Huayu Qutan Recipe promotes lipophagy and cholesterol efflux through the mTORC1/TFEB/ABCA1-SCARB1 signal axis.

This study aims to investigate the mechanism of the anti-atherosclerosis effect of Huayu Qutan Recipe (HYQT) on the inhibition of foam cell formation. In vivo, the mice were randomly divided into three groups: CTRL group, MOD group and HYQT group. The HYQT group received HYQT oral administration twice a day (20.54 g/kg/d), and the plaque formation in ApoE-/- mice was observed using haematoxylin-eosin (HE) staining and oil red O (ORO) staining. The co-localization of aortic macrophages and lipid droplets (LDs) was examined using fluorescent labelling of CD11b and BODIPY fluorescence probe. In vitro, RAW 264.7 cells were exposed to 50 µg/mL ox-LDL for 48 h and then treated with HYQT for 24 h. The accumulation of LDs was evaluated using ORO and BODIPY. Cell viability was assessed using the CCK-8 assay. The co-localization of LC3b and BODIPY was detected via immunofluorescence and fluorescence probe. LysoTracker Red and BODIPY 493/503 were used as markers for lysosomes and LDs, respectively. Autophagosome formation were observed via transmission electron microscopy. The levels of LC3A/B II/LC3A/B I, p-mTOR/mTOR, p-4EBP1/4EBP1, p-P70S6K/P70S6K and TFEB protein level were examined via western blotting, while SQSTM1/p62, Beclin1, ABCA1, ABCG1 and SCARB1 were examined via qRT-PCR and western blotting. The nuclear translocation of TFEB was detected using immunofluorescence. The components of HYQT medicated serum were determined using Q-Orbitrap high-resolution MS analysis. Molecular docking was employed to identify the components of HYQT medicated serum responsible for the mTOR signalling pathway. The mechanism of taurine was illustrated. HYQT has a remarkable effect on atherosclerotic plaque formation and blood lipid level in ApoE-/- mice. HYQT decreased the co-localization of CD11b and BODIPY. HYQT (10% medicated serum) reduced the LDs accumulation in RAW 264.7 cells. HYQT and RAPA (rapamycin, a mTOR inhibitor) could promote cholesterol efflux, while chloroquine (CQ, an autophagy inhibitor) weakened the effect of HYQT. Moreover, MHY1485 (a mTOR agonist) also mitigated the effects of HYQT by reduced cholesterol efflux. qRT-PCR and WB results suggested that HYQT improved the expression of the proteins ABCA1, ABCG1 and SCARB1.HYQT regulates ABCA1 and SCARB1 protein depending on the mTORC1/TFEB signalling pathway. However, the activation of ABCG1 does not depend on this pathway. Q-Orbitrap high-resolution MS analysis results demonstrated that seven core compounds have good binding ability to the mTOR protein. Taurine may play an important role in the mechanism regulation. HYQT may reduce cardiovascular risk by promoting cholesterol efflux and degrading macrophage-derived foam cell formation. It has been observed that HYQT and ox-LDL regulate lipophagy through the mTOR/TFEB signalling pathway, rather than the mTOR/4EBP1/P70S6K pathway. Additionally, HYQT is found to regulate cholesterol efflux through the mTORC1/TFEB/ABCA1-SCARB1 signal axis, while taurine plays a significant role in lipophagy.

Large-Scale, Uniform-Patterned CsCu2 I3 Films for Flexible Solar-Blind Photodetectors Array with Ultraweak Light Sensing.

Cesium copper halide perovskite is one of the promising materials for solar-blind light detection. However, most of the cesium copper halide perovskite-based photodetectors (PDs) are focused on ultraviolet A detection and realized on the rigid substrate in the single device configuration. Here, a flexible solar-blind PDs array (10 × 10 pixels) based on the CsCu2 I3 film patterns for ultraweak light sensing and light distribution imaging is reported. Large-scale CsCu2 I3 film arrays are synthesized with various shapes and uniform dimensions through a simple vacuum-heating-assisted solution method. Benefiting from excellent air stability and superior resistance to the photodegrading of the CsCu2 I3 film, the array device exhibits long-term stable photoswitching behavior for 8 h and ultralow light detection capability to resolve the light intensity of 6.1 nW cm-2 with a high responsivity of 62 A W-1 , and the array device can acquire clear images of "G", "X", and "U" showing the input light distribution. Moreover, the flame detection and warning system based on a curved solar-blind PDs array is demonstrated, which can be used for multi-flame monitoring and locating. These results can encourage potential applications of the CsCu2 I3 film-based PDs array in the field of optical communication and environment monitoring.

Aberrant expression of HDL-bound microRNA induced by a high-fat diet in a pig model: implications in the pathogenesis of dyslipidaemia.

BACKGROUND: A high-fat diet can affect lipid metabolism and trigger cardiovascular diseases. A growing body of studies has revealed the HDL-bound miRNA profiles in familial hypercholesterolaemia; in sharp contrast, relevant studies on high-fat diet-induced dyslipidaemia are lacking. In the current study, HDL-bound miRNAs altered by a high-fat diet were explored to offer some clues for elucidating their effects on the pathogenesis of dyslipidaemia. METHODS: Six pigs were randomly divided into two groups of three pigs each, namely, the high-fat diet and the balanced diet groups, which were fed a high-fat diet and balanced diet separately for six months. HDL was separated from plasma, which was followed by dissociation of the miRNA bound to HDL. miRNA sequencing of the isolated miRNA was performed to identify the differential expression profiles between the two groups, which was validated by real-time PCR. TargetScan, miRDB, and miRWalk were used for the prediction of genes targeted by the differential miRNAs. RESULTS: Compared with the balanced diet group, the high-fat diet group had significantly higher levels of TG, TC, LDL-C and HDL-C at six months. miRNA sequencing revealed 6 upregulated and 14 downregulated HDL-bound miRNAs in the high-fat diet group compared to the balanced diet group, which was validated by real-time PCR. GO enrichment analysis showed that dysregulated miRNAs in the high-fat diet group were associated with the positive regulation of lipid metabolic processes, positive regulation of lipid biosynthetic processes, and positive regulation of Ras protein signal transduction. Insulin resistance and the Ras signalling pathway were enriched in the KEGG pathway enrichment analysis. CONCLUSIONS: Twenty HDL-bound miRNAs are significantly dysregulated in high-fat diet-induced dyslipidaemia. This study presents an analysis of a new set of HDL-bound miRNAs that are altered by a high-fat diet and offers some valuable clues for novel mechanistic insights into high-fat diet-induced dyslipidaemia. Further functional verification study using a larger sample size will be required.

Bisphenol A, S, and F exposure, ESR1/2, CAT, and eNOS genetic polymorphisms, and the risk of hypertension.

While bisphenol A (BPA) exposure was inconsistently associated with hypertension risk, little is known about whether its alternatives bisphenol S and F (BPS and BPF) have similar hypertensive effects. Furthermore, epidemiologic studies on the genetic susceptibility to the hypertensive effects of bisphenols are scarce. We conducted a case-control study in 439 pairs of hypertension cases and matched controls. Urinary bisphenols concentrations were measured to characterize the internal exposure levels. The genotyping of ESR1/2, CAT, and eNOS was performed by a multiplex fluorescent polymerase chain reaction. BPA exposure was positively associated with hypertension risk. Carriers of rs2234693 C allele in ESR1 were associated with increased hypertension risk. Significant associations of BPA exposure with increased hypertension risk were suggested in individuals with the major allele of rs1256049 in ESR2, rs769214 in CAT, and rs1799983 in eNOS. Besides, rs4755374 in CAT might modify the association of BPA exposure with hypertension risk. Individuals with specific genotypes in ESR1/2, CAT, and eNOS might be more susceptible to the hypertensive effects of BPA.

LncRNA NORAD targets miR-410-3p to regulate drug resistance sensitivity of osteosarcoma.

The current experiment was performed to investigate the effect of LncRNA NORAD on the sensitivity of miR-410-3p to drug resistance of osteosarcoma cells. The cisplatin-resistant cell line HOS/DDP was induced; si-NC, si-NORAD, miR-NC, miR-410-3p, pcDNA-NC, and pcDNA-NORAD were transfected into HOS/DDP cells, respectively; record as a si-NC group, si-NORAD group, miR-NC group, miR-410-3p group, pcDNA-NC group, pcDNA-NORAD group; si-NORAD was co-transfected into HOS/DDP cells with anti-miR-NC, anti-miR-410-3p, recorded as an anti-miR-NC+si-NORAD group and anti-miR-410-3p+si-NORAD group. Real-time quantitative PCR (RT-qPCR) was used to detect LncRNA NORAD, miR-410-3p and multidrug resistance protein 1 (MRP1) mRNA expression levels; Western blot was used to detect cyclin D1 (CyclinD1), MRP1, phosphorylated (p-p65), phosphorylated IкBα (p-IкBα) protein expression; cell counting kit 8 (CCK-8) was used to detect cell viability; dual luciferase report assay to detect targeting relationship between LncRNA NORAD and miR-410-3p. Compared with osteosarcoma cells HOS, the expression levels of LncRNA NORAD, MRP1 mRNA and protein in osteosarcoma resistant cells HOS/DDP were significantly increased, and miR-410-3p expression levels were significantly reduced (P<0.05). Low expression of NORAD or high expression of miR-410-3p, CyclinD1, MRP1 expression levels were significantly reduced, the cell survival rate was significantly reduced, and the half inhibitory concentration of cisplatin was significantly reduced (P<0.05). LncRNA NORAD targets and regulates miR-410-3p, and low expression of miR-410-3p can reverse the effects of low NORAD expression on HOS/DDP cell proliferation and cisplatin resistance. Low expressions of NORAD, p-p65, p-IкBα protein expression levels were significantly reduced; low expression of miR-410-3p could reverse the inhibitory effect of low NORAD expression on p-p65, p-IкBα protein expression. Inhibition of LncRNA NORAD expression can inhibit the proliferation of osteosarcoma HOS/DDP cells through targeted regulation of miR-410-3p, increasing its sensitivity to cisplatin, and it may be related to the NF-κB signaling pathway.

Association of dietary patterns with depressive symptoms in Chinese postmenopausal women.

Many components in diet have regulated oxidative stress, inflammatory reaction and even balance oestrogen levels. Because these factors are closely associated with depressive symptoms in postmenopausal women, it is considered that dietary factors are able to prevent and control depressive symptoms. On the other hand, a dietary pattern that considers the correlations and synergies between foods and nutrients is expected to have a greater impact on disease risk. The aim of the present study is to evaluate whether dietary patterns are associated with depressive symptoms in Chinese postmenopausal women. A cross-sectional study of 2051 postmenopausal women (mean age: 58·8 (sd 7·4) years) was conducted in Tianjin, China. Dietary consumption was assessed by a valid self-administered FFQ. Principal component analysis was used to derive three major dietary patterns: 'healthy', 'sweets' and 'traditional Tianjin' from eighty-eight food items. Depressive symptoms were assessed using the Zung Self-Rating Depression Scale, and cut-off point of 48 indicating serious depressive symptoms. The association between quartile of dietary patterns and depressive symptoms was assessed using multiple logistic regression analysis. The multivariable-adjusted OR of having depressive symptoms for increasing quartile of dietary patterns were as follows: healthy, 1·00, 0·79 (95 % CI 0·49, 1·28), 0·62 (95 % CI 0·37, 1·04) and 0·57 (95 % CI 0·33, 0·97); sweets, 1·00, 0·75 (95 % CI 0·42, 1·3), 1·08 (95 % CI 0·64, 1·81) and 1·66 (95 % CI 1·03, 2·71); and traditional Tianjin, 1·00, 1·02 (95 % CI 0·58, 1·79), 0·96 (95 % CI 0·54, 1·71) and 2·53 (95 % CI 1·58, 4·16), respectively. The present study demonstrated that a healthy dietary pattern was inversely associated with depressive symptoms. On the contrary, greater adherence to sweets and traditional Tianjin dietary patterns was associated with a higher prevalence of depressive symptoms.

Pharmacokinetic studies of soyalkaloid A from Portulaca oleracea L. using ultra high-performance liquid chromatography electrospray ionization quadrupole-time of flight mass spectrometry and its antioxidant activity.

Soyalkaloid A was isolated from Portulaca oleracea L. for the first time in our laboratory and then a rapid and sensitive ultra-high-performance liquid chromatography electrospray ionization quadrupole-time of flight mass spectrometry (UHPLC-ESI-Q-TOF/MS) method with hesperidin as internal standard (IS) was developed and validated to investigate the pharmacokinetics of soyalkaloid A in rats after oral and intravenous administrations. The analysis was achieved on an Agilent Zorbax Eclipse Plus C18 Column (2.1 × 50 mm, 1.8 µm) by elution with acetonitrile and water (containing 0.1% formic acid), at a flow rate of 0.3 mL/min. The MS analysis was performed in the positive ion mode with monitored ion m/z 227.0814 [M + H]+ and 611.1971 [M + H]+ for soyalkaloid A and IS, respectively. The linear range was established over the concentration range 7.5-6000 ng/mL (r = 0.9951). The intra- and inter-assay accuracy and precision were between -4.86-4.49 and 1.93-9.66, respectively. The lower limits of detection and quantitation observed were 2.1 and 7.4 ng/mL, respectively. The rapid, sensitive and specific UHPLC-ESI-Q-TOF/MS method was successfully applied to a pharmacokinetic study of soyalkaloid A. Moreover, its antioxidant was studied via a 1,1-diphenyl-2-picryl-hydrazyl radical scavenging assay, the IC50 value being 20.73 ± 0.51 µM.

Investigating the bioavailabilities of olerciamide A via the rat's hepatic, gastric and intestinal first-pass effect models.

Olerciamide A (OA) is a new alkaloid isolated from Portulaca oleracea L. that has been proved to possess a low bioavailability (F) after oral administration in rats in our previous study. Hence, to clarify the reasons for its low bioavailability, hepatic, gastric and intestinal first-pass effect models were established, and a rapid, sensitive UHPLC method was validated and applied for the determination after dosing via the femoral, portal, gastric and intestinal routes. As inhibitors of CYP3A and P-gp, verapamil, midazolam and borneol in low and high dose groups were selected to improve the low bioavailability of olerciamide A. Moreover, a rectal administration method was also carried out to improve the bioavailability of olerciamide A. The results showed that the bioavailability of olerciamide A using hepatic, gastric and intestinal routes were 92.16%, 84.88% and 5.76%, respectively. The areas under the plasma concentration-time curve from zero to infinity (AUC0 → ∞ ) were increased a little after being dosed with 10 and 30 mg/kg verapamil (p > 0.05), but markedly increased after being dosed with 0.4 and 1.2 mg/kg midazolam as well as 8 and 24 mg/kg borneol (p < 0.05). Besides, the AUC0 â†’ ∞ values after the lower and upper rectal administrations were separately similar to the intravenous and intraportal administrations. Our study showed that the intestinal first-pass effect mainly contributed to the low bioavailability of olerciamide A in rats due to it being a substrate of CYP3A and P-gp as well as to its poor intestinal absorption.

Pharmacokinetics and metabolism of olerciamide A from Portulaca oleracea L. in rats by UHPLC-UV and UHPLC-ESI-Q-TOF/MS.

The aim of this study was to elucidate the pharmacokinetics of olerciamide A in rats after oral and intravenous administration of Portulaca oleracea L. extract by a simple and rapid ultra high-performance liquid chromatography method with bergapten as internal standard. The pharmacokinetic results indicated that olerciamide A was rapidly distributed with a time to peak concentration of 30 min after oral administration and presented a low oral absolute bioavailability of 4.57%. The metabolism of olerciamide A in rats was also investigated using ultra-high-performance liquid chromatography electrospray coupled with quadrupole-time of flight mass spectrometry to elucidate the reason for the low absolute bioavailability of olerciamide A and seven metabolites of oleraciamide A were found in rat plasma and urine.

Sini decoction as an adjuvant therapy for angina pectoris: a systematic review of randomized controlled trials.

OBJECTIVE: To systematically assess the effects and safety of Sini decoction as an adjuvant therapy for patients with angina pectoris. METHODS: We searched PubMed, Excerpt Medica Database, the Cochrane library, Wanfang Database, China National Knowledge Infrastructure Database, China Science and Technology Journal Database from the date of its inception until August 1, in 2014. Available literatures were selected according to the inclusion criteria. Two reviewers finished data extraction, checked the data and assessed the methodological quality of studies, independently. The Review Manage Software 5.1.0 was used for data analysis. RESULTS: Six trials involving 453 participants were eligible. None of the trials reported the mortality due to angina pectoris. The secondary outcomes showed that Sini decoction, together with nitroglycerin when necessary, may have some effects on reducing the number of angina attacks and the amount of nitroglycerin. But in terms of reducing the duration of angina and improvement of electrocardiogram, there were no statistical differences between Sini decoction group and isosorbide dinitrate group. Only one reported that no adverse events were found. CONCLUSION: Based on this systematic review, Sini decoction can reduce the dosage of nitroglycerin, when compared with isosorbide dinitrate group. And there were no enough evidence in the papers to draw any conclusions for the safety of Sini decoction.

Tanshinone IIA affects the HDL subfractions distribution not serum lipid levels: Involving in intake and efflux of cholesterol.

AIM OF STUDY: Tanshinone IIA is an active component of the traditional Chinese medicine. This study aimed at investigating the mechanism of tanshinone IIA on anti-atherosclerosis, which may be because of that Tanshinone IIA can affect the HDL subfractions distribution and then regulate reverse cholesterol transport. MATERIALS AND METHODS: A model of hyperlipidaemia in rats was used. Tanshinone IIA was given daily after hyperlipidaemia. In vivo, lipid deposition and morphological changes in liver were analyzed; HDL subfractions and lipid level in serum as well as in liver were measured; the expression of genes related to cholesterol intake in liver and peritoneal macrophage cholesterol efflux were evaluated. In vitro, HepG2 cells and THP-1 cells were pretreated with tanshinone IIA and subsequently with ox-LDL to evaluate the total cholesterol and the expression of related genes. RESULTS: Tanshinone IIA reduced the lipid deposition in liver. Moreover, it did not affect the serum lipid levels but reduced the levels of HDL middle subfractions and increased the levels of HDL large subfractions. Furthermore, tanshinone IIA could regulate the expressions of CYP7A1, LDL-R, SREBP2 and LCAT in the liver as well as the ABCA1 and CD36 in macrophage cells which is involving in the cholesterol intake and efflux respectively. It could reduce lipid accumulation caused by ox-LDL induction, and that also regulate the expressions of LDL-R, HMGCR and SREBP2 in HepG2 and ABCA1, CD36 in THP-1 cells. CONCLUSION: A novel finding that tanshinone IIA was not reduce the serum lipid level but affects the HDL subfractions distribution and thereby regulating the intake and efflux of cholesterol.

[Study on Serum Metabolite Profiling in Pi-deficiency Rats Based on LC-MS Technique].

OBJECTIVE: To explore metabolite profiling changes in serum of rats with pi-qi deficiency syndrome (PQDS) and pi-yang deficiency syndrome (PYDS) based on liquid chromatograph-mass spectrometer (LC-MS) technique, and to explore the essence of Pi-deficiency syndrome (PDS) from small molecule metabolite level. METHODS: Totally 21 male SD rats of SPF grade were randomly divided into three groups, the normal control group, the PQDS group, and the PYDS group, 7 in each group. Rats in the PQDS group overate for 1 day and fasted for 2 days. They drank freely and then swam to be exhausted in water at 35 degrees C - 37 degrees C for 15 successive days. The PYDS model was established by the same method for PQDS rats plus drenching 20% Folium sennae water extract (2 mL/100 g), once in the morning and once in the evening for one successive week. After modeling, models were evaluated according to rat general state, changes in body weight and rectal temperature. Serum metabonomic profiles were detected using LC-MS technique. Difference in inter-group metabolite spectrograms was analyzed using orthogonal partial least squares discriminant analysis (OPLS-DA). Potential biomarkers related to syndrome types in rat serum were selected via the parameter of variable importance in the projection (VIP). RESULTS: The weight of rats in the PQDS group and the PYDS group decreased more significantly after modeling. The difference in prepost weight was statistically significant from that of the normal control group (P < 0.01). It was more obviously lowered in the PYDS group than in the PQDS group (P < 0.05). Compared with the normal control group, the rectal temperature of rats in the PYDS group and the PQDS group decreased (P < 0.05, P < 0.01). It decresed more in the PYDS group than in the PQDS group (P < 0.05, P < 0.01). Compared with the normal control group, levels of PC(19:0)/PE(22:0), PC(17:0)/PE(20:0), capric acid, oleic acid, stearic acid, succinic acid, fumaric acid, malic acid, glucose increased; arachidonic acid, linolenic acid, lauric acid, androsterone, 4-heptanone, dihydroxyacetonephosphate (DHAP) (6:0), and uridine decreased in the PYDS group and the PQDS group. Compared with the PQDS group, levels of PC(22:1), PC (22:6), PE (18:0)/PC (15:0), retinol, and deoxycytidine increased significantly in the PYDS group; PC (18:1), PC(19 :3), PC (20:3), PC (17:0)/PE (20:0), PC (19:1)/PE (22:1), PC (19:0)/PE (22:0), PC (17:1)/PE (20: 1), PC (16:1)/PE (19:1), cholic acid, hippuric acid, furoic acid, undecanedicarboxylic acid, palmitoleic acid, hydroxy stearic acid, eicosatrienoic acid, phenylalanine, tyrosine, glutamic acid, serine, carbamoyl aspartic acid, palmitoyl carnitine, tetradecanoyl carnitine, acetylcarnitine, and linoleylcarnitine decreased more significantly in the PYDS group. CONCLUSIONS: Comparative contents of various serum metabolites changed significantly in PQDS and PYQS model groups. Some potential small molecular biomarkers related to PDS were preliminarily identified. These results might provide some data reference for exploring scientific connotation and pathological mechanisms of PDS.

Effectiveness of acupuncture for angina pectoris: a systematic review of randomized controlled trials.

BACKGROUND: The purpose of this systematic review is to assess the effectiveness of acupuncture for angina pectoris. METHODS: Eleven electronic databases were searched until January 2013. The study included randomized controlled trials that the effectiveness of acupuncture alone was compared to anti-angina medicines (in addition to conventional treatment) and the effectiveness of a combination of acupuncture plus anti-angina medicines was compared to anti-angina medicines alone. The trial selection, data extraction, quality assessment and data analytic procedures outlined in the 2011 Cochrane Handbook were involved. RESULTS: The study included 25 randomized controlled trials (involving 2,058 patients) that met our inclusion criteria. The pooled results showed that the number of patients with ineffectiveness of angina relief was less in the combined acupuncture-anti-angina treatment group than in the anti-angina medicines alone group (RR 0.33, 95% CI 0.23-0.47, p < 0.00001, I2 = 0%). Similarly, compared to the anti-angina medicines alone group, fewer patients in the combined treatment group showed no ECG improvement (RR 0.50, 95% CI 0.40-0.62, p < 0.00001, I2 = 0%). However, no differences were observed between acupuncture treatment alone and anti-angina medicines alone for both outcome measures. Only four trials mentioned adverse effects. One trial found no significant difference between acupuncture and Chinese medicine, and three reported no adverse events. The quality of the trials was found to be low. CONCLUSIONS: The findings showed very low evidence to support the use of acupuncture for improving angina symptoms and ECG of angina patients. However, the quality of the trials included in this study was low. Large and rigorously designed trials are needed to confirm the potential benefit and adverse events of acupuncture.

[Intervention of Huayu Qutan Recipe on liver SREBP-2 signal pathway of hyperlipidemia rats of pi deficiency syndrome].

OBJECTIVE: To explore the intervention of Huayu Qutan Recipe (HQR) on liver SREBP-2 signal pathway of hyperlipidemia rats of Pi deficiency syndrome (PDS). METHODS: Totally 100 SPF grade SD rats were randomly divided into the blank control group, the hyperlipidemia group, the hyperlipidemia treatment group, the PDS hyperlipidemia group, and the PDS hyperlipidemia treatment group, 20 in each group. Common granular forage was fed to rats in the blank control group. High fat forage was fed to rats in the hyperlipidemia group and the hyperlipidemia treatment group. Rats in the PDS hyperlipidemia group and the PDS hyperlipidemia treatment group were treated with excessive labor and improper diet for modeling. They were administered refined lard by gastrogavage (3 mL each time, twice per day) and fed with high fat forage on the odd days, and fed with wild cabbage freely on even days. The modeling lasted for 30 days. Rats in the hyperlipidemia treatment group and PDS hyperlipidemia treatment group were administered with Huayu Qutan Recipe (20 mL/kg) by gastrogavage, once a day, for 30 successive days. Levels of serum cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and serum amylase (AMY) were detected by automatic biochemical analyzer. D-xylose excretion rate was determined using phloroglucinol method. Morphological changes of liver and the lipid deposition in liver were observed using HE stain and oil red O stain respectively, mRNA and protein expression levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase 1 (CYP7A1), LDL-R, and sterol regulatory element binding protein-2 (SREBP-2) were detected using real time RT-PCR and Western blotting. RESULTS: Compared with the blank control group, serum levels of TC (1.84 ± 0.19 mmol/L, 2.23 ± 0.43 mmol/L) and LDL-C (0.99 ± 0.24 mmol/L, 1.13 ± 0.56 mmol/L) were higher in the hyperlipidemia group and the PDS hyperlipidemia group, serum levels of HDL-C (0.41 ± 0.66 mmol/L, 0.41 ± 0.11 mmol/L) and AMY activities (351 ± 45 mmol/L, 153 ± 30 mmol/L) were lower, and urinary D-xylose excretion rates were lower (26.9 ± 2.1 ng/mL, 15.0 ± 1.7 ng/mL) (all P < 0.05). Lipid deposition occurred in liver cells. Much fat vacuoles occurred in the cytoplasm. Expression levels of HMGCR, CYP7A1, LDL-R, and SREBP-2 mRNA and proteins in liver significantly decreased (P < 0.01). Compared with the hyperlipidemia group, serum levels of TC and LDL-C significantly increased (P < 0. 05), AMY activities and urinary D-xylose excre- tion rates significantly decreased in the PDS hyperlipidemia group (P < 0.01). A large amount of lipid deposition occurred in liver. The atrophy of liver cells was obviously seen. Expression levels of CYP7A1, LDL-R, and SREBP-2 mRNA and proteins in liver were significantly lower (P < 0.01, P < 0.05). Serum levels of TC and LDL-C significantly decreased (P < 0.05), AMY activities and urinary D-xylose excretion rates significantly increased in the hyperlipidemia treatment group (P < 0.01). Expression levels of CYP7A1, LDL-R, and SREBP-2 mRNA and proteins in liver were significantly increased (P < 0.01, P < 0.05). Compared with the PDS hyperlipidemia group, serum level of TC significantly decreased (P < 0.05), HDL-C levels, AMY activities and urinary D-xylose excretion rates significantly increased in the PDS hyperlipidemia treatment group (P < 0.01),expression levels of CYP7A1, LDL-R, and SREBP-2 mRNA and proteins in liver were significantly increased (P < 0.01). Similar changes occurred in the two treatment groups. CONCLUSIONS: Pi deficiency exacerbates abnormal serum TC level and the lipid deposition in liver. These might be related to regulating expression levels of LDL-R, HMGCR, and CYP7A1 genes in the SREBP-2 signal pathway. HQR could regulate this pathway to intervene abnormal metabolism of TC.

[Adjunctive therapy of xuezhikang capsule for coronary heart disease: a systematic review and meta-analysis of randomized controlled trials].

OBJECTIVE: To systematically evaluate the effect and safety of Xuezhikang Capsule (XZKC) for adjuvant treatment for coronary heart disease (CHD) patients accompanied with or without dyslipidemia. METHODS: China National Knowledge Infrastructure (CNKI) Database, Chongqing VIP Database (VIP), Wanfang Data base, Cochrane Library, and Medline (PubMed) were retrieved with the deadline of August 30, 2013. Randomized controlled trials (RCT) of XZKC in treating CHD patients with or without dyslipidemia were all included. Assessment of bias risk for included studies was conducted according to the Cochrane Handbook for Systematic Reviews of Intervention (Version 5.0.2): Criteria for judging risk of bias in the "risk of bias" assessment tool. Review Management (5.1.0) was employed for data statistics. If there was no significant heterogeneity, results from the random-effect model were presented. If the heterogeneity was not substantial, a meta-analysis was not performed and a narrative and qualitative summary was performed instead. RESULTS: A total of 28 RCTs (6,949 patients) were included after screening results. The methodological quality of included trial was generally lower. Results of Metaanalysis showed that XZKC was beneficial for CHD patients in decreasing cardiovascular events: when compared with the basic treatment group, the relative risk (RR) was 0.53 and 95% confidence interval (CI) was [0.35, 0.81]; when compared with the placebo + basic treatment group, RR was 0.52 and 95% CI was [0.42, 0.65]; when compared with the basic treatment group, RR for improving symptoms of angina was 1.20 and 95% CI was [1. 12, 1.30]; when compared with the basic treatment group, RR for improving abnormal ECG was 1.38 and 95% CI was [1.21, 1.57]. Thirteen studies showed that XZKC + basic treatment was obviously superior in lowering total cholesterol (TC) to that of the basic treatment group. Three studies showed that XZKC + basic treatment was obviously superior in lowering total cholesterol (TC) to that of the placebo + basic treatment group. Thirteen studies showed that XZKC + basic treatment was obviously superior in lowering low density lipoprotein cholesterol (LDL-C) to that of the basic treatment group. Three studies showed that XZKC + basic treatment was obviously superior in lowering LDL-C to that of the placebo + basic treatment group. A total of 18 studies describing adverse reactions (ADs) involved 61 ADs in the XZKC + basic treatment group. All suffered from mild symptoms or were improved after treatment. No severe ADs occurred. CONCLUSION: Treatment of CHD by XZKC might lower the occurrence of cardiovascular events in CHD patients accompanied with or without dyslipidemia, relieve clinical symptoms, improve ECG, lower blood lipid levels, and with less adverse reactions.

The potential molecular mechanism underlying gypenoside amelioration of atherosclerosis in ApoE-/- mice: A multi-omics investigation.

Gypenosides (Gyp) are bioactive components of Gynostemma pentaphyllum that have a variety of pharmacological properties. Extracts of G. pentaphyllum have been found to be effective in the reduction of blood sugar and lipids and prevention of atherosclerosis. Here, the functions of Gyp and the mechanisms underlying their effects on atherosclerosis were investigated. Mice were allocated to three groups, namely, the control (C57BL/6), atherosclerosis model (ApoE-/- mice with high-fat diet), and Gyp-treated groups. Differentially expressed mRNAs, miRNAs, circRNA, and differential metabolites among the groups were analyzed. The results showed that "Fatty acid metabolism", "Fatty acid elongation", "Cytokine-cytokine receptor interaction", and "PI3K-Akt signaling pathway", amongst others, were involved in treatment process. Differentially expressed genes, including Fabp1, Apoe, FADS1, ADH1, SYNPO2, and Lmod1were also identified. Mmu-miR-30a and mmu-miR-30e showed reduced expression in atherosclerosis models but were increased following Gyp treatment, suggesting involvement in the effects of Gyp. In addition, chr5:150604177-150608440 were found to interact with mmu-miR-30a and mmu-miR-30e to regulate their abundance. In terms of metabolomics, Gyp may regulate biological processes involving PGD2 and PGJ2, potentially alleviating atherosclerosis. In conclusion, Gyp appeared to have complex effects on atherosclerosis, most of which were positive. These results support the use of Gyp in the treatment of atherosclerosis.

Effect of Tianshu capsule in treatment of migraine: a meta-analysis of randomized control trials.

OBJECTIVE: To review the efficacy of Tianshu capsule in the treatment of migraine. METHODS: Retrieving papers from Pubmed, cochrane central register of controlled trials (CENTRAL), Weipu database (VIP), China biology medicine (CBM), China national knowledge infrastructure (CNKI), and Wanfang Data. Two reviewers retrieved and extracted the information independently. Retrieval time scale is up to August 2012. Software Review Manager 5.1 was used for analysis. RESULTS: A total of 10 studies including 937 migraine patients. The merged data shows Tianshu capsule had a higher effective rate in treating migraine, and there is no significant heterogeneity between Tianshu capsule group and control group (Chi2 = 6.33, df = 9, P = 0.71, I2 = 0%), OR = 4.18 [95% CI (2.93,5.95)]. Tianshu capsule alone compared to conventional therapy also showed advantages, and there was low heterogeneity (chi2 = 4.53, df = 3, P = 0.21, I2 = 34%), OR = 3.95 [95% CI (2.32, 6.72)]. Meta-analysis results show that clinical efficacy of Tianshu capsule was better than that of the control group in the treatment of migraine and there was a significant difference (P < 0.000 01). CONCLUSION: Tianshu capsule had better efficacy in the treatment of migraine with fewer adverse effects.

Safflower yellow injection combined with conventional therapy in treating unstable angina pectoris: a meta-analysis.

OBJECTIVE: To evaluate the clinical efficacy of safflower yellow injection combined with conventional therapy in treating unstable angina pectoris. METHODS: We searched online databases: Chinese journal full-text database, China National Knowledge Infrastructure, Wanfang database, Chinese journal full-text database, Pubmed, ScienceDirect, Embase, and the Cochrane Library with manual-screening of relevant literature. Eligible randomized controlled trials (RCT) on angina pectoris were included. We conducted meta-analysis using the RevMan 5.1 software from The Cochrane Collaboration. We treated the relief rate of angina symptoms and electrocardiograph (ECG) as evaluation. RESULTS: Seven articles, including in 1134 patients, were enrolled after the evaluation. There was no significant heterogeneity among the studies (chi2 = 1.08, df = 6, P = 0.98, I2 = 0%). The safflower yellow injection with conventional therapy has a higher effective rate than the control group in relieving the symptoms of angina pectoris [odds ratio (OR)= 2.95, 95% (CI) (1.81, 4.81)] and improving ischemic ECG [OR = 2.85, 95% CI (1.67, 4.86)]. The difference was statistically significant in the "80 mg dosage" and "100 mg dosage" subgroups (P < 0.05) for improving clinical symptoms and ECG. The funnel graphic was nearly symmetrical. Sensitivity analysis suggested that the results were stable. CONCLUSION: Safflower yellow injection as an adjunct therapy with conventional drugs shows advantages in easing the clinical symptoms of unstable angina and improving ECG over basic therapy alone. However, the conclusions should be interpreted with care until more high-quality RCTs are reported.

Simultaneous Determination of Three Compounds in Rat Plasma by UHPLC-QQQ-MS/MS and Its Application to Pharmacokinetics of Banxia Baizhu Tianma Tang.

A rapid and highly selective and sensitive ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-QQQ-MS/MS) method was applied to simultaneously determine ephedrine, gastrodin, and liquiritin in rat plasma. The three analytes and vitexin-2″-O-rhamnoside (I.S.) were analyzed on a Waters Acquity UPLC C18 column (1.7 µm, 2.1 mm × 100 mm) at 30°C with gradient mobile phase consisting of 0.1% formic acid aqueous solution (A) and acetonitrile (B) after one-step direct protein precipitation with acetonitrile. The detection was performed by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source in positive and negative ion modes. The product ions m/z 166.1⟶148.1, 285.1⟶123.1, 417.1⟶255.1, and 579.0⟶433.1 were used for determination of ephedrine, gastrodin, liquiritin, and I.S., respectively. The calibration curves of the three analytes were linear with r 2 greater than 0.994. The intra and interday precision RSD% was less than 11.5 and 13.4. The intra and interday precision RE% was between -10.4% and 9.33%. The average extraction recoveries of the three analytes were no less than 86.88 ± 1.08%. The developed and validated method was for the first time applied to the pharmacokinetics of three compounds in rat plasma after intragastric administration of Banxia Baizhu Tianma Tang.

Two new natural products from Portulaca oleracea L. and their bioactivities.

Two new natural products, belonging to alkaloids, identified as ((2R,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl acetate (1) and (5-hydroxypyridin-2-yl)methyl acetate (2), were isolated from Portulaca oleracea L. The structures were identified by spectroscopic methods, including 1D, 2D NMR, and UHPLC-ESI-QTOF/MS methods. Meanwhile, the anti-inflammatory and anticholinesterase bioactivities were found in these two compounds.