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Abstract Mitochondrial dysfunction, characterized by elevated oxidative stress, impaired energy balance, and dysregulated mitochondrial dynamics, is a hallmark of metabolic syndrome (MetS) and its comorbidities. Ferulic acid (FA), a principal phenolic compound found in whole grains, has demonstrated potential in ameliorating oxidative stress and preserving energy homeostasis. However, the influence of FA on mitochondrial health within the context of MetS remains unexplored. Moreover, the impact of FA on autophagy, which is essential for maintaining energy homeostasis and mitochondrial integrity, is not fully understood. Here, we aimed to study the mechanisms of action of FA in regulating mitochondrial health and autophagy using palmitate-treated HepG2 hepatocytes as a MetS cell model. We found that FA improved mitochondrial health by restoring redox balance and optimizing mitochondrial dynamics, including biogenesis and the fusion/fission ratio. Additionally, FA was shown to recover autophagy and activate AMPK-related cell signaling. Our results provide new insights into the therapeutic potential of FA as a mitochondria-targeting agent for the prevention and treatment of MetS.

With the increasing demand for nutrition and health, many researchers are trying to develop a rice product with lower aging rate and convenient nutrient fortification. Being composed of high amylopectin content, cassava starch (CS) shows a lower retrogradation tendency compared to rice starch. So, it has a broad application prospect to partially replace rice starch with CS in rice by extrusion technology. In this study, a new extruded rice (ER) was prepared by broken rice flour and CS using single-screw extruder through “improved extrusion cooking technology,” and the maximum addition level of CS in ER was 30%. Color parameters and texture profile analysis showed that ER was a little darker in appearance with lower hardness, adhesiveness and chewiness. Rapid visco analysis demonstrated that the viscosity of ER paste appeared earlier during the initial heating phase and displayed a lower retrogradation trend than normal rice in the cooling process. The gelatinization temperature and gelatinization enthalpy decreased with the increasing CS in ER, while the degree of gelatinization increased to 76.36% when the content of CS was 30% after extrusion. The X-ray diffraction patterns of control was typical A-type structure, while ER changed to V-type structure with a lower degree of crystallinity. The microstructure observation showed that ER exhibited a looser and more porous structure with increasing the content of CS, which facilitated easier cooking and nutritional enhancement.

Insulin-like growth factor 1 receptor (IGF-1R) is an influential growth receptor in mammalian cells. Majority of cancers in humans shows an active IGF-1R signaling pathway. Apple peel extracts were investigated for their potential mechanisms of action against regulating cell proliferation in human breast cancer MDA-MB-231 cells under IGF-1 induction. Apple peel extracts significantly inhibited cellular proliferation in breast cancer cells in a dose-dependent manner at a dose ≥ 10 mg/mL. No cytotoxicity was observed in the human breast cancer MDA-MB-231 cells at the doses below 50.2 mg/mL. The IGF-1R/PI3K/Akt pathway expression was suppressed by apple peel extracts treatment. Expressions of cyclin D1-stimulating proteins NF-κ B and GSK-3β were inhibited, whereas p21 expression was upregulated. Apple peel extracts reduced the expression of cyclin D1, stagnating MDA-MB-231 cells in a G1 cell cycle arrest. Apple peel extracts stimulated PTEN, a tumor suppressor protein and an inhibitor of PI3K/Akt signaling pathway. The results suggested that apple peel extracts can induce inhibitory effects through downregulating IGF-1R/PI3K/Akt signal transduction pathway in human breast cancer MDA-MB-231 cells. This study shows the efficacy of apple peel extracts in reversing the IGF-1R signal transduction pathway, thereby hindering tumorigenesis in breast cancer cells.

A novel polysaccharide (MFP4P) was isolated from mulberry fruits (Morus alba L.) pulp using a combination of DEAE-Sepharose fast-flow and Sephadex G-100 chromatographic columns. Structural characterization revealed that MFP4P was composed of arabinose, rhamnose, galactose, glucose and galacturonic acid with a molecular weight of 198.2 kDa. The linkage types of MFP4P were proved to be (1 → 6)-linked α-D-Glc, (1 → 2)-linked α-L-Rha, (1 → 3)-linked α-D-Gal, (1 → 3)-linked β-L-Rha and (1 → )-linked α-L-Ara. The MFP4P showed good antioxidant activity with an oxygen radical absorbance capacity value of 121.8 ± 16.5 μM trolox equivalent/g. In addition, the MFP4P promoted pancreatic cell proliferation, increased insulin secretion, and enhanced glucose consumption. In the non-toxic range, the polysaccharide and zinc complexes (MFP4P-Zn) exhibited higher antioxidant and hypoglycemic activities than MFP4P at the same concentration. In vivo hypoglycemic study, MFP4P and MFP4P-Zn both showed decreased blood glucose level and glucose tolerance compared with the model control group.

In the present study, the digestion properties of a polysaccharide from Rosa roxburghii fruit (RTFP-3) under saliva, simulated gastric and small intestinal conditions were studied for the first time. The results indicated that human saliva had no effect on RTFP-3. RTFP-3 was slightly degraded in simulated gastric and small intestinal juices. The molecular weight (Mw) of RTFP-3 was decreased from 67.59 to 44.22 kDa. Meanwhile, the reducing sugars were increased from 0.503 to 1.744 mM. Then, the prebiotic effects of RTFP-3 were examined by in vitro fermentation model. RTFP-3 could significantly increase the production of total short-chain fatty acids from 23.49 to 44.29 mM, and 60.28% of total carbohydrate was consumed after 48 h fermentation. Furthermore, RTFP-3 could significantly modulate the microbial structure by lowering the ratio of Firmicutes to Bacteroidetes from 14.89 to 4.68 after 48 h fermentation, and improving the relative abundances of some beneficial gut microbiota.

Ultraviolet radiation induces skin damage, inflammation, and aging. To explore the protective effects of blueberry extract (BE) against ultraviolet-C (UV-C) radiation, we analysed human skin keratinocyte (HaCaT) and human foreskin fibroblast (HFF) cells alone or in a co-culture, treated or not with BE, after exposure to UV-C. Surprisingly, MMP-1 was significantly up-regulated in HFF cells and in the co-cultured cell group in response to UV-C irradiation (8 mJ/cm2), but not in HaCaT cells. As expected, BE had a significantly protective effects; it decreased DNA fragmentation and inhibited MMP-1 and inflammatory factors expression in response to UV-C radiation. In addition, BE reduced the accumulation of proteins (MMP-1, c-fos, and c-jnu) in the MAPK (mitogen-activated protein kinase) pathway after UV-C radiation. Taken together, these results showed that BE exerted a protective effect against UV-C irradiation, and modulated MMP-1 production through MAPK signalling by direct and indirect pathways in HaCaT and HFF cells.

Methionine restriction (MR) extends lifespan and delays the onset of aging-associated pathologies. However, the effect of MR on age-related cognitive decline remains unclear. Here, we find that a 3-month MR ameliorates working memory, short-term memory, and spatial memory in 15-month-old and 18-month-old mice by preserving synaptic ultrastructure, increasing mitochondrial biogenesis, and reducing the brain MDA level in aged mice hippocampi. Transcriptome data suggest that the receptor of fibroblast growth factor 21 (FGF21)-related gene expressions were altered in the hippocampi of MR-treated aged mice. MR increased FGF21 expression in serum, liver, and brain. Integrative modelling reveals strong correlations among behavioral performance, MR altered nervous structure-related genes, and circulating FGF21 levels. Recombinant FGF21 treatment balanced the cellular redox status, prevented mitochondrial structure damages, and upregulated antioxidant enzymes HO-1 and NQO1 expression by transcriptional activation of Nrf2 in SH-SY5Y cells. Moreover, knockdown of Fgf21 by i.v. injection of adeno-associated virus abolished the neuroprotective effects of MR in aged mice. In conclusion, the MR exhibited the protective effects against age-related behavioral disorders, which could be partly explained by activating circulating FGF21 and promoting mitochondrial biogenesis, and consequently suppressing the neuroinflammation and oxidative damages. These results demonstrate that FGF21 can be used as a potential nutritional factor in dietary restriction-based strategies for improving cognition associated with neurodegeneration disorders.

Raspberries are rich in phytochemicals with health benefits. Our previous research has shown raspberry extracts (RE) can promote longevity in Caenorhabditis elegans. The objective of this study was to determine whether the extension of lifespan was regulated by oxidative stress, and to explore the underlying mechanisms of action. The results showed that RE could ameliorate oxidative stress, which improved antioxidant enzyme activity and enhanced resistance to paraquat. Meanwhile, treatment with RE could down-regulate the overexpression of reactive oxygen species and affect the expression of antioxidant related genes. However, administration with RE abolished the extension of the lifespan of skn-1(zu135) mutants, and promoted the migration of SKN-1 into the nucleus, which inhibited the expression of skn-1 downstream gene. In conclusion, RE could ameliorate oxidative stress in C. elegans via the SKN-1/Nrf2 pathway. This study provided the theoretical basis to explore the phytochemicals in the prevention of aging regulated by oxidative stress.

A novel polysaccharide (MOP-2) was extracted and purified from the leaves of Moringa oleifera by hot water extraction and chromatographic purification. Structural characterization revealed that MOP-2 had an average molecular weight of 155.35 kDa and consisted of arabinose, glucose and galactose with molar percentages of 35.8, 6.67, and 57.53%, respectively. The backbone chain of MOP-2 was proven to be →3,6)-β-D-Galp(1→ and →6)-β-D-Galp-(1→, and the side chains contained →5)-α-L-Araf-(1→, α-L-Araf-(1→, and α-D-Glcp-(1→. In vitro immunomodulatory assay revealed that MOP-2 could significantly enhance the proliferation and pinocytic capacity of the RAW264.7 macrophage cells. Furthermore, MOP-2 promoted the secretion of reactive oxygen species (ROS), nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) by activating mRNA expressions of iNOS, IL-6 and TNF-α. These findings suggest that MOP-2 can be developed as a novel natural immunoregulatory agent in functional foods.

The phenolic contents, antioxidant, and antiproliferative activities of Malus doumeri were evaluated. Heyuanxiaoguo variety contained higher level of total phenolics (101.9 mg GAE/g fruit, DW), whereas Xinyishanzha variety exhibited the highest total flavonoids (85.35 mg CE/g fruit, DW), and highest cellular antioxidant and antiproliferative activities. Higher ORAC and PSC values were found in Limushan variety. Chlorogenic acid, phloretin-2′-xyloglucoside and ursolic acid were the predominant phenolics in M. doumeri, their contents were highest in Limushan (1850 mg/100g fruit, DW), Xinyishanzha (2212 mg/100g fruit, DW), and Heyuanxiaoguo variety (506.3 mg/100g fruit, DW), respectively. Among the 14 compounds identified, chlorogenic acid and phloretin glycosides accounted for 55.95% of the extracellular antioxidant capacity, while quercetin, luteolin, ursolic acid, and chlorogenic acid contributed significantly to the intracellular antioxidant activity. Furthermore, the intracellular antioxidant property of the Xinyishanzha extracts was related to the protection of endogenous antioxidant enzymes activities and inhibition of reactive oxygen species production.

Tremella fuciformis Berk, a popular nutritious mushroom in China, has attracted increasing attention due to its various bioactivities. In the present work, T. fuciformis polysaccharides (TP) were extracted with hot water. It mainly consisted of mannose, as well as 10.77% (w/w) uronic acid. In additional, the anti-photoaging effects of TP were evaluated using a 30-day UV-irradiated animal assay. TP could efficiently reduce the water and collagen losses of the skin, and inhibit the increase of glycosaminoglycans. Moreover, a histopathological study showed that, UV-induced skin structural alterations were alleviated as well as repairing endogenous collagen breakdown and maintaining the ratio of type I/III collagen, after oral treatment of TP. The activities of SOD, GSH-Px and CAT were increased compared to the irradiated control group without treatment. Accordingly, TP can be used as a potential functional food supplement for skin function protection.

Orange, with various bioactive phytochemicals, exerts various beneficial health effects, including anti-cancer, antioxidant, and anti-inflammatory properties. However, its anti-aging effects remain unclear. In this study, the Caenorhabditis elegans (C. elegans) model was used to evaluate the effects of orange extracts on lifespan and stress resistance. The results indicated that orange extracts dose-dependently increased the mean lifespan of C. elegans by 10.5%, 18.0%, and 26.2% at the concentrations of 100, 200, and 400 mg/mL, respectively. Meanwhile, orange extracts promoted the healthspan by improving motility, and decreasing the accumulation of age pigment and intracellular reactive oxygen species (ROS) levels without damaging fertility. The survival rates of orange extract-fed worms were obviously higher than those of untreated worms against thermal and ultraviolet-B (UV-B) stress. Moreover, the activities of superoxide dismutase (SOD) and catalase (CAT) were significantly enhanced while malondialdehyde (MDA) contents were diminished. Further investigation revealed that worms supplemented with orange extracts resulted in upregulated levels of genes, including daf-16, sod-3, gst-4, sek-1, and skn-1, and the downregulation of age-1 expression. These findings revealed that orange extracts have potential anti-aging effects through extending the lifespan, enhancing stress resistance, and promoting the healthspan.

Free and bound phenolic compounds were extracted from four varieties (BQ, Dulihuang; CHQK, Changheiqingke; ZQ25, Zangqing 25 and ZQ320, Zangqing 320) of dehulled highland barley. Phenolics composition, antioxidant and antiproliferative activities were analysed. Total phenolics ranged from 333.9 ± 17.1 to 460.8 ± 5.7 mg gallic acid equivalents (GAE)/100 g grain (dry weight, DW), total flavonoids are between 145.5 ± 10.0 and 247.4 ± 20.3 mg catechin equivalents (CE)/100 g grain (DW), and ferulic acid is the dominant phenolic compound. These extracts showed excellent antioxidant activities determined by oxygen radical absorbance capacity (ORAC) and cellular antioxidant activity (CAA) assays, as well as potent antiproliferative activity towards HepG2 human liver cancer cells. Bound phenolics make a significant contribution to total phenolics content, antioxidant and anticancer activities. This study suggested that highland barley exhibits the unique phenolic compound profile with potential health benefits, and it may serve as ingredients for functional foods.

The antiproliferative and apoptosis-inducing activities of an acidic polysaccharides fraction from Pholiota dinghuensis Bi mycelium (PDP-3) against human breast cancer MCF-7 cells were investigated. As a result, PDP-3 displayed a significant prevention of cell growth towards MCF-7 cells, with an EC50 value of 38.35 µg/mL. Furthermore, PDP-3 induced significant apoptosis towards MCF-7 cells. From Western blot results, up-regulated p21 and down-regulated cyclin D1, CDK4 and PCNA, up-regulated Bax and down-regulated Bcl-2, caspase-9 and caspase-3 were found in the protein expressions of MCF-7 cells. In MCF-7 cells treated with PDP-3, down-regulated TRAF2 and up-regulated ASK1, phosphorylated of p38 and p53 were also found. Notably, PDP-3 treatment represented a significant decrease in both nuclear and cytoplasmic expression of ERα in MCF-7 cells. Therefore, p38/MAPK signal transduction pathway was the potential mechanism of PDP-3 in regulating both cell proliferation and apoptosis in oestrogen-dependent human breast cancer MCF-7 cells.

The aim of this study was to investigate the synergistic antioxidant potential and protective effect of grape seed procyanidins (GSP) in combination with Auricularia auricular-judae polysaccharides (AAP IV) on radiation injury in splenocytes. Rat splenocyte irradiation resulted in significantly higher apoptosis rate, malondialdehyde (MDA) (p < 0.005), reactive oxygen species (ROS) (p < 0.01); cell viability, total superoxide dismutase (T-SOD) (p < 0.01), catalase (CAT) (p < 0.01), glutathione peroxidase (GSH-PX) (p < 0.05), activity and glutathione (GSH) (p < 0.01) levels were significantly reduced, compared with the control group. “GSP + AAP IV” treatment of rat splenocytes at doses of “GSP (0.3 μg/mL) + AAP IV (50 μg/mL)” displayed higher radioprotective and antioxidative effects than the administration of either GSP or AAP IV, as evident by lower levels of MDA (p < 0.001) concentration, as well as higher cell viability and T-SOD (p < 0.05), CAT (p < 0.005), GSH-PX (p < 0.01) and GSH content compared to the radiation group. In addition, in vivo studies have shown that “GSP + AAP IV” significantly ameliorated the decrease of spleen index (p < 0.005) and spleen GSH (p < 0.005) levels and significantly inhibited the increase of MDA (p < 0.005) levels of spleen with radiation-induced damage, compared with the non-treated group. The in vivo and in vitro results suggested that GSP and AAP IV have a synergistic protective effect against radiation-induced injury by improving the antioxidant and immunomodulation activities.

Ramie (Boehmeria nivea L.) is usually cultivated as a fiber crop, but it is also well known for its potential use in animal feeding with viable commercial applications. In this study, the phenolics profile as well as cellular antioxidant and antiproliferative activities were investigated in free and bound fractions of six different vegetative parts from Boehmeria nivea L. The highest total phenolic content was observed in bud (4585 ± 320 mg GAE/100 g DW), whereas root and petiole had the lowest total phenolic contents, 442.8 ± 9.8 and 630.9 ± 27.0 mg GAE/100 g DW, respectively. Likewise, phloem had the most abundant total flavonoids (2755 ± 184 mg CE/100 g DW), whereas the lowest flavonoid contents was found in root and petiole, 636.9 ± 44.2 and 797.4 ± 87.6 mg CE/100 g DW, respectively. Xylem and bud depicted remarkable antioxidant and antiproliferative activities, which could be explained by their diverse phenolic composition, especially chlorogenic acid and epicatechin. The Boehmeria nivea L. plant might be a valuable resource for high value-added phenolic compounds used in food and non-food industries.

Regular consumption of fruits and vegetables is associated with reduced risk of age-related functional decline and chronic diseases such as cancer and cardiovascular disease. These effects are primarily attributed to phytochemicals, plant compounds with a wide range of biological activities and health benefits. Apples, the top contributor of fruit phenolics in American diets, have high antioxidant, antiproliferative and chemopreventive activity in vitro and in vivo. However, little is known about their effects on aging. The objectives of this study were to determine the effects of whole apple phytochemical extracts on lifespan, healthspan and resistance to various stresses in vivo using Caenorhabditis elegans as a model. The mean and maximum lifespan of animals treated with 2.5, 5 and 10 mg/ml whole apple extracts increased significantly in a dose-dependent manner by up to 39% and 25%, respectively. Healthspan also significantly improved as indicated by improved motility and reduced lipofuscin accumulation. Animals pre-treated with whole apple extracts were more resistant to stresses such as heat, UV radiation, paraquat-induced oxidative stress, and pathogenic infection, suggesting that cellular defense and immune system functions also improved. Our findings indicate that, in C. elegans, whole apple extracts slow aging, extend lifespan, improve healthspan, and enhance resistance to stress.

Cell counting is a common technique in cellular and molecular biology research applications, such as cell culture maintenance, cell plating, cell growth and cell doubling time determinations, as well as cell proliferation and cytotoxicity measurements. Many commonly employed cell counting methods exhibit limitations that influence resulting accuracy or versatility. For example, the trypan blue method typically underestimates cell numbers in culture, and the Lowry protein assay can be influenced by cell cycle. An urgent need exists for a method of cell counting that is both accurate and versatile. This work intended to explore an adaptation of the methylene blue assay to overcome the existing limitations of the procedure, enabling application to a broader range of cell densities and various cell culture plates. This new methylene blue assay was found to be more efficient, accurate and sensitive. A linear relationship (r2 > 0.99) was established between cell number and absorbance at 570 nm wavelength when the new methylene blue assay was applied to three cell lines (HepG2, Caco-2, and MCF-7) plated in a broad range of cell densities (5 × 104 to 2.5 × 106) in four different types of culture plates (6-, 12-, 24-, and 96-well plates). Growth curves were determined using both the trypan blue and methylene blue methods. At each time point in the HepG2 growth curve, the cell count obtained using the trypan blue assay was statistically significantly lower than that obtained using the methylene blue assay (p

Increased consumption of vegetables or plant food has been associated with decreased risk of developing major chronic diseases, such as cancers, diabetes, cardiovascular diseases, and age-related functional decline. Ramie leaves are rich in phenolics and flavonoids, which have been suggested for human health benefits. Phenolic contents, flavonoid contents, phenolic compounds, and anti-cancer properties in six species of ramie leaves were analyzed by Folin-reagent method, sodium borohydride/chloranil-based assay (SBC), HPLC method and antiproliferation, cytoxicity, respectively. Antioxidant activities were measured through peroxyl radical scavenging capacity (PSC) method, oxygen radical absorbance capacity (ORAC) method, and cellular antioxidant activity (CAA). Research indicated that Boehmeria penduliflora contained the highest total phenolic content (2313.7±27.28 mg GAE/100 g FW), and flavonoid content (1682.4±27.70 mg CAE/100 g FW). Boehmeria tricuspis showed the highest PSC value (9574.8±117.63 µM vit. C equiv./100 g FW), while Boehmeria penduliflora indicated the highest ORAC value (330.44±16.88 µmol Trolox equiv./g FW). The antioxidant activities were correlated with phenolic contents and flavonoid contents. Boehmeria tricuspis had the highest antiproliferative capacity with the lowest EC₅₀ (4.11±0.19 mg/mL). The results for the analyzed ramie for CAA were significantly different from each other (p

Grapes are rich in phytochemicals with many proven health benefits. Phenolic profiles, antioxidant and antiproliferative activities of twenty-four selected Vitis vinifera grape cultivars were investigated in this study. Large ranges of variation were found in these cultivars for the contents of total phenolics (95.3 to 686.5 mg/100 g) and flavonoids (94.7 to 1055 mg/100 g) and antioxidant activities (oxygen radical absorbance capacity 378.7 to 3386.0 mg of Trolox equivalents/100 g and peroxylradical scavenging capacity14.2 to 557 mg of vitamin C equivalents/100 g), cellular antioxidant activities (3.9 to 139.9 µmol of quercetin equivalents/100 g without PBS wash and 1.4 to 95.8 µmol of quercetin equivalents /100 g with PBS wash) and antiproliferative activities (25 to 82% at the concentrations of 100 mg/mL extracts).The total antioxidant activities were significantly correlated with the total phenolics and flavonoids. However, no significant correlations were found between antiproliferative activities and total phenolics or total flavonoids content. Wine grapes and color grapes showed much higher levels of phytochemicals and antioxidant activities than table grapes and green/yellow grapes. Several germplasm accessions with much high contents of phenolics and flavonoids, and total antioxidant activity were identified. These germplasm can be valuable sources of genes for breeding grape cultivars with better nutritional qualities of wine and table grapes in the future.