Pharmacological Experiment Research Articles

Functional near-infrared-spectroscopy-based measurement of changes in cortical activity in macaques during post-infarct recovery of manual dexterity

Because compensatory changes in brain activity underlie functional recovery after brain damage, monitoring of these changes will help to improve rehabilitation effectiveness. Functional near-infrared spectroscopy (fNIRS) has the potential to measure brain activity in freely moving subjects. We recently established a macaque model of internal capsule infarcts and an fNIRS system for use in the monkey brain. Here, we used these systems to study motor recovery in two macaques, for which focal infarcts of different sizes were induced in the posterior limb of the internal capsule. Immediately after the injection, flaccid paralysis was observed in the hand contralateral to the injected hemisphere. Thereafter, dexterous hand movements gradually recovered over months. After movement recovery, task-evoked hemodynamic responses increased in the ventral premotor cortex (PMv). The response in the PMv of the infarcted (i.e., ipsilesional) hemisphere increased in the monkey that had received less damage. In contrast, the PMv of the non-infarcted (contralesional) hemisphere was recruited in the monkey with more damage. A pharmacological inactivation experiment with muscimol suggested the involvement of these areas in dexterous hand movements during recovery. These results indicate that fNIRS can be used to evaluate brain activity changes crucial for functional recovery after brain damage.

Systematic Investigation on Multi-Scale Mechanisms of Astragaloside IV in Treating Diabetic Nephropathy

Diabetic nephropathy (DN), a common complication of diabetes mellitus, is the main cause of end-stage nephropathy, and thus developing novel strategies for reversing DN remains urgent. Astragaloside IV (AS-IV), a glycoside extracted from the Astragalus membranaceus (Fisch.) Bunge, is a widely used Traditional Chinese Medicine (TCM) in China and presents diverse pharmacological properties including the protective effect on DN. However, the rudimentary mechanism of AS-IV in remedying DN remains indeterminate. Currently, we systematically explore the pharmacological mechanism of action of AS-IV for treating DN. Firstly, AS-IV was evaluated by ADME assessment, and 26 targets were screened out through target prediction. Then, we decipher the protein-protein interaction (PPI), Gene Ontology (GO) enrichment analysis, disease and pathway network analysis to obtain the specific molecular biological process and pharmacological activity of AS-IV in the treatment of DN. Meanwhile, both in vivo and in vitro experiments confirmed that AS-IV has anti-oxidative stress, anti-inflammatory, anti-epithelial-mesenchymal transition (EMT) effects, and can inhibit the Wnt/β-catenin signaling pathway, ultimately ameliorating the renal injury caused by high glucose. Additionally, we also applied molecular docking and molecular dynamics simulation to predict the specific binding sites and binding capacity of AS-IV and related targets. Overall, the comprehensive system pharmacology method and experiment validations provide an accurate explanation for the molecular mechanism of AS-IV in the treatment of DN. Moreover, it is expected to provide a brand new strategy for exploring the effective components of TCM. Funding Statement: Financial support from the second batch of scientific research projects for the construction of the national TCM clinical research base (No. JDZX2015130), the National Science Foundation for Young Scientists of China (No.81904062), and the high-level introduction of talent special support plan (No. DT19200001). Declaration of Interests: The author(s) declared that this article content has no conflicts of interest. Ethics Approval Statement: All these experimental protocols were authorized by the Animal Experimentation Ethics Committee of the Anhui University of Chinese Medicine.

Network Pharmacology-Based Prediction of Active Ingredients and Potential Targets of ShengDiHuang Decoction for Treatment of Dysfunctional Uterine Bleeding.

Objective To analyze the potential active ingredients and related crucial targets of the ShengDiHuang Decoction (SDHD) formula in the treatment of dysfunctional uterine bleeding (DUB) by using network pharmacology and verification experiment. Methods In this study, we determined the potential active ingredients from the traditional SDHD formula and their targets with the network pharmacology method. The network of “compound-disease-target” was constructed by the software of Cytoscape. Software of DAVID was used to enrich pathways for these 87 targets of SDHD. Further, the therapeutic effect of SDHD on DUB was verified by observing the morphological changes of the uterus and ovaries and determining the expression of ERS2 and progesterone in the plasma. Results 52 compounds of Rheum and 5 compounds of Rehmannia were selected, and 87 potential targets were screened by network pharmacology. Furthermore, 7 main active ingredients were acquired by the ADME process. In addition, enrichment analysis of drug-target networks indicated that SDHD may play a role in overall coordination through “multicomponent and multitarget” in different organ patterns by regulating multiple pathways directly or indirectly. Finally, in the verification experiment of SDHD on DUB, it was found that SDHD can effectively repair the uterus and ovaries and also have an upregulation effect on the target ESR2 and increase the content of progesterone. Conclusion Overall, this study revealed potential mechanisms of multitarget and multicomponent about SDHD in the treatment of DUB and provided a scientific foundation for further studying the mechanism.

The Reform and Practice of Pharmacology Experiment Teaching Based on “PBL +Rain Classroom”

制药工程；药理学实验；PBL；雨课堂；教学改革

Melatonin is responsible for rice resistance to rice stripe virus infection through a nitric oxide-dependent pathway

Rice stripe virus (RSV) causes one of the most important rice virus diseases of plants in East Asia. However, the molecular mechanisms controlling rice resistance to RSV infection are largely unknown. Recently, several studies presented a novel model that melatonin (MT) and nitric oxide (NO) participate in the plant-pathogen interaction in a synergetic manner. In this study, there was a difference in MT content between two rice varieties that correlated with one being susceptible and one being resistant to RSV, which suggested that MT is related to RSV resistance. In addition, a test with two NO biosynthesis inhibitors revealed that NO inhibitor were able to increase the disease incidence of RSV. A pharmacological experiment with exogenous MT and NO showed that increased MT and NO in the MT-pretreated plants led to lower disease incidences; however, only NO increased in a NO-releasing reagent [sodium nitroprusside (SNP)] pretreated plants. The expressions level of OsPR1b and OsWRKY 45 were significantly induced by MT and NO. These results suggest that rice resistance to RSV can be improved by increased MT through a NO-dependent pathway.

In vitro protective effects of plants frequently used traditionally in cancer prevention in Thai traditional medicine: An ethnopharmacological study.

Thai traditional medicine (TTM) has been used widely in cancer management in Thailand. Although several Thai medicinal plants were screened for pharmacological activities related to cancer treatment, such evidence still suffers from the lack of linking with TTM knowledge. To document knowledge and species used in cancer prevention in TTM and to preliminary investigate pharmacological activities related to the documented knowledge of twenty-six herbal drugs used in cancer/mareng prevention. Fieldwork gathering data on TTM concept and herbal medicines used in cancer prevention was performed with TTM practitioners across Thailand. Later, water and ethanol extracts from twenty-six herbal drugs mentioned as being used in cancer prevention were screened for their protective effect against tert-butyl hydroperoxide-induced cell death in HepG2 cells. Then active extracts were investigated for their effects on NQO1 activity, glutathione level, and safety in normal rat hepatocytes. The fieldwork helped in the development of TTM cancer prevention strategy and possible experimental models to test the pharmacological activities of selected medicinal plants. Fifteen plant extracts showed significant protective effect by restoring the cell viability to 40-59.3%, which were comparable or better than the positive control EGCG. Among them, ethanol extracts from S. rugata and T. laurifolia showed the most promising chemopreventive properties by significantly increased NQO1 activity, restored GSH level from oxidative damage, as well as showed non-toxic effect in normal rat hepatocytes. TTM knowledge in cancer prevention was documented and used in the planning of pharmacological experiment to study herbal medicines, especially in cancer, inflammation, and other chronic diseases. The proposed strategy should be applied to in vivo and clinical studies in order to further confirm the validity of such a strategy. Other traditional medical systems that use integrated approaches could also apply our strategy to develop evidence that supports a more rational uses in traditional medicine.

A Preliminary Study on the Comprehensive Design and Experimental Teaching Reform of Pharmacology Curriculum in Biotechnology Specialty

<p>In the biological technology professional teaching process, the analysis and exploration of pharmacology experimental teaching situation should integrate the verification experiment and the method of comprehensive experiment implementation and designing experiment, to stimulate students' intrinsic motivation, so that students can fully master relevant content and pharmacology experiment method under the premise of enhancing their practical learning ability and innovative thinking ability. Cultivating a large number of comprehensive professional talents compliance with medical and biological technology development.</p>

Rv1273c, an ABC transporter of Mycobacterium tuberculosis promotes mycobacterial intracellular survival within macrophages via modulating the host cell immune response

Mycobacterium proteins, especially cell wall associated proteins, interact with host macrophage to regulate the functions and cytokine production. So, identification and characterization of such proteins is essential for understanding tuberculosis pathogenesis. The role of the ABC transporter proteins in the pathophysiology and virulence of Mycobacterium tuberculosis is not clearly understood. In the present study, Rv1273c, an ABC transporter, has been expressed in a non-pathogenic and fast growing Mycobacterium smegmatis strain to explore its role in host pathogen interactions. Over expression of Rv1273c resulted in enhanced intracellular survival in macrophage as well as modified cell wall architecture. We found altered colony morphology and cell surface properties that might be linked with remodelling of bacterial cell wall which may help in the intracellular survival of mycobacterium. However, the enhanced intracellular survival was not found to be the consequence of an increased resistance to intracellular stresses. The activation of macrophage by Rv1273c was associated with perturbed cytokine production. Pharmacological inhibition experiment and western immunoblotting suggested that this altered cytokine profile was mediated possibly by NF-kB and p38 pathway in macrophage. Overall, the present findings indicated that Rv1273c enhanced mycobacterium persistence and mediated the evasion of immune responses during infection.

Burst and Tonic Spinal Cord Stimulation Both Activate Spinal GABAergic Mechanisms to Attenuate Pain in a Rat Model of Chronic Neuropathic Pain.

BackgroundExperimental and clinical studies have shown that tonic spinal cord stimulation (SCS) releases gamma‐aminobutyric acid (GABA) in the spinal dorsal horn. Recently, it was suggested that burst SCS does not act via spinal GABAergic mechanisms. Therefore, we studied spinal GABA release during burst and tonic SCS, both anatomically and pharmacologically, in a well‐established chronic neuropathic pain model.MethodsAnimals underwent partial sciatic nerve ligation (PSNL). Quantitative immunohistochemical (IHC) analysis of intracellular GABA levels in the lumbar L4 to L6 dorsal spinal cord was performed after 60 minutes of burst, tonic, or sham SCS in rats that had undergone PSNL (n = 16). In a second pharmacological experiment, the effects of intrathecal administration of the GABAA antagonist bicuculline (5 μg) and the GABAB antagonist phaclofen (5 μg) were assessed. Paw withdrawal thresholds to von Frey filaments of rats that had undergone PSNL (n = 20) were tested during 60 minutes of burst and tonic SCS 30 minutes after intrathecal administration of the drugs.ResultsQuantitative IHC analysis of GABA immunoreactivity in spinal dorsal horn sections of animals that had received burst SCS (n = 5) showed significantly lower intracellular GABA levels when compared to sham SCS sections (n = 4; P = 0.0201) and tonic SCS sections (n = 7; P = 0.0077). Intrathecal application of the GABAA antagonist bicuculline (5 μg; n = 10) or the GABAB antagonist phaclofen (5 μg; n = 10) resulted in ablation of the analgesic effect for both burst SCS and tonic SCS.ConclusionsIn conclusion, our anatomical and pharmacological data demonstrate that, in this well‐established chronic neuropathic animal model, the analgesic effects of both burst SCS and tonic SCS are mediated via spinal GABAergic mechanisms.

Berzosertib (VE-822) inhibits gastric cancer cell proliferation via base excision repair system.

BackgroundCurrent investigations suggest that the Base Excision Repair (BER) system may change DNA repair capacity and affect clinical gastric cancer progression such as overall survival. However, the prognostic value of BER system members in gastric cancer remains unclear.MethodsWe explored the prognostic correlation between 7 individual BER genes, including uracil-DNA glycosylase (UNG), Single-strand-selective monofunctional uracil-DNA glycosylase 1 (SMUG1), Methyl-CpG binding domain 4 (MBD4), thymine DNA glycosylase (TDG), 8-oxoguanine DNA glycosylase (OGG1), MutY DNA glycosylase (MUTYH) and Nei like DNA glycosylase 1 (NEIL1), expression and overall survival (OS) in different clinical data, such as Lauren classification, pathological stages, human epidermal growth factor receptor-2 (HER2) expression status, treatment strategy, gender and differentiation degree in gastric cancer patients, using Kaplan-Meier plotter (KM plotter) online database. Based on the bioinformatics analysis, we utilized Berzosertib (VE-822) to inhibit DNA damage repair in cancer cells compared to solvent control group via real-time cellular analysis (RTCA), flow cytometry, colony formation and migration assay. Finally, we utilized reverse transcription-polymerase chain reaction (RT-PCR) to confirm the expression of BER members between normal and two gastric cancer cells or solvent and VE-822 treated groups.ResultsOur work revealed that high UNG mRNA expression was correlated with high overall survival probability; however, high SMUG1, MBD4, TDG, OGG1, MUTYH and NEIL1 mRNA expression showed relatively low overall survival probability in all GC patients. Additionally, UNG was associated with high overall survival probability in intestinal and diffuse types, but SMUG1 and NEIL1 showed opposite results. Further, VE-822 pharmacological experiment suggested that inhibition of DNA damage repair suppressed gastric cancer cells’ proliferation and migration ability via inducing apoptosis. Further, real-time polymerase chain reaction results proposed the inhibition of gastric cancer cells by VE-822 may be through UNG, MUTYH and OGG-1 of BER system.ConclusionWe comprehensively analyze the prognostic value of the BER system (UNG, SMUG1, MBD4, TDG, OGG1, MUTYH and NEIL1) based on bioinformatics analysis and experimental confirmation. BER members are associated with distinctive prognostic significance and maybe new valuable prognostic indicators in gastric cancer.

Synergistic nourishing 'Yin' effect of iridoid and phenylpropanoid glycosides from Radix Scrophulariae in vivo and in vitro.

Radix Scrophulariae (RS), is a renowned traditional Chinese medicine used as nourishing 'Yin'. The iridoid glycosides (IG) and phenylpropanoid glycosides (PG) are main chemical constituents in RS. However, there had been no pharmacological experiment studies of synergy between IG and PG. Due to the constituents interactions, exploring their synergy profile is of great important for explaining the essence of nourishing 'Yin' efficacy of RS. The present study was undertaken to evaluate synergistic nourishing 'Yin' effect of IG and PG from RS in vivo and in vitro through their immunoregulation and antioxidant activities. In this study, IG and PG fractions in RS were isolated and identified by High Performance Liquid Chromatography coupled with tandem quadrupole time-of-flight Mass Spectrometry (HPLC-Q-TOF-MS). The synergistic nourishing 'Yin' effect of two fractions were investigated in vivo and in vitro with thyroxine-induced 'Yin' deficiency (YD) mice model and primary splenic lymphocyte, respectively. The exterior syndrome signs and serologic and cellular biomarkers changes were detected. Then, the synergistic coefficient (SC) of IG and PG on every pharmacodynamics index were calculated by Webb method. Compared with model and mono-therapy group (IG or PG group), IG combined with PG group significantly ameliorated YD by exerting immunoregulation and antioxidant effects. Based on the SC, IG and PG possessed a synergistic effect on heart rate, average speed, upright times, spleen index, LPO, SOD, IL-6, Na+-K+-ATP enzyme in vivo, and cAMP/cGMP, IFN-γ/IL-10, and MDA in vitro with SC > 1. The nourishing 'Yin' benefits were clearly produced when IG and PG were used in combination, which provided the scientific evidence of multiple-components and multiple-approach synergistic effect of Chinese traditional herbal medicine to control and management of diseases.

\u22069-Tetrahydrocannabinol, a major marijuana component, enhances the anesthetic effect of pentobarbital through the CB1 receptor

Purpose∆9-Tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD), major psychoactive constituents of marijuana, induce potentiation of pentobarbital-induced sleep in mice. We have elucidated the mechanism of enhancement of the anesthetic effect of pentobarbital by cannabinoids.MethodsWe carried out pharmacological experiment and cannabinoid1 (CB1) receptor binding assay using CB1 antagonists to clarify whether the CB1 receptor is involved in the synergism or not. The affinities of cannabinoids for the CB1 receptor in the mouse brain synaptic membrane were evaluated using a specific CB1 ligand, [3H]CP55940.ResultsAlthough the potentiating effect of ∆9-THC on pentobarbital-induced sleep was attenuated by co-administration of CB1 receptor antagonists, such as SR141716A and AM251, at a dose of 2 mg/kg, intravenously (i.v.) to mice, the CBD-enhanced pentobarbital-induced sleep was not inhibited by SR141716A. The inhibitory constant (Ki) values of ∆9-THC and CBD were 6.62 and 2010 nM, respectively, showing a high affinity of ∆9-THC and a low affinity of CBD for the CB1 receptor, respectively. A high concentration of pentobarbital (1 mM) did not affect specific [3H]CP55940 binding on the mouse brain synaptic membrane.ConclusionsThese results suggest that binding of ∆9-THC to the CB1 receptor is involved in the synergism with pentobarbital, and that potentiating effect of CBD with pentobarbital may differ from that of ∆9-THC. We successfully demonstrated that ∆9-THC enhanced the anesthetic effect of pentobarbital through the CB1 receptor.

Correction to: A Method of Measuring Glutathione Peroxidase Activity in Murine Brain: Application in Pharmacological Experiment.

A method of measuring of glutathione peroxidase activity using H2O2 was adapted for homogenates of murine brains.

Cross Talk between Nitric Oxide and Calcium-Calmodulin Regulates Ganoderic Acid Biosynthesis in Ganoderma lucidum under Heat Stress.

We previously reported that high temperature impacts ganoderic acid (GA) biosynthesis in Ganoderma lucidum via Ca2+ Therefore, to further understand the signal-regulating network of the organism's response to heat stress (HS), we examined the role of nitric oxide (NO) under HS. After HS treatment, the NO level was significantly increased by 120% compared to that under the control conditions. The application of a NO scavenger resulted in a 25% increase in GA compared with that found in the sample treated only with HS. Additionally, the application of a NO donor to increase NO resulted in a 30% lower GA content than that in the sample treated only with HS. These results show that the increase in NO levels alleviates HS-induced GA accumulation. Subsequently, we aimed to detect the effects of the interaction between NO and Ca2+ on GA biosynthesis under HS in G. lucidum Our pharmacological approaches revealed that the NO and Ca2+ signals promoted each other in response to HS. We further constructed the silenced strain of nitrate reductase (NR) and calmodulin (CaM), and the results are in good agreement with the silenced strain and pharmacological experiment. The cross-promotion between NO and Ca2+ signals is involved in the regulation of HS-induced GA biosynthesis in G. lucidum, and this finding is supported by studies with NR-silenced (NRi) and CaM-silenced (CaMi) strains. However, Ca2+ may have a more direct and significant effect on the HS-induced GA increase than NO. These data indicate that NO functions in signaling and has a close relationship with Ca2+ in HS-induced GA biosynthesis.IMPORTANCE HS is an important environmental stress affecting the growth and development of organisms. We previously reported that HS modulates GA biosynthesis in G. lucidum via Ca2+ However, the signal-regulating network of the organism's response to HS has not yet been elucidated. In this study, we found that NO relieved HS-induced GA accumulation, and NO and Ca2+ could exert promoting effects on each other in response to HS. Further research on the effect of NO and Ca2+ on the production of GAs in response to HS indicated that Ca2+ has a notably more direct and significant effect on the HS-induced GA increase than NO. Our results improve our understanding of the mechanism of HS signal transduction in fungi. A greater understanding of the regulation of secondary metabolism in response to environmental stimuli will provide clues regarding the role of these products in fungal biology.

A systems pharmacology-oriented discovery of a new therapeutic use of the TCM formula Liuweiwuling for liver failure

Multiple components of traditional Chinese medicine (TCM) formulae determine their treatment targets for multiple diseases as opposed to a particular disease. However, discovering the unexplored therapeutic potential of a TCM formula remains challenging and costly. Inspired by the drug repositioning methodology, we propose an integrated strategy to feasibly identify new therapeutic uses for a formula composed of six herbs, Liuweiwuling. First, we developed a comprehensive systems approach to enrich drug compound-liver disease networks to analyse the major predicted diseases of Liuweiwuling and discover its potential effect on liver failure. The underlying mechanisms were subsequently predicted to mainly attribute to a blockade of hepatocyte apoptosis via a synergistic combination of multiple effects. Next, a classical pharmacology experiment was designed to validate the effects of Liuweiwuling on different models of fulminant liver failure induced by D-galactosamine/lipopolysaccharide (GalN/LPS) or thioacetamide (TAA). The results indicated that pretreatment with Liuweiwuling restored liver function and reduced lethality induced by GalN/LPS or TAA in a dose-dependent manner, which was partially attributable to the abrogation of hepatocyte apoptosis by multiple synergistic effects. In summary, the integrated strategy discussed in this paper may provide a new approach for the more efficient discovery of new therapeutic uses for TCM formulae.

Understanding cancer and its treatment in Thai traditional medicine: An ethnopharmacological-anthropological investigation

Ethnopharmacological relevanceThai traditional medicine (TTM) is widely practiced in Thailand and continues to gain importance in cancer management, but little is known about the TTM practitioners’ emic concepts and practice. Aim of the studyWith this study we firstly aim to document the practice of cancer treatment and prevention by TTM practitioners and, secondly, to evaluate how such traditional concepts and practices are correlated with biomedical ones. This in turn can form the basis for developing novel strategies for designing pharmacological experiments and longer term strategies to develop TTM practice. MethodsSemi-structured interviews with 33 TTM practitioners were performed in five provinces in different regions of Thailand. The following information were recorded; basic information of informants, descriptions of cancer (mareng in Thai), causes, diagnosis, treatment, and prevention. Plants used in the treatment and prevention of mareng were also collected. ResultsUsing an in depth ethnographic approach four representative case studies to assist in a better understanding of the characteristics of mareng, its diagnosis, treatment, and prevention are reported here. Five characteristics of mareng – waste accumulation (khong sia), chronic illnesses (krasai), inflammation (kan aksep), bad blood (luead) and lymph (namlueang), and the imbalance of four basic elements (dhātu si) – have been identified. Explanatory models of cancer in TTM were linked with biomedical concepts and relevant pharmacological actions. Traditional uses and available scientific evidence of medicinal plants mentioned in the case studies for the treatment or prevention of mareng are presented and discussed. ConclusionHere for the first time five main characteristics of cancer based on Thai traditional medical concepts are analysed. Our findings are relevant not only for the planning of clinical studies or pharmacological experiment in the search for novel compounds for cancer treatment and prevention, but also for the integration of Thai traditional medicine in cancer care.

Assessment of undergraduates’ preferences and opinions on teaching of Pharmacology

Background: The preference and opinion of undergraduate students on teaching of pharmacology was assessed using structured-based questionnaires. The objective was to determine the best way to teach pharmacology and the areas the students prefer most.Methods: The questionnaires were administered to students during academic sessions in any of their pharmacology lectures by the help of technical assistants. It was also ensured that the identity of the students was not made known except for the gender. A total of 8 questions with options ranging from 2-4 were used. Each respondent was to select only one option as the most preferred. A total of 405 students participated during the study period and it was ensured that no student participated more than once. The students recruited were 4th and 5th year medical and pharmacy students of the University of Jos, Jos, Nigeria for the 2014/2015 and 2015/2016 academic sessions.Results: The results showed that the students have high preference for latest technology teaching aids such as power point presentation and use of software for lecture notes.Conclusions: Knowledge of pharmacodynamics, clinical pharmacology and laboratory experiment were preferred and significant differences exist between observed and expected results and also between males and females in preferences among some of the options. Students need to be informed at the beginning of their lectures that pharmacology is a subject that must be regarded as a whole with no areas of preference.

Estrogenic Effects of the Extracts from the Chinese Yam (Dioscorea opposite Thunb.) and Its Effective Compounds in Vitro and in Vivo.

Background: The aim of this study was to explore the estrogenic effects of the extracts from Chinese yam and its effective compounds. Methods: The activity of the yam was investigated by the uterine weight gain of mice and a proliferation assay of breast cancer cell lines (MCF-7 cell); the estrogenic activity was comprehensively evaluated by a serum pharmacology experiment. The levels of estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone (LH) were also measured. Western blot analysis and antagonist assays with faslodex (ICI182,780), methylpiperidino-pyrazole (MPP), Delta (9) –tetrahydrocannabinol (THC), and G-15 were used to explore the mechanism of the effects of the yam. To find the effective compounds of the yam which play a role in its estrogen-like effects, we used the same methods to study the effects of adenosine and arbutin. Results: The Chinese yam and two main compounds, adenosine and arbutin, have estrogen-like effects. The mechanism of the yam which plays a role in its estrogen-like effects was mainly mediated by the estrogen receptors ERα, ERβ, and GPR30; that of adenosine was mainly mediated by estrogen receptors ERα and ERβ, and that of arbutin was mainly mediated by estrogen receptors ERβ and GPR30. Conclusions: The Chinese yam has estrogen-like effects; adenosine and arbutin are two of the effective compounds in the yam which play a role in its estrogen-like effects.

Preparation and characterization of acetylsalicylic acid/chitosan nanoparticles and its antithrombotic effects

ABSTRACTChitosan (CS)-acetylsalicylic acid (ASA) nanoparticles, which are well dispersed and stable in aqueous solution, have been prepared by interpolymer complexation of ASA in CS solution. The physicochemical properties of nanoparticles were investigated by using FT-IR, 1H NMR, scanning electron microscope（SEM）, dynamic light scattering, and UV spectrophotometer. It was found that the carboxyl group of the ASA had firmly integrated on the amino group of CS and the ASA-CS nanoparticles were almost spherical in shape with an average diameter of less than (79.3 ± 24.6) nm in high reproducibility and showed high chemical stability against environmental changes. It was also found that the prepared nanoparticles carried a positive charge and showed the size in the range from 700 to 150 nm. The surface structure and zeta potential of nanoparticles can be controlled by different preparation processes. The factor experiment results indicated that the ASA-CS nanoparticles had satisfactory loading capacity (LC) and encapsulation efficiency (EE), 27.27% and 46.88% (data not shown), respectively. The experiments of in vitro ASA release showed that these nanoparticles provided a sustained and pH-dependent drug release manner, and the release behavior was influenced by the pH value of the medium. Preliminary pharmacology experiment exhibited prolonged circulation and higher bioavailability than that of ASA. All the results indicated that ASA/CS nanoparticles may have promising pharmaceutical application, and further pharmacological research is needed to confirm these beneficial effects.

Protracted motivational dopamine-related deficits following adolescence sugar overconsumption

Adolescence represents a critical period characterized by major neurobiological changes. Chronic stimulation of the reward system during adolescence might constitute an important factor of vulnerability to pathological development. Increasing evidences suggest that adolescent overconsumption of sweet palatable foods impact reward-based processes. However, the neurobiological bases of these deficits remain poorly understood. Previous studies have demonstrated motivational deficits for palatable foods after sweet diet exposure during adolescence that might involve the dopamine (DA) system, a central actor in incentive processes. In the present study, the impact of adolescent sugar overconsumption on the sensitivity of the DA system was tested using pharmacological (Experiment 1) and receptor expression approaches (Experiment 2). Adolescent rats received free and continuous access to 5% sucrose solution from post-natal day 30–46. At adulthood, the functionality of the DA system in motivational processes was tested using systemic injections of specific DA receptors D1R or D2R agonists and antagonists during a motivation-dependent progressive ratio task (Experiment 1). Sucrose-exposed rats showed a lower motivation for saccharin and a decreased sensitivity to the effects of both D1R and D2R stimulation and blockade. In Experiment 2, Sucrose-exposed animals presented a lower expression of both D1R and D2R in the nucleus accumbens, a central brain region for incentive processes, but not in dorsal striatum or prefrontal cortex. These findings highlight the impact of sucrose overconsumption during adolescence on DA system that may support deficits in reward-related disorders.