-
Aging Cell May 2024Senescence is a heterogenous and dynamic process in which various cell types undergo cell-cycle arrest due to cellular stressors. While senescence has been implicated in... (Review)
Review
Senescence is a heterogenous and dynamic process in which various cell types undergo cell-cycle arrest due to cellular stressors. While senescence has been implicated in aging and many human pathologies, therapeutic interventions remain inadequate due to the absence of a comprehensive set of biomarkers in a context-dependent manner. Polyphenols have been investigated as senotherapeutics in both preclinical and clinical settings. However, their use is hindered by limited stability, toxicity, modest bioavailability, and often inadequate concentration at target sites. To address these limitations, nanocarriers such as polymer nanoparticles and lipid vesicles can be utilized to enhance the efficacy of senolytic polyphenols. Focusing on widely studied senolytic agents-specifically fisetin, quercetin, and resveratrol-we provide concise summaries of their physical and chemical properties, along with an overview of preclinical and clinical findings. We also highlight common signaling pathways and potential toxicities associated with these agents. Addressing challenges linked to nanocarriers, we present examples of senotherapeutic delivery to various cell types, both with and without nanocarriers. Finally, continued research and development of senolytic agents and nanocarriers are encouraged to reduce the undesirable effects of senescence on different cell types and organs. This review underscores the need for establishing reliable sets of senescence biomarkers that could assist in evaluating the effectiveness of current and future senotherapeutic candidates and nanocarriers.
Topics: Humans; Polyphenols; Nanoparticles; Senotherapeutics; Drug Carriers; Animals; Cellular Senescence; Quercetin
PubMed: 38685568
DOI: 10.1111/acel.14178 -
International Journal of Molecular... Jul 2023Estrogen deficiency is a major cause of loss of postmenopausal bone mineral density (BMD). This study aimed to evaluate the effects of equol and resveratrol on bone... (Randomized Controlled Trial)
Randomized Controlled Trial
Estrogen deficiency is a major cause of loss of postmenopausal bone mineral density (BMD). This study aimed to evaluate the effects of equol and resveratrol on bone turnover biomarkers in postmenopausal women. Sixty healthy postmenopausal women were randomly assigned to receive 200 mg fermented soy containing 10 mg equol and 25 mg resveratrol or a placebo for 12 months. Whole-body BMD and bone turnover biomarkers, such as deoxypyridinoline (DPD), tartrate-resistant acid phosphatase 5b (TRACP-5b), osteocalcin, and bone-specific alkaline phosphatase (BAP), were measured at baseline and after 12 months of treatment. At the end of treatment, DPD, osteocalcin, and BAP significantly improved in the active group ( < 0.0001 for all) compared to the placebo group. Conversely, TRACP-5b levels were unaffected by supplementation ( = 0.051). Statistically significant changes in the concentrations of DPD ( < 0.0001), osteocalcin ( = 0.0001), and BAP ( < 0.0001) compared to baseline were also identified. Overall, the intervention significantly increased BMD measured in the whole body ( = 0.0220) compared with the placebo. These data indicate that the combination of equol and resveratrol may positively modulate bone turnover biomarkers and BMD, representing a potential approach to prevent age-related bone loss in postmenopausal women.
Topics: Humans; Female; Postmenopause; Equol; Resveratrol; Tartrate-Resistant Acid Phosphatase; Osteocalcin; Bone Density; Alkaline Phosphatase; Biomarkers; Bone Remodeling; Osteoporosis, Postmenopausal
PubMed: 37569440
DOI: 10.3390/ijms241512063 -
Molecules (Basel, Switzerland) Jul 2023Matrix metalloproteinases (MMPs) are zinc-dependent metalloproteinases that play important roles in a variety of diseases, including cancer, cardiovascular disease,... (Review)
Review
Matrix metalloproteinases (MMPs) are zinc-dependent metalloproteinases that play important roles in a variety of diseases, including cancer, cardiovascular disease, diabetes, obesity, and brain diseases. Dietary polyphenols are thought to have a variety of beneficial effects on these diseases characterized by inflammation. Clinical studies have demonstrated that MMPs are in most cases upregulated in various inflammatory diseases, including osteoarthritis, rheumatoid arthritis, inflammatory bowel disease, and Alzheimer's disease. Studies using patient-derived human samples, animal studies, and cellular experiments have suggested that polyphenols may be beneficial against inflammatory diseases by suppressing MMP gene expression and enzyme activity. One important mechanism by which polyphenols exert their activity is the downregulation of reactive oxygen species that promote MMP expression. Another important mechanism is the direct binding of polyphenols to MMPs and their inhibition of enzyme activity. Molecular docking analyses have provided a structural basis for the interaction between polyphenols and MMPs and will help to explore new polyphenol-based drugs with anti-inflammatory properties.
Topics: Animals; Humans; Molecular Docking Simulation; Polyphenols; Antioxidants; Anti-Inflammatory Agents; Matrix Metalloproteinases
PubMed: 37513300
DOI: 10.3390/molecules28145426 -
The American Journal of Clinical... Jul 2023Although increasing evidence suggests that polyphenol helps regulate blood pressure (BP), evidence from large-scale and long-term population-based studies is still...
BACKGROUND
Although increasing evidence suggests that polyphenol helps regulate blood pressure (BP), evidence from large-scale and long-term population-based studies is still lacking.
OBJECTIVES
This study aimed to investigate the association between dietary polyphenol and hypertension risk in the China Health and Nutrition Survey (N = 11,056).
METHODS
Food intake was assessed using 3-d, 24-h dietary recalls and household weighing method; polyphenol intake was calculated by multiplying consumption of each food and its polyphenol content. Hypertension was defined as BP ≥ 140/90 mmHg, physicians' diagnosis, or taking antihypertension medications. HR and 95% CI were estimated using mixed-effects Cox models.
RESULTS
During 91,561 person-years of follow-up, a total of 3866 participants developed hypertension (35%). The lowest multivariable-adjusted HR (95% CI) of hypertension risk occurred in the third quartile intake, which was 0.63 (0.57, 0.70) for total polyphenol, 0.61 (0.55, 0.68) for flavonoid, 0.62 (0.56, 0.69) for phenolic acid, 0.46 (0.42, 0.51) for lignan, and 0.58 (0.52, 0.64) for stilbene, compared with the lowest quartile. The polyphenol-hypertension associations were nonlinear (all P < 0.001), and different patterns were observed. U-shaped relations with hypertension were observed for total polyphenol, flavonoid, and phenolic acid, whereas L-shaped associations were observed for lignan and stilbene. Moreover, higher fiber intake strengthened the polyphenol-hypertension association, especially for lignan (P-interaction = 0.002) and stilbene (P-interaction = 0.004). Polyphenol-containing food, particularly vegetables and fruits rich in lignan and stilbene, were significantly associated with lower hypertension risk.
CONCLUSIONS
This study demonstrated an inverse and nonlinear association between dietary polyphenol, especially lignan and stilbene, and hypertension risk. The findings provide implications for hypertension prevention.
Topics: Humans; Polyphenols; Cohort Studies; Diet; Flavonoids; Hypertension; Eating; Lignans; China
PubMed: 37146758
DOI: 10.1016/j.ajcnut.2023.05.001 -
Nutricion Hospitalaria Nov 2023The microbes that reside in our human body make up our microbiota, and their genes are known as the microbiome. The gut microbiota is involved in a wide variety of...
The microbes that reside in our human body make up our microbiota, and their genes are known as the microbiome. The gut microbiota is involved in a wide variety of functions. At present there is considerable evidence indicating that in the last 60 years there has been an important change in the composition of our microbiota. Dietary changes have been shown to have important effects on the microbiota in a very short space of time. The Mediterranean diet pattern causes changes in the microbiota towards a healthier profile. The changes induced by the Mediterranean diet could be explained, to a large extent, by its richness in polyphenols.
Topics: Humans; Microbiota; Gastrointestinal Microbiome; Diet, Mediterranean; Nutritional Status; Polyphenols; Diet
PubMed: 37929905
DOI: 10.20960/nh.04946 -
Drug Delivery Dec 2023Resveratrol is a polyphenol with diverse pharmacological activities, but its clinical efficacy is limited due to low solubility/permeability, light-induced... (Review)
Review
Resveratrol is a polyphenol with diverse pharmacological activities, but its clinical efficacy is limited due to low solubility/permeability, light-induced isomerization, auto-oxidation, and rapid metabolism. Nanodelivery systems, such as liposomes, polymeric nanoparticles, lipid nanocarriers, micelles, nanocrystals, inorganic nanoparticles, nanoemulsions, protein-based nanoparticles, exosomes, macrophages, and red blood cells (RBCs) have shown great potential for improving the solubility, biocompatibility, and therapeutic efficacy of resveratrol. This review comprehensively summarizes the recent advances in resveratrol nanoencapsulation and describes potential strategies to improve the pharmacokinetics of existing nanoformulations, enhance targeting, reduce toxicity, and increase drug release and encapsulation efficiency. The article also suggests that in order to avoid potential safety issues, resveratrol nanoformulations must be tested in a wide range of diseases.
Topics: Drug Carriers; Resveratrol; Liposomes; Nanoparticle Drug Delivery System; Nanotechnology
PubMed: 36852655
DOI: 10.1080/10717544.2023.2174206 -
Frontiers in Immunology 2023Osteoporosis is a common metabolic disease in middle-aged and elderly people. It is characterized by a reduction in bone mass, compromised bone microstructure,... (Review)
Review
Osteoporosis is a common metabolic disease in middle-aged and elderly people. It is characterized by a reduction in bone mass, compromised bone microstructure, heightened bone fragility, and an increased susceptibility to fractures. The dynamic imbalance between osteoblast and osteoclast populations is a decisive factor in the occurrence of osteoporosis. With the increase in the elderly population in society, the incidence of osteoporosis, disability, and mortality have gradually increased. Polyphenols are a fascinating class of compounds that are found in both food and medicine and exhibit a variety of biological activities with significant health benefits. As a component of food, polyphenols not only provide color, flavor, and aroma but also act as potent antioxidants, protecting our cells from oxidative stress and reducing the risk of chronic disease. Moreover, these natural compounds exhibit anti-inflammatory properties, which aid in immune response regulation and potentially alleviate symptoms of diverse ailments. The gut microbiota can degrade polyphenols into more absorbable metabolites, thereby increasing their bioavailability. Polyphenols can also shape the gut microbiota and increase its abundance. Therefore, studying the synergistic effect between gut microbiota and polyphenols may help in the treatment and prevention of osteoporosis. By delving into how gut microbiota can enhance the bioavailability of polyphenols and how polyphenols can shape the gut microbiota and increase its abundance, this review offers valuable information and references for the treatment and prevention of osteoporosis.
Topics: Middle Aged; Humans; Aged; Polyphenols; Gastrointestinal Microbiome; Antioxidants; Oxidative Stress; Osteoporosis
PubMed: 37936705
DOI: 10.3389/fimmu.2023.1285621 -
International Journal of Molecular... Nov 2023Given their potent antioxidant and biological properties [...].
Given their potent antioxidant and biological properties [...].
Topics: Humans; Polyphenols; Antioxidants
PubMed: 38069006
DOI: 10.3390/ijms242316683 -
Brain Research Bulletin Oct 2023Diabetic encephalopathy (DE) is a central nervous complication of diabetes mellitus which is characterized by cognitive impairment and neurochemical abnormalities....
Diabetic encephalopathy (DE) is a central nervous complication of diabetes mellitus which is characterized by cognitive impairment and neurochemical abnormalities. However, no effective approaches are available to prevent its progression and development. PDE4D serves many functions in the pathogenesis of neurodegenerative diseases involving PKA signaling. This study illustrated the role of PDE4D in DE and investigated whether resveratrol protected against DE via inhibiting PDE4D. db/db male mice and hippocampus cell line (HT22) were used to investigate the role of PDE4D and the protective effect of resveratrol on cognitive function under high glucose (HG). PDE4D overexpression or knockdown lentivirus and PKA specific inhibitor H89 were used to further identify the indispensable role of PDE4D/PKA signaling pathway in resveratrol's amelioration effect of neurotoxicity. Resveratrol attenuated cognitive impairment in db/db mice, reduced PDE4D protein, restored the impaired mitochondrial function in db/db mice. The in vitro study also confirmed the neuroprotective effect of resveratrol on neurotoxicity. PDE4D overexpression resulted in cell injury and downregulation of cAMP, PKA and pDrp1(Ser637) under normal condition. In contrast, PDE4D knockdown improved cell injury and elevated cAMP, PKA and pDrp1(Ser637) levels caused in HG-cultured HT22 cells. PDE4D over-expression blunted the improvement effects of resveratrol on PKA, pDrp1(Ser637) and mitochondrial function. Moreover, PKA inhibitor H89 blunted the inhibitory effects of resveratrol on pDrp1(Ser637) and mitochondrial function in HG-treated HT22. These data indicated that resveratrol may improve cognitive impairment in db/db mice by modulating mitochondrial function through the PDE4D dependent pathway.
Topics: Mice; Animals; Male; Resveratrol; Signal Transduction; Sulfonamides; Diabetes Mellitus
PubMed: 37722608
DOI: 10.1016/j.brainresbull.2023.110763 -
Yakugaku Zasshi : Journal of the... 2024Tannins are a group of polyphenols that possess the ability to precipitate proteins, causing an undesirable astringent taste by interacting with salivary peptides. This... (Review)
Review
Tannins are a group of polyphenols that possess the ability to precipitate proteins, causing an undesirable astringent taste by interacting with salivary peptides. This interaction deactivates the digestive enzymes; therefore, tannins are considered as plant defense substances. The health benefits of tannins and related polyphenols in foods and beverages have been demonstrated by biological and epidemiological studies; however, their metabolism in living plants and the chemical changes observed during processing of foods and medicinal herbs raises some questions. This review summarizes our studies concerning dynamic changes observed in tannins. Ellagitannins present in the young leaves of Camellia japonica and Quercus glauca undergo oxidative degradation as the leaves mature. Similar oxidative degradation is also observed in whiskey when it is kept for aging in oak barrels, and in decaying wood caused by fungi in natural forests. In contrast, ellagitannins have been observed to undergo reduction in the leaves of Carpinus, Castanopsis, and Triadica species as the leaves mature. This phenomenon of reductive metabolism in leaves enabled us to propose a new biosynthetic pathway for the most fundamental ellagitannin acyl groups, which was also supported by biomimetic synthetic studies. Polyphenols undergo dynamic changes during the process of food processing. Catechin in tea leaves undergo oxidation upon mechanical crushing to generate black tea polyphenols. Though detailed production mechanisms of catechin dimers have been elucidated, structures of thearubigins (TRs), which are complex mixtures of oligomers, remain ambiguous. Our recent studies suggested that catechin B-ring quinones couple with catechin A-rings during the process of oligomerization.
Topics: Tannins; Hydrolyzable Tannins; Catechin; Polyphenols; Tea; Oxidation-Reduction
PubMed: 38296496
DOI: 10.1248/yakushi.23-00170