[Network Meta-analysis of Chinese patent medicine in treatment of heart failure with preserved ejection fraction].

This study systematically evaluated the efficacy and safety of different Chinese patent medicines combined with conventional western medicine in the treatment of heart failure with preserved ejection fraction(HFpEF) and ranked for the drug selection. Randomized controlled trial(RCT) on Chinese patent medicines in treatment of HFpEF were obtained from the CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, Web of Science, and other databases from the inception to October 9, 2022. The included RCT was quantitatively analyzed using gemtc and rjags packages of R software for the network Meta-analysis. 74 RCTs were included, with a total of 7 192 patients enrolled, involving 11 different Chinese patent medicines(Shenfu Injection, Shenmai Injection, Qili Qiangxin Capsules, Shexiang Baoxin Pills, Xuezhikang Capsules, Salvia Miltiorrhiza Polyphenols Injection, Tanshinone Ⅱ_A Sulfonate Injection, Xinmailong Injection, Yangxinshi Tablets, Qishen Yiqi Dripping Pills, and Yixinshu Capsules). The results of network Meta-analysis are shown as followed.(1)In terms of improving clinical effective rate, for injection preparations, Xinmailong Injection + conventional western medicine was recommended. while for oral preparations, Shexiang Baoxin Pills + conventional western medicine, Qishen Yiqi Dripping Pills + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were preferred.(2)In terms of improving the mitral ratio of peak early to late diastolic filling velocity(E/A), for injection preparations, Shenmai Injection + Salvia Miltiorrhiza Polyphenols Injection + conventional western medicine, Shenmai Injection + conventional western medicine, Shenfu Injection + conventional western medicine were preferred. While for oral preparations, Yixinshu Capsules + conventional western medicine was preferred.(3)In terms of reducing the ratio of early diastolic mitral inflow to early diastolic mitral annular velocity(E/e'), Shenfu Injection + conventional western medicine could be used as injection preparation, and Qili Qiangxin Capsules + conventional western medicine, Qishen Yiqi Dripping Pills + conventional western medicine for oral preparations.(4)In terms of improving 6-minute walking trail(6MWT), the injection preparations such as Shenmai Injection + conventional western medicine, Xinmailong Injection + conventional western medicine were suitable, while oral preparations like Qishen Yiqi Dripping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine were recommended.(5)In terms of reducing N-terminal pro B-type natriuretic peptide(NT-proBNP), Qili Qiangxin Capsules + conventional western medicine were preferred.(6)In terms of reducing B-type natriuretic peptide(BNP), Xinmailong Injection + conventional western medicine could be used for injection preparation and Qili Qiangxin Capsules + conventional western medicine can be used for oral preparation. In terms of adverse drug reactions, there was no significant difference between Chinese patent medicine combined with conventional western conventional and traditional western medicine alone. The results showe that Chinese patent medicine combined with conventional western medicine in treating HFpEF is superior to conventional western medicine alone in reducing clinical symptoms, improving cardiac function, and improving exercise tolerance, which also has good drug safety. However, the existing evidence is still limited by the quality and quantity of included studies, so the above conclusion requires further validation through more prospective RCT.

Shuxuening Injection Inhibits Apoptosis and Reduces Myocardial Ischemia-Reperfusion Injury in Rats through PI3K/AKT Pathway.

OBJECTIVE: To investigate the main components and potential mechanism of Shuxuening Injection (SXNI) in the treatment of myocardial ischemia-reperfusion injury (MIRI) through network pharmacology and in vivo research. METHODS: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) and PharmMapper databases were used to extract and evaluate the effective components of Ginkgo biloba leaves, the main component of SXNI. The Online Mendelian Inheritance in Man (OMIM) and GeneCards databases were searched for disease targets and obtain the drug target and disease target intersections. The active ingredient-target network was built using Cytoscape 3.9.1 software. The STRING database, Metascape online platform, and R language were used to obtain the key targets and signaling pathways of the anti-MIRI effects of SXNI. In order to verify the therapeutic effect of different concentrations of SXNI on MIRI in rats, 60 rats were first divided into 5 groups according to random number table method: the sham operation group, the model group, SXNI low-dose (3.68 mg/kg), medium-dose (7.35 mg/kg), and high-dose (14.7 mg/kg) groups, with 12 rats in each group. Then, another 60 rats were randomly divided into 5 groups: the sham operation group, the model group, SXNI group (14.7 mg/kg), SXNI+LY294002 group, and LY294002 group, with 12 rats in each group. The drug was then administered intraperitoneally at body weight for 14 days. The main biological processes were validated using in vivo testing. Evans blue/triphenyltetrazolium chloride (TTC) double staining, hematoxylin-eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis were used to investigate the efficacy and mechanism of SXNI in MIRI rats. RESULTS: Eleven core targets and 30 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were selected. Among these, the phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) pathway was closely related to SXNI treatment of MIRI. In vivo experiments showed that SXNI reduced the myocardial infarction area in the model group, improved rat heart pathological damage, and reduced the cardiomyocyte apoptosis rate (all P<0.01). After SXNI treatment, the p-PI3K/PI3K and p-AKT/AKT ratios as well as B-cell lymphoma-2 (Bcl-2) protein expression in cardiomyocytes were increased, while the Bax and cleaved caspase 3 protein expression levels were decreased (all P<0.05). LY294002 partially reversed the protective effect of SXNI on MIRI. CONCLUSION: SXNI protects against MIRI by activating the PI3K/AKT signaling pathway.

Asiatic acid inhibits cardiac fibrosis throughNrf2/HO-1 and TGF-ß1/Smads signaling pathways in spontaneous hypertension rats.

OBJECTIVE: Asiatic acid (AA) has been suggested to inhibit pulmonary and hepatic fibrosis, while its influence on cardiac fibrosis remains unclear. We aimed to investigate whether AA could inhibit overpressure-induced cardiac fibrosis in spontaneous hypertension rats (SHRs). METHOD: SHRs were treated with AA (20 mg kg-1 day-1) for 12 weeks and cultured cardiac fibroblasts (CFs) were treated with Ang II (10-7 mol/L) in vitro. Markers of oxidative stress were measured and extent of cardiac fibrosis was evaluated with Sirius Red staining. Levels of Superoxide Dismutase (SOD), Malondialdehyde (MDA), reactive oxygen spices (ROS) and Glutathione (GSH) were measured by using commercial assay kits. Collagen deposition was detected. The expression of relative protein and mRNA was measured by Western blot and real-time PCR, respectively. RESULTS: AA reduced systolic blood pressure, attenuated myocardial hypertrophy, reduced college deposition and the expression of collagen I and III, connective tissue growth factor, and plasminogen activator inhibitor-1, in mRNA and protein levels, with inhibition of TGF-ß1 expression, phosphorylation of Smad2/3, and increase of Smad7 expression. AA reduced malondialdehyde and reactive oxygen spices, while increased the activities of superoxide dismutase and glutathione, accompanied with elevation of nuclear translocation of nuclear-factor erythroid 2-related factor 2 (Nrf2) and expression of heme oxygenase (HO-1) and NAD(P)H dehydrogenase [quinone] 1 (NQO-1) in vivo and in vitro. Moreover, pretreating CFs with siRNA for Smad7 or Nrf2 both partially reversed the inhibition of AA on Ang II-induced cardiac fibrosis. CONCLUSION: AA attenuates pressure overload-induced cardiac fibrosis via enhancing of Nrf2/HO-1 and suppressing TGF-ß1/Smads phosphorylation.

Tanshinone IIA inhibits lipopolysaccharide­induced inflammatory responses through the TLR4/TAK1/NF­κB signaling pathway in vascular smooth muscle cells.

To aim of the present study was to determine whether Tanshinone IIA (Tan IIA) inhibits lipopolysaccharide (LPS)­induced inflammation in vascular smooth muscle cells (VSMCs) from rats and elucidate the underlying molecular mechanism. VSMCs were primarily cultured and then treated with LPS (1 µg/l) and Tan IIA (25, 50 and 100 µmol/l) for 24 h. Monocyte chemoattractant protein (MCP)­1, interleukin (IL)­6 and tumor necrosis factor (TNF)­α levels were detected by ELISA and reverse transcription­quantitative polymerase chain reaction. Nitric oxide (NO) production was measured using the Griess reaction. The expression of Toll­like receptor 4 (TLR4), nuclear factor (NF)­κB (p65), and inducible NO synthase (iNOS), and the phosphorylation of transforming growth factor­ß­activated kinase 1 (TAK1) were detected by western blot analysis. Tan IIA inhibited the LPS­induced expression of MCP­1, IL­6, and TNF­α in a concentration­dependent manner and inhibited iNOS­mediated NO production. In addition, Tan IIA suppressed the expression of TLR4, the phosphorylation of TAK1, and the nuclear translocation of NF­κB (p65). The anti­TLR4 antibody and TAK1 inhibitor 5Z­7­oxozeaenol partially attenuated the LPS­induced expression of proinflammatory cytokines. In conclusion, Tan IIA inhibits LPS­induced inflammatory responses in VSMCs in vitro through the partial suppression of the TLR4/TAK1/NF­κB signaling pathway.