The efficacy of sodium ferulate combination therapy in coronary heart disease: A systematic review and meta-analysis.

BACKGROUND: Sodium ferulate (SF), a derivative of ferulic acid, is one of the active constituents in medicinal plants thought to be useful in fighting cardiovascular diseases. However, there still lacks a systematic review of the efficacy and safety of SF in treating coronary heart disease (CHD). It is therefore the purpose of this study to comprehensively review all clinical randomized controlled trials (RCTs) of SF in CHD to assess its efficacy and safety. METHODS: All analysis is based on 8 databases as of February 2023, which includes 35 outcomes of RCTs that investigate the effect of SF combination therapy in CHD. The present study evaluates the quality and bias of selected literature by the Jadad scale and Cochrane Collaboration's tools, and also the quality of evidence by GRADE Profiler. Furthermore, it applies sensitivity analysis to assess the high heterogeneity impact of outcomes and conducted subgroup analysis to estimate the influence factors in these studies. The study protocol was set documented, and published beforehand in PROSPERO (Registration No.CRD42022348841). RESULTS: The meta-analysis of 36 studies (with 3207 patients) shows that SF combined with conventional drugs has improved clinical effectiveness for patients with CHD [RR: 1.21 (95% CI 1.17,1.26); p < 0.00001]. Statistically significant results of meta-analyses are also seen in electrocardiography (ECG) efficacy, frequency of angina attacks, endothelium-dependent flow-mediated vasodilation (FMD), nitric oxide (NO), endothelin (ET), whole Blood low shear rate (LS), platelet aggregation test (PAgT), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL6), triglyceride (TG). Adverse events are reported in 6 RCTs. By GRADE approaches, 2 outcomes (clinical efficacy, CRP) indicate a moderate quality of evidence, 17 outcomes indicate low quality of evidence, with the other 16 very low-quality. CONCLUSION: SF combination therapy has a better curative effect than conventional therapy. However, due to items with low-quality evidence demonstrated in the study, the presence of clinical heterogeneity, and imprecision in partial outcome measures, all these led to limitations in the evidence of this study. Thus, the conclusion needs to be further verified by more in-depth research.

A multi-target protective effect of Danggui-Shaoyao-San on the vascular endothelium of atherosclerotic mice.

BACKGROUND: Atherosclerosis (AS) is a chronic disease characterized by abnormal blood lipid metabolism, inflammation and vascular endothelial injury. Vascular endothelial injury is the initial stage during the occurrence of AS. However, the function and mechanism of anti-AS are not well characterized. Danggui-Shaoyao-San (DGSY) is a classic Traditional Chinese Medicine (TCM) prescription for the treatment of gynecological diseases, and has been widely used in the treatment of AS in recent years. METHODS: ApoE-/- atherosclerosis male mice were established by feeding with high-fat diet, and then randomly divided into three groups: Atherosclerosis group (AS), Danggui-Shaoyao-San group (DGSY), and Atorvastatin calcium group (X). The mice were administered with the drugs for 16 weeks. Pathological changes in aortic vessels were examined by staining with Oil red O, Masson and hematoxylin-eosin. In addition, blood lipids were analyzed. The level of IL-6 and IL-8 in aortic vessels were detected by ELISA and the expression of ICAM-1 and VCAM-1 in the aortic vascular endothelium were measured by Immunohistochemical. The mRNA expression of interα5ß1/c-Abl/YAP in the aortic vessels were measured by Real-time quantitative PCR and location of expression was assessed by immunofluorescence. RESULTS: DGSY can significantly reduce the content of TC,TG and LDL-C and increase the level of HDL-C in the serum, reduce the plaque area and inhibit the concentration of IL-6 and IL-8, down-regulate the expression of IVAM-1,VCAM-1 and interα5ß1/ c-Abl/YAP in the aortic vessels. CONCLUSIONS: Collectively, DGSY can alleviate vascular endothelium damage and delay the occurrence of AS, and the underlying mechanism may be related to the multi-target protective of DGSY.

Association between bile acid metabolism and bone mineral density in postmenopausal women

OBJECTIVES: Previous studies have not shown any correlation between bile acid metabolism and bone mineral density (BMD) in women with postmenopausal osteoporosis. Thus, the current study evaluated the association between bile acid levels as well as BMD and bone turnover marker levels in this group of women. METHODS: This single-center cross-sectional study included 150 postmenopausal Chinese women. According to BMD, the participants were divided into three groups: osteoporosis group, osteopenia group, and healthy control group. Serum bile acid, fibroblast growth factor 19 (FGF19), and bone turnover biomarker levels were assessed. Moreover, the concentrations of parathyroid hormone, 25-hydroxy vitamin D [25(OH)D], procollagen type I N-peptide (P1NP), and beta-CrossLaps of type I collagen containing cross-linked C-terminal telopeptide (β-CTX) were evaluated. The BMD of the lumbar spine and proximal femur were examined via dual-energy X-ray absorptiometry. RESULTS: The serum total bile acid levels in the osteoporosis and osteopenia groups (5.28±1.56 and 5.31±1.56 umol/L, respectively) were significantly lower than that in the healthy control group (6.33±2.04 umol/L; p=0.002 and 0.018, respectively). Serum bile acid level was positively associated with the BMD of the lumbar spine, femoral neck, and total hip. However, it negatively correlated with β-CTX concentration. Moreover, no correlation was observed between bile acid and P1NP levels, and the levels of the other biomarkers that were measured did not differ between the groups. CONCLUSION: Serum bile acid was positively correlated with BMD and negatively correlated with bone turnover biomarkers reflecting bone absorption in postmenopausal women. Thus, bile acid may play an important role in bone metabolism.

Regulatory effect of a Chinese herbal medicine formula on non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become a major cause of chronic liver disease. The Chinese herbal medicine (CHM) Dachaihu decoction (DCHD) has been proved to treat NAFLD with good efficacy in previous studies. Based on the TCM principle of formula formation, we divided DCHD into soothing liver part, invigorating spleen part, and dredging intestine part. Marshall officially proposed the concept of "intestinal-hepatic axis", which systematically explains the interactions between the intestine and liver. We hypothesized that the effect of CHM on NAFLD is achieved by regulating the liver and intestine. Thus, we aimed to investigate the possible effect of a CHM formula on NAFLD in a rat model. AIM: To investigate the effects of a CHM formula (a decoction of Chinese thorowax root, scutellaria root, and white peony root) on NAFLD and its regulatory effect on the "intestinal-liver" axis. METHODS: Sixty rats were randomly divided into control, model, pioglitazone hydrochloride (PH), and CHM (a decoction of Chinese thorowax root, scutellaria root, and white peony root) groups. An NAFLD rat model was established using a high-fat high-fructose diet for 16 wk. From the 13th week, rats were administered with PH or a decoction of Chinese thorowax, scutellaria, and white peony root (CHM group) for 4 wk. Rats in the control group and model group were administered with an equal volume of distilled water. At the end of the study, blood was collected via the abdominal aorta. Liver tissues were harvested and any morphological changes were observed by hematoxylin-eosin (HE) staining, Oil red O staining, and Masson staining. In addition, blood lipids, liver function markers, and triglyceride (TG) in liver tissues were analyzed. The levels of transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α (TNF-α), Toll-like receptor-4 (TLR4), and nuclear factor-kappa B (NF-кB) in liver tissues and secreted immunoglobulin A (sIgA) in intestinal tissues were analyzed by ELISA, and protein and mRNA expression of occludin and zonula occludens-1 (ZO-1) in the intestine were measured using Western blot and reverse transcription-quantitative polymerase chain reaction, respectively. The endotoxin level in plasma was detected by endpoint chromogenic assay. RESULTS: Compared to the normal control group, the liver coefficient, serum TG, total cholesterol (TC), low density lipoprotein (LDL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), blood glucose, plasma endotoxin, and the levels of TG, TNF-α, TGF-ß, NF-kB, and TLR4 in liver tissues increased significantly in the model group, while serum high density lipoprotein (HDL), intestinal sIgA, and protein and mRNA expression of occludin and ZO-1 decreased significantly in the model group (P < 0.01). PH and CHM attenuated the elevated liver coefficient, serum TG, TC, LDL, AST, and ALT, blood glucose, plasma endotoxin, and the levels of TG, TNF-α, TGF-ß, NF-kB, and TLR4 in liver tissues and increased serum HDL levels compared to the model group (P < 0.01). Intestinal sIgA and the protein and mRNA expression of intestinal occludin and ZO-1 were significantly increased in the PH group compared to the model and CHM groups (P < 0.01). CONCLUSION: The decoction of Chinese thorowax root, scutellaria root, and white peony root is beneficial in regulating lipid metabolism and liver function, which indicates that it has a good effect on the liver. To a certain extent, this CHM formula can affect both the liver and intestine, while its effect on the liver is superior to that on the intestine.

Measurement of local temperature increments induced by cultured HepG2 cells with micro-thermocouples in a thermally stabilized system.

To monitor the temperature distribution of a cell and its changes under varied conditions is currently a technical challenge. A variety of non-contact methods used for measuring cellular temperature have been developed, where changes of local temperature at cell-level and sub-cell-level are indirectly calculated through the changes in intensity, band-shape, bandwidth, lifetime or polarization anisotropy of the fluorescence spectra recorded from the nano-sized fluorescent materials pre-injected into the target cell. Unfortunately, the optical properties of the fluorescent nano-materials may be affected by complicated intracellular environment, leading to unexpected measurement errors and controversial arguments. Here, we attempted to offer an alternative approach for measuring the absolute increments of local temperature in micro-Testing Zones induced by live cells. In this method, built-in high-performance micro-thermocouple arrays and double-stabilized system with a stability of 10 mK were applied. Increments of local temperature close to adherent human hepatoblastoma (HepG2) cells were continuously recorded for days without stimulus, showing frequent fluctuations within 60 mK and a maximum increment by 285 mK. This method may open a door for real-time recording of the absolute local temperature increments of individual cells, therefore offering valuable information for cell biology and clinical therapy in the field of cancer research.

Synergistic anti-inflammatory effect of Radix Platycodon in combination with herbs for cleaning-heat and detoxification and its mechanism.

OBJECTIVE: To investigate the synergistic anti-inflammatory effect of Radix Platycodon in combination with herbs for cleaning-heat and detoxification and its mechanism for Fel-targeting. METHODS: Forty Wistar rats were randomly divided into five groups (8 per group): the sham-operated group, model group, Radix Platycodon group, Flos Lonicera and Fructus Forsythia (LF) group, and Radix Platycodon, Flos Lonicera and Fructus Forsythia combination (PLF) group, using a random number table. A rat chronic obstructive pulmonary disease (COPD) model was established by passive smoking and intratracheal instillation of lipopolysaccharide (LPS). The treatments started from the 15th day of passive smoking for a total duration of 14 days. At the end of the treatment, changes in the following measurements were determined: lung histopathology, inflammatory cytokines including tumor necrosis factor α (TNF-α), transforming growth factor ß (TGF-ß) and interleukin IL-1ß (IL-1ß) in bronchoalveolar lavage fluid (BALF), and mRNA expression of endogenous active substance intestinal trefoil factor 3 (TFF3) in the lung tissue. RESULTS: Light microscopy showed that compared with the sham-operated group, rats in the COPD model group had disrupted alveolar structure, collapsed local alveoli, significantly widened or even fused alveolar septa, and massive infiltration of inflammatory cells in the alveolar wall and interstitium. In addition, significant bronchial epithelium hyperplasia, partially shed epithelia, and marked inflammatory cell infiltration in the bronchial wall and its surrounding tissues were noticed. Electron microscopy showed that rats in the model group had degeneration of alveolar type II epithelial cell; reduction, breakage or even loss of cell surface microvilli; swollen mitochondria with disappearing cristae and vacuole-like structure; and, increased secondary lysosomes in alveolar macrophages. The TNF-α, TGF-ß and IL-1ß levels and white blood cell (WBC) count in BALF were significantly increased (P < 0.01 or P < 0.05) and TFF3 mRNA expression in the lung tissue was significantly reduced (P < 0.01). After treatment, the pathological morphology of lung injury was less severe in all three treatment groups. In addition, TGF-ß and IL-1ß and WBC count in BALF were decreased (P < 0.01 or P < 0.05), and TFF3 mRNA expression in the lung tissue was significantly increased in the PLF group (P < 0.01). Compared with the LF group, the IL-1ß in BALF was significantly decreased P < 0.05), and TFF3 mRNA expression was significantly increased (P < 0.05) in the PLF group. CONCLUSIONS: Radix Platycodon synergizes with herbs for cleaning-heat and detoxification in reducing inflammatory injury in a rat model of COPD. The synergistic anti-inflammatory effect is reflected in the improvement in pathological changes and in the reduction of IL-1ß levels in BALF. The mechanism of such synergistic action may be related to its effect on maintaining the TFF3 mRNA expression and Fel-targeting function.