Molecular mechanisms of quetiapine bidirectional regulation of bipolar depression and mania based on network pharmacology and molecular docking: Evidence from computational biology.

BACKGROUND: Quetiapine monotherapy is recommended as the first-line option for acute mania and acute bipolar depression. However, the mechanism of action of quetiapine is unclear. Network pharmacology and molecular docking were employed to determine the molecular mechanisms of quetiapine bidirectional regulation of bipolar depression and mania. METHODS: Putative target genes for quetiapine were collected from the GeneCard, SwissTargetPrediction, and DrugBank databases. Targets for bipolar depression and bipolar mania were identified from the DisGeNET and GeneCards databases. A protein-protein interaction (PPI) network was generated using the String database and imported into Cytoscape. DAVID and the Bioinformatics platform were employed to perform the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the top 15 core targets. The drug-pathway-target-disease network was constructed using Cytoscape. Finally, molecular docking was performed to evaluate the interactions between quetiapine and potential targets. RESULTS: Targets for quetiapine actions against bipolar depression (126 targets) and bipolar mania (81 targets) were identified. Based on PPI and KEGG pathway analyses, quetiapine may affect bipolar depression by targeting the MAPK and PI3K/AKT insulin signaling pathways via BDNF, INS, EGFR, IGF1, and NGF, and it may affect bipolar mania by targeting the neuroactive ligand-receptor interaction signaling pathway via HTR1A, HTR1B, HTR2A, DRD2, and GRIN2B. Molecular docking revealed good binding affinity between quetiapine and potential targets. LIMITATIONS: Pharmacological experiments should be conducted to verify and further explore these results. CONCLUSIONS: Our findings suggest that quetiapine affects bipolar depression and bipolar mania through distinct biological core targets, and thus through different mechanisms. Furthermore, our results provide a theoretical basis for the clinical use of quetiapine and possible directions for new drug development.

Producing natural functional and low-carbon milk by regulating the diet of the cattle-The fatty acid associated rumen fermentation, biohydrogenation, and microorganism response.

Conjugated linoleic acid (CLA) has drawn significant attention in the last two decades for its various potent beneficial effects on human health, such as anticarcinogenic and antidiabetic properties. CLA could be generally found in ruminant products, such as milk. The amount of CLA in ruminant products mainly depends on the diet of the animals. In general, the fat content in the ruminant diet is low, and dietary fat supplementation can be provided to improve rumen activity and the fatty acid (FA) profile of meat and milk. Especially, dietary 18-carbon polyunsaturated FA (C18 PUFA), the dominant fat source for ruminants, can modify the milk FA profile and other components by regulating the ruminal microbial ecosystem. In particular, it can improve the CLA in milk, intensify the competition for metabolic hydrogen for propionate producing pathways and decrease methane formation in the rumen. Therefore, lipid supplementation appears to be a promising strategy to naturally increase the additional nutritional value of milk and contribute to lower methane emissions. Meanwhile, it is equally important to reveal the effects of dietary fat supplementation on rumen fermentation, biohydrogenation (BH) process, feed digestion, and microorganisms. Moreover, several bacterial species and strains have been considered to be affected by C18 PUFA or being involved in the process of lipolysis, BH, CLA, or methane emissions. However, no review so far has thoroughly summarized the effects of C18 PUFA supplementation on milk CLA concentration and methane emission from dairy cows and meanwhile taken into consideration the processes such as the microorganisms, digestibility, rumen fermentation, and BH of dairy cattle. Therefore, this review aims to provide an overview of existing knowledge of how dietary fat affects rumen microbiota and several metabolic processes, such as fermentation and BH, and therefore contributes to functional and low-carbon milk production.

Self-Directed Neurofeedback Treatment for Subjective Tinnitus Patients Evaluated by Multimodal Functional Imaging.

Neurofeedback (NFB) is a relatively novel approach to the treatment of tinnitus, and prior studies have demonstrated that the increases in alpha activity rather than reduced delta power seem to drive these NFB-related improvements in tinnitus symptoms. The present study was therefore designed to explore whether the implementation of an alpha training protocol with a portable neurofeedback apparatus would achieve improvements in tinnitus patient symptoms. In this study, 38 tinnitus patients underwent NFB training while 18 were enrolled in a control group. The study was single-blinded such that only participants were not aware of their group assignments. Those in the NFB group underwent 15 NFB training sessions over 5 weeks, in addition to pre- and posttraining tests including the Tinnitus Handicap Inventory (THI), Tinnitus Handicap Questionnaire (THQ), visual analog scales (VAS), electroencephalography (EEG), and functional magnetic resonance imaging (fMRI). Our result find that when the THI, THQ, and VAS scores of patients in the two groups were assessed after a 5-week training period, these scores were unchanged in control patients whereas they had significantly improved in the NFB group patients. EEG analyses revealed that the alpha band was increased in the occipital lobe following NFB treatment, while fMRI indicated an increase in regional homogeneity (ReHo) in the right frontal lobe of patients in the NFB group after treatment that was negatively correlated with THI and VAS scores. The results of this analysis indicate that alpha NFB training can be effectively used to reduce tinnitus-related distress and sound perception in patients.

Cinobufagin inhibits tumor progression and reduces doxorubicin resistance by enhancing FOXO1-mediated transcription of FCGBP in osteosarcoma.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinobufagin (Huachansu), an aqueous extract from the dried skin of the toad Bufo bufo gargarizans Cantor (frog skin), is a biologically active ingredient of a traditional Chinese medicine cinobufacini that can treat multiple bone pathological conditions such as bone pain, bone tumors, and osteosarcoma. AIM OF THE STUDY: The study aimed to explore the roles and molecular mechanisms of cinobufagin underlying osteosarcoma development and doxorubicin (ADR) resistance. MATERIALS AND METHODS: Cell viability, migration, and invasion were examined by CCK-8, wound healing, and Transwell invasion assays, respectively. RNA sequencing analysis was performed in MNNG/HOS cells treated with or without cinobufagin. The relationships of cinobufagin, forkhead box O1 (FOXO1), and Fc fragment of IgG binding protein (FCGBP) were examined by luciferase reporter, immunofluorescence (IF), RT-qPCR, and chromatin immunoprecipitation (ChIP) assays together with weighted gene co-expression network analysis (WGCNA) analysis. Epithelial-mesenchymal transition (EMT) marker levels were examined through the Western blot assay. The function and molecular basis of cinobufagin in osteosarcoma were further investigated by mouse xenograft experiments. RESULTS: Cinobufagin reduced cell viability, weakened ADR resistance, and inhibited cell migration/invasion/EMT in osteosarcoma cells. Cinobufagin enhanced FOXO1-mediated transcription of downstream genes including FCGBP. FCGBP knockdown partly abrogated the effect of cinobufagin on osteosarcoma cell development. Cinobufagin inhibited the growth of mouse osteosarcoma xenografts in vivo. Cinobufagin reduced the expression of Ki-67 and MMP9 and facilitated caspase-3 expression in osteosarcoma xenografts. CONCLUSION: Cinobufagin suppressed tumor progression and reduced ADR resistance by potentiating FOXO1-mediated transcription of FCGBP in osteosarcoma.

Solasodine, Isolated from Solanum sisymbriifolium Fruits, Has a Potent Anti-Tumor Activity Against Pancreatic Cancer.

BACKGROUND: Increasing evidences have revealed that solasodine, isolated from Solanum sisymbriifolium fruits, has multiple functions such as anti-oxidant, anti-tumor and anti-infection. However, its role in pancreatic cancer has not been well studied. METHODS: To explore the role of solasodine in pancreatic cancer, human pancreatic cell lines including SW1990 and PANC1 were treated with different concentrations of solasodine for 48 h, and cell viability was evaluated by MTT assay, cell invasion and migration were evaluated by Transwell assay. The effect of solasodine on the apoptosis of SW1990 and PANC1 cells was detected by flow cytometry. To further explore the antitumor effect of solasodine in vivo, an SW1990 tumor-bearing mouse model was constructed. The effects of solasodine on cytokines in the serum of SW1990 tumor-bearing mice were also evaluated by ELISA assay. RESULTS: Specifically, in vitro, solasodine could significantly inhibit the proliferation of pancreatic cancer cell lines SW1990 and PANC1 cells. Flow cytometric analysis indicated that solasodine could induce apoptosis of SW1990 and PANC1 cells. Western blot assay indicated that solasodine could significantly inhibit the activation of Cox-2/Akt/GSK3ß signal pathway. Meanwhile, the release of Cytochrome c from mitochondria to cytoplasm which can raise the caspases cascade (C-caspase 3 and C-caspase 9) was significantly enhanced by solasodine. In vivo, the results showed that solasodine had potent anti-tumor activities with a lower cytotoxicity. In addition, the serum TNF-α, IL-2 and IFN-γ levels in SW1990 tumor-bearing mice after the treatment of solasodine was significantly increased. CONCLUSION: Taken together, our results suggested that the solasodine could prevent the progression of pancreatic cancer by inhibiting proliferation and promoting apoptosis, as well as stimulating immunity, suggesting that solasodine might be a potential therapeutic strategy for pancreatic cancer.

Protective Effects of Apocynum venetum Against Pirarubicin-Induced Cardiotoxicity.

Pirarubicin (THP) is an anthracycline antibiotic, frequently used for the treatment of various human cancers. Unfortunately, the clinical effectiveness of THP is limited by its dose-related cardiotoxicity. Apocynum leaf extract is an extract of the dried leaves of Apocynum venetum L. (a member of the Apocynaceae family, AVLE) that has many positive effects on the cardiovascular system and is widely consumed as tea in China. In this study we established a cardiactoxicity rat model, which showed that pretreatment with AVLE attenuated THP-induced myocardial histopathological injury, electrocardiogram abnormalities, and cardiac dysfunction. AVLE also significantly reduced serum levels of malondialdehyde (MDA), brain natriuretic peptide (BNP), creatine kinase (CK-MB), cardiac troponin (CTnT), and lactate dehydrogenase (LDH); and increased serum superoxide dismutase (SOD) levels. Treatment with AVLE or dexrazoxane (DZR) resulted in an increase Cytochrome C (cytc) in the mitochondria and reduced Cytc and cleaved-caspase-3 levels (p<0.05) in cytoplasm. We also found that AVLE significantly reduced voltage-dependent anion channel 1 (VDAC1), adenosine nucleotide transporter 1 (ANT1), and cyclophilin D (CYPD) mRNA expression (p<0.05). Furthermore, AVLE appeared to exert therapeutic effects in a dose-dependent manner. Our study suggests the anti-oxidant and anti-apoptotic properties of AVLE may be responsible for the observed cardioprotective effects.

Unconventional Antiferromagnetic Quantum Critical Point in Ba(Fe_{0.97}Cr_{0.03})_{2}(As_{1-x}P_{x})_{2}.

We have systematically studied physical properties of Ba(Fe_{0.97}Cr_{0.03})_{2}(As_{1-x}P_{x})_{2}, where superconductivity in BaFe_{2}(As_{1-x}P_{x})_{2} is fully suppressed by just 3% of Cr substitution of Fe. A quantum critical point is revealed at x∼0.42, where non-Fermi-liquid behaviors similar to those in BaFe_{2}(As_{1-x}P_{x})_{2} are observed. Neutron diffraction and inelastic neutron scattering measurements suggest that the quantum critical point is associated with the antiferromagnetic order, which is not of conventional spin-density-wave type as evidenced by the ω/T scaling of spin excitations. On the other hand, no divergence of low-temperature nematic susceptibility is observed when x is decreased to 0.42 from higher doping level, demonstrating that there are no nematic quantum critical fluctuations. Our results suggest that non-Fermi-liquid behaviors in iron-based superconductors can be solely resulted from the antiferromagnetic quantum critical fluctuations, which cast doubts on the role of nematic fluctuations played in the normal-state properties in iron-based superconductors.

A method to induce human cortical long-term potentiation by acoustic stimulation.

OBJECT: Acoustic stimulation induced LTP in the human auditory cortex was successfully recorded for the first time by electroencephalography (EEG) using a stimulus of 1 kHz pure-tone in 2005. However, it was barely reproduced, given considerable challenges to reliably elicit and accurately record the enhanced potentials in vivo. The purpose of this paper was to explore whether acoustic stimuli other than 1 kHz pure-tone could generate LTP or not. MEASURES: To answer this question, we proposed a tetanic-stimulation paradigm of pure-tones, narrow-band noises (NBNs) and white noise (WN) to elicit LTP in human subjects. RESULTS: The results showed that pure-tones with different frequency could elicit LTP in human auditory cortex, and proved for the first time that NBNs and WN could also achieve the same goal. Interestingly, it was also shown that the noises with certain bandwidth induced the greatest LTP and the WN induced LTP had the least variation over time and across subjects in comparison with pure-tones and NBNs. CONCLUSIONS: In light of the results, we suggested to use the paradigm for broader studies of human in vivo cortical plasticity.

Changes in dissolved organic matter composition and metabolic diversity of bacterial community during the degradation of organic matter in swine effluent.

In this study, an incubation experiment was conducted with effluent collected from the concentrated swine-feeding operations (CSFOs) located in Yujiang County of Jiangxi Province, China. The purpose of this study was to elucidate the relationships between the composition of dissolved organic matter (DOM) and the community-level physiological profiles (CLPPs) of microorganisms in swine effluent. For all samples examined, the concentrations of dissolved organic carbon (DOC) and total dissolved nitrogen (TDN) were decreased by an average of 58.2 ± 30.4 and 49.2 ± 38.7 %, whereas total dissolved phosphorus (TDP) exhibited an average final accumulation of 141.5 ± 43.0 %. In the original samples, ammonium nitrogen accounted for 88.9 ± 4.9 % of the TDN, which was reduced to a final average of 83.9 ± 9.6 %. Two protein-like (tyrosine and tryptophan) and two humic-like (fulvic acids and humic acids) components were identified using a three-dimensional excitation-emission matrix. With the increase in incubation time, the relative concentrations of two protein-like components in effluent were reduced by an average of 83.2 ± 24.7 %. BIOLOG(™) ECO plates were used to determine the metabolic fingerprint of the bacterial community, and a shift in the utilization patterns of substrates was observed over the study period. Additionally, the Shannon-Wiener index of CLPP was ultimately reduced by an average of 43.5 ± 8.5 %, corresponding to the metabolic diversity of the bacterial community. The redundancy analysis identified significant relationships between environmental parameters and the CLPP of microorganisms. To a certain degree, the DOM compositions were linked with the substrate utilization patterns of the bacterial community during the degradation of organic matter in swine effluent.

Enantioselective Separation of 4,8-DHT and Phytotoxicity of the Enantiomers on Various Plant Species.

As a candidate for bioherbicide, 4,8-dihydroxy-1-tetralone (4,8-DHT) was isolated from Caryospora callicarpa epicarp and its two enantiomers, S-(+)-isosclerone and R-(-)-regiolone, were separated by chiral high-performance liquid chromatography (HPLC) on a Chiralcel OD column with chiral stationary phase (CSP)-coated cellulose-tris(3,5-dimethylphenylcarbamate). Then, the phytotoxicity of 4,8-DHT and its enantiomers toward the seeds germination and seedling growth of the five tested plant species, including lettuce (Latuca sativa), radish (Raphanus sativus), cucumber (Cucumis sativus), onion (Allium cepa), and wheat (Triticum aestivum), were investigated and the results indicated a hormesis at low concentration of 4,8-DHT and its enantiomers, but a retardant effect at high concentration. Between the two enantiomers of 4,8-DHT, the S-(+)-isosclerone was more toxic to seeds germination and seedling growth of the five tested plant species than the R-(-)-regiolone, and also the phytotoxicity of S-(+)-isosclerone varied with different plants. For example, S-(+)-isosclerone was the most active to seedling growth of lettuce, indicating that S-(+)-isosclerone had specific effects on different organisms. Thus, all of the chirality and concentration of 4,8-DHT, as well as the affected plant species, need to be taken into consideration in the development and utilization of 4,8-DHT.

Smart MoS2/Fe3O4 Nanotheranostic for Magnetically Targeted Photothermal Therapy Guided by Magnetic Resonance/Photoacoustic Imaging.

The ability to selectively destroy cancer cells while sparing normal tissue is highly desirable during the cancer therapy. Here, magnetic targeted photothermal therapy was demonstrated by the integration of MoS2 (MS) flakes and Fe3O4 (IO) nanoparticles (NPs), where MoS2 converted near-infrared (NIR) light into heat and Fe3O4 NPs served as target moiety directed by external magnetic field to tumor site. The MoS2/Fe3O4 composite (MSIOs) functionalized by biocompatible polyethylene glycol (PEG) were prepared by a simple two-step hydrothermal method. And the as-obtained MSIOs exhibit high stability in bio-fluids and low toxicity in vitro and in vivo. Specifically, the MSIOs can be applied as a dual-modal probe for T2-weighted magnetic resonance (MR) and photoacoustic tomography (PAT) imaging due to their superparamagnetic property and strong NIR absorption. Furthermore, we demonstrate an effective result for magnetically targeted photothermal ablation of cancer. All these results show a great potential for localized photothermal ablation of cancer spatially/timely guided by the magnetic field and indicated the promise of the multifunctional MSIOs for applications in cancer theranostics.

Overexpression of wheat NF-YA10 gene regulates the salinity stress response in Arabidopsis thaliana.

The nuclear factor Y (NF-Y) transcription factor is formed by the interaction of three distinct subunits (NF-YA, -YB and -YC). It targets the CCAAT box, a common cis-element in eukaryotic promoters. Here, the bread wheat gene TaNF-YA10-1 has been isolated from the salinity tolerant cultivar SR3. Recombinant TaNF-YA10-1 was heterologously produced in Escherichia coli, and the purified protein successfully bound to the CCAAT motif in vitro. TaNF-YA10-1 was down-regulated by the imposition of salinity and abscisic acid (ABA). The constitutive expression of TaNF-YA10-1 in Arabidopsis thaliana significantly increased the plant's sensitivity to salinity and repressed its sensitivity to ABA as judged from the seed germination, cotyledon greening and the relative root growth. The transcription of stress-related genes AtRAB18, AtRD29B, AtABI5, AtCBF1 and AtCBF3 was downregulated in TaNF-YA10-1 overexpression transgenic plants. The data provide supportive evidence that TaNFYA10-1 is involved in the regulation of growth under salinity stress conditions.

Effect of low estrogen on neurons in the preoptic area of hypothalamus of ovariectomized rats.

The purpose of this study was to investigate the difference in neuronal activity in the preoptic area of the hypothalamus (POAH) under low estrogen condition induced by ovariectomy. One hundred and twenty sham-operated (SHAM) and ovariectomized (OVX) rats were placed in different temperatures for 2h. Twelve rats from each group were stimulated by 4°C, 10°C, 25°C, 33°C and 38°C, respectively. c-Fos expression in the POAH was detected by immunohistochemistry. Following exposure to warm and cold stimuli, there were markedly lower c-Fos-positive cell densities in the OVX group compared with the SHAM group in the median preoptic nucleus (MnPO) at 4°C, 10°C, 33°C and 38°C, in the medial preoptic area (MPA) at 25°C and 38°C, in the ventromedial preoptic nucleus (VMPO) at 4°C, 10°C and 38°C and in the ventrolateral preoptic nucleus (VLPO) at 4°C and 38°C. Both temperature and surgery had an impact on c-Fos expression by two-way ANOVA method except in the lateral preoptic area (LPO). c-Fos expression differed within different nuclei of the two groups in the same and different temperature stimuli. This indicated that the temperature-sensitive nuclei in the POAH exhibited lower and different activities during temperature stimuli following ovariectomy, which possibly resulted in abnormal thermoregulation and menopausal symptoms.

[The role of MAPK signal pathway in the regulation of AQP3 expression induced by compound danshen injection in human amniotic epithelial cells].

OBJECTIVE: To investigate the role of mitogen-activated protein kinases (MAPKs)-extracellular signal regulated kinase1/2 (ERK1/2) signal pathway in the regulation of Compound Danshen Injection (CDI) induced AQP3 expression in the human amniotic epithelial cells (hAECs). METHODS: hAECs of term pregnancy with normal amniotic fluid volume (AFV) or isolated oligohydramnios were primarily cultured. And the cells were equally divided into four groups, i.e., the vehicle control group, the U0126 group, the CDI group, the CDI + U0126 group. The expressions of phosphorylated ERK1/2 (p-ERK1/2) and AQP3 in hAECs were detected using Western blot analysis. RESULTS: (1) When compared with the control group, the expression level of p-ERK1/2 in hAECs in those with normal AFV and oligohydramnios obviously decreased in the U0126 group (P < 0.05). The expression level of p-ERK1/2 could be elevated in the CDI group (P < 0.05). The expression level of p-ERK1/2 in hAECs was higher in the CDI +U0126 group than in the U0126 group, but lower in the CDI + U0126 group than in the CDI group (P < 0.05). (2) There was no obvious change in AQP3 expression in hAECs with normal AFV between the U0126 group and the vehicle control group (P > 0.05). There was no statistical difference in the expression level of AQP3 between the CDI group and the U0126 +CDI group (P > 0.05), but they were higher than those in the vehicle control group (P < 0.05). (3) Compared with the vehicle control group, the expression level of AQP3 in hAECs with oligohydramnios significantly decreased in the U0126 group and increased in the CDI group (P < 0.05). The expression level of AQP3 was lower in the U0126 + CDI group than in the CDI group, but higher in the U0126 +CDI group than in the U0126 group (P < 0.05). CONCLUSION: CDI could regulate AQP3 expression level in hAECs with oligohydramnios via activating the MAPK-ERK1/2 signal transduction pathway.

[Effects of compound salvia miltiorrhiza injection on aquaporin 3 expression in human amniotic epithelial cells].

OBJECTIVE: To study the effects of Compound Salvia miltiorrhiza Injection (CSI) on aquaporin 3 (AQP3) expression in human amniotic epithelial cells (hAECs), and to explore its mechanisms for treating oligohydramnios. METHODS: The hAECs selected from 8 human term pregnancies with oligohydramnios and no other complications (as the test group)and 8 human term pregnancies with normal amniotic fluid volume (as the control group) were primarily cultured. The mRNA and protein expressions of AQP3 in hAECs were detected using reverse transcription-polymerase chain reaction and Western blot with various concentrations of CSI (0.000, 0.001, 0.010, 0.020, 0.060, and 0.100 mg/mL, respectively) at different time points (0, 6, 12,24, and 48 h, respectively). RESULTS: (1) Compared with the control group, the AQP3 expression was down-regulated in the test group (P < 0.05). (2) The AQP3 expression in the two groups reached the peak when the concentration of CSI was 0.010 mg/mL, showing statistical difference when compared with other concentrations (P < 0.05). (3) The AQP3 expression reached the peak when 0.010 mg/mL CSI acted for 12 h, showing statistical difference when compared with other concentrations (P < 0.05). (4) The AQP3 expression was up-regulated in the two groups when 0.010 mg/mL CSI acted for 12 h. But the up-regulated AQP3 expression was more obvious in the test group than in the control group (P < 0.05). CONCLUSIONS: CSI could regulate the AQP3 expression in hAECs. CSI showed more obvious effects on the AQP3 expression in hAECs of oligohydramnios human term pregnancies.

Bioassay-guided isolation of an alkaloid with antiangiogenic and antitumor activities from the extract of Fissistigma cavaleriei root.

Fissistigma cavaleriei (Levl) Rehd (Annonaceae) is used as a folklore medicine for treatment of inflammation, arthritis, and tuberculosis by Miao people in China. In the present study, the antiangiogenic activity of F. cavaleriei was investigated. The chorioallantoic membrane of the fertilized hen's egg (CAM assay) was used to determine antiangiogenic activity of the plant extract. Compound (1), a compound with antiangiogenic activity, was isolated by bioassay-guided fractionation from F. cavaleriei for the first time. The structure of compound (1) was elucidated on the basis of spectroscopic methods. Colorimetric COX (ovine) inhibitor screening assay was used to determine its inhibitory effect on COX-1 and COX-2. MTT and Sulforhodamine B assays were used to investigate its cytotoxic effects on tumor cell lines. As a result, compound (1) showed a selectively inhibiting effect on COX-2 and could inhibit the growth of tumor cells in vitro. The antitumor activity of compound (1) was further confirmed by the observation that compound (1) administration significantly inhibited the growth of S-180 cells in mice. Moreover, compound (1) was able to enhance the antitumor activity of doxorubicin in the mice bearing with S-180 cells while combined with doxorubicin. In conclusion, compound (1) is a multi-target molecule and further experimental investigations are needed to determine whether it can be used as a lead molecule for tumor treatment.

[Effects and mechanism of Sibiraea angustata on lipid metabolism in hight-fatted rats].

OBJECTIVE: To investigate the effect and mechanism of Sibiraea angustata on lipid metabolism in hight-fatted SD rats. METHODS: After the obese model was built,Sibiraea angustata was administrated intragastrically to obese rats for 8 weeks. Peeled off fat around kidneys and made pathological tissue sections. The number and size of adipocytes were detected. The levels of adiponectin, adipoR2, AMPK, and PPARgamma mRNA in adipose tissue were detected by RT-PCR. AMPK protein expression in adipose tissue were detected by Western Blot. RESULTS: Compared with the model group, the diameter of adipocytes were reduced while the number increased after adminiseration of Sibiraea angustata for 8 weeks. The levels of adiponectin, adipoR2, AMPK and PPARgamma mRNA were increased siginficantly. The expression of AMPK protein was also up-regulated significantly. CONCLUSION: Sibiraea angustata has anti-obesity effect. The mechanism may be related to the adiponectin signal transduction pathway.

Effects of an isopropanolic-aqueous black cohosh extract on central body temperature of ovariectomized rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Black cohosh (Cimicifuga racemosa) is widely used in menopause symptoms strategy. AIM OF THE STUDY: The aim of this study was to examine the effect of isopropanolic black cohosh extract (iCR) on the central body temperature (CBT) of ovariectomized rats (OVX) and elaborate its possible effects in alleviating menopause related hot flushes. MATERIALS AND METHODS: 64 female Sprague-Dawley rats, weighing 230 ± 10g and aged 6-8 weeks, were divided into four groups: ovariectomy (OVX), sham, ovariectomy plus estradiol valerate (OVX+E), and ovariectomy plus iCR (OVX+ICR). The sham group underwent a sham surgery without ovariectomies, while the other three groups underwent bilateral ovariectomies under sterile conditions and a temperature implant was embedded in the abdominal cavity of all four groups. After 2-week recovery period, the temperature of all animals was monitored for 6 weeks. RESULTS: CBT of four groups maintained a normal circadian rhythm, with a low day CBT and a high night CBT. CBTs of the sham group were lower than that of the other three groups. The day CBTs of the (OVX+E) group and (OVX+ICR) group were lower than that of the OVX group from day 2 and day 22 respectively. For the difference between day and night CBT, the sham group was smallest, while (OVX+E) and (OVX+ICR) groups were higher than that of OVX group. The amplitude of day and night CBT, CBT fluctuation frequency at 5 min intervals, were higher for the OVX group than the sham group; the amplitude of day and night CBT of (OVX+E) group and the amplitude of night CBT of (OVX+ICR) group were higher than those of OVX group; while the amplitude of day CBT of (OVX+ICR) group was lower than that of OVX group; CBT fluctuation frequency at 5 min intervals was higher for the (OVX+E) and (OVX+ICR) groups than the OVX group. CONCLUSIONS: Ovariectomized rats had abnormal thermoregulation, demonstrating an increase in day and night CBT, greater difference between day and night CBT, higher amplitude of day and night CBT, and more CBT fluctuation frequency. For the herbal extract iCR, the onset of affecting abnormal thermoregulation took longer than that of estradiol valerate. ICR had a significant effect on day CBT but was only little effective on night CBT of ovariectomized rats.

Beta-lactamase inhibitory component from the roots of Fissistigma cavaleriei.

Therapeutic control of beta-lactamase-producing bacteria has been a major clinical problem. Development of drug combinations containing the beta-lactamase inhibitors has given clinicians a novel approach to controlling resistant organisms. In our search for beta-lactamase inhibitors from natural resources, we found that the methanol extract of the roots of Fissistigma cavaleriei showed an inhibitory effect on beta-lactamase. Bioassay-guided isolation of the extract yielded an active compound that was identified as salicylsalicylic acid by physical and spectroscopic methods. The compound showed inhibitory effects on beta-lactamase in a dose-dependent manner with IC(50) values of 71 microM. Salicylsalicylic acid is not as potent as the original inhibitors such as clavulanic acid, but it may be developed to be potent beta-lactamase inhibitor by chemical modification.