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Frontiers in Endocrinology 2023The aim was to conduct a systematic review and meta-analysis for assessing the effectiveness and safety of dietary polyphenol curcumin supplement on metabolic,... (Meta-Analysis)
Meta-Analysis Review
Effects of dietary polyphenol curcumin supplementation on metabolic, inflammatory, and oxidative stress indices in patients with metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials.
OBJECTIVE
The aim was to conduct a systematic review and meta-analysis for assessing the effectiveness and safety of dietary polyphenol curcumin supplement on metabolic, inflammatory, and oxidative stress indices in patients with metabolic syndrome (MetS).
METHODS
A comprehensive search for clinical trials was conducted in the following scientific databases: PubMed, SCOPUS, Cochrane Library, EMBASE, Web of Science, and China Biological Medicine. Randomized controlled trials (RCTs) evaluating the efficacy and safety of curcumin supplement for MetS were identified. A random-effects meta-analysis was performed using inverse variance, and efficacy was expressed as mean difference (MD) with 95% confidence interval (CI). The metabolic syndrome markers that were evaluated in the present study included waist circumference (WC), fasting blood sugar (FBS), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), tumor necrosis factor-a (TNF-a), interleukin 6 (IL-6), C-reactive protein (CRP), ultrasensitive c-reactive protein (hsCRP), and malondialdehyde (MDA). By employing the Cochrane tool, RCTs were assessed for bias risk.
RESULTS
A total of 785 participants from 13 RCTs were included, with intervention durations ranging from 4 to 12 weeks. Compared with the control group, the curcumin group had positive effects on WC (MD = -2.16, 95% CI: -3.78 to -0.54, = 0.009, seven studies), FBS (MD = -8.6, 95% CI: -15.45 to -1.75, = 0.01, nine studies), DBP (MD = -2.8, 95% CI: -4.53 to - 1.06, = 0.002, five studies), HDL-C (MD = 4.98, 95% CI: 2.58 to 7.38, < 0.0001, eight studies), TNF-a (MD = -12.97, 95% CI: -18.37 to -7.57, < 0.00001, two studies), CRP (MD = - 1.24, 95% CI: -1.71 to -0.77, < 0.00001, two studies), and MDA (MD = -2.35, 95% CI: -4.47 to -0.24, = 0.03, three studies). These improvements were statistically significant. Meanwhile, there was no significant improvement in SBP (MD = -4.82, 95% CI: -9.98 to 0.35, = 0.07, six studies), TG (MD = 1.28, 95% CI: -3.75 to 6.30, = 0.62, eight studies), IL-6 (MD = -1.5, 95% CI: -3.97 to 0.97, = 0.23, two studies), or hsCRP (MD = -1.10, 95% CI: -4.35 to 2.16, < 0.51, two studies). FBS, SBP, HDL-C, IL-6, CRP, hsCRP, and MDA had a relatively high heterogeneity.
CONCLUSION
Curcumin exhibited promising potential in enhancing markers associated with metabolic syndrome, including inflammation. However, additional studies are required to confirm such findings since the included evidence is limited and has a relatively high heterogeneity.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42022362553.
Topics: Randomized Controlled Trials as Topic; Curcumin; Dietary Supplements; Metabolic Syndrome; Oxidative Stress; Polyphenols; Inflammation; Humans; Curcuma
PubMed: 37522129
DOI: 10.3389/fendo.2023.1216708 -
European Journal of Clinical Nutrition May 2022Taurine (Tau) has modulatory effects on inflammatory and oxidative stress biomarkers; however, the results of clinical studies are not comprehensive enough to determine... (Meta-Analysis)
Meta-Analysis Review
Taurine (Tau) has modulatory effects on inflammatory and oxidative stress biomarkers; however, the results of clinical studies are not comprehensive enough to determine the effect of different durations and doses of Tau supplementation on inflammatory and oxidative stress biomarkers. The current study was conducted based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. For this purpose, PubMed/Medline, Scopus, and Embase databases were systematically searched to obtain the relevant studies published before 30th March 2021. Meta-analysis was performed on controlled clinical trials by using the random-effects method. Non-linear relationship between variables and effect size was performed using dose-response and time-response analyses. The Cochrane Collaboration's tool was used to evaluate the quality of included studies. Tau supplementation can reduce the levels of malondialdehyde (MDA) (SMD = -1.17 µmol/l; 95% CI: -2.08, - 0.26; P = 0.012) and C-reactive protein (CRP) (SMD = -1.95 mg/l; 95% CI: -3.20, - 0.71; P = 0.002). There have been no significant effects of Tau supplementation on the levels of tumor necrosis factors-alpha (TNF-α) (SMD = -0.18 pg/ml; 95% CI: -0.56, 0.21; P = 0.368), and interleukin-6 (IL-6) (SMD = -0.49 pg/ml; 95% CI: -1.13, 0.16; P = 0.141). Besides, Tau has more alleviating effect on oxidative stress and inflammation on 56 days after supplementation (P < 0.05). Tau can decrease the levels of CRP and MDA. Based on the currently available evidence, Tau has no significant effect on the level of TNF-α and IL-6. Eight-week of Tau supplementation has more beneficial effects on inflammatory and oxidative stress biomarkers.
Topics: Biomarkers; C-Reactive Protein; Dietary Supplements; Humans; Inflammation; Interleukin-6; Oxidative Stress; Taurine; Tumor Necrosis Factor-alpha
PubMed: 34584225
DOI: 10.1038/s41430-021-01010-4 -
Journal of Clinical Pharmacology Nov 2015The establishment of drug dosing in children is often hindered by the lack of actual pediatric efficacy and safety data. To overcome this limitation, scaling approaches... (Review)
Review
The establishment of drug dosing in children is often hindered by the lack of actual pediatric efficacy and safety data. To overcome this limitation, scaling approaches are frequently employed to leverage adult clinical information for informing pediatric dosing. The objective of this review is to provide a comprehensive overview of the different scaling approaches used in pediatric pharmacotherapy as well as their proper implementation in drug development and clinical use. We will start out with a brief overview of the current regulatory requirements in pediatric drug development, followed by a review of the most commonly employed scaling approaches in increasing order of complexity ranging from simple body weight-based dosing to physiologically-based pharmacokinetic (PBPK) modeling approaches. Each of the presented approaches has advantages and limitations, which will be highlighted throughout the course of the review by the use of clinically-relevant examples. The choice of the approach employed consequently depends on the clinical question at hand and the availability of sufficient clinical data. The main effort while establishing and qualifying these scaling approaches should be directed towards the development of safe and effective dosing regimens in children rather than identifying the best model, ie models should be fit for purpose.
Topics: Age Factors; Body Size; Dose-Response Relationship, Drug; Drug Discovery; Humans; Models, Biological; Pharmacokinetics; Pharmacology, Clinical
PubMed: 26009792
DOI: 10.1002/jcph.555 -
Current Drug Delivery 2017In recent years, colloidal delivery systems based on nano-emulsion are gaining popularity; being used for encapsulation and delivery of many drugs. This review therefore... (Review)
Review
BACKGROUND
In recent years, colloidal delivery systems based on nano-emulsion are gaining popularity; being used for encapsulation and delivery of many drugs. This review therefore aims at summarizing various methods of nano-emulsion formulation and their use as a topical and transdermal delivery vehicle for a number of active pharmaceutical ingredients from different pharmacological classes.
METHODS
This article represents a systematic review of nano-emulsions for topical and transdermal drug delivery. A vast literature was searched and critically analysed.
RESULTS
Nano-emulsions are thermokinetically stable dispersion systems, which have been used in topical and transdermal delivery of a number of pharmaceutically active compounds. Nano-emulsions have a narrow droplet size range with tuneable surface properties, which make them an ideal delivery vehicle. Nanoemulsions have a number of advantages over conventional emulsions, including easy preparation using various low and high energy methods, optical transparency, high solubilisation capacity, high stability to droplet aggregation and the ability to penetrate the skin; thus allowing the transdermal delivery of drugs.
CONCLUSION
This review indicated that nano-emulsions are promising vehicle for entrapping various drugs and are suitable for traversing the skin barrier for systemic effects.
Topics: Administration, Cutaneous; Chemistry, Pharmaceutical; Emulsions; Humans; Nanoparticles; Skin; Skin Absorption
PubMed: 27557672
DOI: 10.2174/1567201813666160824125444 -
Nucleic Acids Research Jun 2022At the time of writing, although siRNA therapeutics are approved for human use, no official regulatory guidance specific to this modality is available. In the absence of...
At the time of writing, although siRNA therapeutics are approved for human use, no official regulatory guidance specific to this modality is available. In the absence of guidance, preclinical development for siRNA followed a hybrid of the small molecule and biologics guidance documents. However, siRNA differs significantly from small molecules and protein-based biologics in its physicochemical, absorption, distribution, metabolism and excretion properties, and its mechanism of action. Consequently, certain reports typically included in filing packages for small molecule or biologics may benefit from adaption, or even omission, from an siRNA filing. In this white paper, members of the 'siRNA working group' in the IQ Consortium compile a list of reports included in approved siRNA filing packages and discuss the relevance of two in vitro reports-the plasma protein binding evaluation and the drug-drug interaction risk assessment-to support siRNA regulatory filings. Publicly available siRNA approval packages and the literature were systematically reviewed to examine the role of siRNA plasma protein binding and drug-drug interactions in understanding pharmacokinetic/pharmacodynamic relationships, safety and translation. The findings are summarized into two decision trees to help guide industry decide when in vitro siRNA plasma protein binding and drug-drug interaction studies are warranted.
Topics: Biological Products; Blood Proteins; Decision Trees; Drug Interactions; Humans; Protein Binding; RNA, Small Interfering
PubMed: 35687098
DOI: 10.1093/nar/gkac456 -
Biomedicine & Pharmacotherapy =... Feb 2017Embelia ribes (ER) has been documented in Ayurveda for treating various diseases, including diabetes mellitus (DM). The present systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis Review
Embelia ribes (ER) has been documented in Ayurveda for treating various diseases, including diabetes mellitus (DM). The present systematic review and meta-analysis evaluated the efficacy and safety of ER and its active bio-marker, embelin and its derivatives in the treatment of DM. Literature search was performed in PubMed/MEDLINE, EMBASE, Scopus, ScienceDirect, Scifinder, and Google Scholar. Using Review Manager, meta-analysis of ER/embelin/derivatives of embelin versus diabetic control was performed with inverse-variance model, providing mean differences (MDs) and 95% confidence intervals (CIs). Heterogeneity was determined by I statistic. A total of 13 studies were included in the systematic review and meta-analysis, and were conducted in experimental rats. ER and embelin significantly (P≤0.01) resorted blood glucose (MD, -231.30; CI, -256.79, -205.82; and MD, -154.70; CI, -168.65, -140.74) and glycosylated haemoglobin (MD, -6.36; CI, -8.33, -4.39; and MD,-4.68; CI, -7.76, -1.60), respectively. Meta-analysis findings also reported considerable restoration of insulin, lipid profile, haemodynamic parameters, serum and oxidative stress markers. The derivatives of embelin, 6-bromoembelin and vilangin, also improved diabetic condition. In addition, treatments also ameliorated body weight changes due to diabetes. The present systematic review and meta-analysis supports scientific evidence for the antidiabetic activity of ER/embelin/derivatives of embelin. However, further research is warranted in clinical trials to validate the present findings.
Topics: Animals; Diabetes Mellitus; Embelia; Humans; Hypoglycemic Agents; Oxidative Stress; Plant Extracts
PubMed: 27984799
DOI: 10.1016/j.biopha.2016.12.001 -
Seminars in Cardiothoracic and Vascular... Dec 2013Cerebral oximetry is a Food and Drug Administration-approved technology that allows monitoring of brain oxygen saturation in accessible superficial brain cortex regions,... (Review)
Review
Cerebral oximetry is a Food and Drug Administration-approved technology that allows monitoring of brain oxygen saturation in accessible superficial brain cortex regions, which are amongst the most vulnerable in regard to ischemic or hypoxic injury. Since most oxygen in the area of interest is located in the venous compartment, the determined regional brain oxygen saturation approximately reflects the local balance between oxygen delivery and oxygen consumption. Major systemic alterations in blood oxygen content and oxygen delivery will be accompanied by corresponding changes in regional brain saturation. This systematic review, which is based on a Medline search, focuses on the characteristic changes in regional cerebral oxygen saturation that occur, when global oxygen supply to the brain ceases. It further highlights the potential application of cerebral oximetry in the management of cardiac arrest victims, the predictability of clinical outcome after global cerebral ischemia, and it also indicates possible potentials for the management of cerebral reperfusion after having instituted return of spontaneous circulation.
Topics: Animals; Brain; Brain Ischemia; Device Approval; Equipment Design; Heart Arrest; Humans; Oximetry; Oxygen; Oxygen Consumption; United States; United States Food and Drug Administration
PubMed: 23782549
DOI: 10.1177/1089253213492861 -
Journal of Agricultural and Food... Nov 2023Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous system that occurs in old age and pre-aging, characterized by progressive cognitive... (Meta-Analysis)
Meta-Analysis Review
Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous system that occurs in old age and pre-aging, characterized by progressive cognitive dysfunction and behavioral impairment. Salidroside (Sal) is a phenylpropanoid mainly isolated from species with various pharmacological effects. However, the exact anti-AD mechanism of Sal has not been clearly elucidated. This meta-analysis aims to investigate the possible mechanisms by which Sal exerts its anti-AD effects by evaluating behavioral indicators and biochemical characteristics. A total of 20 studies were included, and the results showed that the Sal treatment significantly improved behavior abnormalities in AD animal models. With regard to neurobiochemical indicators, Sal treatment could effectively increase the antioxidant enzyme superoxide dismutase, decrease the oxidative stress indicator malondialdehyde, and decrease the inflammatory indicators interleukin 1β, interleukin 6, and tumor necrosis factor α. Sal treatment was effective in reducing neuropathological indicators, such as amyloid-β levels and the number of apoptotic cells. When the relevant literature on the treatment of rodent AD models is combined with Sal, the therapeutic potential of Sal through multiple mechanisms was confirmed. However, further confirmation by higher quality studies, larger sample sizes, and more comprehensive outcome evaluations in clinical trials is needed in the future.
Topics: Animals; Alzheimer Disease; Neurodegenerative Diseases; Oxidative Stress; Amyloid beta-Peptides; Neuroprotective Agents
PubMed: 37934032
DOI: 10.1021/acs.jafc.3c06672 -
Pharmacotherapy Jul 2020Risperidone is a second-generation antipsychotic drug metabolized to an active metabolite, 9-hydroxyrisperidone, primarily by cytochrome P450 (CYP) 2D6 and to a lesser... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Risperidone is a second-generation antipsychotic drug metabolized to an active metabolite, 9-hydroxyrisperidone, primarily by cytochrome P450 (CYP) 2D6 and to a lesser extent by CYP3A4. The extent to which drug metabolism genetics impacts risperidone and 9-hydroxyrisperidone exposure has not been clarified.
OBJECTIVE
A systematic review and meta-analysis evaluated the impact of genetically defined CYP2D6 function on risperidone pharmacokinetics applying a standardized genotype-phenotype translation system.
METHODS
A comprehensive electronic database search identified studies reporting relationships between genetically determined CYP2D6 metabolism and risperidone pharmacokinetic properties. The exposure of risperidone or active moiety (risperidone + 9-hydroxyrisperidone) was measured by dose-adjusted steady-state serum or plasma concentration or area under the concentration-time curve as primary outcomes. Subjects were assigned to CYP2D6 poor metabolizer, intermediate metabolizer, normal metabolizer, or ultrarapid metabolizer groups using a standardized genotype-phenotype translation method. Effect sizes between groups were pooled and stratified by single or multiple dosing regimens.
RESULTS
A total of 15 studies involving 2125 adult subjects were included in the meta-analysis. Following multiple-dose oral administration, compared with CYP2D6 normal metabolizers, the risperidone dose-adjusted steady-state serum/plasma concentration was 2.35-fold higher in intermediate metabolizers (95% confidence interval [CI] 1.77-3.13, p<0.0001) and 6.20-fold higher in poor metabolizers (95% CI 5.05-7.62, p<0.0001); the active moiety dose-adjusted steady-state concentration was 1.18-fold higher in intermediate metabolizers (95% CI 1.11-1.25, p<0.0001) and 1.44-fold higher in poor metabolizers (95% CI 1.23-1.69, p<0.0001). Higher area under the concentration-time curve of risperidone and active moiety was also found in single-dose studies.
CONCLUSION
Genetically defined impaired CYP2D6 activity is associated with increased exposure of both risperidone and risperidone + 9-hydroxyrisperidone in adults receiving oral formulations. Additional studies are needed to quantify the clinical impact of these relationships.
Topics: Antipsychotic Agents; Cytochrome P-450 CYP2D6; Humans; Polymorphism, Genetic; Risperidone
PubMed: 32519344
DOI: 10.1002/phar.2434 -
Child and Adolescent Psychiatry and... 2018The second generation antipsychotic drug risperidone is widely used in the field of child and adolescent psychiatry to treat conditions associated with disruptive... (Review)
Review
The second generation antipsychotic drug risperidone is widely used in the field of child and adolescent psychiatry to treat conditions associated with disruptive behavior, aggression and irritability, such as autism spectrum disorders. While risperidone can provide symptomatic relief for many patients, there is considerable individual variability in the therapeutic response and side-effect profile of the medication. One well established biological factor that contributes to these individual differences is genetic variation in the cytochrome P450 enzyme 2D6. The 2D6 enzyme metabolizes risperidone and therefore affects drug levels and dosing. In the present review, we summarize the current literature on 2D6 variants and their effects on risperidone responses, specifically in children and adolescents. Relevant articles were identified through systematic review, and after irrelevant articles were discarded, ten studies were included in the review. Most prospective studies were well controlled, but often did not have a large enough sample size to make robust statements about rarer variants, including those categorized as ultra-rapid and poor metabolizers. Individual studies demonstrated a role for different genetic variants in risperidone drug efficacy, pharmacokinetics, hyperprolactinemia, weight gain, extrapyramidal symptoms and drug-drug interactions. Where studies overlapped in measurements, there was typically a consensus between results. These findings indicate that the value of 2D6 genotyping in the youth population treated with risperidone requires further study, in particular with the less common variants.
PubMed: 30026806
DOI: 10.1186/s13034-018-0243-2