Extracts of tamarillo, horned melon, and raspberries, but not extract of pear, inhibit human blood platelet aggregation: Investigating the underlying factors for their differential mechanisms

Fruit extracts may be cardioprotective via favorable modulation of platelet-blood vessel interaction. We here show that sugar-free extracts of tamarillo, horned melon (kiwano), and raspberry in a dose-dependent manner inhibited ADP-induced platelet aggregation in platelet-rich plasma. In contrast, pear extract had no such effect. Furthermore, analysisof untargeted metabolites revealed the presence of platelet inhibitory components such as benzoic acid, caffeic acid, and gallic acid in the sugar-free extracts of tamarillo, raspberry, and kiwano, but not in pear extract. All these three fruit extracts inhibited the platelet production of TxB2 and the release of platelet factor 4. In conclusion, our work suggests that tamarillo, raspberry, and kiwano inhibit platelet aggregation partly due to the high levels of anti-platelet compounds such as benzoic, caffeic, and gallic acids

Maternal obesity and gut microbiota are associated with fetal brain development

Obesity in pregnancy induces metabolic syndrome, low-grade inflammation, altered endocrine factors, placental function, and the maternal gut microbiome. All these factors impact fetal growth and development, including brain development. The lipid metabolic transporters of the maternalfetal- placental unit are dysregulated in obesity. Consequently, the transport of essential long-chain PUFAs for fetal brain development is disturbed. The mother’s gut microbiota is vital in maintaining postnatal energy homeostasis and maternal-fetal immune competence. Obesity during pregnancy changes the gut microbiota, affecting fetal brain development. Obesity and a high-fat diet in pregnancy can induce placental and intrauterine inflammation and thus influence the neurodevelopmental outcomes of the offspring. Several epidemiological studies observed an association between maternal obesity and adverse neurodevelopment. This review discusses the effects of maternal obesity and gut microbiota on fetal neurodevelopment outcomes. In addition, the possible mechanisms of the impacts of obesity and gut microbiota on fetal brain development are discussed

Evaluation of the equivalence of different intakes of Fruitflow in affecting platelet aggregation and thrombin generation capacity in a randomized, double-blinded pilot study in male subjects

Background The water-soluble tomato extract, Fruitflow® is a dietary antiplatelet which can be used to lower platelet aggregability in primary preventative settings. We carried out a pilot study to investigate the range of intakes linked to efficacy and to make an initial assessment of variability in response to Fruitflow®. Methods Platelet response to adenosine diphosphate (ADP) agonist and thrombin generation capacity were monitored at baseline and 24 h after consuming 0, 30, 75, 150 or 300 mg of Fruitflow® in a randomized, double-blinded crossover study in male subjects 30–65 years of age (N = 12). Results were evaluated for equivalence to the standard 150 mg dose. Results Results showed that the changes from baseline aggregation and thrombin generation observed after the 75 mg, 150 mg, and 300 mg supplements were equivalent. Aggregation was reduced from baseline by − 12.9 ± 17.7%, − 12.0 ± 13.9% and − 17.7 ± 15.7% respectively, while thrombin generation capacity fell by − 8.6 ± 4.1%, − 9.2 ± 3.1% and − 11.3 ± 2.3% respectively. Effects observed for 0 mg and 30 mg supplements were non-equivalent to 150 mg and not different from baseline (aggregation changed by 3.0 ± 5.0% and − 0.7 ± 10.2% respectively, while thrombin generation changed by 0.8 ± 3.0% and 0.8 ± 3.1% respectively). Conclusions The data suggest that the efficacious range for Fruitflow® lies between 75 mg and 300 mg, depending on the individual. It may be pertinent to personalize the daily intake of Fruitflow® depending on individual platelet response. Trial registration ISRCTN53447583, 24/02/2021

Bioactives and their roles in bone metabolism of osteoarthritis: evidence and mechanisms on gut-bone axis

Bioactives significantly modify and maintain human health. Available data suggest that Bioactives might play a beneficial role in chronic inflammatory diseases. Although promised, defining their mechanisms and opting to weigh their benefits and limitations is imperative. Detailed mechanisms by which critical Bioactives, including probiotics and prebiotics such as dietary lipids (DHA, EPA, alpha LA), vitamin D, polysaccharides (fructooligosaccharide), polyphenols (curcumin, resveratrol, and capsaicin) potentially modulate inflammation and bone metabolism is limited. Certain dietary bioactive significantly impact the gut microbiota, immune system, and pain response via the gut-immune-bone axis. This narrative review highlights a recent update on mechanistic evidence that bioactive is demonstrated demonstrated to reduce osteoarthritis pathophysiology

Bioactive food components and their inhibitory actions in multiple platelet pathways

In addition to hemostasis and thrombosis, blood platelets are involved in various processes such as inflammation, infection, immunobiology, cancer metastasis, wound repair and angiogenesis. Platelets\u27 hemostatic and non-hemostatic functions are mediated by the expression of various membrane receptors and the release of proteins, ions and other mediators. Therefore, specific activities of platelets responsible for the non-hemostatic disease are to be inhibited while leaving the platelet\u27s hemostatic function unaffected. Platelets\u27 anti-aggregatory property has been used as a primary criterion for antiplatelet drugs/bioactives; however, their non-hemostatic activities are not well known. This review describes the hemostatic and non-hemostatic function of human blood platelets and the modulatory effects of bioactive food components. PRACTICAL APPLICATIONS: In this review, we have discussed the antiplatelet effects of several food components. These bioactive compounds inhibit both hemostatic and non-hemostatic pathways involving blood platelet. Platelets have emerged as critical biological factors of normal and pathologic vascular healing and other diseases such as cancers and inflammatory and immune disorders. The challenge for therapeutic intervention in these disorders will be to find drugs and bioactive compounds that preferentially block specific sites implicated in emerging roles of platelets\u27 complicated contribution to inflammation, tumour growth, or other disorders while leaving at least some of their hemostatic function intact

Evaluation of the synergistic effects of curcumin-resveratrol co-loaded biogenic silica on colorectal cancer cells

Colorectal cancer (CRC) remains a significant global health concern, being the third most diagnosed cancer in men and the second most diagnosed cancer in women, with alarming mortality rates. Natural phytochemicals have gained prominence among various therapeutic avenues explored due to their diverse biological properties. Curcumin, extracted from turmeric, and resveratrol, a polyphenol found in several plants, have exhibited remarkable anticancer activities. However, their limited solubility and bioavailability hinder their therapeutic efficacy. To enhance the bioavailability of these compounds, nanomaterials work as effective carriers with biogenic silica (BS) attracting major attention owing to their exceptional biocompatibility and high specific surface area. In this study, we developed Curcumin-resveratrol-loaded BS (Cur-Res-BS) and investigated their effects on colorectal cancer cell lines (HCT-116 and Caco-2). Our results demonstrated significant concentration-dependent inhibition of cell viability in HCT-116 cells and revealed a complex interplay of crucial proto-onco or tumor suppressor genes, such as TP53, Bax, Wnt-1, and CTNNB1, which are commonly dysregulated in colorectal cancer. Notably, Cur-Res-BS exhibited a synergistic impact on key signaling pathways related to colorectal carcinogenesis. While these findings are promising, further investigations are essential to comprehensively understand the mechanisms and optimize the therapeutic strategy. Moreover, rigorous safety assessments and in vitro studies mimicking the in vivo environment are imperative before advancing to in vivo experiments, ensuring the potential of Cur-Res-BS as an efficient treatment for CRC

Mitochondrial dysfunction and its association with age-related disorders

Aging is a complex process that features a functional decline in many organelles. Various factors influence the aging process, such as chromosomal abnormalities, epigenetic changes, telomere shortening, oxidative stress, and mitochondrial dysfunction. Mitochondrial dysfunction significantly impacts aging because mitochondria regulate cellular energy, oxidative balance, and calcium levels. Mitochondrial integrity is maintained by mitophagy, which helps maintain cellular homeostasis, prevents ROS production, and protects against mtDNA damage. However, increased calcium uptake and oxidative stress can disrupt mitochondrial membrane potential and permeability, leading to the apoptotic cascade. This disruption causes increased production of free radicals, leading to oxidative modification and accumulation of mitochondrial DNA mutations, which contribute to cellular dysfunction and aging. Mitochondrial dysfunction, resulting from structural and functional changes, is linked to age-related degenerative diseases. This review focuses on mitochondrial dysfunction, its implications in aging and age-related disorders, and potential anti-aging strategies through targeting mitochondrial dysfunction

Applications of nanotechnologies for miRNA-based cancer therapeutics: current advances and future perspectives

MicroRNAs (miRNAs) are short (18–25 nt), non-coding, widely conserved RNA molecules responsible for regulating gene expression via sequence-specific post-transcriptional mechanisms. Since the human miRNA transcriptome regulates the expression of a number of tumor suppressors and oncogenes, its dysregulation is associated with the clinical onset of different types of cancer. Despite the fact that numerous therapeutic approaches have been designed in recent years to treat cancer, the complexity of the disease manifested by each patient has prevented the development of a highly effective disease management strategy. However, over the past decade, artificial miRNAs (i.e., anti-miRNAs and miRNA mimics) have shown promising results against various cancer types; nevertheless, their targeted delivery could be challenging. Notably, numerous reports have shown that nanotechnology-based delivery of miRNAs can greatly contribute to hindering cancer initiation and development processes, representing an innovative disease-modifying strategy against cancer. Hence, in this review, we evaluate recently developed nanotechnology-based miRNA drug delivery systems for cancer therapeutics and discuss the potential challenges and future directions, such as the promising use of plant-made nanoparticles, phytochemical-mediated modulation of miRNAs, and nanozymes

Supplementation of a western diet with golden kiwifruits (Actinidia chinensis var.'Hort 16A':) effects on biomarkers of oxidation damage and antioxidant protection

<p>Abstract</p> <p>Background</p> <p>The health positive effects of diets high in fruits and vegetables are generally not replicated in supplementation trials with isolated antioxidants and vitamins, and as a consequence the emphasis of chronic disease prevention has shifted to whole foods and whole food products.</p> <p>Methods</p> <p>We carried out a human intervention trial with the golden kiwifruit, Actinidia chinensis, measuring markers of antioxidant status, DNA stability, plasma lipids, and platelet aggregation. Our hypothesis was that supplementation of a normal diet with kiwifruits would have an effect on biomarkers of oxidative status. Healthy volunteers supplemented a normal diet with either one or two golden kiwifruits per day in a cross-over study lasting 2 × 4 weeks. Plasma levels of vitamin C, and carotenoids, and the ferric reducing activity of plasma (FRAP) were measured. Malondialdehyde was assessed as a biomarker of lipid oxidation. Effects on DNA damage in circulating lymphocytes were estimated using the comet assay with enzyme modification to measure specific lesions; another modification allowed estimation of DNA repair.</p> <p>Results</p> <p>Plasma vitamin C increased after supplementation as did resistance towards H₂O₂-induced DNA damage. Purine oxidation in lymphocyte DNA decreased significantly after one kiwifruit per day, pyrimidine oxidation decreased after two fruits per day. Neither DNA base excision nor nucleotide excision repair was influenced by kiwifruit consumption. Malondialdehyde was not affected, but plasma triglycerides decreased. Whole blood platelet aggregation was decreased by kiwifruit supplementation.</p> <p>Conclusion</p> <p>Golden kiwifruit consumption strengthens resistance towards endogenous oxidative damage.</p