Regulation of Neuropeptide Y Receptor Gene Expression and Hormone Level in Obese Male Rats Receiving 6-Gingerol and L-Arginine Supplementation.

Obesity and its associated disorders, such as hyperlipidemia, have become a global issue following the consumption of unhealthy, high-fat, and high- carbohydrate foods, which burdens the economies and the health systems of human societies worldwide. This study aimed to evaluate the effect of oral consumption of 6-gingerol and L-arginine supplements on obesity factors. Thirty rats in five groups were fed a diet specific to each group for 12 weeks and then treated with the oral administration of L-arginine (200 mg/day) and 6-gingerol (100 mg/day) for 12 weeks. The food and water intake and weight change, were then measured. In addition, plasma glucose, triglyceride, cholesterol, high-density lipoprotein (HDL), very-low-density lipoprotein (VLDL) , low-density lipoprotein (LDL), and serum hormone levels, including corticosterone, testosterone, and insulin, were measured, and NPY, Y1, and Y5 receptor gene expression were recorded using real-time PCR. Administration of 6-gingerol and L-arginine decreased food intake, weight gain, glucose levels, insulin levels, and homeostasis model assessment-insulin resistance (HOMA-IR) index compared to the HCD control group. In addition, corticosterone and testosterone levels in the study groups showed a significant decrease (P<0.05) and increase (P<0.01) compared to the control groups, respectively. Triglyceride, total cholesterol, HDL, and VLDL levels in the groups treated with L-arginine and gingerol alone or combined significantly decreased compared to the control group (P<0.01). This study confirms that 6-gingerol and L-arginine supplements prevent HCD-induced hyperlipidemia by controlling hormones and neurotransmitters involved in the general metabolism. .

Privileged small molecules against neglected tropical diseases: A perspective from structure activity relationships.

Neglected tropical diseases (NTDs) comprise diverse infections with more incidence in tropical/sub-tropical areas. In spite of preventive and therapeutic achievements, NTDs are yet serious threats to the public health. Epidemiological reports of world health organization (WHO) indicate that more than 1.5 billion people are afflicted with at least one NTD type. Among NTDs, leishmaniasis, chagas disease (CD) and human African trypanosomiasis (HAT) result in substantial morbidity and death, particularly within impoverished countries. The statistical facts call for robust efforts to manage the NTDs. Currently, most of the anti-NTD drugs are engaged with drug resistance, lack of efficient vaccines, limited spectrum of pharmacological effect and adverse reactions. To circumvent the issue, numerous scientific efforts have been directed to the synthesis and pharmacological development of chemical compounds as anti-infectious agents. A survey of the anti-NTD agents reveals that the majority of them possess privileged nitrogen, sulfur and oxygen-based heterocyclic structures. In this review, recent achievements in anti-infective small molecules against parasitic NTDs are described, particularly from the SAR (Structure activity relationship) perspective. We also explore current advocating strategies to extend the scope of anti-NTD agents.

Effects of Intracerebroventricular Injection of the Steroidal and Non-Steroidal Anti-Inflammatory Drugs on the Seizures during the Estrous Cycle in Rat.

Because of the mutual relationship between neural inflammation and seizure, this study aimed to determine the effects of intracerebroventricular (ICV) injection of the steroidal and non-steroidal anti-inflammatory drugs on pentylenetetrazol (PTZ)-induced seizures during the estrous cycle in rats. A total of 105 adult female Wistar rats were selected and divided into seven groups, including the control (saline), ketorolac tris salt (7.5, 15, and 30 µg), and methylprednisolone acetate (0.15, 0.3, and 0.6 µg), each with four subgroups (proestrus, estrus, metestrus, and diestrus) and three replicates (n=5). After a week of acclimatization, the estrous phase determination and synchronization were performed. Acute epilepsy was inspired by the intraperitoneal injection of 80 mg/kg of PTZ 30 min after the ICV injection of ketorolac and methylprednisolone acetate. The initiation time of myoclonic seizures (ITMS), the initiation time of tonic-clonic seizures (ITTS), seizure duration (SD), and mortality rate (MR) were measured for 30 min. Data were shown as mean±SD and analyzed using One-way ANOVA followed by Tukey-Kramer multiple comparison post hoc test (P<0.05). According to the results, ketorolac (15 and 30 µg) and methylprednisolone acetate (0.3 and 0.6 µg) significantly increased the ITTS and ITMS but decreased SD during the estrous cycle, compared to the control (P<0.05). Moreover, MR and SD were significantly decreased by ketorolac (7.5, 15, and 30 µg) and methylprednisolone (0.3 and 0.6 µg), compared to the control during the estrous cycle (P<0.05). Therefore, it seems that both ketorolac and methylprednisolone possess dose-dependent anticonvulsant effects that may decrease neural inflammation.

Central Phoenixin Protective Role on Pentylenetetrazol-Induced Seizures during Various Stages of the Estrous Cycle among Rats.

It is known that phoenixin-14 (PNX-14) has a mediatory role in reproduction; however, there is no report on the role of the PNX-14 on epilepsy. Therefore, this study aimed to investigate the antiepileptic effects of the PNX-14 on the pentylenetetrazol (PTZ)-induced epilepsy in the stages of the estrous cycle among rats. A total of 168 adult female Wistar rats were randomly divided into seven groups, including control (intracerebroventricular injection was performed with saline), PNX-14 (5 µg), PNX-14 (10 µg), bicuculline (competitive antagonist of GABAA receptors; 5 nmol)+PNX-14 (5 µg), bicuculline (BIC) (5 nmol)+PNX-14 (10 µg), saclofen (competitive antagonist of GABAB receptors; 2.5 µg)+PNX-14 (5 µg), and saclofen (2.5 µg)+PNX-14 (10 µg) in proestrus, estrus, metestrus, and diestrus. Afterward, the control and treatment groups were followed by intraperitoneal administration of 80 mg/kg PTZ. Initiation time of myoclonic seizures (ITMS), initiation time of tonic-clonic seizures (ITTS), seizure duration (SD), and mortality rate (MR) were monitored and recorded for 30 min. According to the results, PNX-14 alone significantly reduced the SD and seizure mortality in all phases of estrus (P<0.05). The injection of PNX-14 with BIC significantly reduced SD and seizure mortality in all estrus phases (P<0.05). PNX-14 alone increased both ITMS and ITTS in all phases of estrus (P<0.05). Furthermore, the injection of PNX-14 with BIC significantly reduced the effects of the PNX-14 on ITMS and ITTS in all estrus stages (P<0.05). These results showed that the antiepileptic activity of PNX-14 was probably mediated by GABAA receptors, and this effect was more prominent during the luteal phase than the follicular phase.

Interconnection between Adrenergic and Dopaminergic Systems in Feeding Behavior in Neonatal Chicks.

Central dopaminergic (DAergic) and adrenergic systems have a prominent role in appetite regulation; however, their interaction(s) have not been studied in neonatal layer chickens.Therefore, the current study aimed to determine the interaction of central DAergic and noradrenergic systems in food intake regulation in neonatal layer chickens. In the first experiment, chickens received the intracerebroventricular (ICV) injection of a control solution, prazosin (i.e., &alpha;1 adrenergic receptor antagonist; 10 nmol), dopamine (DA; 40 nmol), and prazosin plus DA. The second to fifth experiments were similar to the first experiment except that the birds were injected with yohimbine (i.e., &alpha;2 receptor antagonist; 13 nmol), metoprolol (i.e., &beta;1 adrenergic receptor antagonist; 24 nmol), ICI 118,551 (i.e., &beta;2 adrenergic receptor antagonist; 5 nmol), and SR59230R (i.e., &beta;3 adrenergic receptor antagonist; 20 nmol) instead of prazosin. In the sixth experiment, the chickens received ICV injection with the control solution and noradrenaline (NA; 75, 150, and 300 nmol). In the seventh experiment, the birds were injected with the control solution, SCH23390 (i.e., D1 DAergic receptor antagonist; 5 nmol), NA (300 nmol), and SCH23390 plus NA In the eighth experiment, the control solution, AMI-193 (i.e., D2 DAergic receptor antagonist; 5 nmol), NA (300 nmol), and AMI-193 plus NA were injected. Then, cumulative food intake was recorded at 30, 60, and 120 min after the injection. According to the obtained results, the ICV injection of DA (40 nmol) significantly decreased food intake in comparison to that reported for the control group (p &lt;0.05). The co-injection of yohimbine plus DA significantly amplified DA-induced hypophagia in the neonatal chickens (p &lt;0.05). In addition, the co-administration of ICI 118,551 plus DA significantly inhibited the hypophagic effect of DA in the neonatal chickens (p &lt;0.05). Furthermore, NA (75, 150, and 300 nmol) significantly reduced food intake in a dose-dependent manner (p &lt;0.05). The co-injection of SCH23390 plus NA decreased the hypophagic effect of NA in the neonatal chickens, compared to that reported for the control group (p &lt;0.05). The co-injection of AMI-193 plus NA diminished NA-induced hypophagia, compared to that reported for the control group (p &lt;0.05). The aforementioned results suggested that there is an interconnection between central DAergic and noradrenergic systems through &alpha;2/&beta;2 adrenergic and D1/D2 DAergic receptors in food intake regulation in neonatal chicks.

Metabolomic biomarkers of low BMD: a systematic review.

Due to the metabolic nature of osteoporosis, this study was conducted to identify metabolomic studies investigating the metabolic profile of low bone mineral density (BMD) and osteoporosis. A comprehensive systematic literature search was conducted through PubMed, Web of Science, Scopus, and Embase databases up to April 08, 2020, to identify observational studies with cross-sectional or case-control designs investigating the metabolic profile of low BMD in adults using biofluid specimen via metabolomic platform. The quality assessment panel specified for the "omics"-based diagnostic research (QUADOMICS) tool was used to estimate the methodologic quality of the included studies. Ten untargeted and one targeted approach metabolomic studies investigating biomarkers in different biofluids through mass spectrometry or nuclear magnetic resonance platforms were included in the systematic review. Some metabolite panels, rather than individual metabolites, showed promising results in differentiating low BMD from normal. Candidate metabolites were of different categories including amino acids, followed by lipids and carbohydrates. Besides, certain pathways were suggested by some of the studies to be involved. This systematic review suggested that metabolic profiling could improve the diagnosis of low BMD. Despite valuable findings attained from each of these studies, there was great heterogeneity regarding the ethnicity and age of participants, samples, and the metabolomic platform. Further longitudinal studies are needed to validate the results and confirm the predictive role of metabolic profile on low BMD and fracture. It is also mandatory to address and minimize the heterogeneity in future studies by using reliable quantitative methods. Summary: Due to the metabolic nature of osteoporosis, researchers have considered metabolomic studies recently. This systematic review showed that metabolic profiling including different categories of metabolites could improve the diagnosis of low BMD. However, great heterogeneity was observed and it is mandatory to address and minimize the heterogeneity in future studies.

Endothelium-independent vasorelaxant activity of Trachyspermum ammi essential oil on rat aorta.

Several pharmacological activities of the essential oil of Trachyspermum ammi seeds (TAEO) have been previously studied. These include antitussive, antihypertensive, and antispasmodic effects. However, its action on isolated aorta has not yet been studied. This study was aimed to investigate the vasorelaxant activity of TAEO and characterize its mechanism of action. Extraction of TAEO was performed using Clevenger-type apparatus with the final content of 4.5% (v/w). To evaluate some probable mechanisms of action of TAEO, the action isometric tension was then measured in the aortic rings from Wistar rats which were precontracted with phenylephrine (PHE) (1 µM) or KCl (60 mM). The major constituents of TAEO included Thymol (38.1%), gamma-terpinene (33.3%), and p-cymene (23.1%), as was analyzed by GC-MS. The cumulative concentrations of TAEO reduced precontraction caused by PHE and KCl (p < 0.05) significantly, which was dose dependent. The vasorelaxation caused by TAEO was not influenced in the presence of methylene blue and L-NAME in the endothelium-intact and denuded aorta ring. The inhibitory effect of TAEO on the aortic rings precontracted with KCl and PHE was considerably reduced by nifedipine. These findings hypothesized that the vasorelaxation caused by TAEO is completely endothelium independent and the extracellular Ca2+ influx was also inhibited by TAEO.

Citrate and celecoxib induce apoptosis and decrease necrosis in synergistic manner in canine mammary tumor cells.

Celecoxib and citrate have been shown to possess antitumor activity in a variety of cancer cells. However, the antitumor activities of these agents in canine mammary tumors have not been well demonstrated. The aim of our study was to investigate the apoptotic and antiproliferative effects of citrate and celecoxib, individually and in combination, on canine mammary tumor cell line CF41­Mg. MTT assay was performed to determine cell viability, and Annexin­PI test was performed to evaluate apoptosis induction. MTT assay results revealed that compared with the control groups, treatment groups, as both single and combined treatments, showed significant inhibition of tumor growth in a dose­dependent manner. IC50 concentrations of citrate and celecoxib were defined 26mM and 22µM, respectively. In another set of experiment, significant increase in cell apoptosis was observed at IC50 concentrations of citrate and celecoxib after 48h incubation. In spite of that, simultaneous treatment of cells with citrate and celecoxib eventuated with meaningful toxicity augmentation and induction of apoptosis at lower concentrations. Also necrotic cells were decreased by coadministration of the two agents. In conclusion, the present study indicates significant cytotoxic and apoptotic effects of citrate and celecoxib coadministration on CF41­Mg cells, and proposes new strategies for counteracting cancer cells proliferation and overcoming chemo resistance.