Pharmacology Research & Perspectives最新文献

{"title":"In Vitro Hepatic Metabolism Input Parameters Support Toxicokinetic Simulations for the Formation of Methoxy Propionic Acid From β-Isomer Propylene Glycol Methyl Ether.","authors":"Sophie Werner, Lucie Hegg, Nancy B Hopf, Myriam Borgatta, Laura Suter-Dick","doi":"10.1002/prp2.70037","DOIUrl":"10.1002/prp2.70037","url":null,"abstract":"<p><p>Propylene glycol ethers (PGEs) are organic solvents commonly found as technical grade on the commercial market, as mixtures of secondary (α-isomer) and primary (β-isomer, generally < 5%) alcohols. After handling products containing PGEs, they readily enter the human body where they are metabolized. The minor β-isomer is oxidized by alcohol dehydrogenase (ADH) followed by aldehyde dehydrogenase (ALDH) to a potentially harmful metabolite. Although the enzymatic rate is needed to estimate both parent and metabolite internal exposures, kinetic data for many PGEs are still scarce. Therefore, we generated in vitro hepatic intrinsic clearance data for propylene glycol methyl ether β-isomer (β-PGME) and its metabolite methoxy propionic acid (2-MPA) and integrated these data into an in silico toxicokinetic (TK) model. Hepatic clearance values for the model were generated using an established in vitro 3D culture of the human HepaRG cell line and human S9 liver fraction. Our results showed the presence of ADH and ALDH and consequently, the formation of 2-MPA in the 3D HepaRG and S9 fraction, which was slow to medium. We integrated the hepatic clearance values into the TK model to predict urinary 2-MPA concentrations. The simulated urinary 2-MPA concentrations fitted well (within twofold error from observed experimental data) for both liver systems, showing that they were both able to reliably predict the hepatic clearance of β-PGME. Although S9 is suitable for short-term studies, 3D cell culture models maintain metabolic competence over days and weeks. This opens the opportunity for long-term metabolism studies applying the 3D HepaRG model alone or in multi-organ systems.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 6","pages":"e70037"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of the Incidence and Magnitude of Hyponatremia Among Patients With Poststroke Depression Receiving Either Escitalopram or Sertraline.","authors":"Lina Naseralallah, Zahra Noureddine, Somaya Koryash","doi":"10.1002/prp2.70041","DOIUrl":"10.1002/prp2.70041","url":null,"abstract":"<p><p>Depression is the most frequent psychiatric condition experienced in stroke survivors. Selective serotonin reuptake inhibitors (SSRIs) are frequently used as first-line antidepressants; however, they have been strongly associated with hyponatremia which, in poststroke patients, can worsen outcomes. This study aims to determine and compare the incidence and magnitude of hyponatremia and potential risk factors in patients receiving either escitalopram or sertraline for the management of poststroke depression (PSD). A retrospective observational study involving all hospitalized patients who received either escitalopram or sertraline for the treatment of PSD. Electronic medical records were reviewed over a 5-year period with data collected on various demographic, laboratory, comorbidity, and medication-related variables. Data were analyzed using multivariate logistic regression. A total of 401 patients met the inclusion criteria. Overall, 36.7% of patients experienced hyponatremia, with 67 (38.3%) cases in patients receiving escitalopram and 76 (33.6%) in sertraline group. The median drop in sodium level from baseline was 5 mmol/L in both groups; with the majority of cases being of mild nature (73.1% and 69.7% for escitalopram and sertraline, respectively). Findings from the multivariate logistic regression did not yield a model with significant association (p = 0.353). Escitalopram and sertraline were both associated with an increased risk of hyponatremia in poststroke patients, with most cases being mild. There was no significant difference between treatment arms regarding the incidence or magnitude of hyponatremia. Caution should be exercised when prescribing escitalopram or sertraline.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 6","pages":"e70041"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Teneurin C-Terminal Associated Peptide (TCAP)-1 Attenuates Restraint Stress-Induced Corticosterone Increases in Male Mice and Rats.","authors":"Lauren E Mueller, Roseanne S Wexler, David A Lovejoy, Robert B Stein, Andrew M Slee","doi":"10.1002/prp2.70045","DOIUrl":"10.1002/prp2.70045","url":null,"abstract":"<p><p>Hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis response can result in anxiety and other neuropsychiatric disorders and effective therapeutics are needed to mitigate this maladaptive response. Here we examined the effects of Teneurin C-terminal Associated Peptide (TCAP)-1, a peptide known to inhibit corticotropin releasing factor (CRF)-mediated stress, on the physiological expression of stress, and whether the effects of TCAP-1 were dependent on the route of administration. We first examined whether subcutaneous administration of TCAP-1 influenced tube restraint stress-induced corticosterone (CORT) increases in both male mice and rats. Using a similar model, we further examined the efficacy and time course of intranasal TCAP-1. Results showed that subcutaneous TCAP-1 administration attenuated the expression of the physiological manifestation of stress in male mice and rats, and that intranasal TCAP-1 delivered prophylactically is effective at attenuating stress-induced CORT increases in male rats. These data indicate that TCAP-1 delivered though non-invasive routes of administration could have potential as a clinically relevant anxiolytic.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 6","pages":"e70045"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating Blood-Brain Barrier Permeability, Cytotoxicity, and Activity of Potential Acetylcholinesterase Inhibitors: In Vitro and In Silico Study.","authors":"L M Maboko, A Theron, J-L Panayides, W Cordier, D Fisher, V Steenkamp","doi":"10.1002/prp2.70043","DOIUrl":"https://doi.org/10.1002/prp2.70043","url":null,"abstract":"<p><p>Acetylcholinesterase inhibitors (AChEIs) remain the first-line treatment for Alzheimer's disease. However, these drugs are largely symptomatic and often associated with adverse effects. This study aimed to evaluate novel pharmacophores for their in vitro AChEI activity, blood-brain barrier (BBB) permeability, and cytotoxic potential, hypothesizing that a combination of AChEIs could enhance symptom management while minimizing toxicity. A library of 1453 synthetic pharmacophores was assessed using in vitro and in silico methods to determine their feasibility as an inhibitor of the AChE enzyme. An in-house miniaturized Ellman's assay determined acellular AChEI activities, while pharmacokinetic properties were evaluated using the SwissADME web tool. The combinational effects of in silico BBB-permeable pharmacophores and donepezil were examined using a checkerboard AChEI assay. Cytotoxicity of active compounds and their synergistic combinations was assessed in SH-SY5Y neuroblastoma and bEnd.5 cells using the sulforhodamine B assay. Cellular AChEI activity of active in silico BBB-permeable predicted compounds was determined using an SH-SY5Y AChE-based assay. An in vitro BBB model was used to assess the effect of compounds on the integrity of the bEnd.5 monolayer. Out of the screened compounds, 12 demonstrated 60% AChEI activity at 5 μM, with compound A51 showing the lowest IC₅₀ (0.20 μM). Five compounds were identified as BBB-permeable, with the donepezil-C53 combination at ¼IC₅₀ exhibiting the strongest synergy (CI = 0.82). Compounds A136 and C129, either alone or with donepezil, showed cytotoxicity. Notably, compound C53, both alone and in combination with donepezil, demonstrated high AChEI activity and promising BBB permeability, warranting further investigation.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 6","pages":"e70043"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Student Comprehension of Glucose Metabolism Visualization Through Virtual Simulation Platform: An Educational Approach.","authors":"Luna Ge, Tingting Feng, Shuo Cao, Hang Yin, Yuang Zhang, Jihong Pan, Wei Chen, Kai Cheng, Lin Wang","doi":"10.1002/prp2.70042","DOIUrl":"10.1002/prp2.70042","url":null,"abstract":"<p><p>With the rapid progression of biotechnology, the significance translational research on glycolysis in molecular pharmacology has become increasingly evident. To deepen students' understanding of glycolytic processes and facilitate their comprehension of drug action mechanisms, we have developed a visual virtual simulation platform dedicated glycolysis. The educational approach commenced with theoretical lectures on glycolysis, followed by practical laboratory sessions where students measured glycolysis-related parameters such as hexokinase, pyruvate kinase, and lactate. Students then engaged with the virtual simulation training platform to explore glycolytic stress tests and positron emission tomography/computed tomography (PET/CT) imaging, with their progress tracked through an assessment mode. The study involved 67 s-year undergraduate students majoring in biomedical sciences, all of whom had received instruction in glucose metabolism theories and completed the associated questionnaires. The results showed that the students gained a deeper understanding of glycolysis and the clinical application of PET/CT imaging in the context of glycolysis. The majority also agreed that the integration of scientific and clinical cases in teaching is beneficial and that the project sparked their interest in scientific research. These findings align with existing literature that emphasizes the importance of innovative educational tools in enhancing student engagement and understanding of the underlying theories of the curriculum. This project designed an innovative glycolytic metabolism teaching system encompassing the monitoring of traditional glycolytic indicators, glycolytic stress tests, and PET/CT imaging based on glycolysis. The visual virtual simulation platform for glycolysis can serve as an innovative educational tool in the molecular pharmacology curriculum or other courses involving glycolysis, assisting students in deeply understanding the molecular mechanisms of glycolysis and its significance in disease and drug action.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 6","pages":"e70042"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence-based safety profile of oral ketorolac in adults: Systematic review and meta-analysis.","authors":"Vicente Esparza-Villalpando, Gladys Ortiz-Barroso, David Masuoka-Ito","doi":"10.1002/prp2.70033","DOIUrl":"10.1002/prp2.70033","url":null,"abstract":"<p><p>The primary objective of the present review was to report the safety profile of oral ketorolac in adults using the systematic review and meta-analysis methodology based on clinical trials. The present study is a PRISMA-based systematic review and risk ratio (RR) meta-analysis of the adverse events reported in clinical trials that used oral ketorolac; the review includes 50 clinical trials. The RR for the comparison of a single intake of oral ketorolac versus placebo, including all types of adverse events, was RR = 2.59, IC95% (1.5102; 4.4360) with p = 0.02, the RR for the comparison of a multiple intakes of oral ketorolac versus placebo for all types of adverse events was RR = 1.39, IC95% (0.95; 2.05) with p = 0.093, the RR for the comparison of a single intake of oral ketorolac versus active drugs for all types of adverse events was RR = 0.61, IC95% (0.49; 0.77) with p < 0.0001, the RR for the comparison of multiple intakes of oral ketorolac versus active drugs for all types of adverse events was RR = 0.78, IC95%(0.65; 0.93) with p = 0.006. Multiple intakes of 5, 10, or 20 mg of oral ketorolac, in treatment over 1-10 days, do not increase the risk of adverse events compared to placebo and show a tendency to reduce the risk of adverse events compared to active drugs. When a single intake of ketorolac (5, 10, 20, or 30 mg) is compared to a placebo, the risk increases only for trivial and mild adverse events.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 6","pages":"e70033"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro screening of UGT2B10 in silico prioritized putative ligands from drugs used in the pediatric hematopoietic stem cell transplantation setting.","authors":"Yahia Bennani, Khalil Ben Hassine, Muhammed Gencaslan, Mary Boudal-Khoshbeen, Caroline Samer, Marc Ansari, Youssef Daali, Chakradhara Rao Satyanarayana Uppugunduri","doi":"10.1002/prp2.70011","DOIUrl":"10.1002/prp2.70011","url":null,"abstract":"<p><p>UGT2B10 is a phase II drug metabolizing enzyme with limited information on its role in the metabolism of drugs, especially in the pediatric hematopoietic stem cell transplantation setting. Previously, we investigated UGT2B10's role through in silico analyses and prioritized acetaminophen (APAP), lorazepam (LOR), mycophenolic acid (MPA), and voriconazole N-oxide (VCZ N-oxide) for in vitro investigations. In this report, we present in vitro screening of these candidates and of voriconazole (VCZ) to assess their potential to be substrates and/or inhibitors of UGT2B10. Enzyme kinetics experiments included recombinant UGT2B10 and analytical methods based on ultra high-performance liquid chromatography coupled to mass spectrometry (UHPLC-MS). To determine potential substrates, candidates were incubated at various therapeutically observed concentrations with recombinant UGT2B10 to identify the corresponding glucuronide metabolite. Inhibition capacity was tested using the selective probe cotinine for its glucuronidation to cotinine N-ß-d-glucuronide. IC₅₀ was determined for compounds exhibiting inhibition. Among the tested compounds, LOR (IC₅₀ = 0.01 μM, R² = 0.9257) and MPA (IC₅₀ = 0.38 mM, R² = 0.9212) exhibited inhibition potential for UGT2B10. None of the other tested compounds featured inhibition potential and none of the compounds tested exhibited metabolism through UGT2B10. Further exploration on the clinical relevance of this inhibition using modeling strategies, overlapping nature with other UGT isoforms, and screening other molecules for their inhibition potential on UGT2B10 is warranted.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 6","pages":"e70011"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of vitamin D supplementation on clinical outcomes in adult patients with COVID-19: A GRADE-assessed systematic review and meta-analysis of randomized controlled trials.","authors":"Zohreh-Al-Sadat Ghoreshi, Javad Charostad, Nasir Arefinia, Mohsen Nakhaie, Mohammad Rezaei Zadeh Rukerd, Faranak Salajegheh","doi":"10.1002/prp2.70013","DOIUrl":"10.1002/prp2.70013","url":null,"abstract":"<p><p>The COVID-19 pandemic has emerged as a major global health crisis. Vitamin D, a crucial fat-soluble vitamin, has been recommended for COVID-19 patients, though evidence of its effectiveness is inconsistent. This systematic literature review and meta-analysis aimed to evaluate the impact of vitamin D supplementation on COVID-19-related outcomes. A comprehensive search was conducted across PubMed, Scopus, Web of Science, Embase, and Cochrane databases. Primary outcomes included mortality and hospital length of stay, while secondary outcomes encompassed C-reactive protein (CRP), ferritin, D-dimer, hemoglobin (Hb) concentrations, and lymphocyte, neutrophil, and platelet counts. Data analysis was performed using Stata™ Version 14. A total of 16 trials were analyzed. The meta-analysis revealed that vitamin D supplementation significantly reduced hospital length of stay (mean difference = -1.16; 95% confidence interval [CI]: -2.23, -0.09; p = .033) with significant heterogeneity (I² = 69.2%, p = .002). Subgroup analysis showed a more pronounced reduction in studies with vitamin D dosages ≤10 000 international units (IU) (mean difference = -1.27; 95% CI: -1.96, -0.57; p < .001) and in patients over 60 years old (mean difference = -1.84; 95% CI: -2.53, -1.14; p < .001). Additionally, vitamin D significantly reduced CRP concentrations in older adults (>60 years) (mean difference = -1.13; 95% CI: -2.07, -0.18; p = .019). No significant changes were found in ferritin, D-dimer, Hb concentrations, or in lymphocyte, neutrophil, and platelet counts (p > .05). In conclusion, while vitamin D supplementation did not significantly affect most COVID-19-related biomarkers, however, it reduces the length of hospital stay.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 5","pages":"e70013"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The epsilon toxin from Clostridium perfringens stimulates calcium-activated chloride channels, generating extracellular vesicles in Xenopus oocytes.","authors":"Mercè Cases, Jonatan Dorca-Arévalo, Marta Blanch, Sergi Rodil, Beatrice Terni, Mireia Martín-Satué, Artur Llobet, Juan Blasi, Carles Solsona","doi":"10.1002/prp2.70005","DOIUrl":"https://doi.org/10.1002/prp2.70005","url":null,"abstract":"<p><p>The epsilon toxin (Etx) from Clostridium perfringens has been identified as a potential trigger of multiple sclerosis, functioning as a pore-forming toxin that selectively targets cells expressing the plasma membrane (PM) myelin and lymphocyte protein (MAL). Previously, we observed that Etx induces the release of intracellular ATP in sensitive cell lines. Here, we aimed to re-examine the mechanism of action of the toxin and investigate the connection between pore formation and ATP release. We examined the impact of Etx on Xenopus laevis oocytes expressing human MAL. Extracellular ATP was assessed using the luciferin-luciferase reaction. Activation of calcium-activated chloride channels (CaCCs) and a decrease in the PM surface were recorded using the two-electrode voltage-clamp technique. To evaluate intracellular Ca²⁺ levels and scramblase activity, fluorescent dyes were employed. Extracellular vesicles were imaged using light and electron microscopy, while toxin oligomers were identified through western blots. Etx triggered intracellular Ca²⁺ mobilization in the Xenopus oocytes expressing hMAL, leading to the activation of CaCCs, ATP release, and a reduction in PM capacitance. The toxin induced the activation of scramblase and, thus, translocated phospholipids from the inner to the outer leaflet of the PM, exposing phosphatidylserine outside in Xenopus oocytes and in an Etx-sensitive cell line. Moreover, Etx caused the formation of extracellular vesicles, not derived from apoptotic bodies, through PM fission. These vesicles carried toxin heptamers and doughnut-like structures in the nanometer size range. In conclusion, ATP release was not directly attributed to the formation of pores in the PM, but to scramblase activity and the formation of extracellular vesicles.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 5","pages":"e70005"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The gut-brain axis in appetite, satiety, food intake, and eating behavior: Insights from animal models and human studies.","authors":"Georgia S Clarke, Amanda J Page, Sally Eldeghaidy","doi":"10.1002/prp2.70027","DOIUrl":"https://doi.org/10.1002/prp2.70027","url":null,"abstract":"<p><p>The gut-brain axis plays a pivotal role in the finely tuned orchestration of food intake, where both homeostatic and hedonic processes collaboratively control our dietary decisions. This interplay involves the transmission of mechanical and chemical signals from the gastrointestinal tract to the appetite centers in the brain, conveying information on meal arrival, quantity, and chemical composition. These signals are processed in the brain eventually leading to the sensation of satiety and the termination of a meal. However, the regulation of food intake and appetite extends beyond the realms of pure physiological need. Hedonic mechanisms, including sensory perception (i.e., through sight, smell, and taste), habitual behaviors, and psychological factors, exert profound influences on food intake. Drawing from studies in animal models and human research, this comprehensive review summarizes the physiological mechanisms that underlie the gut-brain axis and its interplay with the reward network in the regulation of appetite and satiety. The recent advancements in neuroimaging techniques, with a focus on human studies that enable investigation of the neural mechanisms underpinning appetite regulation are discussed. Furthermore, this review explores therapeutic/pharmacological strategies that hold the potential for controlling food intake.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 5","pages":"e70027"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}