Anti-hypertensive and endothelia protective effects of Fufang Qima capsule on primary hypertension via adiponectin/adenosine monophosphate activated protein kinase pathway.

OBJECTIVE: To investigate the potential mechanism of the vascular remodeling effect and provide additional information about anti-hypertension activity of Fufang Qima capsule. METHODS: Spontaneous hypertensive rats (SHRs) were used to study the underlying mechanism of the anti-hypertension activity of QM. In this study, SHRs were randomly divided into 5 groups: model group, Telmisartan group (7.2 mg/kg, p.o.), and three QM groups (0.9298, 1.8596, and 3.7192 g/kg, p.o.). Wistar Kyoto rats (WKY) were used as normal control group. Blood pressure (BP), aorta, perivascular adipose tissue (PVAT) histology were investigated to evaluate the effect of QM. Nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) phosphorylation were measured. Adiponectin (APN) secretion, as well as APN signal pathway proteins including APN, adiponectin receptors (R1 and R2) and adenosine 5'-monophosphate-activated protein kinase (AMPK) were all analyzed. RESULTS: QM significantly reduced BP and ameliorated the vascular pathological change, i.e. intima media thicken and collagen fiber hyperplasia. Meanwhile, QM increased concentration of NO and the phosphorylation of eNOS in the aorta. The anti-hypertensive and endothelia-protective effect of QM could be attributed to activating APN/ AMPK pathway by up-regulating the expression of APN in PVAT and APN Receptor 2, AMPKα and phosphorylated AMPKα in the aorta. CONCLUSION: The QM alleviation effect mechanism for primary hypertension was via modulating the APN/AMPK signal pathway.

Mechanism of YLTZ on glycolipid metabolism based on UPLC/TOF/MS metabolomics.

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by dysfunction of glycolipid metabolism. YLTZ is used to treat hyperlipidemia, yet its hypolipidemic and hypoglycemic mechanism on T2DM are unknown. Thus, UPLC/TOF/MS was applied in this study to identify the potential bio-markers, and deduce the possible metabolic pathways. According to bio-indexes, the increased blood lipid levels, including TC, TG, LDL and FA, and the decreased HDL, the elevated glucose, reduced insulin level and impaired OGTT were observed in diabetic rat model. While YLTZ can decrease the lipid levels and glucose content, as well as increased insulin standards and improve OGTT. After data from UPLC/TOF/MS processed, 17 metabolites were obtained, including phospholipids (LPCs, PCs and PGP (18:1)), beta-oxidation production (HAA, VAG and CNE) and precursors (THA), bile acid (CA, CDCA and IDCA), hydrolysate of TG (MG (22:4)), glycometabolism (G6P), cholesterol-driven synthetics (ADO) and production of arachidonate acid (THETA). As a result, YLTZ was able to reduce LPCs, PCs, PGP (18:1), HAA, VAG, CNE, CA, ADO and THETA, as well as enhance MG (22:4) and G6P. After analyzing results, several metabolic pathways were deduced, which containing, cholesterol synthesis and elimination, FA beta-oxidation, TG hydrolysis, phospholipids synthesis, glycolysis, gluconeogenesis and inflammation. Consequently, YLTZ performed to prohibit the FA beta-oxidation, synthesis of cholesterol and phospholipids, gluconeogenesis and inflammation level, as well as promote TG hydrolysis, glycolysis and blood circulation. Hence, applying metabonomics in TCM research can uncover its pharmacological edges, elucidating comprehensively that YLTZ has capacity of hypolipidemic, hypoglycemic and promoting blood circulation, matching the effect of removing blood stasis, eliminating phlegm and dampness.

Hypotriglyceridemic effects of apple polyphenols extract via up-regulation of lipoprotein lipase in triton WR-1339-induced mice.

OBJECTIVE: To investigate the anti-hyperlipidemic effects of apple polyphenols extract (APE) in Triton WR-1339-induced endogenous hyperlipidemic model. METHODS: Firstly, APE was isolated and purified from the pomace of Red Fuji Apple and contents of individual polyphenols in APE were determined using high-performance liquid chromatography-mass spectrometry (HPLC-MS). Secondly, forty male National Institude of Health (NIH) mice were randomly divided into 5 groups with 8 animals in each group. The Fenofibrate Capsules (FC) group and APE groups received oral administration of respective drugs for 7 consecutive days. All mice except those in the normal group were intravenously injected through tail vein with Triton WR-1339 on the 6th day. Serum and livers from all the mice were obtained 18 h after the injection. The changes in serum total cholesterol (TC), triglyceride (TG), lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) were measured by respective kits. Finally, expression of hepatic peroxisome proliferator-activated receptor alpha (PPARα) mRNA was measured by real-time reverse transcription-polymerase chain reaction (RT-PCR) method. RESULTS SERUM TC AND TG LEVELS SIGNIFICANTLY INCREASED IN TRITON WR-1339-INDUCED MODEL GROUP COMPARED WITH THE NORMAL GROUP (P<0.01). ORAL ADMINISTRATION OF APE [200 AND 400 MG/(KG DAY)] DOSE-DEPENDENTLY REDUCED THE SERUM LEVEL OF TG IN HYPERLIPIDEMIC MICE (P<0.01). SERUM LPL AND HTGL ACTIVITIES SIGNIFICANTLY DECREASED IN TRITON WR-1339-INDUCED MODEL GROUP COMPARED WITH THE NORMAL GROUP (P<0.05). ORAL ADMINISTRATION OF APE [200 AND 400 MG/(KG DAY)] DOSE-DEPENDENTLY ELEVATED THE SERUM ACTIVITY OF LPL IN HYPERLIPIDEMIC MICE (P<0.05 OR P<0.01). FURTHERMORE, COMPARED WITH THE NORMAL GROUP, HEPATIC MRNA LEVEL OF PPARα IN THE MODEL GROUP SIGNIFICANTLY DECREASED (P<0.01). ORAL ADMINISTRATION OF APE [200 AND 400 MG/(KG DAY)] DOSE-DEPENDENTLY ELEVATED THE EXPRESSION OF PPARα IN HYPERLIPIDEMIC MICE (P<0.05 OR P<0.01): CONCLUSION: APE could reduce TG level via up-regulation of LPL activity, which provides new evidence to elucidate the anti-hyperlipidemic effects of APE.

Insufficient processing resources in Parkinson's disease: evaluation using multimodal event-related potentials paradigm.

The purpose of our study was to demonstrate impaired allocation of processing resources in non-demented patients with early-stage mild Parkinson's disease (PD) using a multimodal event-related potential (ERP) paradigm. The multimodal ERP paradigm was performed in 18 non-demented medicated patients with early-stage PD (Mini-Mental State Examination Score >26) and 16 matched normal controls, the Global Field Power (GFP) was employed for ERP components analysis, and the new modified Wisconsin Card Sorting Test (WCST) was used to evaluate frontal lobe function. Patients with PD did not exhibit novelty P3s, and P3 latency to non-target novel stimuli in visual and auditory modalities was significantly longer in PD patients than in controls. P3 amplitude for the target stimuli (P3b) was higher in PD in both auditory and visual modalities; however, P3b latency was not different between the two groups. Patients with PD showed a significantly lower score of achieved categories and made more perseverative errors in WCST as compared to controls. Our results showed that there were no natural novelty P3s in patients with PD; this finding suggests that non-demented patients with mild PD do not have sufficient mental resources to allocate to the central executive, due to dysfunction of the frontal lobe.