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J Med Food [JOURNAL]

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Intermittent Versus Continuous Wild Blueberry Feeding Alters Inflammation and Behavior in Aged Male Rats.

Shukitt-Hale B, Fisher DR, Cahoon DS … +3 more , Miller MG, Carey AN, Zheng T

J Med Food · 2025 Jul · PMID 40295036 · Publisher ↗

Previous studies have shown that continuous daily consumption of polyphenolic-rich blueberries (BB) reduced neuroinflammation and improved age-related declines in motor and cognitive function in rodents and humans, but t... Previous studies have shown that continuous daily consumption of polyphenolic-rich blueberries (BB) reduced neuroinflammation and improved age-related declines in motor and cognitive function in rodents and humans, but the optimal intake of BBs is currently unknown. To evaluate the beneficial effects of BBs on neuroinflammation and motor and cognitive function relative to the frequency of consumption, the diets of aged F344 rats (18 months; = 15/group) were supplemented with either a continuous control diet, a continuous 2% wild BB diet, or an intermittent (3 days on, 4 days off) 2% wild BB diet for 2 months prior to behavioral testing. Because neuroinflammation has been identified as a major contributing factor to the behavioral declines seen in aging and neurodegenerative diseases, serum was collected pre-diet and at the end of the study to assess whether diet-induced changes in serum can alter the production of inflammatory stress signals in activated HAPI rat microglial cells . Serum from rats continuously and intermittently fed BBs had beneficial effects by reducing the expression of inflammatory enzymes cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in microglia, but only continuous feeding attenuated nitrite production. Intermittent BB-fed rats performed better on the rotarod and committed fewer errors in the radial arm water maze on Day 2 compared to control-fed animals. Based on these findings, BBs may not have to be consumed daily to elicit beneficial effects, possibly due to the retention of polyphenols and their metabolites in tissue and circulation.

The and Assessment of the Cytotoxic Effect of Daidzein Alone or in Combination with 5-Fluorouracil on Human Colorectal Adenocarcinoma Cell Line Caco-2.

Altinkaynak A, Kocak O, Tanyel Akcit E … +3 more , Simsek E, Yildirim K, Coban AY

J Med Food · 2025 Jul · PMID 40285466 · Publisher ↗

We aimed to evaluate the cytotoxic effect of daidzein alone and in combination with 5-fluorouracil (5-FU) on Caco-2 cells and investigate potential interactions between daidzein and 5-FU with apoptosis-related tumor necr... We aimed to evaluate the cytotoxic effect of daidzein alone and in combination with 5-fluorouracil (5-FU) on Caco-2 cells and investigate potential interactions between daidzein and 5-FU with apoptosis-related tumor necrosis factor-related apoptosis-inducing ligand receptor-2, tumor necrosis factor -alpha receptor-1 and Interferon gamma receptor-1. In this study, we used trypan blue and MTT assays to evaluate the cytotoxic effect of daidzein and the effect of daidzein on the amount of substance P released from the cells using the ELISA method. We utilized the ligand-protein molecular docking method for our assessments. According to our cytotoxicity experiment results, daidzein decreased the proliferation of Caco-2 cells. It should be pointed out that our ELISA test results daidzein and 5-FU increase the level of Substance-P (SP), a proinflammatory cytokine released by Caco-2 cells. Based on our results, daidzein interacted with all three apoptosis-related receptors on the membrane of Caco-2 cells to a better extent than 5-FU. In sum, although daidzein increases the amount of SP, it is a compound that has significant cytotoxic effect on colon cancer cells and promise as a potential therapeutic agent for the treatment of colon cancer.

The Curative Effects of Vitamins D3&K2 on the Expressions of p53, Bax, Bcl-2, and Oxidative Stress Induced by Methotrexate in ZFL Epithelial Cells.

Kaymak G

J Med Food · 2025 Jul · PMID 40274392 · Publisher ↗

Methotrexate (MTX), a folate antimetabolite, is a cytotoxic drug known to cause cytotoxicity associated with free oxygen radicals. This study investigated the effect of vitamins D3 and K2 on MTX-induced liver cell injury... Methotrexate (MTX), a folate antimetabolite, is a cytotoxic drug known to cause cytotoxicity associated with free oxygen radicals. This study investigated the effect of vitamins D3 and K2 on MTX-induced liver cell injury using the zebrafish liver cell line (CRL-2643). Observed effects, levels of antioxidant enzymes, lipid peroxidation marker, and total antioxidant/oxidant status were evaluated by spectrophotometric methods. The mRNA expressions of p53, Bax, and Bcl-2 were measured using RT-PCR. In addition, acridine orange/ethidium bromide staining was performed to analyze the apoptosis status of the cells. The IC value of MTX at 48 h was calculated as 442 g/mL with an MTT assay. The doses of D3&K2 are determined based on the recommended dose to be taken daily. As a result, this study suggests that MTX treatment induced oxidative damage on the liver cell, as assessed by increased reactive oxygen levels, lipid peroxidation, and decreased glutathione levels. In addition, while MTX increased the expression of the p53 and proapoptotic marker Bax, it decreased the expression of the anti-apoptotic factor Bcl-2. In conclusion, D3&K2 treatment protects against MTX-induced liver cell toxicity. It is thought that they can be used as a potential agent in clinical applications with MTX in treatment.

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Joo Y, Lee H, Jeong H … +7 more , Suh C, Hong H, Kim Y, Yu S, Lee C, Shim Y, Yoon S

J Med Food · 2025 Jul · PMID 40272820 · Publisher ↗

Given the increasing interest in the potential cognitive benefits of green tea, this study evaluated the efficacy of processed green tea products as nootropic agents. We conducted a 12-week, randomized, double-blinded, p... Given the increasing interest in the potential cognitive benefits of green tea, this study evaluated the efficacy of processed green tea products as nootropic agents. We conducted a 12-week, randomized, double-blinded, placebo-controlled trial to assess the effects of heat-treated green tea extract (HT-GTE) supplementation on memory performance in individuals with subjective memory impairment (SMI). A total of 80 participants with SMI (mean age 49.6 ± 5.6 years) were randomly assigned to either the HT-GTE group ( = 40) or the placebo group ( = 40). Memory performance was assessed using standardized composite scores at baseline and week 12. Additionally, we examined changes in functional connectivity (FC) within the default mode network (DMN), a key resting-state network associated with memory function, at both time points. Compared to the placebo group, the HT-GTE group demonstrated significant improvements in memory function after 12 weeks, as evidenced by a greater increase in composite scores ( = 2.535, for interaction = .011). Furthermore, the HT-GTE group exhibited increased FC within the right precuneus region of the DMN ( = 2.554, for interaction = .011). These findings underscore the potential of HT-GTE supplementation to enhance memory performance and FC within the DMN in middle-aged individuals with SMI, offering valuable insights into the cognitive benefits of green tea.

Bioactive Properties of Murici () and Bacuri () and Their Antioxidant and Anti-Inflammatory Effects in Rats.

Martinez RM, Cintra AC, Almeida CORP … +11 more , Lima TPB, Moraes de Souza I, de Almeida MAP, Frankenfeld SP, Cahuê FLC, de Queiroz Pereira Lopes G, Pinto VS, Silva AR, Gonçalves-de-Albuquerque CF, Dolisnky M, Teodoro AJ

J Med Food · 2025 May · PMID 40272785 · Publisher ↗

Fruit consumption favors energy balance, ensures essential nutrients, and provides bioactive compounds with antioxidant and anti-inflammatory activities capable of preventing and treating noncommunicable diseases. Tremen... Fruit consumption favors energy balance, ensures essential nutrients, and provides bioactive compounds with antioxidant and anti-inflammatory activities capable of preventing and treating noncommunicable diseases. Tremendous Brazilian biodiversity favors countless fruit and vegetable crops, including exotic fruits. This study aimed to describe the nutritional characteristics of murici and bacuri and their effects on oxidative stress and inflammation. The murici lyophilized extract (MLE) and bacuri lyophilized extract (BLE) were evaluated for their antioxidant activity and total phenolic compounds content. Healthy female Wistar rats were divided into control and supplemented groups (50, 100, and 250 mg/kg body weight) for each fruit, with a 14-day supplementation. Parameters of oxidative damage and antioxidant system in plasma and inflammatory biomarkers in the kidney and liver tissues were evaluated. Murici has carotenoids as the main bioactive compound, whereas bacuri is a source of polyphenols, with relevant antioxidant activity for human health. Treatment with MLE in healthy rats resulted in increased plasma antioxidant capacity measured by DPPH assay, reduced plasma levels of lipid peroxidation (TBARS) and carbonylated proteins, and lower TNF-α production in the kidney and liver. BLE supplementation reduced plasma lipid peroxidation levels and led to lower activity of IL-1 β, IL-6, and TNF-α in supplemented animals' kidneys. Both fruits showed positive antioxidant and anti-inflammatory effects against oxidative stress and inflammation in an model. The results point to new antioxidant and anti-inflammatory resources to be studied.

Anti-Inflammatory Effects of Extracts Through Inhibition of Nuclear Factor-κB and Mitogen-Activated Protein Kinase Pathways.

Oh SJ, Jang YS, Kim ER … +8 more , Kim JI, Kim H, Kim Y, Park CW, Jang HS, Tran TB, Nguyen TT, Hong IK

J Med Food · 2025 May · PMID 40256789 · Publisher ↗

Inflammation is a crucial response to harmful stimuli, but its chronic activation contributes to various diseases, including inflammatory bowel disease, osteoarthritis, and neurological disorders. While nonsteroidal anti... Inflammation is a crucial response to harmful stimuli, but its chronic activation contributes to various diseases, including inflammatory bowel disease, osteoarthritis, and neurological disorders. While nonsteroidal anti-inflammatory drugs are widely used as anti-inflammation drugs, their extended usage often results in severe side effects, emphasizing the need for safer alternatives. Therefore, it is of the greatest importance to identify and discover new anti-inflammatory agents that exhibit a reduced incidence of adverse side effects. This study investigates the anti-inflammatory potential of methanol extracts from eight native Vietnamese plant species. These extracts were screened for their ability to inhibit nitric oxide production and pro-inflammatory cytokine expression in lipopolysaccharides-stimulated RAW264.7 macrophages. Among the tested extracts, those derived from (Pierre) Chaowasku and (Lour.) Merr. demonstrated notable reductions in NO, TNF-α, interleukin (IL)-1β, and IL-6 levels. Further analysis revealed that these extracts are abundant in polyphenols and flavonoids, compounds recognized for their anti-inflammatory effects. Furthermore, these extracts exerted their effects by inhibiting the kappa-light-chain-enhancer of activated B cells and mitogen-activated protein kinase signaling pathways, as evidenced by reduced phosphorylation of the proteins. These results suggest that the methanol extracts obtained from and possess considerable potential in paving the way towards the innovative development of new therapeutic approaches aimed at alleviating chronic inflammation.

Fermented Strawberry ( Duch.) Mitigates Renal Fibrosis in a Unilateral Ureteral Obstruction Model by Reducing Inflammation, Oxidative Stress, and Regulating Smad Signaling.

Chang CC, Kao ES, Lee YC … +1 more , Lee HJ

J Med Food · 2025 May · PMID 40250990 · Publisher ↗

Renal fibrosis is a common outcome in many progressive renal diseases. Unilateral ureteral obstruction (UUO) is known to induce oxidative stress and inflammation in the kidneys, leading to the development of renal fibros... Renal fibrosis is a common outcome in many progressive renal diseases. Unilateral ureteral obstruction (UUO) is known to induce oxidative stress and inflammation in the kidneys, leading to the development of renal fibrosis. Fermented strawberry () possesses antioxidant properties; however, its effect on renal fibrosis remains unclear. This study aimed to evaluate the impact of fermented strawberry dry powder (FSP) on renal fibrosis by assessing proinflammatory cytokines, oxidative stress markers, and underlying mechanisms. Male Sprague-Dawley rats were subjected to UUO surgery to induce tubulointerstitial fibrosis and obstructive nephropathy. Ten days postsurgery, the rats were randomly divided into four groups ( = 6), including a sham-operated control group. FSP was administered orally at doses of 0.05 or 0.5 g kg body weight daily for 21 days. FSP treatment significantly improved renal function, reduced tubular dilation, and decreased interstitial volume in UUO rats. FSP decreased levels of tumor necrosis factor-α and interleukin-6, while enhancing the activities of antioxidant enzymes such as superoxide dismutase and catalase. Treatment with 0.05 and 0.5 g kg FSP resulted in a reduction of collagen deposition in the kidneys by 49% and 69%, respectively, compared with UUO group. FSP increased E-cadherin expression and decreased α-smooth muscle actin level in the kidneys of UUO rats. Furthermore, FSP reduced transforming growth factor-β and Smad2/3 levels while upregulating Smad7 expression. These findings suggest that FSP mitigates renal tubulointerstitial fibrosis, likely through modulation of Smad signaling and attenuation of oxidative stress and inflammation.

Application of Metabolomics and Microbiome Analysis for Revealing the Endogenous Mechanism of Baizhu Xiaozhong San in Postpartum Rats with Spleen-qi Deficiency.

Cao D, Chen J, Zhang Y … +6 more , Rui H, Guang K, Zhang L, Wu R, Nian S, Song X

J Med Food · 2025 Jun · PMID 40238668 · Publisher ↗

Postpartum women are in a state of physical weakness and suffering from fatigue. Metabolic disturbances in the postpartum period may lead to an increased prevalence of postpartum depression, hemorrhage, and obesity, unde... Postpartum women are in a state of physical weakness and suffering from fatigue. Metabolic disturbances in the postpartum period may lead to an increased prevalence of postpartum depression, hemorrhage, and obesity, underscoring the importance of prioritizing maternal health. The combination (Baizhu Xiaozhong San, BZXZS) of charred Koidz. (Baizhu, BZ) and charred Immaturus (Zhishi, ZS) has primary applications for invigorating the spleen and promoting diuresis. This study utilized serum/spleen metabolomics in conjunction with 16S rDNA sequencing analysis to investigate the endogenous metabolic alterations and intestinal homeostasis in postpartum rats exhibiting spleen-deficiency syndrome (SDS). The pathological symptoms of postpartum SDS rats in the administration groups were gradually restored, in particular, the symptoms of the BZXZS-H group rats improved significantly. As a result, 32 differential metabolites and 7 correlated metabolic pathways (impact value > 0.1) demonstrated the improvement effect of BZXZS on postpartum SDS rats mostly focusing on disorders of energy, carbohydrate, and lipid metabolism. 16S rDNA gene sequencing indicated that BZXZS had a significantly better regulatory effect on . The findings suggest that BZXZS exerts a positive impact on the intestinal health and the immune system of postpartum SDS rats through an intricate cascade of interactions with various targets.

Chemometric and Dereplication Analyses of the Anti- Strains Activity of L. Seeds.

Herbert-Doctor LA, Uc-Cachón AH, Dzul-Beh A … +6 more , González-Sánchez AA, Araujo-León JA, Molina-Salinas GM, Pilotzi-Xahuentitla H, Martín-Quintal ZDR, Ortiz-Andrade R

J Med Food · 2025 Jun · PMID 40216529 · Publisher ↗

Although the bactericidal activity of other spp. has been documented, research on seeds is sparse. This study examined the effects of seed extracts against drug-resistant reference strains and clinical isolates. Anti... Although the bactericidal activity of other spp. has been documented, research on seeds is sparse. This study examined the effects of seed extracts against drug-resistant reference strains and clinical isolates. Antibacterial effect was assessed using the minimal inhibitory concentration. Antibiofilm activity was evaluated using ATCC 43300 and SAU-UIMY-31 strains, and antihemolytic effects were evaluated using ATCC 29213 and SAU-UIMY-31. Biological effects and phytochemical profiles were analyzed through gas chromatography and mass spectrometry and chemometric tools. The nonpolar extract demonstrated antibiofilm activity with IC values of 93.9 ± 5.4 µg/mL and 146.2 ± 2.4 µg/mL against ATCC 43300 and SAU-UIMY-31, respectively. The median polar extract showed an IC of 168.1 ± 13.9 µg/mL against ATCC 43,300 and >250 µg/mL against SAU-UIMY-31. Antihemolysis IC values for both extracts were 48.5 ± 3.3 and 52.9 ± 3.1 µg/mL against ATCC 29213 and 58.0 ± 1.4 and 87.9 ± 2.4 µg/mL against SAU-UIMY-31, respectively. Chemometric analyses suggested that fatty acid methyl esters are potential contributors to biological activity. These findings provide a foundation for future studies on the use of seeds in antibacterial therapies.

Safety Pharmacological Assessment of Oral Theophylline Administration on Respiratory Function in Sprague-Dawley Rats.

Cho SH, Cho M, Doguer C … +2 more , Doo M, Ha JH

J Med Food · 2025 Sep · PMID 40216527 · Publisher ↗

In this study, we evaluated the safety pharmacological effects and potential adverse reactions of orally administered theophylline. Theophylline, a commonly used bronchodilator, is a xanthine derivative that exerts stimu... In this study, we evaluated the safety pharmacological effects and potential adverse reactions of orally administered theophylline. Theophylline, a commonly used bronchodilator, is a xanthine derivative that exerts stimulatory effects on the central nervous system. Using an experimental rat model, we explored the impact of theophylline on respiratory parameters, including respiratory rate, tidal volume, and minute volume. Thirty-two 6-week-old male Sprague-Dawley rats were randomly divided into control and experimental groups. The experimental group received a single oral dose of 100 mg/kg theophylline. Respiratory parameters were measured at baseline (0 h) and at 0.5, 1, 2, 4, and 6 h post oral administration of theophylline using a whole-body plethysmograph. Oral theophylline administration significantly increased the respiratory rate and minute volume at all postdose time points compared with those in the control group, and peak values were observed at 0.5 h postadministration ( < .05). In contrast, the tidal volume remained consistent across all time points, indicating that theophylline enhances respiratory efficiency primarily by increasing the frequency of breaths rather than by altering their depth. Our study demonstrated the ability of theophylline to enhance respiratory efficiency via increased breathing frequency without affecting tidal volume, thus offering insights into the clinical significance of oral theophylline in managing chronic respiratory diseases.

Polysaccharide Ameliorates Renal Dysfunction by Inhibiting Inflammatory Reactions and Oxidative Stress in Diabetic Rats.

Wang C, Li T, Lin C … +6 more , Qiu X, Zhuang W, Li H, Feng X, Du X, Sun J

J Med Food · 2025 Jul · PMID 40201944 · Publisher ↗

() polysaccharide (SCP) is an active ingredient from used mainly for the treatment of diabetes, owing to its antioxidant, hypoglycemic, and lipidemic-modulating activities. A rat type II diabetes mellitus model was esta... () polysaccharide (SCP) is an active ingredient from used mainly for the treatment of diabetes, owing to its antioxidant, hypoglycemic, and lipidemic-modulating activities. A rat type II diabetes mellitus model was established by giving rats a high-fat diet and streptozotocin (STZ) to investigate the protective effect of SCP against renal injury in diabetic rats. It was found in this study that fasting blood glucose, serum lipids, serum creatinine, and blood urea nitrogen levels were decreased, the insulin sensitivity was increased, and pathological injuries of the kidney were alleviated in SCP-treated groups, indicating that SCP should have a protective effect against renal injury in diabetic rats. SCP treatment reduced serum C-reactive protein and inhibited the expression of nuclear factors-κB and related inflammatory factors in the renal tissue of diabetic rats. SCP treatment also regulated the expression of Nuclear factor (erythroid-derived 2) like-2, heme oxygenase-1, and kelch-like ECH-associated protein-1, reduced serum malondialdehyde content, and increased superoxide dismutase activity. Furthermore, SCP down-regulated the expression of fibronectin, α-SMA, transforming growth factor β1, and p-Smad3, up-regulated Smad7 expression, and mitigated the collagen fiber deposition in the renal interstitium in diabetic rats. It can be concluded that the mechanism of SCP in alleviating renal injury may be related to inhibiting inflammation, increasing antioxidant stress capacity, and improving renal fibrosis in diabetic rats.

The Effect of Prebiotics and Probiotics (Synbiotics) on Weight Loss and Biochemical Parameters in Obese Individuals.

Son NE, Son E

J Med Food · 2025 Jun · PMID 40192559 · Publisher ↗

This study examined the effects of prebiotic and probiotic (synbiotic) supplementation on weight loss and biochemical parameters in treating obesity. The study was conducted with 110 participants in Eskisehir Anadolu Hos... This study examined the effects of prebiotic and probiotic (synbiotic) supplementation on weight loss and biochemical parameters in treating obesity. The study was conducted with 110 participants in Eskisehir Anadolu Hospital, Turkiye, between February 15, 2019 and February 15, 2020. Individuals with obesity, who were following a weight loss diet, were randomly assigned to two groups. While one group (the control group) followed the diet only, the other group received synbiotic tablets in the morning and evening, in addition to the diet. Anthropometric values and biochemical parameters of the patients were measured at the beginning of the study and 3 months after. A significant decrease was found in weight, body mass index (BMI), and waist circumference values compared with baseline in both groups (: .001; < .05). A significant decrease was found in fasting blood sugar and HOMA-IR values compared with baseline in both groups. Furthermore, there was a significant increase in vitamin B12 and vitamin D values in the group receiving synbiotics compared with their baseline values. As a result of our study, both groups experienced similar weight loss and a decrease in BMI values. The vitamin B12 and vitamin D values of the group that took supplements increased significantly. The HOMA-IR values were significantly lower in both groups, albeit more in the synbiotic group. Changes in vitamin B12, vitamin D, and HOMA-IR values are extremely important for improving the health parameters in the long term.

Bioimpedance Phase Angle as a Diagnostic Tool of Nutritional Status in Children with Crohn's Disease on Exclusive Enteral Nutrition Therapy: One-Year Follow-Up Study.

Wasilewska A, Tomasik P, Gałaś A … +4 more , Stochel-Gaudyn A, Drożdż D, Fyderek K, Sładek M

J Med Food · 2025 May · PMID 40178970 · Publisher ↗

Exclusive enteral nutrition (EEN) is highly effective in achieving remission and improving nutritional status in pediatric Crohn's disease (CD), commonly associated with altered body mass composition (BC). Bioimpedance a... Exclusive enteral nutrition (EEN) is highly effective in achieving remission and improving nutritional status in pediatric Crohn's disease (CD), commonly associated with altered body mass composition (BC). Bioimpedance analysis (BIA) with phase angle (PA) assessment is a noninvasive, reliable tool in screening for BC alterations. In the present study we aimed to assess the PA's usefulness in the detection of malnutrition in newly diagnosed pediatric CD, ongoing EEN treatment, and during 1-year follow-up. Patients and study design: Fourty-three patients with CD, qualified for EEN, were enrolled in the study. Additionally, 22 healthy children, being in the same age category, served as controls. Fat-free mass (FFM), fat-free mass index (FFMI), and BIA-derived PA were assessed at diagnosis, after EEN completion, and at week 52. The same parameters were obtained in the control group once. The majority of patients presented with normal body mass index at diagnosis. PA values were lower than 5 degrees in 65% of the study group. FFMI deficiencies were observed in 74% of patients. After EEN completion, an increase in FFM ( < .001) was observed. The highest mean of FFM ( < .001) and PA ( < .001) were observed at week 52. A strong correlation between PA and FFM at CD diagnosis (Spearman's rho = 0.671, = 0.702, < .001), after EEN completion (Spearman's rho = 0.781, < .00) and at week 52 (Spearman's rho = 0.657, < .001) was present. PA has been observed as positively associated with albumin concentrations both at diagnosis and after EEN. Our study provides some support that PA may be a reliable tool for screening alteration in BC, especially FFM and lean tissue mass (LTM). Moreover, PA has been observed as positively associated with albumin levels at CD diagnosis, which provides some evidence that it may be considered as a risk indicator of malnutrition and protein deficiency in newly diagnosed CD pediatric patients.

Functional Observation Battery Test for Single Intravenous Caffeine Exposure in Male ICR Mice.

Cho SH, Kim YW, Doo M … +1 more , Ha JH

J Med Food · 2025 Jul · PMID 40178934 · Publisher ↗

This study investigated the behavioral responses of male Institute for Cancer Research (ICR) mice to intravenous caffeine exposure via a functional observation battery (FOB) test. Thirty-two experimental mice were random... This study investigated the behavioral responses of male Institute for Cancer Research (ICR) mice to intravenous caffeine exposure via a functional observation battery (FOB) test. Thirty-two experimental mice were randomly assigned to four groups ( = 8 per group) and received intravenous caffeine at a dose of 0, 5, 10, or 20 mg/kg. Functional behaviors were observed at 0, 0.25, 1.5, 6, and 24 h after intravenous caffeine administration. Among the hand-held observations, the ease of removal from the cage and the ease of handling were significantly altered in all caffeine-exposed mice in both a dose-dependent and a time-dependent manner. In terms of physiological responses, both stimulus responses and locomotor activities were significantly affected by intravenous caffeine exposure. Specifically, the tail pinch response was significantly impaired in half of the mice in the 10 mg/kg and 20 mg/kg groups. Moreover, the rearing count decreased in the 10 mg/kg group at 1.5 to 6 h and in the 20 mg/kg group at 1.5 h after intravenous caffeine exposure. Furthermore, locomotor activity was markedly increased 0.25 h after intravenous caffeine administration in the 20 mg/kg group. These findings clearly indicate that intravenous caffeine exposure significantly impacts functional behaviors, as assessed by an FOB test, which is consistent with widely accepted safety pharmacology testing guidelines.

The Therapeutic Role of Saffron and Its Components Mediated Through Nrf2 in Diabetes and Related Pathologies.

Sabeti Akbar-Abad M, Farkhondeh T, Majidpour M … +4 more , Samini F, Aschner M, Alemzadeh E, Samarghandian S

J Med Food · 2025 Apr · PMID 40172359 · Publisher ↗

Today, diabetes is considered a growing global epidemic. In the diabetic environment, a large amount of reactive oxygen species are produced. This type of active oxygen causes severe damage to cell membranes, proteins, a... Today, diabetes is considered a growing global epidemic. In the diabetic environment, a large amount of reactive oxygen species are produced. This type of active oxygen causes severe damage to cell membranes, proteins, and DNA. Therefore, finding a solution to deal with and reduce this type of reactive oxygen is very important. One of the most effective ways to deal with oxidative damage and inflammation is the modulation of the nuclear factor erythroid 2 (Nrf2) signaling pathway. One of the useful natural substances that can be used for treatment in the signaling system is saffron. In this article, research evaluating the medicinal effects of saffron and its compounds and their mechanisms of action, especially the Nrf2 signaling pathway, have been investigated and studied. The results show that saffron and its components have the potential to treat diabetes due to their unique properties.

Fraction-3 Enhances Antioxidant Capacity and Apoptotic Cell Death in HEK293 Kidney Cells.

Naidoo DB, Phulukdaree A, Chuturgoon AA … +1 more , Sewram V

J Med Food · 2025 May · PMID 40160106 · Publisher ↗

The traditional medicinal plant is commonly used in Chinese and Ayurvedic medicine due to its vast range of therapeutic properties. Previously, the ethanolic leaf extract was subjected to silica column fractionation, a... The traditional medicinal plant is commonly used in Chinese and Ayurvedic medicine due to its vast range of therapeutic properties. Previously, the ethanolic leaf extract was subjected to silica column fractionation, and the C3 fraction was obtained. We investigated the antioxidant and anti-proliferative effects of C3 in human embryonic kidney (HEK293) cells. In HEK293 cells, C3 cytotoxicity was assessed (viability assay; 24 h; [0.2-3 mg/mL]), and a half maximal inhibitory concentration (IC) was determined. Malondialdehyde (MDA), lactate dehydrogenase (LDH) (spectrophotometry), mitochondrial depolarization (), intracellular reactive oxygen species (flow cytometry), glutathione (GSH), oxidized glutathione (GSSG) concentrations, caspase activities, ATP levels (luminometry), and fragmentation of DNA (SCGE assay) were evaluated. Protein expressions were assessed by western blotting. Gene expressions were quantified by qPCR. Cell viability in HEK293 cells was decreased in a dose-dependent manner by C3. MDA, , LDH, caspase activities, and DNA fragmentation ( < .0004) were significantly increased by C3. Nuclear factor erythroid 2-related factor 2 (Nrf-2) protein expression, GSH, and GSSG concentrations were increased, whereas antioxidant (, , and ) gene expression was significantly decreased by C3 ( < .001). C3 decreased both Bax and Bcl-2 protein expression ( < .03). Gene expression of was significantly increased, whereas was significantly reduced by C3 ( < .05). C3 reduced antioxidant gene expression, increased antioxidant levels, and elevated anti-proliferative effects in HEK293 cells, suggesting that high concentrations of C3 are potentially toxic to kidney cells, thus rendering cause for concern with its human use.

Comparative Study of Two Bulb Polysaccharide Fractions in Alleviating Airway Remodeling by Affecting Autophagy and Apoptosis.

Gao SS, Cheng YX, Zhou Y … +4 more , Liu RC, Li X, Xie XY, Chen C

J Med Food · 2025 Jun · PMID 40151882 · Publisher ↗

(), which is an indigenous herb in China, is gathered and consumed by nomads in Xinjiang due to its medicinal value. Only a few studies have evaluated its possible pharmacological activity. This study aims to examine and... (), which is an indigenous herb in China, is gathered and consumed by nomads in Xinjiang due to its medicinal value. Only a few studies have evaluated its possible pharmacological activity. This study aims to examine and compare the ways in which two bulb polysaccharide fractions (ESBP and E1P) alleviate airway remodeling based on apoptosis and autophagy. In a mouse model of chronic asthma produced by ovalbumin, the anti-asthmatic effects of E1P and ESBP were investigated. The expression levels of the proteins linked to autophagy and apoptosis (cleaved-caspase 3, Beclin1, LC3B, Bad, and Bax) as well as the activity of the PI3K/Akt/mTOR signaling pathway were assessed. Airway remodeling was alleviated by E1P and ESBP. While E1P could only prevent the increase in PI3K, ESBP was capable of inhibiting the PI3K/Akt/mTOR signaling pathway. Furthermore, ESBP decreased the levels of cleaved-caspase 3, Beclin1, LC3B, Bad, and Bax protein expressions. By modifying signaling pathways linked to autophagy and apoptosis, bulb polysaccharides successfully improved the airway remodeling of asthma. Additionally, ESBP exhibited more potent inhibitory effects on asthmatic defective autophagy than E1P.

A Mixture of Nicotinamide Mononucleotide, Decursin, and l-Cysteine Lowered Senescence-Associated Markers In Vitro and Was Effective Against 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis In Vivo: An Application of Network Pharmacology.

Shin HR, Choi Y, Bae SH … +17 more , Kim TG, Cho HT, Cho TJ, Oh NS, Shim YY, Reaney MJT, Pan JH, Shin JO, Shin EC, Ko SG, Park J, Han Y, Choi KC, Kim YJ, Heo W, Lee K, Kim JK

J Med Food · 2025 May · PMID 40127227 · Publisher ↗

Skin aging, accelerated by oxidative stress from environmental factors, results in the breakdown of collagen and elastin, causing visible signs like wrinkles and inflammation. Natural antioxidants such as nicotinamide mo... Skin aging, accelerated by oxidative stress from environmental factors, results in the breakdown of collagen and elastin, causing visible signs like wrinkles and inflammation. Natural antioxidants such as nicotinamide mononucleotide (NMN), decursin, and l-cysteine have shown potential in combating oxidative damage and inflammation. This study explored the effects of a formulated mixture of these compounds on skin aging and atopic dermatitis (AD) through a combination of , , and methods. Using human keratinocyte cells, we assessed cytotoxicity via a cell viability assay, confirming NMN and l-cysteine were nontoxic up to 100 µM, while decursin exhibited toxicity above 10 µM. The intracellular oxidative stress measurement demonstrated that mixtures A and B, composed of the same concentrations of decursin and l-cysteine but differing in NMN levels (low in mixture A and moderate in mixture B), significantly reduced oxidative stress levels induced by 2,2'-azobis(2-amidinopropane) dihydrochloride, whereas mixture C, which contained the highest NMN concentration, was ineffective. Mixture B further reduced senescence-associated heterochromatin foci formation under oxidative stress, while mixture C caused cell structure disruptions. In the dinitrochlorobenzene-induced AD model in BALB/c mice, both, mixture-L and mixture-H treatments reduced epidermal thickness, scratching behavior, and transepidermal water loss, with mixture-L also lowering dermal thickness and mast cell infiltration. Gene expression analysis confirmed that mixture B decreased proinflammatory cytokines like and , while network pharmacology predicted key antioxidant pathways, validated through restored gene expression. Overall, the findings highlight the potential of these compound mixtures to mitigate oxidative stress and inflammation, offering a promising approach for skin aging and dermatitis management, though further validation is needed to optimize efficacy and safety.
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