[Determination of 10 mycotoxins in Hippophae Fructus medicinal and edible products by ultra-performance liquid chromatography- tandem mass spectrometry].

An analytical method for 10 mycotoxins in Hippophae Fructus medicinal and edible products was established in this study, and the contamination of their mycotoxins was analyzed. First of all, the mixed reference solution of ten mycotoxins such as aflatoxin, ochratoxin, zearalenone, and dexoynivalenol was selected as the control, and the Hippophae Fructus medicinal and edible products were prepared. Secondly, based on the ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) technology, 10 mycotoxins in Hippophae Fructus medicinal and edible products were quantitatively investigated and their content was determined. Finally, the contamination of mycotoxins was analyzed and evaluated. The optimal analysis conditions were determined, and the methodological inspection results showed that the 10 mycotoxins established a good linear relationship(r>0.99). The method had good repeatability, test sample specificity, stability, and instrument precision. The average recovery rates of 10 mycotoxins in Hippophae Fructus medicinal products, edible solids, and edible liquids were 90.31%-109.4%, 87.86%-107.8%, and 85.61%-109.1%, respectively. Relative standard deviation(RSD) values were 0.22%-10%, 0.75%-13%, and 0.84%-8.5%, repsectively. Based on UPLC-MS/MS technology, the simultaneous determination method for the limits of 10 mycotoxins established in this study has fast detection speed, less matrix interference, high sensitivity, and accurate results, which is suitable for the limit examination of 10 mycoto-xins in Hippophae Fructus medicinal and edible products.

Rheum officinale Baill. Treats zebrafish embryo thrombosis by regulating NOS3 expression in the arginine biosynthesis pathway.

BACKGROUND: Rheum officinale Baill. (ROB), as one of the traditional Chinese medicines for promoting blood circulation and removing blood stasis, has a wide range of pharmacological effects, such as cardiovascular protection, and has become a common drug in the clinical care of thrombosis. OBJECTIVE: Although there are some pharmacological studies on ROB in the treatment of thrombotic diseases, the mechanism and material basis are still unclear. Based on the arginine biosynthesis signalling pathway, this research explored the target proteins and metabolites related to the intervention of ROB in thrombosis and expounded on the antithrombotic mechanism of ROB from the comprehensive perspectives of target prediction, intermediate metabolites and potential metabolic pathways. METHODS: In this research, ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) technology was used to qualitatively detect the chemical compounds of ROB, and the antithrombotic activity of ROB was evaluated by establishing a zebrafish model. The target function was predicted by network pharmacology, and differential metabolites were screened by metabolomics and multivariate statistical analysis methods. Correlation analysis of network pharmacology and metabolomics screening results was conducted to identify the potential pathway of ROB intervention in thrombosis, and the prediction results were further verified. RESULTS: ROB significantly reduced the reactive oxygen species (ROS) staining intensity in zebrafish induced by phenylhydrazine (PHZ) and improved the inhibition rate of thrombosis. By constructing the "herb-disease-component-target" network, it was concluded that the active ingredients of ROB in treating thrombosis involved emodin, aloe-emodin and physcion, and the key targets included nitric oxide synthase 2 (NOS2) and nitric oxide synthase 3 (NOS3). A total of 341 differential metabolites in zebrafish with thrombosis were screened by partial least squares discriminant analysis (PLS-DA). The results of reverse transcription-polymerase chain reaction (RT-PCR) experiments and targeted metabolomics verification showed that ROB was mainly involved in improving thrombosis by upregulating the expression of NOS3 mRNA and regulating the levels of arginine, glutamate and glutamine in the arginine biosynthesis pathway. CONCLUSIONS: ROB improved thrombosis by regulating the expression of NOS3 mRNA and the contents of arginine, glutamate and glutamine in the arginine biosynthesis signalling pathway.

Poria cum Radix Pini Rescues Barium Chloride-Induced Arrhythmia by Regulating the cGMP-PKG Signalling Pathway Involving ADORA1 in Zebrafish.

The traditional Chinese medicine Poria cum Radix Pini (PRP) is a fungal medicinal material that has been proven to play an important role in the treatment of arrhythmia. However, the mechanism of its effect on arrhythmia is still unclear. In this study, network pharmacology and metabolomics correlation analysis methods were used to determine the key targets, metabolites and potential pathways involved in the effects of PRP on arrhythmia. The results showed that PRP can significantly improve cardiac congestion, shorten the SV-BA interval and reduce the apoptosis of myocardial cells induced by barium chloride in zebrafish. By upregulating the expression of the ADORA1 protein and the levels of adenosine and cGMP metabolites in the cGMP-PKG signalling pathway, PRP can participate in ameliorating arrhythmia. Therefore, we believe that PRP shows great potential for the treatment of arrhythmia.

Early intervention with Di-Dang Decoction prevents macrovascular fibrosis in diabetic rats by regulating the TGF-ß1/Smad signalling pathway.

Macroangiopathy is a complication of Type II Diabetes Mellitus (T2DM), which is mainly caused by fibrosis of blood vessels. Using T2DM rat models, we investigated whether the traditional Chinese medicine, Di-Dang Decoction (DDD), exhibited anti-fibrotic actions on great vessels. T2DM rats were randomly divided into non-intervention group, early-, middle-, late-stage DDD intervention groups and control groups, including pioglitazone group and aminoguanidine group. After administration of DDD to T2DM rats at different times, we detected the amount of extracellular matrix (ECM) deposition in the thoracic aorta. The results showed that early-stage intervention with DDD could effectively protect great vessels from ECM deposition. Considering that TGF-ß1 is the master regulator of fibrosis, we further validated at the molecular level that, compared to middle- and late-stage intervention with DDD, early-stage intervention with DDD could significantly decrease the expression levels of factors related to the activated TGF-ß1/Smad signalling pathway, as well as the expression levels of downstream effectors including CTGF, MMP and TIMP family proteins, which were directly involved in ECM remodelling. Therefore, early-stage intervention with DDD can reduce macrovascular fibrosis and prevent diabetic macroangiopathy.

Efficacy and safety of Xuebijing injection (a Chinese patent) for sepsis: A meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Xuebijing injection (XBJ), a Chinese patent medicine that was approved for treating sepsis in China in 2004, consists of Carthamus tinctorius L. (Carthami Flos, hong hua), Paeonia lactiflora Pall. (Paeoniae Radix Rubra, chi shao), Ligusticum chuanxiong Hort. (Chuanxiong Rhizoma, chuan xiong), Salvia miltiorrhiza Bge. (Salviae Miltiorrhizae Radix Et Rhizoma, dan shen) and Angelica sinensis (Oliv.) Diels (Angelicae Sinensis Radix, dang gui). AIM OF THE STUDY: This study aimed to assess the efficacy and safety of XBJ combined with routine treatment (RT) for treating sepsis through systematic review and meta-analysis. MATERIALS AND METHODS: Databases including Embase, PubMed, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journal Database (VIP) and the Wanfang database were searched from inception to June 6, 2017 to collect relevant RCTs comparing XBJ combined with RT and RT alone for sepsis. The primary clinical outcomes were 28-day mortality and mortality during treatment. The secondary outcomes of our study included APACHE Ⅱ scores, WBC counts, body temperature, and adverse events or reactions. We excluded low-quality studies (Jadad score < 3) and calculated risk ratios (RR) for primary outcomes with fixed effects models. We assessed quality of evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. RESULTS: We identified 1602 records, and 16 RCTs (1144 patients) were included. Moderate-quality evidence suggested that combined therapy reduced 28-day mortality (934/1144, RR 0.62, 95% CI 0.51-0.76 P < 0.000 01, I2 = 0%), APACHE Ⅱ scores (792/1144, MD -3.53, 95% CI -4.49 to -2.54; P < 0.000 01, I2 = 59%) and body temperature (362/1144, MD -0.43, 95% CI -0.55 to -0.31; P < 0.000 01, I2 = 0%). Very low-quality evidence showed that WBC count improved with combined medication at high dosages (one study included, 40/1144, MD -8.00, 95% CI -10.18 to -5.82), but there was no reduction at moderate dosages (230/1144, MD -2.38, 95% CI -5.01 to 0.25; P = 0.08, I2 = 70%). However, moderate-quality evidence indicated positive results with low dosages (142/1144, MD -2.88, 95% CI -3.79 to -1.96; P < 0.000 01, I2 = 0%). Nevertheless, due to the insufficient number of studies and the poor quality of the current evidence, more studies of dose-effect relationships and safety concerns of XBJ are needed. Low-quality evidence showed no risk difference for mortality during treatment (210/1144, RR 0.65, 95% CI 0.36-1.17; P = 0.15, I2 = 0%). CONCLUSIONS: This study suggested that supplementation with XBJ in addition to regular treatment may improve the 28-day mortality rate, APACHE Ⅱ scores, WBC count and body temperature of sepsis patients without serious adverse events, but it may not reduce mortality during treatment, revealing a specific, remote effect of traditional Chinese medicine. However, given the high risk of bias and the low quality of the included trials, we may be unable to draw any conclusions about its routine use. Rigorously designed, multicentre, large-scale, methodologically sound trials are warranted.

Three New Triterpenoid Saponins from Notoginseng Medicinal Fungal Substance.

Three new triterpenoid saponins, named ginsenoside-Rh23 (1), ginsenoside-Rh24 (2), and ginsenoside-Rh25 (3), were isolated from notoginseng medicinal fungal substance. Their structures were elucidated by a combination of 1D- and 2D-NMR, MS and chemical analysis. Compounds 1 - 3 exhibited moderate cytotoxic activity against MCF-7 and NCI-H460 cancer cell lines.

Early intervention with Didang decoction delays macrovascular lesions in diabetic rats through regulating AMP-activated protein kinase signaling pathway.

The study aimed to investigate the intervening role of Didang decoction (DDD) at different times in macrovascular endothelial defense function, focusing on its effects on the AMP-activated protein kinase (AMPK) signaling pathway. The effects of DDD on mitochondrial energy metabolism were also investigated in rat aortic endothelial cells (RAECs). Type 2 diabetes were induced in rats by streptozotocin (STZ) combined with high fat diet. Rats were randomly divided into non-intervention group, metformin group, simvastatin group, and early-, middle-, late-stage DDD groups. Normal rats were used as control. All the rats received 12 weeks of intervention or control treatment. Western blots were used to detect the expression of AMP-activated protein kinase α1 (AMPKα1) and peroxisome proliferator-activated receptor 1α (PGC-1α). Changes in the intracellular AMP and ATP levels were detected with ELISA. Real-time-PCR was used to detect the mRNA level of caspase-3, endothelial nitric oxide synthase (eNOS), and Bcl-2. Compared to the diabetic non-intervention group, a significant increase in the expression of AMPKα1 and PGC-1α were observed in the early-stage, middle-stage DDD groups and simvastatin group (P < 0.05). The levels of Bcl-2, eNOS, and ATP were significantly increased (P < 0.05), while the level of AMP and caspase-3 were decreased (P < 0.05) in the early-stage DDD group and simvastatin group. Early intervention with DDD enhances mitochondrial energy metabolism by regulating the AMPK signaling pathway and therefore may play a role in strengthening the defense function of large vascular endothelial cells and postpone the development of macrovascular diseases in diabetes.

Chinese herbal medicine for obesity: a randomized, double-blinded, multicenter, prospective trial.

Obesity is a serious medical problem worldwide. As a holistic therapy, traditional Chinese medicine (TCM) may have a potential in obesity management. In this controlled trial, we evaluated the safety and effectiveness of xin-ju-xiao-gao-fang (XJXGF), a TCM herbal formulation, in 140 obese subjects over a 24-week period. The XJXGF formula mainly consists of rhubarb, coptis, semen cassia, and citrus aurantium. Subjects with body mass index (BMI) 28-40 kg/m(2) were recruited at 5 centers in China. We assessed the changes in subjects' body weight, its related parameters, and the reduction of insulin resistance (IR) after administration of XJXGF formula or low-dose XJXGF (10% of the XJXGF formula, as control). After 24-week treatment, among participants in the XJXGF formula group and low-dose XJXGF group, the mean ± SE changes in the body weight were -3.58 ± 0.48 and -1.91 ± 0.38 kg, respectively (p < 0.01). The changes in the IR-index of two groups were -2.65 ± 1.04 and -1.58 ± 1.3, respectively (p < 0 .05). There were no serious adverse events reported during the 24-week trial. Participants reported 7 minor adverse events, 4 in the XJXGF formula group and 3 in the low-dose XJXGF group (p = 0.578). Future studies are needed to investigate the clinical utility of this TCM formulation in the treatment of obese subjects.

Improving participant adherence in clinical research of traditional chinese medicine.

Ensuring good participant adherence in clinical trials plays an important role in that poor adherence may jeopardize the internal validity of the trial. Improving adherence in clinical trials on traditional Chinese medicine (TCM) has long been a concern for Chinese researchers who are conducting clinical trials. Drawing on from our past experiences in managing patient adherence in large-scale clinical trials, we identified factors that influence adherence and categorized them by sources into factors with respect to the trial protocol, on the part of the patients and the investigators. On this basis, we developed a series of ways to improve participants' adherence, while taking into account the characteristics of TCM trials, in the hope of providing reference for peer clinical researchers.

Prospective multicenter clinical trial of Chinese herbal formula JZQG (Jiangzhuoqinggan) for hypertension.

A prospective multicenter clinical trial was conducted to compare the beneficial effects of a Chinese herbal medicine formula Jiangzhuoqinggan (JZQG) and western antihypertension drug irbesartan. JZQG is mainly composed of rhubarb, coptis, cassia, and uncaria. A total of 240 patients with mild to moderate hypertension were enrolled in the trial. Patients were assigned into two groups after screening: JZQG group and the irbesartan group. After four weeks of treatment, we compared the changes in routine blood pressure, 24 h ambulatory blood pressure, and waist circumference. There was a significant reduction in systolic blood pressure and diastolic blood pressure in the JZQG group (both p < 0.01). There were no significant differences between the reduction of systolic and diastolic blood pressures in the two treatment groups. From the 24 h ambulatory blood pressure measurement, the JZQG group showed a greater reduction in both systolic and diastolic blood pressures (in both daytime and nighttime) than the irbesartan group. Furthermore, there was a significant difference in waist circumference in the JZQG group (1.51 cm reduction; P < 0.05) but not the irbesartan group (0.42 cm). Thus, the JZQG formula may have therapeutic value in patients with both hypertension and metabolic syndrome.

Euonymus alatus in the treatment of diabetic nephropathy in rats.

Diabetic nephropathy is a leading cause of chronic renal failure. Recently, Euonymus alatus showed therapeutic potential in the treatment of diabetes and its chronic complications. In this study, effects of Euonymus alatus and its mechanism in the treatment of diabetic nephropathy were investigated. Diabetic nephropathy was induced in Sprague-Dawley rats by uninephrectomy plus streptozotocin (STZ) administration. Euonymus alatus and irbesartan, as a positive control, were lavaged to these rats for 12 weeks. Our data showed that Euonymus alatus was efficient in lowering HbA1c, improving blood lipids, decreasing 24 h urine protein and protecting kidney function. Pathological studies found kidney damage, including extracellular matrix expansion and glomerulosclerosis, were improved by Euonymus alatus treatment. Further investigation found that the herb had a role in downregulating the expression of transform growth factor ß(1). In conclusion, Euonymus alatus has a protective role in diabetic nephropathy, which may be related to its downregulation of transform growth factor ß(1) expression.

Hepatic PTP1B expression involvement in the effects of Chinese medicine formula xiao-gao-jiang-zhuo using an obese rat model.

In this study, we investigated the effects of a Chinese herbal medicine formula xiao-gao-jiang-zhuo (XGJZ) in obese rats induced by a high-fat diet. Ten male rats in the normal group were fed with a standard diet. Another 50 male obese rats were induced by a 12-week high-fat diet feeding, and were randomly divided into five groups (n = 10 per group): the model group, the high-dose XGJZ group, the middle-dose XGJZ group, the low-dose XGJZ group, and the sibutramine group. After 14 weeks of treatment, body weight, abdominal fat, blood lipid and serum insulin level were measured, and the protein and gene expression of PTP1B in liver tissue was tested. Our data showed that the body weight of the high-dose and middle-dose groups and the sibutramine group had significant differences in comparison with the model group (p < 0.05), and all three dose groups had significantly reduced abdominal fat (p < 0.05). The triglyceride level of the three dose groups and the sibutramine group, and the total cholesterol level of the middle-dose group were all significantly reduced (p < 0.05). The serum insulin of the high-dose and middle-dose groups also decreased significantly (p < 0.05). The expression of hepatic PTP1B mRNA of the three dose groups decreased significantly in comparison with the model group (p < 0.05 or 0.01). The expression of hepatic PTP1B protein of the high-dose and middle-dose groups decreased significantly (p < 0.05). Our data suggested that XGJZ can modulate the body weight, abdominal fat and blood lipid in the obese rats, and this modulation might improve insulin resistance by inhibiting the PTP1B signal pathway.

Anti-diabetic effects of a Coptis chinensis containing new traditional Chinese medicine formula in type 2 diabetic rats.

The Chinese formula Tang-Min-Ling (TML), an improved product of the decoction of Dachaihu which has a history of more than 2000 years, has main constituents of Coptis chinensis Franch, Scutellaria baicalensis Georgi, Rheum officinale Baill and Bupleurum chinense DC. A multi-central randomized controlled investigation performed previously by us has showed that TML has positive effects on regulating glycometabolism in type 2 diabetes (T2DM) patients, but the mechanisms remain unclear. Using Otsuka Long-Evans Tokushima Fatty (OLETF) rats as an animal model with rosiglitazone as a positive control, we were able to detect TML's effect on the serum glucose, serum lipid, serum leptin and adiponcetin after oral administration for 12 weeks. We were also able to detect the insulin resistance level by a glucose clamp test and study the mechanisms of TML in improving insulin resistance by detecting skeletal muscle AMP-activated protein kinase (AMPK) and glucose transporter 4 (GLUT4). Results showed that TML significantly reduced the glucose area under a curve of the oral glucose tolerance test, and had a positive effect in regulating serum lipid metabolism. TML treatment also significantly reduced the serum leptin level, but it had no effect on the serum adiponectin level. The AMPK enzymatic activity and GLUT4 expression in Skeletal Muscle were also upregulated in the TML group. The results suggest that the Chinese medicine TML, which contains Coptis chinensis Franch as one of its components, improves glycometabolism and its possible mechanisms may involve in improvement of insulin resistance of OLETF rats.

Osteogenetic effect of mechanical vibration on bone / 中国骨伤

Mechanical loading is the main "instructive" factor of bone formation. The mechanism becomes the heat point in the field of bone science, biomedicine project and rehabilitation research. Mechanical vibration is one of the mechanic stimulation. Evidences show that vibration has obvious anabolic effect, and will have a broad landscape in the treatment of osteoporosis. But in the present studies, there were incorporated with the vibration frequency, and intensity, in particularly, few reports about the mechanism of vibration to bone. It will provide theoretic foundation for further systematic, sound research and its clinical application.

Studies on chemical constituent and quantitative determination of Mallotus apelta / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the chemical constituents and establish a quantitative method of Mallotus apelta.</p><p><b>METHOD</b>Compound was isolated by silica gel, Sephadex LH-20 column chromatography and Pre-HPLC chromatography. Its structure was identified by physicochemical properties and spectral evidences. The content of M. apelta was determined by HPLC. Chromatographic conditions included Inertsil ODS-3 C18 column (4.6 mm x 150 mm, 5 microm) and the mobile phase consisting of a mixture of methanol-water (24:76). The detection wavelength was set at 335 nm.</p><p><b>RESULT</b>One compound was isolated from n-butanol extract of the M. apelta and its structure was identified as vicenin II. The calibration cure was linear in the range of 0.053-10.60 microg (r = 0.9999), the average recovery was 99. 32%, RSD 1.82% (n = 6).</p><p><b>CONCLUSION</b>The compound was isolated from this plant for the first time. The method to determine the content of vicenin II by HPLC was established for the first time. This method is simple, accurate and reliable.</p>

Gastric mucosal injury due to hemorrhagic reperfusion and efficacy of Salvia miltiorrhizae extract F and cimetidine.

AIM: To observe the gastric mucosal injury caused by hemorrhagic shock and reperfusion and to compare the effect between Salvia miltiorrhizae extract F (SEF) and cimetidine (CI) on it. METHODS: A model of hemorrhage/reperfusion injury was produced by Itoh method. Wistar rats were randomly divided into three groups: 0.9% sodium chloride treatment group (NS group), SEF treatment group (SEF group), and CI treatment group (CI group). Saline, SEF and CI were injected respectively. The index of gastric mucosal lesions (IGML) was expressed as the percentage of lesion area in the gastric mucosa. The degree of gastric mucosal lesions was categorized into grades 0, 1, 2, 3. Atom absorption method was used to measure the intracellular calcium content. Radioimmunoassay was used to measure the concentrations of prostaglandins. RESULTS: IGML (%) and grade 3 (%) were 23.18+/-6.82, 58.44+/-9.07 in NS group, 4.42+/-1.39, 20.32+/-6.95 in SEF group and 3.74+/-1.56, 23.12+/-5.09 in CI group, and the above parameters in SEF group and CI group decreased significantly (IGML: SEF vs NS, t = 6.712, P = 0.000<0.01; CI vs NS, t = 6.943, P = 0.000<0.01; grade 3: SEF vs NS, t = 8.386, P = 0.000; CI vs NS, t = 8.411, P = 0.000), but the grade 0 and grade 1 damage in SEF group (22.05+/-5.96, 34.12+/-8.12) and CI group (18.54+/-4.82, 30.15+/-7.12) were markedly higher than those in NS group (3.01+/-1.01, 8.35+/-1.95; grade 0: SEF vs NS, t = 8.434, P = 0.000<0.01; CI vs NS, t = 7.950, P = 0.000<0.01; grade 1: SEF vs NS, t = 8.422, P = 0.000<0.01; CI vs NS, t = 8.448, P = 0.000<0.01). The intracellular calcium content (microg/mg) in SEF group (0.104+/-0.015) and CI group (0.102+/-0.010) was markedly lower than that in NS group (0.131+/-0.019, SEF vs NS, t = 2.463, P = 0.038<0.05; CI vs NS, t = 3.056, P = 0.017<0.05). The levels (pg/mg) of PGE(2), 6-keto-PGF(1alpha) and 6-keto-PGF(1alpha)/TXB(2) were 540+/-183, 714+/-124, 17.38+/-5.93 in NS group and 581+/-168, 737+/-102, 19.04+/-8.03 in CI group, 760+/-192, 1 248+/-158, 33.42+/-9.24 in SEF group, and the above parameters in SEF group markedly raised (PGE(2): SEF vs NS, t = 2.282, P = 0.046<0.05; SEF vs CI, t = 2.265, P = 0.047<0.05; 6-keto-PGF(1alpha): SEF vs NS, t = 6.583, P = 0.000<0.000; SEF vs CI, t = 6.708, P = 0.000<0.01; 6-keto-PGF(1alpha)/TXB(2): SEF vs NS, t = 3.963, P = 0.003<0.001; SEF vs CI, t = 3.243, P = 0.009<0.01), whereas TXB(2) level in SEF group (45.37+/-7.54) was obviously lower than that in NS group (58.28+/-6.74, t = 3.086, P = 0.014<0.05) and CI group (54.32+/-6.89, t = 2.265, P = 0.047<0.05). No significant difference was shown between NS group and CI group (PGE(2): t = 0.414, P = 0.688>0.05; 6-keto-PGF(1alpha): t = 0.310, P = 0.763>0.05; TXB(2): t = 1.099, P = 0.298>0.05; 6-keto-PGF(1alpha)/TXB(2): t = 0.372, P = 0.718>0.05). CONCLUSION: Both SEF and CI could inhibit reperfusion-induced injury in gastric mucosa, but with different mechanisms. SEF could not only enhance the protective effect of gastric mucosa, but also abate the injury factors, while CI can only abate the injury factors.