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New meta-analyses, RCTs and systematic reviews that we monitor daily in PubMed. Independently indexed, not editorially curated.
Molecules (Basel, Switzerland) · 2023
This review article describes studies published over the past five years on the combination of polyphenols, which are the most studied in the field of anticancer effects (curcumin, quercetin, resveratrol, epigallocatechin gallate, and apigenin) and chemotherapeutics such as cisplatin, 5-fluorouracil, oxaliplatin, paclitaxel, etc. According to WHO data, research has been limited to five cancers with the highest morbidity rate (lung, colorectal, liver, gastric, and breast cancer). A systematic review of articles published in the past five years (from January 2018 to January 2023) was carried out with the help of all Web of Science databases and the available base of clinical studies. Based on the preclinical studies presented in this review, polyphenols can enhance drug efficacy and reduce chemoresistance through different molecular mechanisms. Considering the large number of studies, curcumin could be a molecule in future chemotherapy cocktails. One of the main problems in clinical research is related to the limited bioavailability of most polyphenols. The design of a new co-delivery system for drugs and polyphenols is essential for future clinical research. Some polyphenols work in synergy with chemotherapeutic drugs, but some polyphenols can act antagonistically, so caution is always required.
The Journal of asthma : official journal of the Association for the Care of Asthma · 2024
This study aimed to investigate the potential anti-inflammatory and antioxidant effects of apigenin in rats with acute lung injury (ALI). We also examined changes in levels of inflammatory and antioxidant factors after apigenin treatment in a rat model of ALI.Methods: We searched several databases, including PubMed, Scopus, EMBASE, Web of Science, ProQuest, and GoogleScholar, to retrieve relevant articles for our systematic review and meta-analysis.Five studies with 226 rat models of ALI were included in this study. We investigated inflammatory factors and oxidative stress with the corresponding 95% confidence interval in three groups: 1. Group1 (control vs. ALI), 2. Group2 (ALI vs. apigenin10), and 3. Group3 (ALI vs. apigenin20). Estimating the correlation and 95% confidence intervals for the inflammatory agents and oxidative stress in the intervention group (ALI), compared with that in the control group, respectively (correlation: 0.194; 95% confidence intervals, 0.101-0.282, p value = .001, z-value= 4.08) and (correlation: 0.099; 95% confidence intervals, 0.016-0.182, p value = .020, z value= 2.325). Estimating the correlation and 95% confidence intervals for the inflammatory agents and oxidative stress in the intervention group (apigenin 10 mg/kg), compared with that in the control group (ALI), respectively (correlation: 0.476; 95% confidence intervals, 0.391-0.553, p value = .001, z-value= 9.678) and (correlation: 0.415; 95% confidence intervals, 0.313-0.508, p value= .001, z-value= 7.349). Apigenin may have potential anti-inflammatory and antioxidant effects in rat models of ALI. However, the efficacy of apigenin as a therapeutic strategy requires further investigation through prospective controlled randomized trials.
Mini reviews in medicinal chemistry · 2024
Diabetes is one of the important and growing diseases in the world. Among the most common diabetic complications are renal adverse effects. The use of apigenin may prevent the development and progression of diabetes-related injuries. The current study aims to review the effects of apigenin in the treatment of diabetic nephropathy. In this review, a systematic search was performed based on PRISMA guidelines for obtaining all relevant studies on "the effects of apigenin against diabetic nephropathy" in various electronic databases up to September 2022. Ninety-one articles were obtained and screened in accordance with the predefined inclusion and exclusion criteria. Seven eligible articles were finally included in this review. The experimental findings revealed that hyperglycemia led to the decreased cell viability of kidney cells and body weight loss and an increased kidney weight of rats; however, apigenin administration had a reverse effect on these evaluated parameters. It was also found that hyperglycemia could induce alterations in the biochemical and renal function-related parameters as well as histopathological injuries in kidney cells or tissue; in contrast, the apigenin administration could ameliorate the hyperglycemia-induced renal adverse effects. The results indicated that the use of apigenin could mitigate diabetes-induced renal adverse effects, mainly through its antioxidant, anti-apoptotic, and anti-inflammatory activities. Since the findings of this study are based on experimental studies, suggesting the use of apigenin (as a nephroprotective agent) against diabetic nephropathy requires further clinical studies.
Journal of ethnopharmacology · 2024
Traditional Chinese medicine (TCM) has been used for centuries to treat various types of inflammation and tumors of the digestive system. Portulaca oleracea L. (POL), has been used in TCM for thousands of years. The chemical composition of POL is variable and includes flavonoids, alkaloids, terpenoids and organic acids and other classes of natural compounds. Many of these compounds exhibit powerful anti-inflammatory and anti-cancer-transforming effects in the digestive system. In this review, we focus on the potential therapeutic role of POL in NASH, gastritis and colitis and their associated cancers, with a focus on the pharmacological properties and potential mechanisms of action of the main natural active compounds in POL. The information and data on Portulaca oleracea L. and its main active ingredients were collated from various resources like ethnobotanical textbooks and literature databases such as CNKI, VIP (Chinese literature), PubMed, Science Direct, Elsevier and Google Scholar (English literatures), Wiley, Springer, Tailor and Francis, Scopus, Inflibnet. Kaempferol, luteolin, myricetin, quercetin, genistein, EPA, DHA, and melatonin were found to improve NASH and NASH-HCC, while kaempferol, apigenin, luteolin, and quercetin played a therapeutic role in gastritis and gastric cancer. Apigenin, luteolin, myricetin, quercetin, genistein, lupeol, vitamin C and melatonin were found to have therapeutic effects in the treatment of colitis and its associated cancers. The discovery of the beneficial effects of these natural active compounds in POL supports the idea that POL could be a promising novel candidate for the treatment and prevention of inflammation-related cancers of the digestive system. The discovery of the beneficial effects of these natural active compounds in POL supports the idea that POL could be a promising novel candidate for the treatment and prevention of inflammation-related cancers of the digestive system. However, clinical data describing the mode of action of the naturally active compounds of POL are still lacking. In addition, pharmacokinetic data for POL compounds, such as changes in drug dose and absorption rates, cannot be extrapolated from animal models and need to be measured in patients in clinical trials. On the one hand, a systematic meta-analysis of the existing publications on TCM containing POL still needs to be carried out. On the other hand, studies on the hepatic and renal toxicity of POL are also needed. Additionally, well-designed preclinical and clinical studies to validate the therapeutic effects of TCM need to be performed, thus hopefully providing a basis for the validation of the clinical benefits of POL.
Frontiers in nutrition · 2024
Thymus serpyllum L. (Lamiaceae), known in English as 'wild thyme', is primarily found in the Palearctic realm (Eurasia, North Africa) and has been utilized traditionally for culinary, nutritional, medicinal, and aromatic purposes. The essential oil extracted from wild thyme is particularly noteworthy, being used extensively in the food industry as a flavoring agent and preservative. The plant's aerial parts are commonly employed as an element of the diet (e.g., tea)/for culinary uses and in local/traditional medicine (primarily for managing respiratory and gastrointestinal conditions), similar to the use of common thyme. There is practically no information available on the species' nutritional benefits. Pharmacological studies, including in vitro and in vivo research, alongside a limited number of clinical trials, have investigated extracts of Thymus serpyllum, although these extracts are often phytochemically poorly characterized in different experimental protocols and models. These studies have demonstrated a range of therapeutic effects, such as antimicrobial (notably the essential oil) and anti-inflammatory, as well as its preventative health benefits and nutritional value of wild thyme. Preclinical studies have corroborated the plant's anti-inflammatory potential, particularly in conditions like inflammatory bowel diseases (IBD) and irritable bowel syndromes (IBS). Additionally, evidence of hepatoprotective activities and benefits in managing metabolic syndrome and cardiovascular health issues, such as lipid metabolism regulation, cholesterol reduction, antidiabetic, antihypertensive, and immunomodulatory effects, have been observed predominantly in rodent models. Phytochemical analysis of wild thyme reveals an essential oil fraction below 1%, along with non-volatile compounds predominantly comprising phenolic acids (such as rosmarinic, salvianolic, and caffeic acids) and flavonoids (mainly glucosides of luteolin, apigenin, and their derivatives). These components are believed to contribute significantly to the plant's medicinal, nutritional, and preventive health properties. Despite promising findings, there is a need for more rigorously designed controlled clinical trials using phytochemically characterized wild thyme. The plant has an excellent safety and tolerability record. This review at the interface of nutritional/preventive health properties and as pharmacological activities highlights the current role of wild thyme in nutrition and general healthcare as well as its future potential, and also points to important gaps in the literature.
Inflammopharmacology · 2024
Apigenin is a flavone-kind of flavonoid present in fruits and vegetables. Apigenin exhibits biological activities including neuropharmacological effects against different neurological disorders. In this study, we summarize and discuss the molecular mechanisms of the anti-neuroinflammatory effects of apigenin in neurological disorders. A systematic review was conducted by searching Google Scholar, Web of Science, Scopus and PubMed. A total of 461 records were retrieved from the search. After screening of the records based on the inclusion criteria, 16 articles were selected and discussed in this study. The results from the selected studies showed that apigenin exhibited anti-neuroinflammatory effect in preclinical studies. The anti-neuroinflammatory mechanisms exhibited by apigenin include inhibition of overproduction of pro-inflammatory cytokines, attenuation of microglia activation via reduction of CD-11b-positive cells, inhibition of ROCK-1 expression and upregulation of miR-15a, p-ERK1/2, p-CREB, and BDNF, downregulation of NLRP3 inflammasome, iNOS and COX-2 expression, reduction of Toll-like receptor-4 expression and inhibition of nuclear factor-kappa B (NF-kB) activation. Overall, apigenin inhibited neuroinflammation which suggests it confers neuroprotective effect against neuronal degeneration in some neurodegenerative conditions. This review provides important neuropharmacological information on the neuroprotective mechanisms of apigenin against neuroinflammation which may be useful for future preclinical and clinical studies.
Cancer medicine · 2024
Therapeutic management of colorectal cancer (CRC) does not yet yield promising long-term results. Therefore, there is a need for further investigation of possible therapeutic options. Various experiments have studied the effects of apigenin on CRC and have shown conflicting results. This systematic review and meta-analysis investigates the currently existing evidence on the effect of apigenin on CRC. Medline, Embase, Scopus, and Web of Science databases were searched for articles related to apigenin and its effect on CRC in the preclinical setting. Cell viability, growth inhibition, apoptosis, and cell cycle arrest for in-vitro, and body weight, tumor size, and mortality in in-vivo studies were extracted as outcomes. Thirty-nine articles investigating colorectal adenocarcinoma were included in this meta-analysis. Thirty-seven of these studies had data for in vitro experiments, with eight studies having data for in vivo experiments. Six articles had both in vitro and in vivo assessments. Our analysis showed apigenin reduces cell viability and induces growth inhibition, apoptosis, and cell cycle arrest in in vitro studies. The few in vivo studies indicate that apigenin decreases tumor size while showing no effects on the body weight of animal colorectal adenocarcinoma models. Our results demonstrated that apigenin, through reducing cell viability, inducing growth inhibition, apoptosis, and cell cycle arrest, and also by decreasing the tumor size, can be considered as a possible adjuvant agent in the management of colorectal adenocarcinoma. However, further in vivo studies are needed before any efforts to translate the current evidence into clinical studies.
Current neuropharmacology · 2025
Alzheimer's Disease (AD) is the most common dementia in clinics. Despite decades of progress in the study of the pathogenesis of AD, clinical treatment strategies for AD remain lacking. Apigenin, a natural flavonoid compound, is present in a variety of food and Chinese herbs and has been proposed to have a wide range of therapeutic effects on dementia. To clarify the relevant pharmacological mechanism and therapeutic effect of apigenin on animal models of AD. Computer-based searches of the PubMed, Cochrane Library, Embase, and Web of Science databases were used to identify preclinical literature on the use of apigenin for treating AD. All databases were searched from their respective inception dates until June 2023. The meta-analysis was performed with Review manager 5.4.1 and STATA 17.0. Thirteen studies were eventually enrolled, which included 736 animals in total. Meta-analysis showed that apigenin had a positive effect on AD. Compared to controls, apigenin treatment reduced escape latency, increased the percentage of time spent in the target quadrant and the number of plateaus traversed; apigenin was effective in reducing nuclear factor kappa-B (NF-κB) p65 levels; apigenin effectively increased antioxidant molecules SOD and GSH-px and decreased oxidative index MDA; for ERK/CREB/BDNF pathway, apigenin effectively increased BDNF and pCREB molecules; additionally, apigenin effectively decreased caspase3 levels and the number of apoptotic cells in the hippocampus. The results show some efficacy of apigenin in the treatment of AD models. However, further clinical studies are needed to confirm the clinical efficacy of apigenin.
Menopause (New York, N.Y.) · 2025
Menopausal symptoms can significantly impact women's quality of life. Herbal interventions like Matricaria chamomilla (chamomile) have been suggested as potential remedies. However, their efficacy and safety remain underexplored. This triple-blind clinical trial enrolled 80 postmenopausal women meeting specific criteria. Inclusion criteria included participants in early or late perimenopause, defined by a symptom score >15, FSH levels >40, or 2 years since menopause, with no significant comorbidities. Participants were randomly assigned to intervention and placebo groups. In a triple-blind clinical trial with 80 postmenopausal women (aged 47-62) from Babol City Health Center, participants were randomly assigned to receive either chamomile (100 mg capsules with 1.2% apigenin, four times daily) or a placebo over 12 weeks. Symptoms of menopause were assessed using the Australian Menopause Association's Scorecard Symptom Questionnaire. Over 12 weeks, they received either chamomile or placebo capsules, with side effect assessments every 4 weeks. Notable differences were found between the intervention and control groups in the overall scores on the symptom scorecard from baseline to 12 weeks' postintervention (-10.36; 95% confidence interval [CI], -13.84 to -6.92; P < 0.001). Specific subscores also improved in the intervention group: vasomotor (-2.25; 95% CI, -3.09 to -1.42; P < 0.001), psychological (-3.74; 95% CI, -5.29 to -2.20; P < 0.001), locomotor (-2.70; 95% CI, -3.63 to -1.77; P < 0.001), and urological (-1.89; 95% CI, -2.77 to -1.00; P < 0.001). Both groups showed significant changes in total symptom scores over time ( P < 0.001). Two participants experienced side effects, including mouth sores, skin spots, and itching, in the chamomile group, which led to their dropping out of the study. Chamomile intervention shows promise in alleviating menopausal symptoms, but its use warrants caution due to associated side effects. Further research is necessary to optimize dosage and mitigate adverse reactions for safer and more effective management of menopausal symptoms.
Pharmaceutical biology · 2025
Flavones, the key active components in Traditional Chinese Medicine (TCM), have demonstrated antidepressant activity. Given the numerous animal studies conducted, a systematic analysis is essential to provide a valuable reference for future research. This study investigated the antidepressant activity of flavones based on animal models and summarized the underlying mechanisms. We systematically searched 7 bibliographic Databases as of August 12, 2023, such as Web of Science, PubMed, China National Knowledge Infrastructure, etc. The meta-analysis was performed using either the random or fixed-effect model, supplemented by trial sequential analysis (TSA). The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to assess the quality of evidence. A total of 25 studies involving 458 mice were included, identifying five flavones (baicalin, baicalein, apigenin, luteolin, vitexin) with antidepressant activity. Compared to the control group, flavones significantly reduced immobility time in forced swimming and tail suspension tests. Flavones also decreased serum and hippocampal levels of interleukin (IL)-1β and tumor necrosis factor-alpha (TNF-α), reduced nuclear factor kappa B (NF-κB) levels, and increased brain-derived neurotrophic factor (BDNF) levels. Relative to the positive group, flavones raised IL-6, sucrose preference rate, and corticosterone (CORT) levels, with no significant differences in other factors. The TSA showed the efficacy of flavones for treating depression with adequate 'information size' for the primary outcome. The results demonstrate that flavones exert protective effects against depression in mice, primarily by stimulating neurotrophic factors and modulating inflammatory pathways. These findings emphasize their potential as promising candidates for the development of novel antidepressant therapies.
Renal failure · 2025
Diabetic nephropathy (DN) is a diabetes mellitus (DM)-induced complication that poses high morbidity and mortality risks. The Astragalus and Salvia miltiorrhiza couplet medicines (AS) are commonly employed in DN clinical treatment in China, but their clinical efficacy and potential pharmacological mechanisms are yet to be evaluated. A meta-analysis of 15 studies involving 1,443 patients was conducted. Furthermore, network pharmacology predicted components and targets, which were verified by molecular docking and in vivo validation. In our meta-analysis, AS notably elevated clinical outcomes and renal function among patients with DN. Meanwhile, when the treatment duration exceeds 12 weeks, AS demonstrated a significant reduction in fasting blood glucose levels, indicating a time-dependent effect. Moreover, based on network pharmacology results, AS likely enhanced clinical outcomes by interacting with vital signaling pathways, including PI3K/Akt, MAPK, and NF-kappa B. Molecular docking studies have confirmed that PTGS2, the key therapeutic target of AS, can be closely combined with bioactive components GLY, quercetin, apigenin, and daidzein. Additionally, in vivo experiments have corroborated that AS can ameliorate renal function, UACR, and biomarkers associated with iron metabolism, such as GPX4, PTGS2, FTH1, and FTL1. Through rigorous experimental validation, our study demonstrates AS's significant clinical efficacy in managing DN. Specifically, AS has been shown to enhance renal function, ameliorate renal fibrosis, and positively influence iron metabolism. Despite these promising outcomes, future research with a larger sample size must be conducted to further substantiate these findings.
Inflammopharmacology · 2025
Neurodegenerative disease represents a significant public health concern, with conditions, such as Alzheimer's disease and Parkinson's disease, being among the most prevalent. The primary risk factor for these neurodegenerative diseases is the process of aging. Key factors, such as oxidative stress and mitochondrial dysfunction, play a crucial role in initiating neurodegeneration. The progressive deterioration and neuronal loss in both the central and peripheral nervous systems are hallmark features of neurodegenerative diseases. Plant-derived natural products and their bioactive components, such as curcumin, resveratrol, genistein, marine algae, quercetin, apigenin, and luteolin, have shown promise as therapeutic agents for treating neurodegenerative diseases. There are various medications approved for the management of neurodegenerative diseases; their usage is primarily limited to providing symptomatic relief. The utilization of natural products holds significant promise for the prevention and treatment of neurodegenerative diseases (ND). The review provides evidence that natural products and their bioactive compounds could be beneficial in the treatment of neurodegenerative disorders. This article delineates the Keap1-Nrf2-ARE pathway's role in ND progression, shedding light on the therapeutic efficacy of natural products and their bioactive constituents that have demonstrated neuroprotective properties.
Nutrients · 2019
Recently, it was demonstrated that spermidine-induced autophagy reduces the risk of cardiovascular disease in mice. Intestinal bacteria are a major source of polyamines, including spermidine. We previously reported that the intake of both Bifidobacterium animalis subsp. lactis (Bifal) and arginine (Arg) increases the production of putrescine, a spermidine precursor, in the gut. Here, we investigated the effects of Bifal and Arg consumption on endothelial function in healthy subjects. Healthy individuals with body mass index (BMI) near the maximum value in the "healthy" range (BMI: 25) (n = 44) were provided normal yogurt containing Bifal and Arg (Bifal + Arg YG) or placebo (normal yogurt) for 12 weeks in this randomized, double-blinded, placebo-controlled, parallel-group comparative study. The reactive hyperemia index (RHI), the primary outcome, was measured using endo-peripheral arterial tone (EndoPAT). The change in RHI from week 0 to 12 in the Bifal + Arg YG group was significantly higher than that in the placebo group, indicating that Bifal + Arg YG intake improved endothelial function. At week 12, the concentrations of fecal putrescine and serum putrescine and spermidine in the Bifal + Arg YG group were significantly higher than those in the placebo group. This study suggests that consuming Bifal + Arg YG prevents or reduces the risk of atherosclerosis.
Journal of Alzheimer's disease : JAD · 2019
Alzheimer's disease (AD)-associated sequence (ADAS) of cultured fecal bacteria was discovered in human gut targeted screening. This study provides important information to expand our current understanding of the structure/activity relationship of ADAS and putative inhibitors/activators that are potentially involved in ADAS appearance/disappearance. The NCBI database analysis revealed that ADAS presents at a large proportion in American Indian Oklahoman (C&A) with a high prevalence of obesity/diabetes and in colorectal cancer (CRC) patients from the US and China. An Oklahoman non-native group (NNI) showed no ADAS. Comparison of two large US populations reveals that ADAS is more frequent in individuals aged ≥66 and in females. Prevalence and levels of fecal metabolites are altered in the C&A and CRC groups versus controls. Biogenic amines (histamine, tryptamine, tyramine, phenylethylamine, cadaverine, putrescine, agmatine, spermidine) that present in food and are produced by gut microbiota are significantly higher in C&A (e.g., histamine/histidine 95-fold) versus NNI (histamine/histidine 16-fold). The majority of these bio-amines are cytotoxic at concentrations found in food. Inositol phosphate signaling implicated in AD is altered in C&A and CRC. Tryptamine stimulated accumulation of inositol phosphate. The seizure-eliciting tryptamine induced cytoplasmic vacuolization and vesiculation with cell fragmentation. Present additions of ADAS-carriers at different ages including infants led to an ADAS-comprising human sample size of 2,830 from 27 studies from four continents (North America, Australia, Asia, Europe). Levels of food-derived monoamine oxidase inhibitors and anti-bacterial compounds, the potential modulators of ADAS-bacteria growth and biogenic amine production, were altered in C&A versus NNI. ADAS is attributable to potentially modifiable risk factors of AD associated diseases.
Wiener klinische Wochenschrift · 2021
The worldwide prevalence of dementia is estimated at 35.6 million and will rise to 115 million by 2050. There is therefore an urgent need for well-founded dementia diagnostics and well-researched therapeutic options. Previous studies have highlighted that spermidine has the ability to trigger the important process of dissolving amyloid-beta plaques by autophagy. They also confirmed that nutritional intervention with the natural polyamine spermidine can prevent memory loss in aging model organisms. This multicentric double-blind preliminary study focused on the effect of oral spermidine supplementation on older adults' cognitive performance. Memory tests were carried out on 85 subjects aged between 60 and 96 years in 6 nursing homes in Styria. Blood samples were taken for the determination of spermidine concentration and measurement of metabolic parameters. The results demonstrated a clear correlation between the intake of spermidine and the improvement in cognitive performance in subjects with mild and moderate dementia in the group treated with the higher spermidine dosage. The most substantial improvement in test performance was found in the group of subjects with mild dementia with an increase of 2.23 points (p = 0.026) in the mini mental state examination (MMSE) and 1.99 (p = 0.47) in phonematic fluidity. By comparison, the group which had a lower spermidine intake showed consistent or declining cognitive performance.
Investigative ophthalmology & visual science · 2021
Glaucoma remains a poorly understood disease, and identifying biomarkers for early diagnosis is critical to reducing the risk of glaucoma-related visual impairment and blindness. The aim of this review is to provide current metabolic profiles for glaucoma through a summary and analysis of reported metabolites associated with glaucoma. We searched PubMed and Web of Science for metabolomics studies of humans on glaucoma published before November 11, 2020. Studies were included if they assessed the biomarkers of any types of glaucoma and performed mass spectrometry-based or nuclear magnetic resonance-based metabolomics approach. Pathway enrichment analysis and topology analysis were performed to generate a global view of metabolic signatures related to glaucoma using the MetaboAnalyst 3.0. In total, 18 articles were included in this review, among which 13 studies were focused on open-angle glaucoma (OAG). Seventeen metabolites related to OAG were repeatedly identified, including seven amino acids (arginine, glycine, alanine, lysine, methionine, phenylalanine, tyrosine), two phosphatidylcholine (PC aa C34:2, PC aa C36:4), three complements (acetylcarnitine, propionylcarnitine, butyrylcarnitine), carnitine, glutamine, hypoxanthine, spermine, and spermidine. The pathway analysis implied a major role of amino metabolism in OAG pathophysiology and revealed the metabolic characteristics between different biological samples. In this review, we summarize existing metabolomic studies related to glaucoma biomarker identification and point out a series of metabolic disorders in OAG patients, providing information on the molecular mechanism changes in glaucoma. Additional studies are needed to validate existing findings, and future research will need to explore the potential overlap between different biological fluids.
JAMA network open · 2022
Developing interventions against age-related memory decline and for older adults experiencing neurodegenerative disease is one of the greatest challenges of our generation. Spermidine supplementation has shown beneficial effects on brain and cognitive health in animal models, and there has been preliminary evidence of memory improvement in individuals with subjective cognitive decline. To determine the effect of longer-term spermidine supplementation on memory performance and biomarkers in this at-risk group. This 12-month randomized, double-masked, placebo-controlled phase 2b trial (the SmartAge trial) was conducted between January 2017 and May 2020. The study was a monocenter trial carried out at an academic clinical research center in Germany. Eligible individuals were aged 60 to 90 years with subjective cognitive decline who were recruited from health care facilities as well as through advertisements in the general population. Data analysis was conducted between January and March 2021. One hundred participants were randomly assigned (1:1 ratio) to 12 months of dietary supplementation with either a spermidine-rich dietary supplement extracted from wheat germ (0.9 mg spermidine/d) or placebo (microcrystalline cellulose). Eighty-nine participants (89%) successfully completed the trial intervention. Primary outcome was change in memory performance from baseline to 12-month postintervention assessment (intention-to-treat analysis), operationalized by mnemonic discrimination performance assessed by the Mnemonic Similarity Task. Secondary outcomes included additional neuropsychological, behavioral, and physiological parameters. Safety was assessed in all participants and exploratory per-protocol, as well as subgroup, analyses were performed. A total of 100 participants (51 in the spermidine group and 49 in the placebo group) were included in the analysis (mean [SD] age, 69 [5] years; 49 female participants [49%]). Over 12 months, no significant changes were observed in mnemonic discrimination performance (between-group difference, -0.03; 95% CI, -0.11 to 0.05; P = .47) and secondary outcomes. Exploratory analyses indicated possible beneficial effects of the intervention on inflammation and verbal memory. Adverse events were balanced between groups. In this randomized clinical trial, longer-term spermidine supplementation in participants with subjective cognitive decline did not modify memory and biomarkers compared with placebo. Exploratory analyses indicated possible beneficial effects on verbal memory and inflammation that need to be validated in future studies at higher dosage. ClinicalTrials.gov Identifier: NCT03094546.
Food & function · 2023
Cinnamon is a spice obtained from the bark of Cinnamomum and contains anti-inflammatory ingredients such as coumarin, cinnamaldehyde, and cinnamic acid. This study evaluated the effect of cinnamon water extract (CWE) on the symptoms of subjects with diarrhea in an 8-week randomized controlled trial. Seventy subjects with diarrhea symptoms were randomized and received three capsules of 400 mg CWE or placebo twice daily for 8 weeks. CWE intake significantly increased colonic transit time (p = 0.019) and fecal isobutyric acid (p = 0.008) and spermidine (p = 0.009) contents compared to placebo intake. In contrast, CWE decreased fecal indole (p = 0.032) and agmatine (p = 0.018) contents. Gut microbiota analysis showed increased alpha diversity and significant changes in strains such as Bifidobacterium longum ATCC 55813 (LDA = 1.38) in the CWE group compared with the placebo group. Bifidobacterium longum ATCC 55813 showed a positive correlation with colon transit time and stool phenol and spermidine contents. CWE improved diarrhea symptoms and changed the composition of stools and the gut microbiota. These results indicate that cinnamon intake relieves diarrhea symptoms through metabolic changes due to changes in intestinal microbial groups.
The American journal of clinical nutrition · 2023
Periodic prolonged fasting (PF) extends lifespan in model organisms and ameliorates multiple disease states both clinically and experimentally owing, in part, to its ability to modulate the immune system. However, the relationship between metabolic factors, immunity, and longevity during PF remains poorly characterized especially in humans. This study aimed to observe the effects of PF in human subjects on the clinical and experimental markers of metabolic and immune health and uncover underlying plasma-borne factors that may be responsible for these effects. In this rigorously controlled pilot study (ClinicalTrial.gov identifier, NCT03487679), 20 young males and females participated in a 3-d study protocol including assessments of 4 distinct metabolic states: 1) overnight fasted baseline state, 2) 2-h postprandial fed state, 3) 36-h fasted state, and 4) final 2-h postprandial re-fed state 12 h after the 36-h fasting period. Clinical and experimental markers of immune and metabolic health were assessed for each state along with comprehensive metabolomic profiling of participant plasma. Bioactive metabolites identified to be upregulated in circulation after 36 h of fasting were then assessed for their ability to mimic the effects of fasting in isolated human macrophage as well as the ability to extend lifespan in Caenorhabditis elegans. We showed that PF robustly altered the plasma metabolome and conferred beneficial immunomodulatory effects on human macrophages. We also identified 4 bioactive metabolites that were upregulated during PF (spermidine, 1-methylnicotinamide, palmitoylethanolamide, and oleoylethanolamide) that could replicate these immunomodulatory effects. Furthermore, we found that these metabolites and their combination significantly extended the median lifespan of C. elegans by as much as 96%. The results of this study reveal multiple functionalities and immunological pathways affected by PF in humans, identify candidates for the development of fasting mimetic compounds, and uncover targets for investigation in longevity research.
Nutrients · 2023
(1) Background: Spermidine is a biogenic polyamine that plays a crucial role in mammalian metabolism. As spermidine levels decline with age, spermidine supplementation is suggested to prevent or delay age-related diseases. However, valid pharmacokinetic data regarding spermidine remains lacking. Therefore, for the first time, the present study investigated the pharmacokinetics of oral spermidine supplementation. (2) Methods: This study was designed as a randomized, placebo-controlled, triple-blinded, two-armed crossover trial with two 5-day intervention phases separated by a washout phase of 9 days. In 12 healthy volunteers, 15 mg/d of spermidine was administered orally, and blood and saliva samples were taken. Spermidine, spermine, and putrescine were quantified by liquid chromatography-mass spectrometry (LC-MS/MS). The plasma metabolome was investigated using nuclear magnetic resonance (NMR) metabolomics. (3) Results: Compared with a placebo, spermidine supplementation significantly increased spermine levels in the plasma, but it did not affect spermidine or putrescine levels. No effect on salivary polyamine concentrations was observed. (4) Conclusions: This study's results suggest that dietary spermidine is presystemically converted into spermine, which then enters systemic circulation. Presumably, the in vitro and clinical effects of spermidine are at least in part attributable to its metabolite, spermine. It is rather unlikely that spermidine supplements with doses <15 mg/d exert any short-term effects.