Effectiveness and safety of Tiaogan formula in the treatment of coronary heart disease: A protocol for systematic review and meta-analysis.

BACKGROUND: The morbidity and mortality of coronary heart disease (CHD) has remained high, which greatly increases people's economic burden. Several studies have showed that Tiaogan formula (TGF), as a kind of Chinese herbal medicine, was of benefit to relieving angina pectoris symptoms and improving the quality of life for CHD patients. However, the intensity of evidence has been poor, limiting the further clinical application of TGF to CHD. This systematic review and meta-analysis will assess the effectiveness and safety of studies of TGF in CHD patients. METHODS: A systematic search for literature up to December 2022 will be conducted in following public electronic databases: PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journals Database Database, and Wanfang Database. Inclusion criteria are randomized controlled trials of Tiaogan formula in the treatment of coronary heart disease. The primary outcome measures will be mortality, acute cardiovascular events, total efficacy rate, and improvement of angina symptoms. The secondary outcome measures will be electrocardiogram, levels of blood lipid, and adverse events. RevMan 5.4 software Cochrane Collaboration (London, United Kingdom) will be applied for data synthesis, sensitivity analysis, subgroup analysis, and risk of bias assessment. A funnel plot will be developed to evaluate reporting bias and Egger tests will be used to assess funnel plot symmetries. We will use the Grading of Recommendations Assessment, Development and Evaluation system to assess the quality of evidence. RESULTS: This study will provide a systematic review of Tiaogan formula in the treatment of CHD. CONCLUSION: This study will provide a high-quality synthesis of the effects and safety of Tiaogan formula in the treatment of CHD patients.

Pollen Typhae Total Flavone Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis in Human Aortic-Vascular Smooth Muscle Cells through Down-Regulating PERK-eIF2α-ATF4-CHOP Pathway / 中国结合医学杂志

OBJECTIVE@#To test the hypothesis that the inhibition of endoplasmic reticulum (ER) stress-induced apoptosis in oxidized low-density lipoproteins (ox-LDL)-induced human aortic-vascular smooth muscle cells (HA-VSMCs) was associated with suppression of the protein kinase RNA-like ER kinase (PERK)-eukaryotic translation initiation factor 2α (eIF2α)-activating transcription factor 4 (ATF4)-CCAAT/enhancer binding protein homologous protein (CHOP) signaling pathway by Pollen Typhae total flavone (PTF).@*METHODS@#Primary HA-VSMCs were cultured and identified. The cultured HA-VSMCs were randomized into 5 groups, including a normal control group, an ox-LDL group (70 μg/mL high ox-LDL), an HPTF group (70 μg/mL high ox-LDL+500 μg/mL PTF), an MPTF group (70 μg/mL high ox-LDL+250 μg/mL PTF), and a LPTF group (70 μg/mL high ox-LDL+100 μg/mL PTF) in the first part; and a normal control group, an ox-LDL group (70 μg/mL high ox-LDL), an MPTF group (70 μg/mL high ox-LDL+250 μg/mL PTF), a shRNA group (transducted with PERK shRNA lentiviral particles), a scramble shRNA group (transducted with control shRNA lentiviral particles), an MPTF+ox-LDL+shRNA group (250 μg/mL PTF+70 μg/mL high ox-LDL+PERK shRNA lentiviral particles) and an ox-LDL+shRNA group (70 μg/mL high ox-LDL+PERK shRNA lentiviral particles) in the second part. The protein expression levels of ER-associated apoptosis proteins were detected by Western blot, and their mRNA expression levels were detected by quantitative real-time reverse transcription-polymerase chain reaction. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was applied to test cell viability, and the level of apoptosis was monitored by flow cytometry.@*RESULTS@#The MTT assay and flow cytometry showed that the ox-LDL group had a significant increase in apoptosis, which was attenuated in PTF treatment groups and shRNA groups. Moreover, the ox-LDL group had increased protein and mRNA levels of binding immunoglobulin protein and ER-associated apoptosis proteins, such as PERK, eIF2α, ATF4 and CHOP, which were attenuated in PTF treatment groups and shRNA groups.@*CONCLUSIONS@#The apoptosis induced by ox-LDL had a strong relation to ER stress. The protective effect of PTF on ER stressinduced apoptosis was associated with inhibition of the PERK-eIF2α-ATF4-CHOP pathway, which might be a potential therapeutic strategy for enhancing the stability of atherosclerotic plaques.