Effectiveness and pharmacological mechanisms of Chinese herbal medicine for coronary heart disease complicated with heart failure.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicine (CHM) is widely used for treating coronary heart disease complicated with heart failure (CHD-HF). However, the exact mechanisms involved are still not fully understood. AIM OF THE STUDY: To assess the clinical effectiveness and potential pharmacological mechanisms of CHM for treating CHD-HF. METHODS: Eight databases were retrieved for Randomized Controlled Trials of CHM for CHD-HF published from their inception to March 2023. Quality assessment of include studies was performed by the Cochrane risk-of-bias. Meta-analysis was used to assess the effectiveness of CHM for CHD-HF, and then core drugs and active ingredients were selected by data mining and network pharmacology. Finally, cluster and enrichment analysis were adopted to explore the potential targets and signaling pathways. RESULTS: A total of 52 studies enrolling 5216 patients were included. Meta-analysis revealed that CHM treatment groups significantly improved left ventricular ejection fraction (LVEF), 6-min walk test (6-MWT), left ventricular end-diastolic dimension (LVEDD) and left ventricular end systolic diameter (LVESD) than control groups: [LVEF: SMD = 0.7, 95%CI (0.54, 0.87), p < 0.00001, I2 = 80%; 6-MWT: SMD = 0.72, 95%CI (0.58, 0.86), p < 0.0001, I2 = 67%; LVEDD: SMD = -0.79, 95%CI (-0.89, -0.69), p < 0.0001, I2 = 49%; LVESD: SMD = -0.6 (-0.74, -0.46), p < 0.0001, I2 = 0%]. The results of various biological information analysis showed the internal relationship between prescriptions, core drugs, active ingredients and therapeutic targets. Twelve core herbs with the most commonly use and high correlation were selected from 110 CHMs of 52 prescriptions for CHD-HF treatment, and further 65 effective components were screened out according to the most strength value, which were divided into 12 compounds such as terpenoids, flavonoids, steroids and alkaloids and etc. At the same time, 67 therapeutic targets of active ingredients in CHD-HF were filtrated. On these bases, cluster and enrichment analysis of the components and targets were used to explore relevant pharmacological mechanisms, mainly including anti-myocardial cell damage, anti-inflammation, anti-apoptosis, anti-fibrosis, regulation of oxidative stress, anticoagulation and angiogenesis, and improvement of glucose and fatty acid metabolism. CONCLUSION: CHM are effective in treating CHD-HF compared with conventional treatment. Some of the included studies have high risks in the implementation of blinding, so more high-quality studies are needed. The active ingredients of CHM could protect the myocardium and improve pathological environment of CHD-HF in various ways. And CHM has the advantage of multi-component and multi-target treatment for complex diseases.

The effects of fluctuations in the nutrient supply on the expression of five members of the AGL17 clade of MADS-box genes in rice.

The ANR1 MADS-box gene in Arabidopsis is a key gene involved in regulating lateral root development in response to the external nitrate supply. There are five ANR1-like genes in Oryza sativa, OsMADS23, OsMADS25, OsMADS27, OsMADS57 and OsMADS61, all of which belong to the AGL17 clade. Here we have investigated the responsiveness of these genes to fluctuations in nitrogen (N), phosphorus (P) and sulfur (S) mineral nutrient supply. The MADS-box genes have been shown to have a range of responses to the nutrient supply. The expression of OsMADS61 was transiently induced by N deprivation but was not affected by re-supply with various N sources. The expression of OsMADS25 and OsMADS27 was induced by re-supplying with NO3(-) and NH4NO3, but downregulated by NH4(+). The expression of OsMADS57 was significantly downregulated by N starvation and upregulated by 3 h NO3(-) re-supply. OsMADS23 was the only gene that showed no response to either N starvation nor NO3(-) re-supply. OsMADS57 was the only gene not regulated by P fluctuation whereas the expression of OsMADS23, OsMADS25 and OsMADS27 was downregulated by P starvation and P re-supply. In contrast, all five ANR1-related genes were significantly upregulated by S starvation. Our results also indicated that there were interactions among nitrate, sulphate and phosphate transporters in rice.