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Plants (Basel, Switzerland) Dec 2023Quercetin (QUA), a flavonoid compound, is ubiquitously found in plants and has demonstrated a diverse range of biological activities. The primary objective of the...
Quercetin (QUA), a flavonoid compound, is ubiquitously found in plants and has demonstrated a diverse range of biological activities. The primary objective of the current study is to assess the potential antiemetic properties of QUA using an in vivo and in silico approach. In this experiment, 4-day-old chicks were purchased to induce emesis by orally administering copper sulfate pentahydrate (CuSO·5HO) at a dose of 50 mg/kg (orally). Domperidone (DOM) (6 mg/kg), Hyoscine (HYS) (21 mg/kg), and Ondansetron (OND) (5 mg/kg) were treated as positive controls (PCs), and distilled water and a trace amount of Tween 80 mixture was employed as a negative control (NC). QUA was given orally at two distinct doses (25 and 50 mg/kg). Additionally, QUA (50 mg/kg) and PCs were administered separately or in combination to assess their antagonistic or synergistic effects on the chicks. The binding affinity of QUA and referral ligands towards the serotonin receptor (5HT3), dopamine receptors (D2 and D3), and muscarinic acetylcholine receptors (M1-M5) were estimated, and ligand-receptor interactions were visualized through various computational tools. In vivo findings indicate that QUA (25 and 50 mg/kg) has a significant effect on reducing the number of retches (16.50 ± 4.65 and 10.00 ± 4.19 times) and increasing the chick latency period (59.25 ± 4.75 and 94.25 ± 4.01 s), respectively. Additionally, QUA (50 mg/kg) in combination with Domperidone and Ondansetron exhibited superior antiemetic effects, reducing the number of retches and increasing the onset of emesis-inducing time. Furthermore, it is worth noting that QUA exhibited the strongest binding affinity against the D2 receptor with a value of -9.7 kcal/mol through the formation of hydrogen and hydrophobic bonds. In summary, the study found that QUA exhibited antiemetic activity in chicks, potentially by interacting with the D2 receptor pathway.
PubMed: 38140516
DOI: 10.3390/plants12244189 -
Journal of Ethnopharmacology Mar 2024Liansu capsule could alleviate dyspeptic symptoms; however, the mechanisms underlying its role in treating functional dyspepsia (FD) remain unclear.
ETHNOPHARMACOLOGICAL RELEVANCE
Liansu capsule could alleviate dyspeptic symptoms; however, the mechanisms underlying its role in treating functional dyspepsia (FD) remain unclear.
AIM OF THE STUDY
To elucidate the mechanism underlying the efficacy of Liansu capsule in alleviating FD symptoms.
MATERIALS AND METHODS
Thirty-six male mice were randomly divided into the following six groups: control, model, low-strength Liansu, moderate-strength Liansu, high-strength Liansu, and domperidone groups. Small intestine propulsion rate, gastric residual rate and histopathological analysis were performed to evaluate efficacy of Liansu capsule. Levels of interleukin-1β, interleukin-6, tumor necrosis factor α, phosphorylation of p65, ghrelin and gastrin were verified by real-time quantitative polymerase chain reaction and immunofluorescence assays. Targeted metabolomic analyses, western blotting and immunofluorescence assays were used to explore the mechanism of Liansu capsule in ameliorating FD.
RESULTS
The Liansu capsule significantly ameliorated the symptoms of FD, and markedly increased the levels of ghrelin and gastrin. Moreover, Liansu capsule significantly downregulated the levels of the proinflammatory cytokine interleukin-1β, interleukin-6, tumor necrosis factor α, and inhibited the phosphorylation of p65. Targeted metabolomic analyses showed that Liansu capsule significantly reduced the levels of deoxycholic acid and hyodeoxycholic acid, which were significantly elevated in the model group. Furthermore, these results showed that deoxycholic acid and hyodeoxycholic acid markedly promoted the levels of Takeda G-protein-coupled receptor 5 (TGR5), phosphorylated signal transducer and activator of transcription 3 (STAT3), and Kruppel-like factor 5 (KLF5) in vitro. whereas, Liansu capsule significantly reduced the levels of TGR5, phosphorylated STAT3, and KLF5.
CONCLUSION
Our findings indicated that Liansu capsule improved FD by regulating the deoxycholic acid/hyodeoxycholic acid-TGR5-STAT3-KLF5 axis. The findings reveal a novel mechanism underlying the role of Liansu capsule, which may be a promising therapeutic strategy for FD.
Topics: Male; Mice; Animals; Dyspepsia; Ghrelin; Tumor Necrosis Factor-alpha; Gastrins; Interleukin-6; Interleukin-1beta; Deoxycholic Acid
PubMed: 38092317
DOI: 10.1016/j.jep.2023.117568 -
Cureus Oct 2023Background Acute gastroenteritis (AGE) is a major health concern in pediatric populations because of its associated vomiting, which worsens dehydration and the severity...
Background Acute gastroenteritis (AGE) is a major health concern in pediatric populations because of its associated vomiting, which worsens dehydration and the severity of illness. Objective The purpose of the research was to compare the relative effectiveness of oral ondansetron in treating AGE in children's vomiting when compared to oral domperidone and oral metoclopramide. Methodology A clinical investigation involving 120 pediatric patients diagnosed with AGE was conducted in Pakistan from November 2022 to April 2023 using a single-blind randomized design and convenience sampling. The participants received oral suspensions of ondansetron, metoclopramide, and domperidone, with doses of 0.15 mg/kg, 0.1-0.2 mg/kg, and 0.5 mg/kg, respectively, adjusted according to their body weight. The outcome in different groups was analyzed using the Statistical Package for the Social Sciences (SPSS) (version 20.0; IBM SPSS Statistics for Windows, Armonk, NY). Results At six hours, vomiting cessation rates were 80.0% for ondansetron (n=32), 72.5% for domperidone (n=29), and 67.5% for metoclopramide (n=27; p=0.29). By 24 hours, ondansetron exhibited significantly higher efficacy (92.5%; n=37) compared to domperidone (82.5%; n=33) and metoclopramide (77.5%; n=31; p=0.03). Adverse effects were minimal and comparable across groups. Conclusion Oral ondansetron demonstrated superior efficacy in managing AGE-related vomiting in children within 24 hours compared to metoclopramide and domperidone.
PubMed: 38022212
DOI: 10.7759/cureus.47611 -
Endocrinology, Diabetes & Metabolism... Oct 2023With rising rates of adoption and surrogacy, induced lactation is likely to become increasingly relevant, allowing women who did not undergo pregnancy to breastfeed. We...
SUMMARY
With rising rates of adoption and surrogacy, induced lactation is likely to become increasingly relevant, allowing women who did not undergo pregnancy to breastfeed. We describe the case of a woman with complete androgen insensitivity syndrome (CAIS) on conventional oestrogen therapy who was expecting a child via surrogacy and who wished to breastfeed. The woman was commenced on supplementary oestrogen therapy, domperidone and breast stimulation by mechanical breast pump 8 weeks prior to the delivery of her child. Following delivery, the patient produced a small, unquantified amount of milk, allowing her to suckle the infant for a short period of time. Induced lactation is possible in chromosomally XY individuals. It has been most successful in cis-women and transwomen, both of whom have had progesterone/progestogen exposure to the breast. We suggest that the addition of a progestogen to our patient's treatment regimen, either as part of her original hormone therapy or part of the lactation induction program, would have improved her changes of establishing successful lactation.
LEARNING POINTS
Induced lactation is possible in chromosomally XY individuals with the use of pharmacological and non-pharmacological therapies. There are no standardised guidelines regarding the optimal regimen for induced lactation. Progesterone exposure to the breast is essential for ductal branching and alveolar maturation. In the published literature, induced lactation is more successful in transwomen and other XY individuals who have had prior progesterone exposure. The addition of progestogen to our patient's treatment regimen would have improved her chances of establishing successful lactation.
PubMed: 37965919
DOI: 10.1530/EDM-23-0063 -
BMJ Paediatrics Open Nov 2023This study aims: (a) to evaluate patterns of domperidone dispensing to mothers of very preterm (<32 weeks gestation) infants born before and after 2014 when...
OBJECTIVE
This study aims: (a) to evaluate patterns of domperidone dispensing to mothers of very preterm (<32 weeks gestation) infants born before and after 2014 when international recommendations were made to limit its use and (b) to examine characteristics associated with domperidone dispensing and impacts on breast milk feeding rates at infant hospital discharge.
DESIGN
Retrospective audit using linked electronic medical records and hospital pharmacy records.
SETTING
Tertiary-referral neonatal intensive care unit at the Women's and Children's Hospital in South Australia.
PATIENTS
Mothers of preterm infants admitted to neonatal intensive care from January 2004 to December 2018.
MAIN OUTCOME MEASURES
Rate of domperidone dispensing compared pre-2014 and post-2014 recommendations using interrupted time series analyses, and breast milk feeding rates at infant discharge based on domperidone treatment status, adjusted for other factors known to influence breast milk production.
RESULTS
Overall, domperidone was dispensed to 691 (41%) of 1688 mothers. Prior to 2014 recommendations, the proportion of women dispensed domperidone was stable. Following the recommendations, there was a significant reduction in trend (-2.55% per half year, 95% CI -4.57% to -0.53%;), reflecting less domperidone dispensing.Breast milk feeding rates at discharge remained consistently lower in infants of women dispensed domperidone than those who were not (adjusted OR 0.58, 95% CI 0.45 to 0.75).
CONCLUSION
Domperidone dispensing in mothers of hospitalised very preterm infants has declined over time following international regulatory warnings. Breast milk feeding rates remain lower in mothers prescribed domperidone, suggesting further research is needed to optimise lactation support for mothers of very preterm infants.
Topics: Child; Infant; Humans; Infant, Newborn; Female; Domperidone; Milk, Human; Retrospective Studies; Lactation; Infant, Premature; Patient Discharge
PubMed: 37923344
DOI: 10.1136/bmjpo-2023-002195 -
BMC Gastroenterology Oct 2023Since the previous network meta-analysis assessing the efficacy of prokinetics for functional dyspepsia (FD), there have been a number of new studies and cinitapride is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Since the previous network meta-analysis assessing the efficacy of prokinetics for functional dyspepsia (FD), there have been a number of new studies and cinitapride is a new prokinetic agent for FD. This updated meta-analysis aimed to explore the efficacy and safety of prokinetics for FD.
METHODS
An updated study search in Pubmed, EMBASE, Cochrane Library and Web of Science was conducted in literatures published from July 2015 to March 2023. Randomized controlled trials investigating the use of prokinetics in adult FD patients were included. The primary outcome was the total efficacy rate and the secondary outcome was adverse events. A Bayesian network meta-analysis was performed using R software.
RESULTS
A total of 28 studies were included. Network meta-analysis showed that metoclopramide had a higher total efficacy rate than mosapride (OR: 3.53, 95%CI: 1.70-7.47), domperidone (OR: 2.29, 95%CI: 1.16-4.63), itopride(OR: 2.77, 95%CI: 1.41-5.59), acotiamide(OR: 2.63, OR: 1.33-5.36), and placebo(OR: 5.68, 95%CI: 2.98-11.10), however similar to cinitapride (OR: 1.62, 95%CI: 0.75-3.53). Cinitapride had a higher total efficacy rate than mosapride (OR: 2.18, 95%CI: 1.16-4.14) and placebo (OR: 3.52, 95%CI: 2.01-6.24). Cinitapride had lower risk of total adverse events than domperidone. There was no difference in the risk of drug-related adverse events between the prokinetics.
CONCLUSIONS
Metoclopramide and cinitapride may have a better efficacy than other prokinetics in the treatment of FD, and cinitapride may have a lower risk of total adverse events. Further studies using uniform definitions or validated tools to measure the total efficacy rate are needed.
Topics: Adult; Humans; Dyspepsia; Domperidone; Metoclopramide; Network Meta-Analysis; Bayes Theorem; Randomized Controlled Trials as Topic
PubMed: 37907846
DOI: 10.1186/s12876-023-03014-9 -
Biomolecules & Therapeutics Nov 2023The lack of molecular targets hampers the treatment of triple-negative breast cancer (TNBC). In this study, we determined the cytotoxicity of domperidone, a dopamine D2...
The lack of molecular targets hampers the treatment of triple-negative breast cancer (TNBC). In this study, we determined the cytotoxicity of domperidone, a dopamine D2 receptor (DRD2) antagonist in human TNBC BT-549 and CAL-51 cells. Domperidone inhibited cell growth in a dose- and time-dependent manner. The annexin V/propidium iodide staining showed that domperidone induced apoptosis. The domperidone-induced apoptosis was accompanied by the generation of mitochondrial superoxide and the down-regulation of cyclins and CDKs. The apoptotic effect of domperidone on TNBC cells was prevented by pre-treatment with Mito-TEMPO, a mitochondria-specific antioxidant. The prevention of apoptosis with Mito-TEMPO even at concentrations as low as 100 nM, implies that the generation of mitochondrial ROS mediated the domperidone-induced apoptosis. Immunoblot analysis showed that domperidone-induced apoptosis occurred through the down-regulation of the phosphorylation of JAK2 and STAT3. Moreover, domperidone downregulated the levels of D2-like dopamine receptors including DRD2, regardless of their mRNA levels. Our results support further development of DRD2 antagonists as potential therapeutic strategy treating TNBC.
PubMed: 37899746
DOI: 10.4062/biomolther.2023.173 -
Annals of Medicine 2023The clinical effect of domperidone against COVID-19 has been investigated in a double-blind phase III clinical trial (EudraCT number 2021-001228-17). Domperidone has... (Randomized Controlled Trial)
Randomized Controlled Trial
A randomized, double-blind study on the efficacy of oral domperidone versus placebo for reducing SARS-CoV-2 viral load in mild-to-moderate COVID-19 patients in primary health care.
INTRODUCTION
The clinical effect of domperidone against COVID-19 has been investigated in a double-blind phase III clinical trial (EudraCT number 2021-001228-17). Domperidone has shown in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential immudolatory properties through the stimulation of prolactin secretion.
PATIENTS AND METHODS
The efficacy of oral domperidone plus standard of care (SOC; = 87) versus placebo plus SOC ( = 86) was evaluated in a 28-day randomized double-blind multicentre study in primary health care centres. A total of 173 outpatients with mild-to-moderate COVID-19 were included. Three daily doses of 10 mg (30 mg/day) of domperidone or placebo were administered for 7 days. Reduction of viral load on day 4 was the primary efficay endpoint. It was estimated in saliva samples by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), as the cycle thresholds detected ORF1ab, N Protein and S Protein genes.
RESULTS
A significant reduction in the viral load was observed ( < 0.001) from baseline to days 4, 7 and 14 of the three genes studied with non-significant differences between domperidone and placebo groups. Twenty-three patients (13.3%) experienced adverse events, 14 patients in the domperidone group (16.1%) and 9 patients in the placebo group (10.5%). No patients needed to be hospitalized.
CONCLUSION
Results do not prove the use of domperidone as antiviral in patients with COVID-19.
Topics: Humans; COVID-19; SARS-CoV-2; Domperidone; Double-Blind Method; Viral Load; Treatment Outcome; Antiviral Agents; Primary Health Care
PubMed: 37847999
DOI: 10.1080/07853890.2023.2268535 -
Heliyon Sep 2023Two key properties of excipients for inclusion in direct compression tablets are flowability and compactibility. Glutinous rice starch (GRS) has poor flowability, which...
Two key properties of excipients for inclusion in direct compression tablets are flowability and compactibility. Glutinous rice starch (GRS) has poor flowability, which limits its use in direct compression tablets. This study aimed to create a multifunctional direct compression excipient (filler binder disintegrant) with improved flowability from GRS by the co-precipitation method. The physicochemical and pharmaceutical properties of the co-precipitated GRS (cpGRS) were investigated. The optimum conditions for producing cpGRS (0.43 M sodium hydroxide solution, 7.09% PVP K30, 14.02% calcium carbonate, 95 min of mixing time and pH of 6.97) resulted in 68.80% yield, fair to good flowability, acceptable tablet strength, and fast disintegration. The FT-IR spectra of cpGRS showed no significant shifts in the key peaks, which indicates that there was an absence of chemical interactions within cpGRS. X-ray diffractograms also showed no significant changes, indicating that the GRS granules, calcium carbonate, and PVP K30 components remained unaltered during co-precipitation. cpGRS also demonstrated a dilution capacity of 50% when paracetamol was used as model drug. When cpGRS was combined with domperidone or propranolol hydrochloride it showed a better deformation capability than the physical mixtures. Although cpGRS was sensitive to lubricant, the hardness and tensile strength were higher than common strength for general purpose use in tablets. When compared to the physical mixture, pregelatinized starch and directly compressible calcium carbonate, the results showed that cpGRS tablets of both model drugs passed the friability test, demonstrated the best disintegration property, provided the fastest and highest drug release profile for propranolol, and improved the drug release profile for domperidone. For propranolol-cpGRS tablets, dissolution medium at different pH did not affect the dissolution profile. For domperidone-cpGRS tablets, the pH of dissolution medium did affect the dissolution profile of the tablets. This was according to the API solubility. These results reveal that cpGRS is an excellent multifunctional i.e., filler, binder, and disintegrant excipient suitable for direct compression tablets. The main component is natural. The preparation method is simple, quick, and efficient. This method does not produce harmful waste and requires only basic equipment, and affordable reactants and devices.
PubMed: 37809676
DOI: 10.1016/j.heliyon.2023.e19904 -
BMJ Open Oct 2023Experimental studies suggest a role of gut microbiota in the pathophysiology of Parkinson's disease (PD) via the gut-brain axis. The gut microbiota can also influence... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Experimental studies suggest a role of gut microbiota in the pathophysiology of Parkinson's disease (PD) via the gut-brain axis. The gut microbiota can also influence the metabolism of levodopa, which is the mainstay of treatment of PD. Therefore, modifying the gut microbiota by faecal microbiota transplantation (FMT) could be a supportive treatment strategy.
METHODS AND ANALYSIS
We have developed a study protocol for a single-centre, prospective, self-controlled, interventional, safety and feasibility donor-FMT pilot study with randomisation and double-blinded allocation of donor faeces. The primary objectives are feasibility and safety of FMT in patients with PD. Secondary objectives include exploring whether FMT leads to alterations in motor complications (fluctuations and dyskinesias) and PD motor and non-motor symptoms (including constipation), determining alterations in gut microbiota composition, assessing donor-recipient microbiota similarities and their association with PD symptoms and motor complications, evaluating the ease of the study protocol and examining FMT-related adverse events in patients with PD. The study population will consist of 16 patients with idiopathic PD that use levodopa and experience motor complications. They will receive FMT with faeces from one of two selected healthy human donors. FMT will be administered via a gastroscope into the duodenum, after treatment with oral vancomycin, bowel lavage and domperidone. There will be seven follow-up moments during 12 months.
ETHICS AND DISSEMINATION
This study was approved by the Medical Ethical Committee Leiden Den Haag Delft (ref. P20.087). Study results will be disseminated through publication in peer-reviewed journals and international conferences.
TRIAL REGISTRATION NUMBER
International Clinical Trial Registry Platform: NL9438.
Topics: Humans; Feasibility Studies; Fecal Microbiota Transplantation; Feces; Levodopa; Parkinson Disease; Pilot Projects; Prospective Studies; Treatment Outcome
PubMed: 37798034
DOI: 10.1136/bmjopen-2023-071766