promising drug with great research potential.

Mitochondria play a key role in cellular metabolism. Mitochondrial dynamics (fusion and fission) and mitophagy, are critical to mitochondrial function. Fusion allows organelles to share metabolites, proteins, and mitochondrial DNA, promoting complementarity between damaged mitochondria. Fission increases the number of mitochondria to ensure that they are passed on to their offspring during mitosis. Mitophagy is a process of selective removal of excess or damaged mitochondria that helps improve energy metabolism. Cardiometabolic disease is characterized by mitochondrial dysfunction, high production of reactive oxygen species, increased inflammatory response, and low levels of ATP. Cardiometabolic disease is closely related to mitochondrial dynamics and mitophagy. This paper reviewed the mechanisms of mitochondrial dynamics and mitophagy (focus on MFN1, MFN2, OPA1, DRP1, and PINK1 proteins) and their roles in diabetic cardiomyopathy, myocardial infarction, cardiac hypertrophy, heart failure, atherosclerosis, and obesity.

Background: Ischemic heart disease is one of the leading causes of mortality worldwide, and thus calls for development of more effective therapeutic strategies. This study aimed to identify potential therapeutic targets for coronary heart disease (CHD) and myocardial infarction (MI) by investigating the causal relationship between plasma proteins and these conditions. Methods: A two-sample Mendelian randomization (MR) study was performed to evaluate more than 1600 plasma proteins for their causal associations with CHD and MI. The MR findings were further confirmed through Bayesian colocalization, Summary-data-based Mendelian Randomization (SMR), and Transcriptome-Wide Association Studies (TWAS) analyses. Further analyses, including enrichment analysis, single-cell analysis, MR analysis of cardiovascular risk factors, phenome-wide Mendelian Randomization (Phe-MR), and protein-protein interaction (PPI) network construction were conducted to verify the roles of selected causal proteins. Results: Thirteen proteins were causally associated with CHD, seven of which were also causal for MI. Among them, FES and PCSK9 were causal proteins for both diseases as determined by several analytical methods. PCSK9 was a risk factor of CHD (OR = 1.25, 95% CI: 1.13–1.38, P = 7.47E-06) and MI (OR = 1.36, 95% CI: 1.21–1.54, P = 2.30E-07), whereas FES was protective against CHD (OR = 0.68, 95% CI: 0.59–0.79, P = 6.40E-07) and MI (OR = 0.65, 95% CI: 0.54–0.77, P = 5.38E-07). Further validation through enrichment and single-cell analysis confirmed the causal effects of these proteins. Moreover, MR analysis of cardiovascular risk factors, Phe-MR, and PPI network provided insights into the potential drug development based on the proteins. Conclusions: This study investigated the causal pathways associated with CHD and MI, highlighting the protective and risk roles of FES and PCSK9, respectively. FES. Specifically, the results showed that these proteins are promising therapeutic targets for future drug development.

The estimated glucose disposal rate (eGDR) has been linked to incident cardiovascular disease (CVD) in individuals without diabetes. However, few studies have accounted for long-term cumulative eGDR exposure. The aim of this study was to explore whether long-term cumulative eGDR was independently associated with incident CVD in individuals over the age of 50 years and without diabetes. This study used data from the China Health and Retirement Longitudinal Study (CHARLS) and Health and Retirement Study (HRS). The cumulative eGDR was calculated as the summation of the average eGDR for each pair of consecutive examinations multiplied by the time between these two consecutive visits, in years. The outcome was incident CVD. Cox proportional hazards regression models and restricted cubic spline (RCS) regression models were used to evaluate the association between cumulative eGDR and incident CVD. A total of 2430 participants from CHARLS and 2008 participants from HRS were included in the analysis. The median age of the participants in CHARLS at baseline was 59 years [IQR: 55–65 years], and 1205 (49.59%) were men. The median age of the participants in HRS at baseline was 64 years [IQR: 57–70 years], and 705 (35.11%) were men. The RCS regression model showed a negative and linear association between the cumulative eGDR and incidence of CVD (CHARLS: P < 0.001, P for nonlinearity = 0.248; HRS: P = 0.013, P for nonlinearity = 0.121). After multivariate adjustment, the higher levels of cumulative eGDR were independently associated with a lower risk of CVD (per SD, CHARLS: HR: 0.802, 95% CI: 0.716–0.898, HRS: HR: 0.791, 95% CI: 0.665–0.940, pooled analysis: HR: 0.799, 95% CI: 0.726–0.878). A lower level of cumulative eGDR was associated with an increased risk of incident CVD in individuals over the age of 50 years and without diabetes. Continuous monitoring of cumulative eGDR exposure over time, based on consideration of traditional risk factors, may prove beneficial for the early identification and intervention of individuals at high risk of CVD. In regions with limited healthcare resources, among individuals with limited ability to access, process, and understand health information and services, cumulative eGDR may offer improved clinical applicability.

Objective. To systematically evaluate the efficacy and safety of XFZYD for coronary heart disease (CHD). Methods. A comprehensive literature search of randomized controlled trials using XFZYD for CHD was conducted in 10 electronic databases from their establishment to December 20, 2020. The researchers screened the relevant trials in NoteExpress, extracted the data in duplicate independently, assessed the risk of bias in the trials using the Cochrane collaboration tool, and then used Rev Man 5.3 for data analysis. Results. 30 trials with 3126 participants were included for meta-analysis. The results showed that the clinical effects of XFZYD and its combination with chemical drugs (CD) were 1.13 (RR; 1.13; 95 CI, 1.03 to 1.24) and 1.26 (RR; 1.26; 95 CI, 1.20 to 1.32) times those of CD, respectively. And, it could also improve electrocardiogram effect, which was 1.63 (RR; 1.63; 95 CI, 1.04 to 2.53) times that of CD. XFZYD could not only decrease duration of angina pectoris and improve vascular endothelial function but also obviously reduce the TCM syndrome score. When used in combination with CD, it could also lower AF, correct the dyslipidemia, and reduce the blood viscosity. Conclusion. These results demonstrated that XFZYD had great advantages in treating CHD with no obvious adverse reactions. Therefore, it is believed that XFZYD is more suitable for CHD patients with clinical indicators of dyslipidemia, high blood viscosity, or vascular endothelial dysfunction. This study is the first systematic review and meta-analysis with some unique ways, including its comprehensiveness, large-scale search, the novelty of findings, and transparent approach.