Shengyu Decoction treating vascular cognitive impairment by promoting AKT/HIF-1α/VEGF related cerebrovascular generation and ameliorating MAPK/NF-κB mediated neuroinflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Shengyu Decoction (SYD), a classical Chinese medicine formula, is good at nourishing blood, promoting blood circulation, and soothe the nerves. SYD can improve cognitive ability. This decoction is suitable for treating vascular cognitive impairment (VCI). however, its active ingredients and possible mechanism have not been investigated. AIM OF THE STUDY: This study was conducted to observe the effects of SYD on improving the cognitive abilities of rats with VCI, to explore its active ingredients and mechanism. MATERIALS AND METHODS: The rats with VCI model were established by bilateral common carotid artery occlusion (BCCAO), and the effects of SYD (5, 2.5 g/kg) on the cognitive abilities of VCI rats were evaluated using the Morris water maze (MWM) and neurological assessment. The pathological changes of hippocampal CA1 were observed by H &E and Nissl staining. The effect of SYD on cerebral blood flow (CBF) was evaluated by Laser Speckle Contrast Imager. The expression of CD31 in the cerebral cortex was measured by immunofluorescence (IF) to evaluate the number of cerebral micro vessels. The levels of IL-6, IL-1ß, and TNF-α in the hippocampus were determined using an ELISA kit, and the active components in the plasma and brain tissues of rats after SYD administration were analyzed using UPLC-Q-TOF-MS/MS. The interaction network of the compound-target pathway was established using the SWISS Target, GO, and DAVID databases. The expression of AKT/HIF-1α/VEGF and p38 MAPK signaling pathway in the brain tissues was determined using western blotting (WB). RESULTS: SYD (2.5, 5 g/kg) significantly improved the cognitive abilities of VCI rats in the MWM and neurological assessment. H&E and Nissl staining showed that SYD significantly ameliorated the pathological hippocampal CA1 area and increased the number of Nissl bodies. The Laser Speckle Contrast Imager showed that the cortical CBF of VCI rats in the SYD group was significantly increased, and the IF results showed that CD31 expression was significantly increased in the SYD group. The ELISA results showed that the contents of IL-6, IL-1ß, and TNF-α in SYD were significantly reduced. A total of 29 compounds were found in the plasma and brain tissues of the rats treated with SYD. Network pharmacology revealed 99 targets for the treatment of VCI. Pathway enrichment analysis showed that the HIF-1 and MAPK signaling pathways might be important for SYD to ameliorate VCI. WB showed that the expressions of AKT, HIF-1α, and VEGF in the brain tissues of rats were significantly increased; in addition, NF-κB and p38 MAPK were significantly reduced in the SYD group. CONCLUSION: SYD can improve the cognitive abilities of VCI rats. The mechanism of action of its active ingredients improves cognitive impairment by affecting the AKT/HIF-1α/VEGF and p38 MAPK/NF-κB signaling pathways, promoting cerebrovascular generation, and ameliorating neuroinflammation.

Danhe granule ameliorates nonalcoholic steatohepatitis and fibrosis in rats by inhibiting ceramide de novo synthesis related to CerS6 and CerK.

ETHNOPHARMACOLOGICAL RELEVANCE: Danhe granule (DHG) is used by Chinese doctors to treat blood stasis, phlegm and dampness. Its lipid-lowering ability has been investigated in our previous research. However, the anti-liver inflammatory and fibrotic effects and mechanism of action of DHG in non-alcoholic steatohepatitis (NASH) have not been explored. AIM OF THE STUDY: To evaluate the ameliorative effects of DHG on liver inflammation and fibrosis in a methionine/choline-deficient (MCD) diet-induced NASH rat model, and its underlying mechanism. MATERIALS AND METHODS: Sprague-Dawley rats were fed an MCD diet for two weeks and then treated with or without DHG by oral gavage for eight weeks. Their body weight and liver index were measured. The serum alanine aminotransferase (ALT) and aspartate transaminase (AST) activities as well as the liver triglyceride (TG) and free fatty acid (FFA) levels were tested using reagent kits. Inflammatory cytokines, including Tnf-α, Il-ß and Il-6, and fibrosis genes, including Acta2, Col1a1, Col1a2 and Tgf-ß were examined by real-time quantitative PCR (RT-qPCR). Hematoxylin-eosin (H&E), Oil Red O, Masson's and Sirius Red staining were used to observe liver changes. The plasma and liver ceramide levels were analyzed using HPLC-QQQ-MS/MS. The expression of serine palmitoyl-CoA transferase (Spt), ceramide synthase 6 (Cers6), dihydroceramide desaturase 1 (Des1), glucosylceramide synthase (Gcs), and ceramide kinase (Cerk) mRNA was assayed by RT-qPCR, while the protein expression of CerS6, DES1, GCS, CerK, and casein kinase 2α (CK2α) was tested by western blotting (WB). CerS6 degradation was evaluated using a cycloheximide (CHX) assay in vitro. RESULTS: The liver index decreased by 20% in DHG groups and the serum ALT and AST decreased by approximately 50% and 30%, respectively in the DHG-H group. The liver Oil Red O staining, TG, and FFA changes showed that DHG reduced hepatic lipid accumulation by approximately 30% in NASH rats. H&E, Masson's and Sirius Red staining and the mRNA levels of Tnf-α, Il-ß, Il-6, Acta2, Col1a1, Col1a2 and Tgf-ß revealed that DHG alleviated liver inflammation and fibrosis in NASH rats. The ceramide (Cer 16:0), and hexosylceramide (HexCer 16:0, HexCer 18:0, HexCer 22:0, HexCer 24:0 and HexCer 24:1) levels decreased by approximately 17-56% in the plasma of the DHG-M and H rats. The Cer 16:0 content in the liver decreased by 20%, 50%, and 70% with the DHG-L, M, and H treatments; additionally, the dhCer 16:0, Cer 18:0, HexCer 18:0, HexCer 20:0 Cer 22:0-1P, Cer 24:0-1p, Cer 24:1-1p, and Cer 26:1-1p levels decreased in the DHG groups. The mRNA and protein expression levels of DES1, GCS, Cerk, CerS6, and CHX assay indicated that DHG decreased the mRNA and protein expression levels of CerK and reduced CerS6 protein expression by promoting its degradation. Additionally, DHG attenuated the protein expression of CK2α which could increase CerS6 enzymatic activity by phosphorylating its C-terminal region. CONCLUSION: DHG ameliorated the levels of liver FFA and TG and inflammation and fibrosis in MCD-induced rats, which were associated with decreasing ceramide species in the plasma and liver by reducing the expression levels of CerS6 and CerK.

Discovery of Hepatotoxic Equivalent Markers and Mechanism of Polygonum multiflorum Thunb. by Metabolomics Coupled with Molecular Docking.

Polygonum multiflorum Thunb. (PMT), a commonly used Chinese herbal medicine for treating diseases such as poisoning and white hair, has attracted constant attention due to the frequent occurrence of liver injury incidents. To date, its hepatotoxic equivalent markers (HEMs) and potential hepatotoxic mechanisms are still unclear. In order to clarify the HEMs of PMT and further explore the potential mechanisms of hepatotoxicity, firstly, the chemical constituents in PMT extract were globally characterized, and the fingerprints of PMT extracts were established along with the detection of their hepatotoxicity in vivo. Then, the correlations between hepatotoxic features and component contents were modeled by chemometrics to screen HEMs of PMT, which were then further evaluated. Finally, the hepatotoxic mechanisms of PMT were investigated using liver metabolomics and molecular docking. The results show that the chemical combination of 2,3,5,4-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) and emodin-8-O-glucoside (EG) was discovered as the HEMs of PMT through pre-screening and verifying process. Liver metabolomics revealed that PMT caused liver injury by interfering with purine metabolism, which might be related to mitochondrial function disorder and oxidative injury via the up-regulations of xanthosine and xanthine, and the down-regulation of 5' nucleotidase (NT5E) and adenylate kinase 2 (AK2). This study not only found that the HEMs of PMT were TSG and EG, but also clarified that PMT might affect purine metabolism to induce liver injury, which contributed to our understanding of the underlying mechanisms of PMT hepatotoxicity.

Erzhi pills ameliorate cognitive dysfunction and alter proteomic hippocampus profiles induced by d-galactose and Aß1-40 injection in ovariectomized Alzheimer's disease model rats.

CONTEXT: Erzhi pills are a classic Chinese medicine prescription, but their effects on Alzheimer's disease (AD) are not clear. OBJECTIVE: The protective effects of Erzhi pills in AD rats and their potential mechanisms were investigated. MATERIALS AND METHODS: An AD rat model was established by ovariectomy combined with d-galactose and Aß1-40 injection. Rats were randomly divided into five groups: sham-operated, model, oestradiol valerate (0.80 mg/kg), Erzhi pills high-dose (1.50 g/kg), and Erzhi pills low-dose (0.75 g/kg). Learning and memory abilities were evaluated with the Morris water maze test, oestrogen levels with an ELISA kit, and hippocampal neuron morphology and Nissl bodies in the cytoplasm with H&E and Nissl staining. The expression of ERß, Aß1-40, and p-tau404 was determined by immunohistochemistry. Nano LC-LTQ-Orbitrap Proteomics determined potential targets and related signalling pathways. Western blotting was used to detect the expression of the related proteins. RESULTS: Erzhi pills (1.5, 0.75 g/kg) markedly reduced escape latencies on the MWM, increased numbers of platform crossings, numbers of neurons, Nissl bodies, oestrogen levels (100.18, 43.04 pg/mL), and ERß-positive cells (57.42, 39.83); Aß1-40 (18.85, 36.83)- and p-tau404 (14.42, 29.71)-positive cells were significantly decreased. Proteomics identified more than 100 differentially expressed proteins involved in 48 signalling pathways, five of which are involved in the PI3K/Akt signalling pathway. Western blotting showed decreased expression of GSK3ß and Bad, while Akt, PI3K, 14-3-3, Bcl-xl, and Bcl-2 were upregulated. DISCUSSION AND CONCLUSION: Erzhi pills may serve as a potential agent for AD therapeutics by improving learning and memory.

α-Hederin inhibits the growth of lung cancer A549 cells in vitro and in vivo by decreasing SIRT6 dependent glycolysis.

CONTEXT: α-Hederin, a potent bioactive compound of Pulsatilla chinensis (Bunge) Regel (Ranunculaceae), has many pharmacological uses, but its effect on cancer cell metabolism is still unclear. OBJECTIVE: To elucidate the role of α-hederin in the glucose metabolism of lung cancer cells. MATERIALS AND METHODS: Cell Counting Kit 8 and colony formation assays were employed to assess the antiproliferative effects of α-hederin. Glucose uptake, ATP generation, and lactate production were measured. Glycolysis-related proteins were detected using western blotting, and a sirtuin 6 (SIRT6) inhibitor was used to verify A549 cell proliferation. Sixty male BALB/c nude mice were divided into normal control, 5-FU (25 mg/kg), and α-hederin (5 and 10 mg/kg) groups to assess the antitumor effect for 32 days. Glycolysis-related protein expression was evaluated using immunohistochemical analysis. RESULTS: α-Hederin inhibited A549 (IC50 = 13.75 µM), NCI-H460 (IC50 = 17.57 µM), and NCI-H292 (IC50 = 18.04 µM) proliferation; inhibited glucose uptake and ATP generation; and reduced lactate production. Furthermore, α-hederin (10 and 15 µM) markedly inhibited hexokinase 2, glucose transporter 1, pyruvate kinase M2, lactate dehydrogenase A, monocarboxylate transporter, c-Myc, hypoxia-inducible factor-1α, and activated SIRT6 protein expression. Using a SIRT6 inhibitor, we demonstrated that α-hederin inhibits glycolysis by activating SIRT6. A tumour xenograft mouse model of lung cancer confirmed that α-hederin (5 and 10 mg/kg) inhibits lung cancer growth by inhibiting glycolysis in vivo. DISCUSSION AND CONCLUSIONS: α-Hederin inhibits A549 cell growth by inhibiting SIRT6-dependent glycolysis. α-Hederin might serve as a potential agent to suppress cancer.

Molecular mechanistic insight into the anti-hyperuricemic effect of Eucommia ulmoides in mice and rats.

CONTEXT: Eucommia ulmoides Oliver (Eucommiaceae) has various medicinal properties. Our previous studies revealed that Eucommia ulmoides has a protective effect on hyperuricaemia. OBJECTIVE: This study investigates the effect of Eucommia ulmoides cortex ethanol extract (EU) on hyperuricaemia and explores the underlying mechanism in Kunming mice and Sprague-Dawley rats. MATERIAL AND METHODS: Sixty mice and sixty rats were divided into normal control, hyperuricaemia, allopurinol (10 mg/kg) and three EU groups. The EU groups received intragastric EU at 80, 160, 320 mg/kg in mice and 100, 200, 400 mg/kg in rats for 7 days. Serum uric acid (SUA) was measured using a kit. mRNA and proteins were quantified by RT-qPCR and immunohistochemical assays (IHC), respectively. RESULTS: The Maximal Tolerable Dose (MTD) of EU administered intragastrically was 18 g/kg in mice. The intermediate (160 mg/kg) and high (320 mg/kg) EU treatment significantly reduced (p < 0.05) SUA levels to 130.16 µmol/L and 109.29 µmol/L, respectively, and markedly elevated the mRNA expression of organic anion transporters 1 (OAT1) and organic anion transporters 3 (OAT3), while significantly deceasing the mRNA levels of glucose transporter 9 (GLUT9) and uric acid transporter 1 (URAT1) in the mouse kidney (p < 0.05). In hyperuricemic rats, high EU (400 mg/kg) significantly reduced SUA levels to 253.85 µmol/L, and increased OAT1 and OAT3 levels, but decreased URAT1 and GLUT9, compared to the hyperuricaemia group (p < 0.05). DISCUSSION AND CONCLUSIONS: This study demonstrated the potential hyperuricaemia ameliorating effect of EU. Specific active ingredients in EU should be evaluated. These results are valuable for the development of antihyperuritic agents from EU.

Effects of Aquatic Taiji Quan on Balance Function of Patients with Incomplete Spinal Cord Injury / 中国康复理论与实践

Objective To investigate the effects of aquatic Taiji Quan on balance function of patients with incomplete spinal cord injury. Methods From March to December, 2015, 30 patients with incomplete spinal cord injury received aquatic Taiji Quan exercise based on rou-tine rehabilitation, 30 minutes every day, five times a week for five weeks. They were assessed with Berg Balance Scale (BBS) before and after exercise. Dynamic balance function and static balance function were also assessed with Active Balancer assessment. Results The BBS score significantly improved after exercise (t=-9.652, P3.528, Z>-2.590, P0.05). The dynamic stability limit range enlarged (t=-4.516, P<0.01), and the time to target significantly shortened (t=4.530, P<0.001). Conclusion Aquatic Taiji Quan can improve the balance function of patients with incomplete spinal cord injury.

Formulation of intumescent flame retardant coatings containing natural-based tea saponin.

Natural product tea saponin (TS), extracted from the nutshell of camellia (Camellia oleifera Abel, Theaceae), was introduced into intumescent flame retardant formulations as blowing agent and carbon source. The formulations of the flame retardant system were optimized to get the optimum proportion of TS, and intumescent flame retardant coatings containing tea saponin (TS-IFRCs) were then prepared. It was found that TS can significantly affect the combustion behavior and the thermal stability of TS-IFRCs evaluated by cone calorimetry and simultaneous thermal analyzer, respectively. It was shown that TS, degraded to water vapor and carbon at high temperatures, can combine with other components to form a well-developed char layer. The char layer was supposed to inhibit erosion upon exposure to heat and oxygen and enhance the flame retardancy of TS-IFRCs. In addition, the smoke release of TS-IFRCs was also studied, which provided a low amount of smoke production.

Effects of Traditional Chinese Medicine Bubble Bath on Spastic Diplegia Cerebral Palsy / 中国康复理论与实践

@#Objective To observe the effects of Traditional Chinese Medicine bubble bath on the children with spastic diplegia cerebral palsy. Methods 13 children with spastic diplegia cerebral palsy received routine rehabilitation and bubble bath (control group), while 14 children received routine rehabilitation and Traditional Chinese Medicine bubble bath (experimental group). All the children were assessed with Gross Motor Function Measure (GMFM-66) and Modified Ashworth Scale (MAS) of triceps surae muscle before and 10 weeks after treatment.Results The total score of GMFM-66 increased (P<0.001) and the MAS score decreased in both groups (P<0.01) after treatment. The dimensions B, D, and E of GMFM-66 only increased in the experimental group (P<0.05). The MAS score decreased more in the experimental group than in the control group after treatment (P<0.05). Conclusion Traditional Chinese Medicine bubble bath can improve gross motor function and reduce triceps surae muscle tension of the children with spastic diplegia cerebral palsy.

The effectiveness of oral placement therapy in management of sialorrhea of stroke patients / 中华物理医学与康复杂志

Objective To observe the therapeutic effects of oral placement therapy (OPT) on managing sialorrhea after stroke.Methods A total of 37 stroke inpatients with sialorrhea were enrolled from January 2011 to September 2013 in the authors' department for the study and divided into 2 group on the basis of the time of enrollment.The control group (n =18) received 30min of routine treatment (including such neuromuscular facilitation techniques as Bobath and Rood techniques,motor relearning program,neuromuscular electrical stimulation and ice stimulation),twice daily,and the treatment group (n =19) received 15 min of routine treatment plus 15 min of OPT,twice daily.Frenchay Dysarthria Assessment was used to evaluate the sialorrhea severity and clinical efficacy before and 1,2 and 4 weeks after initiation of treatment.Results Sialorrhea symptom was significantly improved in treatment group after 1 week (P ＜ 0.05),while no significant improvement was observed in control group (P ＞ 0.05).After 2 and 4 weeks of treatments,significant improvements of sialorrhea were noted in both groups.After 1,2 and 4weeks of treatment,the total effective rate were 63.16％,94.74％ and 94.74％,respectively,in the treatment group,versus 5.88％,61.11％ and 61.11％,respectively,in the control group.The total effective rate of the treatment group were significantly higher in the above three time-points than the control group (P ＜ 0.05).Conclusions Oral placement therapy can improve sialorrhea symptom after stroke more effectively than routine treatment.

Effects of Hydrotherapy on Pulmonary Function of Children with Spastic Diplegia / 中国康复理论与实践

@#ObjectiveTo observe the characteristic of pulmonary function of children with spastic diplegia and the effects of hydrotherapy on it. Methods30 children with spastic diplegia were divided into hydrotherapy group and control group, who received hydrotherapy and routine rehabilitation or routine rehabilitation only. All patients were tested their pulmonary function and the maximum phonation time before and 2 months after treatment. The longest breath holding time in water of the hydrotherapy group were recorded. ResultsThe vital capacity (VC), expiratory reserve volume (ERV), inspiratory capacity (IC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), maximum ventilatory volume (MVV), peak expiratory flow (PEF) in all the children decreased significantly compared with the predicted value (P=0.000), but a second rate (FEV1/FVC) didn't （P=0.141）. After treatment, the VC, FVC, FEV1, FEV1/FVC, MVV, PEF values and their percentage of predicted value improved （P＜0.05）, as well as the maximum phonation time （P＜0.05）. ERV, IC values and their percentage of predicted value improved a little from pre-treatment in the control group （P＞0.05）, but significantly in the hydrotherapy group （P<0.05）. The percentage of predicted value of VC, ERV, IC, FVC, FEV1, FEV1/FVC, MVV, and PEF, and the maximum phonation time improved more in the hydrotherapy group than in the control （P＜0.05）. The longest breath holding time in water improved in the hydrotherapy group after treatment （P=0.000）. ConclusionThe pulmonary function impaired in spastic diplegic children, and can be improved with the rehabilitation, especially with the hydrotherapy in addition.

[Effect of several physiochemical factors on cell growth and isoflavone accumulation of Pueraria lobata cell suspension culture].

OBJECTIVE: To illustrate the effects of several physiochemical factors on cell growth and isoflavone accumulation of Pueraria lobata cell suspension cultures. METHOD: High performance liquid chromatography and plant tissue culture were applied. RESULT AND CONCLUSION: Cell growth and isoflavone accumulation were significantly stimulated in P. lobata cell suspension cultures by the increase of the sucrose concentration. Maintaining the pH value at the range over 5. 4 to 5. 8 was most suitable for isoflavone accumulation in P. lobata cell suspension cultures. Cell dried weight and isoflavone accumulation decreased sharply with the increase of the treated concentration of active carbon, while XAD-4 significantly stimulated cell growth and isoflavone accumulation.