[Comparative analysis of clinical effects according to syndrome differentiation of Qili Qiangxin Capsules on ischemic heart failure: Meta-analysis].

Databases including CNKI,Wan Fang,CBM,VIP,PubMed and Cochrane Library were searched to collect qualified researches,and the quality of articles was evaluated according to scales. Meta-analysis including subgroup analysis was performed by using Rev Man 5. 3 software and Meta-regression test was performed by using Stata 12. 0 software. All of these methods were used to systematically evaluate the safety and clinical efficacy of Qili Qiangxin Capsules in treatment of ischemic heart failure under two circumstances( with or without syndrome differentiation). A total of 22 randomized controlled trials( RCTs) involving 1 942 patients were included,with generally low quality. RESULTS: of Meta-analysis showed that as compared with the routine Western treatment alone,additional use of Qili Qiangxin Capsules could improve the clinical efficacy( RR = 1. 21,95%CI[1. 16,1. 27],P<0. 000 01) in treatment of ischemic heart failure,with its combined effect of syndrome differentiation group greater than that of non-syndrome differentiation group( P= 0. 03,I~2= 78. 9%),Meta-regression( sig = 0. 9,P = 0. 057); left ventricular ejection fraction( WMD = 7. 28,95% CI[5. 18,9. 38],P<0. 000 01),with combined effect of syndrome differentiation group greater than that of non-syndrome differentiation group( P= 0. 01,I2= 83. 2%),Meta-regression( I~2= 81. 09%,R2= 29. 08%,sig = 0. 47,P = 0. 029); 6-minute walk test( WMD = 33. 20,95%CI[24. 70,41. 70 ],P < 0. 000 01); left ventricular end diastolic diameter( WMD =-4. 61,95% CI[-5. 38,-3. 84 ],P <0. 000 01); left ventricular end diastolic volume( WMD =-34. 43,95%CI[-38. 81,-30. 05],P< 0. 000 01); and left ventricular end systolic volume( WMD =-9. 60,95% CI[-13. 16,-6. 05],P < 0. 000 01). Adverse effects were reported in 11 patients taking Qili Qiangxin Capsules and in 20 patients with routine treatment group,tolerable in both groups. None of the patients had obvious abnormality in liver and kidney function. Qili Qiangxin Capsules were effective and safe in the treatment of ischemic heart failure,which can further improve clinical efficacy as compared with routine treatment alone. Qili Qiangxin Capsules with syndrome differentiation showed more significant effects than those without syndrome differentiation,indicating better efficacy of clinical syndrome differentiation. However,these conclusions still need to be verified with more high-quality and large-sample literature.

Suxiao Jiuxin pill promotes exosome secretion from mouse cardiac mesenchymal stem cells in vitro.

Cardiac mesenchymal stem cells (C-MSCs) are endogenous cardiac stromal cells that play a role in heart repair after injury. C-MSC-derived exosomes (Exo) have shown protective effects against apoptosis induced by acute myocardial ischemia/reperfusion. Suxiao Jiuxin pill (SJP) is a traditional Chinese medicine (TCM) formula used in China for the treatment of acute myocardial ischemia, which contains tetramethylpyrazine (TMP) and borneol (BOR) as major components. In this study, we investigated whether SJP treatment affected exosome release from C-MSCs in vitro. C-MSCs prepared from mice were treated with SJP (62.5 µg/mL), TMP (25 µg/mL) or BOR (15 µg/mL). Using an acetylcholinesterase activity assay, we found that both SJP and TMP treatment significantly increased exosome secretion compared to the control ethanol treatment. The neutral sphingomyelinase 2 (nSMase2) pathway was important in exosome formation and packaging. But neither the level of nSMase2 mRNA nor the level of protein changed following SJP, TMP or BOR treatment, suggesting that SJP stimulated exosome release via an nSMase2-independent pathway. The Rab27a and Rab27b GTPases controlled different steps of the exosome secretion pathway. We showed that SJP treatment significantly increased the protein levels of Rab27a, SYTL4 (Rab27a effector) and Rab27b compared with the control treatment. SJP treatment also significantly upregulated the mRNA level of Rab27b, rather than Rab27a. Moreover, SJP-induced increase of C-MSC-exosome release was inhibited by Rab27b knockdown, suggesting that SJP promotes exosome secretion from C-MSCs via a GTPase-dependent pathway. This study reveals a novel mechanism for SJP in modulating cardiac homeostasis.

Exosomes from Suxiao Jiuxin pill-treated cardiac mesenchymal stem cells decrease H3K27 demethylase UTX expression in mouse cardiomyocytes in vitro.

Suxiao Jiuxin pill (SJP) is a traditional Chinese medicine for the treatment of acute coronary syndrome in China, which contains two principal components, tetramethylpyrazine (TMP) and borneol (BOR). Thus far, however, the molecular mechanisms underlying the beneficial effects of SJP on the cardiac microenvironment are unknown. Cardiac mesenchymal stem cells (C-MSCs) communicate with cardiomyocytes (CMs) through the release of microvesicles (exosomes) to restore cardiac homeostasis and elicit repair, in part through epigenetic regulatory mechanisms. In this study, we examined whether SJP treatment altered C-MSC-derived exosomes (SJP-Exos) to cause epigenetic chromatic remodeling in recipient CMs. C-MSC isolated from mouse hearts were pretreated with SJP (SJP-Exos), TMP (TMP-Exos) or BOR (BOR-Exos). Then, HL-1 cells, a mouse cardiomyocyte line, were treated with exosomes from control C-MSCs (Ctrl-Exos), SJP-Exos, TMP-Exos or BOR-Exos. Treatment with SJP-Exos significantly increased the protein levels of histone 3 lysine 27 trimethylation (H3K27me3), a key epigenetic chromatin marker for cardiac transcriptional suppression, in the HL-1 cells. To further explore the mechanisms of SJP-Exo-mediated H3K27me3 upregulation, we assessed the mRNA expression levels of key histone methylases (EZH1, EZH2 and EED) and demethylases (JMJD3 and UTX) in the exosome-treated HL-1 cells. Treatment with SJP-Exo selectively suppressed UTX expression in the recipient HL-1 cells. Furthermore, PCNA, an endogenous marker of cell replication, was significantly higher in SJP-Exo-treated HL-1 cells than in Ctrl-Exo-treated HL-1 cells. These results show that SJP-Exos increase cardiomyocyte proliferation and demonstrate that SJP can modulate C-MSC-derived exosomes to cause epigenetic chromatin remodeling in recipient cardiomyocytes; consequently, SJP-Exos might be used to promote cardiomyocyte proliferation.

Bornyl acetate: A promising agent in phytomedicine for inflammation and immune modulation.

BACKGROUND: Bornyl acetate (BA), as a bicyclic monoterpene, is an active volatile component widely found in plants across the globe. BA can be used as essence and food flavor agent and is widely used in perfumes and food additives. It remains a key component in several proprietary Chinese medicines. PURPOSE: This review summarized the pharmacological activity and research prospects of BA, making it the first of its kind to do so. Our aim is to provide a valuable resource for those pursuing research on BA. METHODS: Databases including PubMed, Web of Science, and CNKI were used based on search formula "(bornyl acetate) NOT (review)" from 1967 to 2022. For the relevant knowledge of TCM, we quoted Chinese literature. Articles related to agriculture, industry, and economics were excluded. RESULTS: BA showed rich pharmacological activities: It inhibits the NF-κB signal pathway via affecting the phosphorylation of IKB and the production of IKKs, inhibits the MAPK signal pathway via inhibiting the phosphorylation of ERK, JNK, and p38, down-regulates pro-inflammatory cytokines such as TNF-α, IL-1ß, IL-6, up-regulates IL-11, reduces NO production, regulates immune response via up-regulating CD86+, decreases catecholamine secretion, and reduces tau protein phosphorylation. In addition to the pharmacological activities of BA, its toxicity and pharmacokinetics were also discussed in this paper. CONCLUSION: BA has promising pharmacological properties, especially anti-inflammatory and immunomodulatory effects. It also has sedative properties and potential for use in aromatherapy. Compared to traditional NSAIDs, it has a more favorable safety profile while maintaining efficacy. BA has potential for developing novel drugs for treating various conditions.

Effects of Kanlijian on exercise tolerance, quality of life, and frequency of heart failure aggravation in patients with chronic heart failure.

OBJECTIVE: To observe the effects of conventional therapy combined with Kanlijian (KLJ) on exercise tolerance, quality of life and frequency of heart failure aggravation in patients with chronic heart failure (CHF). METHODS: Sixty CHF patients differentiated as sufferring from the syndrome of Xin-Shen Yang deficiency were included in the study and randomly assigned at the ratio of 2:1 into the KLJ group (n = 39) and the control group (n = 21). All the patients were treated with conventional therapy of Western medicine, but to those in the KLJ group, KLJ was medicated additionally one dose daily with 24 wks as one therapeutic course. The efficacy on TCM syndrome and changes of scores on TCM syndrome were observed after treatment. The indexes, including 6-minute walking distance (6MWD), quality of life (QOL, accessed by LHFQ scoring), NYHA grade, hemodynamic indexes and reducing/withdrawal rate of diuretic and digoxin before and after treatment were recorded and compared. Also the frequency of re-admission due to aggravation of heart failure in one year's time were observed. RESULTS: (1) The efficacy on TCM syndrome, improvement on scores of TCM syndrome, therapeutic effects on 6MWD, QOL, and NYHA grade in the KLJ group were superior to those in the control group. (2) Hemodynamic indexes after treatment, left ventricular fractional shortening (LVFS) and E peak/A peak (E/A), between the two groups had no significant difference, while left ventricular ejection fraction (LVEF) was increased significantly in the KLJ group, but with no obvious change in the control group. (3) The reducing/withdrawal rate of diuretic and digoxin in the KLJ group was significantly higher than that in the control group. (4) The 1-year frequency of re-admission significantly decreased in the KLJ group. CONCLUSION: The adjuvant treatment of KLJ on the basis of Western conventional therapy can significantly improve CHF patients' exercise tolerance, quality of life and cardiac function, reduce the dosage of diuretic and digoxin needed, and decrease the re-admission frequency due to aggravation of heart failure.