Abstract:
:Gestational diabetes mellitus (GDM) is a major pregnancy-related disorder with an increasing prevalence worldwide. GDM is associated with altered placental vascular functions and has severe consequences for fetal growth. There is no commonly accepted medication for GDM due to safety considerations. Actions of the currently limited therapeutic options focus exclusively on lowering the blood glucose level without paying attention to the altered placental vascular reactivity and remodelling. We used the fat-sucrose diet/streptozotocin (FSD/STZ) rat model of GDM to explore the efficacy of cinnamaldehyde (Ci; 20 mg/kg/day), a promising antidiabetic agent for GDM, and glyburide/metformin-HCl (Gly/Met; 0.6 + 100 mg/kg/day), as a reference drug for treatment of GDM, on the placenta structure and function at term pregnancy after their oral intake one week before mating onward. Through genome-wide transcriptome, biochemical, metabolome, metal analysis and histopathology we obtained an integrated understanding of their effects. GDM resulted in maternal and fetal hyperglycemia, fetal hyperinsulinemia and placental dysfunction with subsequent fetal anemia, hepatic iron deficiency and high serum erythropoietin level, reflecting fetal hypoxia. Differentially-regulated genes were overrepresented for pathways of angiogenesis, metabolic transporters and oxidative stress. Despite Ci and Gly/Met effectively alleviated the maternal and fetal glycemia, only Ci offered substantial protection from GDM-associated placental vasculopathy and prevented the fetal hypoxia. This was explained by Ci's impact on the molecular regulation of placental angiogenesis, metabolic activity and redox signaling. In conclusion, Ci provides a dual impact for the treatment of GDM at both maternal and fetal levels through its antidiabetic effect and the direct placental vasoprotective action. Lack of Gly/Met effectiveness to restore it's impaired functionality demonstrates the vital role of the placenta in developing efficient medications for GDM.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Hosni A,El-Twab SA,Abdul-Hamid M,Prinsen E,AbdElgawad H,Abdel-Moneim A,Beemster GTSdoi
10.1016/j.phrs.2021.105426subject
Has Abstractpub_date
2021-01-13 00:00:00pages
105426eissn
1043-6618issn
1096-1186pii
S1043-6618(21)00009-8pub_type
杂志文章abstract::It has been suggested that hypertension results from a loss of immunological tolerance and the resulting autoimmunity may be an important underlying factor of its pathogenesis. This stems from the observations that many of the features involved in autoimmunity are also implicated in hypertension. Furthermore, the unde...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2016.09.008
更新日期:2016-11-01 00:00:00
abstract::Despite our insufficient understanding of the exact molecular mechanisms of general anesthetics and sedatives, every year millions of children are treated with these drugs in a seemingly safe manner. However, increasing evidence particularly from animal studies has suggested the possibility for deleterious effects in ...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2011.10.001
更新日期:2012-03-01 00:00:00
abstract::The activity of short porcine galanin (Gal) analogues was tested in vitro using rat gastric fundus strips. The peptides contracted longitudinal smooth muscle in a concentration-dependent manner with the following order of potency: Gal(1-29) >[Cit(14)]Gal(1- 15) >[Asp(14)]Gal(1- 15) >[Dab(14)]Gal(1- 15) >[Nle(14)] Gal(...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.2001.0827
更新日期:2001-07-01 00:00:00
abstract::Effect of moclobemide, a selective monoamine oxidase-type A enzyme inhibitor, was investigated on the body temperature of male mice. Moclobemide (15-30 mg kg(-1), i.p.) produced significant reductions of body temperature in both normal and yeast-induced hyperthermic male mice. The hypothermic effect of moclobemide was...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/s1043-6618(03)00108-7
更新日期:2003-09-01 00:00:00
abstract::The pharmacological physiological effects of the endogenous cannabinomimetic (endocannabinoid) anandamide have been well characterized. Another endocannabinoid, 2-arachidonoyl-glycerol (2-AG), has been less-widely studied. 2-AG occurs in vertebrate and invertebrate tissues and binds to both cannabinoid receptors (CB1 ...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.2000.0702
更新日期:2000-10-01 00:00:00
abstract::Posttranslational modifications of proteins are important regulatory processes endowing the proteins functional complexity. Over the last decade, numerous studies have shed light on the roles of palmitoylation, one of the most common lipid modifications, in various aspects of neuronal functions. Major players regulati...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2016.06.008
更新日期:2016-09-01 00:00:00
abstract:AIM:Acute myocardial infarction and subsequent post-infarction heart failure are among the leading causes of mortality worldwide. The endocannabinoid system has emerged as an important modulator of cardiovascular disease, however the role of endocannabinoid metabolic enzymes in heart failure is still elusive. Herein, w...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2019.104578
更新日期:2020-01-01 00:00:00
abstract::Aging has a remarkable effect on cardiovascular homeostasis and it is known as the major non-modifiable risk factor in the development of hypertension. Medications targeting sympathetic nerve system and/or renin-angiotensin-aldosterone system are widely accepted as a powerful therapeutic strategy to improve hypertensi...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2017.03.013
更新日期:2017-06-01 00:00:00
abstract::Nerve growth factor (NGF) is the prototype of the neurotrophin family and promotes the survival of specific populations of neurons, stimulates their morphological differentiation and regulates neuronal gene expression. Since its discovery, NGF attracted clinicians for its potential application in the treatment of neur...
journal_title:Pharmacological research
pub_type: 临床试验,杂志文章
doi:10.1016/j.phrs.2007.03.007
更新日期:2007-07-01 00:00:00
abstract::Diabetic erectile dysfunction (DED) hugely affected the patients' sexual life quality. However, there are no satisfactory therapeutic methods and intervention targets for this subtype of erectile dysfunction (ED). Inspired by the clinical practice of traditional Chinese medicine (TCM), we found that hirudin, the main ...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2020.105244
更新日期:2021-01-01 00:00:00
abstract::The aminosteroid derivative RM-133 is an effective anticancer molecule for which proof of concept has been achieved in several mouse xenograph models (HL-60, MCF-7, PANC-1 and OVCAR-3). To promote this new family of molecules toward a clinical phase 1 trial, the mechanism of action governing the anticancer properties ...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2017.12.024
更新日期:2018-02-01 00:00:00
abstract::When chemerin was discovered in 1997, it was relegated to being a protein associated with the normal skin function contrasting the setting of psoriasis. However, with the discovery of multiple receptors for the chemerin protein and a vast collection of associations with various pathologies, chemerin has global influen...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2015.07.018
更新日期:2015-09-01 00:00:00
abstract::The pharmacokinetics of doxycycline hydrochloride (DoxHcl) at a dose of 5 mg kg-1 BW was studied after an intravenous (i.v.) bolus and intramuscular (i.m.) injections in non lactating goats. A microbiological assay employing Bacillus subtilis as the test organism was used to measure its concentrations in serum and uri...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2003.10.012
更新日期:2004-05-01 00:00:00
abstract::Levosulpiride is the (-)-enantiomer of sulpiride. It has shown greater central antidopaminergic activity, antiemetic and antidyspeptic effects and lower acute toxicity than both the racemic and dextro forms. Several clinical studies indicate that levosulpiride has therapeutic efficacy in depressive and somatoform diso...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/1043-6618(95)80053-0
更新日期:1995-02-01 00:00:00
abstract::Biotechnologicals are an invaluable resource in the treatment of patients with inflammatory rheumatic diseases (IRD) non-responsive or intolerant to conventional therapies. However, they are the main driver for increase in direct costs and represent a significant economic burden to healthcare systems worldwide. Since ...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2019.104467
更新日期:2019-11-01 00:00:00
abstract::To assess the potential role of vasoactive cardiac eicosanoids in the modulation of coronary flow, we measure thromboxane(TX)B2, 6-keto-prostaglandin(PG)F1 alpha, PGE2 and sulphido-peptide leukotrienes (LTC4, D4, E4) in the coronary effluent of isolated perfused rat heart in both baseline and post-ischaemic conditions...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/1043-6618(92)90233-2
更新日期:1992-12-01 00:00:00
abstract::A growing number of evidences from clinical and preclinical studies have shown that dysregulation of microRNA (miRNA) function contributes to the progression of cancer and thus miRNA can be an effective target in therapy. Dietary phytochemicals, such as quercetin, are natural products that have potential anti-cancer p...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2019.104346
更新日期:2019-09-01 00:00:00
abstract::The review emphasizes the role of NGF, the most representative member of the neurotrophins family, in cardiac physiopathology with a particular focus on healing and sprouting processes occurring after tissue damage. Cardiac and circulating NGF levels dramatically increase following myocardial injury (MI). A very early...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2010.12.017
更新日期:2011-04-01 00:00:00
abstract::As an essential component of the innate immune system, Toll-like receptors (TLRs) are a family of well-recognized ligand-binding receptors found in various organisms and initiate host immune responses. Activation of TLRs signaling pathways lead to the induction of numerous genes that function in host defense. Baicalin...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2020.104890
更新日期:2020-08-01 00:00:00
abstract::The natural resin collected from the trunk wood of Protium heptaphyllum is used in folk medicine to treat inflammatory conditions and to hasten wound repair. In the search of new potential anti-inflammatory agents with gastroprotective property, the present study evaluated its effects in experimental models of gastric...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2003.09.001
更新日期:2004-02-01 00:00:00
abstract::This paper discusses the discovery of ligands for orphan receptors and the identification of the natural endogenous ligands for those receptors in physiology. The central thesis is that orphan seven transmembrane receptors (7TMRs) are allosteric conduits of chemical information exchange from extracellular ligands to i...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2016.01.022
更新日期:2016-12-01 00:00:00
abstract::Most solid tumor cells adapt to their heterogeneous microenvironment by depending largely on aerobic glycolysis for energy production, a phenomenon called the Warburg effect, which is a hallmark of cancer. The altered energy metabolism not only provides cancer cell with ATP for cellular energy, but also generate essen...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2019.104511
更新日期:2019-12-01 00:00:00
abstract::Evodiae fructus is a widely used herbal drug in traditional Chinese medicine. Evodia extract was found to inhibit hERG channels. The aim of the current study was to identify hERG inhibitors in Evodia extract and to investigate their potential proarrhythmic effects. Dehydroevodiamine (DHE) and hortiamine were identifie...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2018.02.024
更新日期:2018-05-01 00:00:00
abstract::Given the high and increasing prevalence of obesity, the safe and effective treatment of obesity would be beneficial. Here, we examined whether oral hydroxysafflor yellow A (HSYA), an active compound from the dried florets of Carthamus tinctorius L., can reduce high-fat (HF) diet-induced obesity in C57BL/6 J mice. Our...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2018.05.012
更新日期:2018-08-01 00:00:00
abstract::Green tea and its major polyphenols constituents, tea catechins, have been shown to have many health benefits including cancer prevention. Tea catechins and tea catechin metabolites/catabolites are bioavailable in the systemic circulation after oral intake of green tea or green tea catechins. The metabolites/catabolit...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2011.05.007
更新日期:2011-08-01 00:00:00
abstract::Sixteen adult hypertensive patients of both sexes, classified as having 'medium' (total lipid profile 240-300 mg dl(-1)), and 'high' (total lipid profile >300 mg dl(-1)) baseline values, underwent serum lipids, lipoproteins and plasma fibrinolytic parameters evaluations after 3 months of cilnidipine treatment. Patient...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1999.0558
更新日期:2000-01-01 00:00:00
abstract::Severely obese patients undergoing bariatric surgery (BS) are at increased risk for venous thromboembolism (VTE). How standard low molecular weight heparin (LMWH) regimen should be adapted to provide both sufficient efficacy and safety in this setting is unclear. We aimed to compare the influence of four body size des...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2018.02.012
更新日期:2018-05-01 00:00:00
abstract::As a function of the structural modification of the steroid nucleus, the inhibitory interaction of 11 progesterone derivatives with human Na/K-ATPase (Na+/K(+)-transporting ATPase, EC 3.6.1.37), through C3-O-rhamnosylation, is either much decreased or weakly up to strongly increased, so that the rhamnosyl residue cont...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/s1043-6618(05)80102-1
更新日期:1991-01-01 00:00:00
abstract::The Ras-Raf-MEK-ERK (Map kinase) cellular pathway is a highly conserved eukaryotic signaling module that transduces extracellular signals from growth factors and cytokines into intracellular regulatory events that are involved in cell growth and proliferation or the contrary pathway of cell differentiation. Dysregulat...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2016.12.009
更新日期:2017-03-01 00:00:00
abstract::TMEM16A plays critical roles in physiological process and may serve as drug targets for diverse diseases. Recently, TMEM16A has started to be regarded as potential primary lung adenocarcinoma targets. Here, we identified that arctigenin, a natural compound, is a novel TMEM16A inhibitor, and it can suppress lung adenoc...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2020.104721
更新日期:2020-05-01 00:00:00