Search Results (545)

Gamma-aminobutyric acid (GABA) is a bioactive, non-protein amino acid recognized for its role as an inhibitory neurotransmitter in the human central nervous system. Increasing interest in functional foods has increased attention on GABA due to its potential health benefits, including antihypertensive, anxiolytic, antidepressant, and neuroprotective effects. This review summarizes the natural dietary sources of GABA and explores advanced strategies for enriching dairy products, particularly yogurt and frozen yogurt (froyo), with GABA. Key microbial species capable of GABA biosynthesis via the glutamate decarboxylase (GAD) pathway are discussed, alongside enzymatic production techniques that support controlled GABA synthesis. A major focus of this review is the evaluation of various methods for incorporating GABA into dairy matrices, including direct GABA fortification and in situ fermentation using GABA-producing strains, with comparisons of yield, sensory attributes, and product stability. Physicochemical analyses and sensory evaluations are presented as essential tools for assessing product performance. Furthermore, the review outlines the therapeutic effects of GABA-fortified foods and their potential roles in managing hypertension, stress, and neurodegenerative disorders. Key challenges, including strain-dependent variability in GABA-production, storage stability, and regulatory compliance are addressed, along with market and legislative considerations for GABA-fortified foods. Future perspectives include the development of novel high GABA-producing strains, process optimization to improve product stability and sensory acceptance, and expanded applications within the functional food sector. Overall, this review provides an integrated, up-to-date overview of technological, functional and regulatory aspects, offering a clear scientific foundation for the development and commercialization of GABA-fortified dairy products. Full article

The development of plant-based synbiotic beverages is gaining increasing attention as consumers seek sustainable, functional alternatives to dairy products. This preliminary study investigated the fortification of tibicos (water kefir) with lemon catnip (Nepeta cataria var. citriodora) hydrolate, an aromatic distillation byproduct rich in bioactive terpenoids. After 72 h-fermentation of tibicos, physicochemical, microbiological, health-promoting and sensory parameters were evaluated. Both control and fortified beverages exhibited typical fermentation kinetics, including a decrease in pH, reduction of soluble solids, and accumulation of organic acids. Lactic acid bacteria count remained stable, while yeast proliferation was slightly reduced in the hydrolate-fortified sample, consistent with the known yeast-sensitive nature of certain hydrolate-derived terpenoids. Importantly, hydrolate fortification significantly enhanced antioxidant capacity (DPPH: +34%; ABTS: +39%; RP: +38%). Enzyme-inhibitory activities also increased significantly in the hydrolate-fortified samples (α-Amylase and α-Glucosidase inhibition rates increased by 9% and 11%, respectively). ACE inhibition similarly increased from 32% to 44%, indicating an enhanced antihypertensive potential. HMG-CoA reductase inhibition increased from 31% to 42%, showing improved hypolipidemic activity. Sensory evaluation indicated improved sensory acceptability, imparting citrus–floral notes that balanced the acidic profile of tibicos. These findings highlight the potential of valorizing lemon catnip hydrolate as a functional fortifier in non-dairy synbiotic beverages. Full article

Background/Objectives: Although information and communication technology (ICT) offers opportunities to address challenges, evidence among frail populations is limited. We aimed to evaluate the effectiveness and feasibility of an ICT-based intervention incorporating an artificial intelligence (AI)-assisted smartphone dietary application and group communication tools to improve dietary quality and social connection among community-dwelling older adults with frailty. Methods: A non-randomized, quasi-experimental study was conducted among 29 older adults (≥65 years) in Tokyo, Japan. Participants were assigned to the intervention (n = 11) or control (n = 18) group. The 3-month intervention included weekly photo uploads of meals via an AI-based dietary application providing automated image analysis and personalized feedback, supervised by registered dietitians, along with peer communication through a group chat. The primary outcome was dietary quality. The secondary outcomes included body weight, body mass index (BMI), skin carotenoid score, and loneliness. Results: The adjusted Japanese Food Guide Spinning Top Score at 3-month follow-up was 49.0 (standard error [SE] = 2.6) and 39.5 (SE = 2.0) in the intervention and control groups, respectively. The adjusted mean difference between groups was +9.5 (95% confidence interval: 2.3 to 16.7, p = 0.01). After using analysis of covariance for adjusting for respective baseline values, age, education status, and antihypertension drug use, no statistically significant between-group differences were observed at 3-month follow-up for any secondary outcomes. Conclusions: AI-based dietary intervention and peer communication effectively improved dietary quality among older adults, highlighting the potential of such an intervention to promote healthier eating habits in this population. Full article

Background: Hypertension and its complications are a major global health problem, and natural compounds with vasorelaxant effects are being investigated as potential antihypertensive agents. Objective: This study aimed to determine whether rosmarinic acid (RA) induces vasorelaxation in the rat thoracic aorta and to elucidate the underlying mechanisms. Methods: Isolated thoracic aortic rings, with or without endothelium, were precontracted with phenylephrine and subsequently exposed to cumulative concentrations of RA. The roles of endothelium-derived factors, potassium channels, and calcium signaling were evaluated using selective pharmacological inhibitors and activators. In addition, the involvement of the AMPK pathway, adenylate cyclase/cAMP pathway, PKC signaling, β-adrenergic receptors, muscarinic receptors, and angiotensin II in RA-induced vasorelaxation was investigated. Results: RA induced a concentration-dependent vasorelaxation in endothelium-intact thoracic aortic rings (p < 0.001; pD₂ = 7.67 ± 0.04). The vasorelaxant effect of RA was attenuated in endothelium-denuded vessels (pD2: 5.26 ± 0.18). The relaxation response was significantly attenuated by inhibitors of the PI3K/Akt/eNOS/NO/cGMP pathway and by blockers of BK_Ca, IK_Ca, and Kv potassium channels (p < 0.001). Furthermore, RA markedly inhibited both extracellular Ca²⁺ influx and intracellular Ca²⁺ release from the sarcoplasmic reticulum (p < 0.001). RA incubation also significantly reduced the contractions induced by angiotensin II (Ang II) and by the PKC activator PMA (p < 0.001). Other tested pathways had no significant influence on the vasorelaxant effect of RA (p > 0.05). Conclusions: These findings demonstrate that rosmarinic acid induces both endothelium-dependent and endothelium-independent vasorelaxation in the rat thoracic aorta through activation of the PI3K/Akt/eNOS/NO/cGMP pathway, opening of BK_Ca, IK_Ca, and Kv potassium channels, and suppression of Ca²⁺ mobilization. Additionally, inhibition of PKC- and angiotensin II-mediated vascular contraction contributes to RA-induced vasorelaxation. RA may therefore have therapeutic potential in the management of hypertension. Full article

Renin, a key aspartic protease central to the renin–angiotensin–aldosterone system (RAAS), remains a therapeutic target for hypertension despite the withdrawal of the only approved direct renin inhibitor, Aliskiren, due to unfavorable drug–drug interactions and safety concerns. Here, we report a computational protein design-driven evaluation of (S)-3-((3-(1H-imidazol-1-yl)propyl)amino)-2-(((S)-1-carboxy-2-(cyclooctanecarboxamido)ethyl)amino)-3-oxopropanoic acid (N-CDAH), a novel lipophilic cyclooctanoyl- derivative, as a next-generation renin inhibitor scaffold. This scaffold was designed based on the rationale of leveraging the carnosine like backbone while optimizing lipophilicity and metabolic stability. Pharmacokinetic, ADME, and toxicity predictions (SwissADME, pkCSM) revealed greater predicted aqueous solubility, enhanced metabolic stability, and significantly reduced off-target liabilities compared with Aliskiren (specifically, non-inhibition of major CYP isoforms). Molecular docking (AutoDock Vina binding affinity: −8.08 kcal/mol; Maestro Induced Fit Docking score: −11.149 kcal/mol) and molecular dynamics simulations confirmed favorable binding interactions, conformational adaptability, and complex stability within the renin active site. To contextualize its performance within the broader chemical space, the diastereomeric analog of N-CDAH as well as structurally related compounds identified through SwissSimilarity were also examined using computational workflow. The MD analysis (200 ns) demonstrated that the inhibitor is anchored via a dual stabilization mechanism: hydrophobic enclosure coupled with persistent ionic interactions. These integrative in silico results highlight the potential of this derivative to overcome Aliskiren’s pharmacological shortcomings, providing a strong computational rationale for experimental validation and underscoring the role of structure-based drug design in antihypertensive drug discovery. Full article

Pines are edifying woody species for forest habitats, having crucial importance for ecosystems in both cold (boreal or mountainous) and warm (Mediterranean and tropical) areas. Pine trees include about 120 species, many of which have had an important ornamental role. Despite their ecological importance, many pine forests are threatened by increasing deforestation and habitat degradation, leading to progressive declines in species distribution and genetic diversity worldwide. Humans have used pine wood since the Stone Age, gradually discovering their outstanding medical properties. This review synthesizes global knowledge on the medicinal potential of pines. Using a comprehensive literature survey of major international scientific databases, we evaluated documented traditional and modern medical applications across all regions where pines naturally occur. The vast majority (86) of pine species were described as having medicinal properties, and the uses of the main pine species in representative regions of all continents supporting forest vegetation were examined. Various organs or secretions (needles, branches, bark, buds, cones, seeds, pollen, roots, wood, sap, resin, pitch, etc.) have been used to prevent or treat numerous diseases or to strengthen the organism. Their reported therapeutic activities include antioxidant, antimutagenic, antitumor, antimicrobial, skin-protective, antinociceptive, anti-inflammatory, neuroprotective, antiallergenic, laxative, circulatory-enhancing, antihypertensive, anti-atherosclerotic, anti-aging, and antithrombotic effects. Given the remarkable phytochemical diversity and broad pharmacological value of these species, the conservation of pine genetic resources and natural habitats is urgent. Protecting these species is essential not only for maintaining ecosystem resilience but also for preserving their substantial pharmaceutical and industrial potential. Full article

Background/objective: Online platforms for sharing prescription drug experiences are becoming increasingly available, yet their validity as measures of patient satisfaction remains unclear. This study aimed to evaluate the potential of an online drug review system, WePharm, as a proxy for treatment satisfaction among older adults taking antihypertensive medications. Methods: A cross-sectional survey using a convenience sample was conducted from February to July 2018 among patients aged 50–80 years recruited from four senior welfare centers and one community pharmacy in Seoul. Participants completed both an online review via WePharm and a paper-based Treatment Satisfaction Questionnaire for Medication (TSQM). Satisfaction attributes included drug efficacy, side effects, convenience, affordability, and willingness to recommend. Pearson correlation coefficients and ANOVA were used to examine concordance and associated factors. Results: A total of 313 participants were included. Online review scores were significantly correlated with TSQM scores across all domains as follows: effectiveness (r = 0.451), side effects (r = 0.363), convenience (r = 0.285), and overall satisfaction (r = 0.256), all p < 0.0001. Key factors associated with satisfaction included region, stage of hypertension, income, duration of antihypertensive use, and comorbidity count. Conclusions: Online patient medication reviews, as implemented in WePharm, demonstrated moderate correlation with validated treatment satisfaction measures. These findings support the potential utility of online drug review systems as complementary tools for capturing real-world patient experience and informing shared decision-making in clinical practice, and as these findings were from a convenience sample, further research is expected with the aim of improving generalizability. Full article

Pulmonary arterial hypertension (PAH) is a devastating cardiovascular disorder caused by right heart failure leading to premature death. The TGFBR2 and BMPR-II receptors, which are members of the TGF-β receptor family, are considered promising targets for developing novel drugs in PAH. Lupeol and ψ-taraxasterol, naturally occurring triterpene molecules with proven anti-inflammatory, anti-cancer, and cardioprotective activities, hold considerable potential in the treatment of PAH. Hence, the present study aimed to evaluate the impacts of lupeol and ψ-taraxasterol isolated from Cirsium sintenisii Freyn on the TGF-β and BMP pathways, aiming to determine their therapeutic values in PAH. The effects of the compounds were extensively investigated using both in silico and wet lab experiments, including reporter assays, RT-PCR/QPCR, Western blots, and cell proliferations assays. Both lupeol and ψ-taraxasterol demonstrated interactions with the majority of components of these signaling pathways, including the TGFBR2 and BMPR-II receptors, suggesting that both compounds were capable of modulating the BMP and TGF-β pathways. Data derived from reporter assays, RT-PCR/QPCR, and Western blots demonstrated that lupeol and ψ-taraxasterol inhibited the TGF-β signaling pathway by reducing the phosphorylation of the SMAD3 protein and the expression of pai-1 transcripts. Additionally, ψ-taraxasterol enhanced BMP signaling via regulating the phosphorylation of SMAD1/5 proteins and upregulated the expression of id-1 transcripts. Finally, lupeol and ψ-taraxasterol inhibited abnormal proliferation of mutant-type (bmpr2^R899X+/-) PAMSCs stimulated with the TGF-β1 ligand with no discernible effects on wild-type cells. This is the first comprehensive report outlining the potential therapeutic effects of lupeol and ψ-taraxasterol in PAH, which may have immediate experimental and clinical applications not only in PAH but also other BMP- and TGF-β-associated disorders. Full article

Background/Objectives: Hyposalivation is a prevalent yet underrecognized factor contributing to oral health deterioration, often influenced by systemic disease, medication use, and recreational drug exposure. With rising use of mental health and cardiovascular medications, as well as increasing marijuana use among younger populations, there is a need to assess real-world data on xerostomia and hyposalivation prevalence and associated risk factors. This study aimed to evaluate the prevalence of hyposalivation and xerostomia, and its etiological associations among adult patients at the University of Nevada, Las Vegas (UNLV) School of Dental Medicine Clinics. Methods: A retrospective cohort study was conducted using electronic health record (EHR) data from 1600 randomly selected patients aged 30 years and older, treated between 1 January 2014, and 31 May 2023. Data on demographics, medical and social history, medication use, and oral health status were extracted. Hyposalivation was identified via chart review, and multivariate logistic regression was used to analyze associated risk factors. Results: Hyposalivation and xerostomia were identified in 705 patients (44.06%). Marijuana use was the strongest independent predictor across all age groups (RR = 3.10, p < 0.05). Among patients aged 30–35, use of antihypertensive (OR = 3.05, p < 0.05) and mental health medications (OR = 1.81, p < 0.05) were significantly associated with hyposalivation. A strong correlation was also found between hyposalivation and elevated caries risk (χ² = 205.99, p < 0.001). Conclusions: Hyposalivation and xerostomia are increasingly observed in younger adults, linked to pharmacological and behavioral factors. Full article

Background/Objectives: Marine-derived bioactive peptides have been reported to possess blood pressure-regulatory effects. However, most studies have focused on the antihypertensive effects after single-dose administration, and research on long-term administration and its protective effects against hypertension-induced tissue damage remains limited. Therefore, this study aimed to investigate the long-term antihypertensive efficacy of IGTGIPGIW, a bioactive peptide derived from Hippocampus abdominalis (H. abdominalis), and its protective effects on hypertension-related tissue damage. Methods: To evaluate the blood pressure-regulatory effects, spontaneously hypertensive rats (SHRs) were orally administered a high-dose (50 mg/kg) IGTGIPGIW peptide group (H-IGTGIPGIW) for 8 weeks. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were monitored weekly. Serum levels of angiotensin II (Ang II), angiotensin-converting enzyme (ACE), and angiotensin-converting enzyme 2 (ACE2) were measured to assess the peptide’s regulatory effects on the renin–angiotensin system. Histological analyses of the aorta and heart tissues were performed to evaluate the protective effects against hypertension-induced tissue damage. Results: After 8 weeks of treatment, H-IGTGIPGIW significantly reduced SBP, DBP, and MAP compared with SHRs. Serum Ang II and ACE levels were significantly decreased, while ACE2 levels were significantly increased. Histological analyses demonstrated that IGTGIPGIW alleviated aortic wall thickening and reduced renal and cardiac tissue damage in SHR. Conclusions: IGTGIPGIW, a bioactive peptide derived from H. abdominalis, effectively regulated blood pressure by modulating serum Ang II, ACE, and ACE2 levels. Moreover, it protected against hypertension-induced aortic, renal and cardiac tissue damage, suggesting its potential as a functional ingredient for managing hypertension. Full article

Hypertension, a leading factor for cardiovascular diseases (CVD), is a particularly heavy burden in women during middle age, when cardioprotective hormones begin to decline. The abnormal handling of calcium (Ca²⁺) in vascular smooth muscle cells (VSMCs) leads to increased vasoconstriction, remodeling, and altered arterial compliance during hypertension. The Spontaneously Hypertensive Rats (SHR) is a model of essential hypertension, and middle-aged females with hypertension represent a stage of disease where vascular dysfunction is prominent but understudied. Losartan, a widely prescribed angiotensin II (AngII) receptor (AT1R) blocker, exerts antihypertensive effects by affecting Ang II/Ca²⁺ signaling. However, whether it corrects the Ca²⁺ mishandling in the aorta of middle-aged female SHR has not been established. In this study, the thoracic aorta from 36-week-old female SHRs treated with losartan was assessed for Ca²⁺ mishandling using myography and biochemical assays. Meanwhile, biomechanical properties and stiffness were evaluated using Pulse Wave Velocity (PWV), Atomic Force Microscopy (AFM), and assessments of collagen and elastin contents. Compared with normotensive controls, SHR demonstrated disrupted Ca²⁺ handling, increased stiffness, and Extracellular Matrix (ECM) remodeling in middle-aged females. Treatment with losartan abrogated Ca²⁺ mishandling influx and efflux in the VSMC, decreased stiffness, and restored the aortic structural changes. These findings demonstrate that losartan abolishes Ca²⁺ mishandling and highlight a mechanistic role of AT1R blockade in restoring vascular function in the aorta of middle-aged females during hypertension. Full article

Zilebesiran represents an innovative antihypertensive therapy employing small interfering RNA (siRNA) to inhibit hepatic angiotensinogen, a key regulator of the renin–angiotensin–aldosterone system. By directly targeting the source of angiotensin II production, zilebesiran offers a novel mechanism distinct from conventional antihypertensive treatments. In the clinical studies KARDIA-1 and KARDIA-2, zilebesiran demonstrated clinically significant reductions in systolic blood pressure, with effects lasting up to 24 weeks after a single subcutaneous injection. In KARDIA-1, doses of 300 mg and 600 mg administered every 6 months resulted in reductions of over 15 mmHg in systolic blood pressure at 3 months compared with placebo. KARDIA-2 further showed an additional reduction of up to 12.1 mmHg at 3 months when zilebesiran was used as an adjunct to standard antihypertensive therapy. KARDIA-3 is currently evaluating the therapy in a larger global population to assess its impact on major cardiovascular outcomes. Zilebesiran has demonstrated a favorable safety profile with minimal adverse events, offering potential advantages for patients with resistant or uncontrolled hypertension and those at high cardiovascular risk, especially where adherence to daily oral medications is challenging. Beyond blood pressure reduction, zilebesiran may protect target organs, including the heart, kidneys, and retina. In conclusion, zilebesiran represents a promising siRNA-based therapy that may redefine the management of difficult-to-control hypertension, offering durable, targeted, and patient-friendly treatment with broad cardiovascular benefits. Future studies will clarify its long-term safety, efficacy across diverse populations, and integration into personalized hypertension management strategies. Full article

Natural deep eutectic solvents (NaDESs) have emerged as green and sustainable alternative solvents for extracting valuable bioactive compounds from agro-industrial by-products. NaDESs are stable, soluble, and biodegradable with low melting points and a wide range of applications. These characteristics align closely with the principles of green chemistry, making NaDESs promising for use in the food industry. Recent studies demonstrate that NaDESs can effectively extract proteins, polysaccharides, polyphenols, carotenoids, alkaloids, and other bioactives from sources such as vegetable waste, cereal by-products, and fruit pomace, often performing better than traditional solvents such as methanol and ethanol. The bioactive components of these extracts may exhibit antioxidant, anti-inflammatory, antihypertensive, anticancer, or antimicrobial activity and can be used as functional ingredients, nutraceuticals, or preservatives. Furthermore, NaDES-derived extracts have been shown to have hypoglycemic effects by inhibiting enzymes involved in the metabolism of carbohydrates and reducing oxidative stress. As a result, they may find use as functional food ingredients in diabetes management. This review presents the recent research on the extraction of bioactive compounds from agro-industrial by-products using NaDESs and an evaluation of their antidiabetic potential. Full article

Verjuice, a green grape juice traditionally produced from grapes obtained through thinning, represents a sustainable alternative for the utilization of viticulture by-products. No standardized methods of production are utilized to make verjuice, highlighting the need for further research. This study evaluated three extraction methods—pressing extraction (PE), steam extraction (SE), and centrifuge juicer extraction (CJE)—to produce verjuice from three Vitis labrusca varietals (Bordô, Concord, and White Niágara). Physicochemical parameters, volatile compounds (VOC), total polyphenol content, antioxidant and anti-hypertensive activities were analyzed. Extraction method and grape varietal influenced physicochemical composition, antioxidant capacity, and VOC. The SE method resulted in higher yields but lower polyphenolic content, while the CJE was more efficient in extracting phenolic compounds and preserving antioxidant properties. Higher concentrations of malic acid were observed in verjuice extracted by PE and CJE methods from Bordô and Concord grapes, while higher tartaric acid content was found in Bordô and Niágara grapes extracted by CJE. Within grapes, verjuices presented wider volatile profile than those described in the literature, and CJE and PE methods yielded higher amounts of VOC. Thus, V. labrusca presents great potential to produce verjuices and CJE shows to be an efficient alternative to the pressing method. Full article

Objective: To evaluate the efficacy and safety of osilodrostat in patients with Cushing’s disease (CD). Methods: A retrospective, multicenter, real-world study of patients with CD. The main efficacy endpoint was the proportion of patients who were complete responders (urinary free cortisol [UFC] < the upper limit of normal and/or with adrenal insufficiency development). Results: Thirty-seven CD patients were enrolled. There were 33 patients who initially received osilodrostat in monotherapy and 4 in combination. However, 3 patients of the monotherapy group were switched to combination therapy. The median duration of osilodrostat treatment was 5 months (range 1–93). All the patients were classified as responders: 33 (89.2%) had complete response and 4 partial response. A positive correlation was detected between the percentage of UFC decrease and the maximum (r = 0.481, p = 0.006) and the maintenance doses (r = 0.440, p = 0.011). The initial doses of osilodrostat were a predictor of complete response (vs. partial) (Odds ratio [OR] 2.82, p = 0.030). The median time to UFC normalization in the group of complete responders was 4 weeks (range 1–20) and UFC normalized before or at month 1 in 67% (n = 20/30) of the patients. Osilodrostat led to a significant decrease in systolic and diastolic blood pressure in parallel with a reduction of antihypertensive medications. Conclusions: Osilodrostat leads to a complete UFC normalization in up to 90% of the patients with CD, in parallel with an improvement in the cardiometabolic profile. A proper titration of osilodrostat is important to achieve a complete response since a positive correlation between the doses and the UFC reduction was observed. Full article