Phytochemical profiles, antioxidant activities, and synergistic antiproliferative effects of blueberry and apple peel extracts.

BACKGROUND: Blueberries and apples exhibit favorable bioactivity and health benefits as a result of their rich phytochemicals. Natural phytochemicals exist in complex forms, but there are few reports on whether have additive, synergistic or antagonistic effects between different phytochemicals. The present study aimed to elucidate the synergistic effects of blueberry extract (BE) and apple peel extract (APE) together with respect to inhibiting the proliferation of HepG2 liver cancer cells. Meanwhile, phytochemical characterization of BE and APE was conducted by HPLC, and total antioxidant activity was determined via a cellular antioxidant activity assay, oxygen radical absorption capacity assay and peroxy radical scavenging capacity assay. RESULTS: The results showed that BE and APE were rich in phytochemicals and had potent antioxidant activities, which synergistically inhibited cell proliferation. In the bilateral combination, the dose reduction index value increased by two-fold, and the combination index value at 95% inhibition was less than 1. Additionally, BE + APE supplementation could promote the expression levels of p53 and c-myc genes. In conclusion, the BE and APE had strong antioxidant activity and exhibited synergistic inhibition against proliferation of HepG2 cells. CONCLUSION: The present study can provide a theoretical basis for the synergistic effect of different phytochemicals in health care. © 2023 Society of Chemical Industry.

Hypsizygus marmoreus extract exhibited antioxidant effects to promote longevity and stress resistance in Caenorhabditis elegans.

In this study, we explored the lifespan extension effect of a popular edible mushroom, Hypsizygus marmoreus, using the model organism Caenorhabditis elegans (C. elegans). The results showed that Hypsizygus marmoreus extract (HME) could increase the lifespan of C. elegans and ameliorate the healthspan by improving motility, attenuating lipofuscin accumulation, and enhancing the ability to withstand oxidative and heat stress. Then, we found noteworthy enhancements in SOD and CAT activities and reactive oxygen species (ROS) scavenging activity in vivo. Combined with the up-regulation of the expression of antioxidant genes (skn-1, sod-1, sod-3, mev-1, and gst-4), HME may function as an antioxidant in nematodes, which may be closely related to its phenolic compounds. Furthermore, we found that HME promoted the transfer of the transcription factor SKN-1 to the nucleus but had no impact on the lifespan of skn-1 mutants, indicating that SKN-1 was essential for Hypsizygus marmoreus to exert beneficial biological effects in C. elegans. Our findings elucidated that dietary supplementation with Hypsizygus marmoreus might have beneficial anti-aging effects and contribute to exploring the lifespan extension and underlying mechanisms of Hypsizygus marmoreus in C. elegans.

Apple peel polyphenol alleviates antibiotic-induced intestinal dysbiosis by modulating tight junction proteins, the TLR4/NF-κB pathway and intestinal flora.

The intestine and its flora have established a strong link with each other and co-evolved to become a micro-ecological system that plays an important role in human health. Plant polyphenols have attracted a great deal of attention as potential interventions to regulate the intestinal microecology. In this study, we investigated the effects of apple peel polyphenol (APP) on the intestinal ecology by establishing an intestinal ecological dysregulation model using lincomycin hydrochloride-induced Balb/c mice. The results showed that APP enhanced the mechanical barrier function of mice by upregulating the expression of the tight junction proteins at the transcriptional and translational levels. In terms of the immune barrier, APP downregulated the protein and mRNA expression of TLR4 and NF-κB. As for the biological barrier, APP promoted the growth of beneficial bacteria as well as increasing the diversity of intestinal flora. In addition, APP treatment significantly increased the contents of short-chain fatty acids in mice. In conclusion, APP can alleviate intestinal inflammation and epithelial damage as well as inducing potentially beneficial changes in the intestinal microbiota, which helps to reveal the potential mechanisms of host-microbial interactions and polyphenol regulation of intestinal ecology.

Ferulic Acid Mediates Metabolic Syndrome via the Regulation of Hepatic Glucose and Lipid Metabolisms and the Insulin/IGF-1 Receptor/PI3K/AKT Pathway in Palmitate-Treated HepG2 Cells.

Ferulic acid (FA) is one of the most abundant bound phenolics in whole grains, partly contributing to its preventive effects on metabolic syndrome (MetS). The study aims to investigate if FA mediates MetS through the regulation of hepatic metabolisms and the insulin receptor related pathways in the palmitate-treated HepG2 cells (MetS model). We found that FA (50, 100, and 200 µM) dramatically ameliorated the lipid accumulation in the MetS model. FA significantly decreased the activities of the gluconeogenic enzymes, G6Pase and PEPCK, downregulated the lipogenic enzyme FAS-1, and upregulated the lipolytic enzyme CPT-1 by regulating a series of transcriptional factors including HNF4α, FOXO-1, SREBP-1c, and PPAR-γ. Notably, we found that FA's ability to alleviate MetS is achieved by activating the insulin receptor/PI3K/AKT pathway. Our results validated the effects of FA on mediating the metabolic disorders of lipid and glucose pathways and unveiled its potential intracellular mechanisms for the prevention of MetS.

Phytochemical Profiles, Antioxidant Activity and Antiproliferative Mechanism of Rhodiola rosea L. Phenolic Extract.

The phenolic profiles, antioxidant activity, antiproliferative property and the underlying molecular mechanisms of cell apoptosis of Rhodiola rosea free phenolic (RFE) were analyzed in this work. Overall, Rhodiola rosea rhizome phenolic extract (RE) contained Rhodiola rosea rhizome free phenolic extract (RFE) and Rhodiola rosea rhizome bound phenolic extract (RBE). Compared with RBE, RFE contained higher phenolic contents and possessed stronger antioxidant activity. High-performance liquid chromatography (HPLC) results demonstrated that the main phenolics of were epigallocatechin (EGC), epigallocatechin gallate (EGCG), gallic acid (GA) and catechin. Gas chromatography-mass spectrometry (GC-MS) analysis found that Rhodiola rosea L. was rich in volatile phytochemicals. In addition, many types of vitamin E and a few kinds of carotenoids were found in Rhodiola rosea. In addition, the main compounds in RFE (GA, EGC, EGCG) and RFE all exhibited excellent antiproliferative activity, indicating the antiproliferative activity of RFE was partly attributed to the synergy effects of the main compounds. Further study confirmed that RFE could block 16.99% of HepG2 cells at S phase and induce 20.32% programmed cell death compared with the control group. Specifically, RFE dose-dependently induced cell apoptosis and cell cycle arrest via modulating the p53 signaling pathway including up-regulation of the expression of p53 and Bax while down-regulation of the Bcl-2, cyclin D1 and CDK4 levels. Therefore, RFE exhibited the potential of being developed as an auxiliary antioxidant and a therapeutic agent for cancer.

Quantification of Phytochemicals, Cellular Antioxidant Activities and Antiproliferative Activities of Raw and Roasted American Pistachios (Pistacia vera L.).

The consumption of pistachios has been linked to many potential health benefits. Phytochemicals in pistachios, including phenolics, vitamin E and carotenoids, have been considered to make contributions to the health benefits. The objectives of this study were (1) to explore the phytochemical profiles (total phenolics and total flavonoids, including both free and bound forms), selected phytochemicals, vitamin E and carotenoids of raw and roasted pistachios; (2) to determine total antioxidant activity and cellular antioxidant activity (CAA); and (3) to explore antiproliferative activities of pistachio extracts against human breast, liver and colon cancer cells in vitro. Both raw and roasted pistachios contained high total phenolics, at 479.9 ± 10.2 (raw) and 447.9 ± 9.4 (roasted) mg GAE/100 g, respectively, and high flavonoids, at 178.4 ± 10.6 (raw) and 144.1 ± 7.4 (roasted) mg GAE/100 g, respectively. The contributions of the free form to the total phenolics in pistachios were 82% (raw) and 84% (roasted), respectively, and the contributions of the free form to the total flavonoids in pistachios were 65% (raw) and 70% (roasted), respectively. Gentisic acid and catechin were the major phenolics in raw and roasted pistachios, respectively. Both raw and roasted pistachios had similar total antioxidant activity evaluated by Oxygen-Radical-Scavenging Capacity (ORAC) assay, at 7387.9 ± 467 (raw) and 7375.3 ± 602 (roasted) µmol TE/100 g, respectively. Both raw and roasted pistachio extracts exhibited cellular antioxidant activity inhibiting peroxyradical radical-induced oxidation, with CAA values of 77.39 ± 4.25 (wash) and 253.71 ± 19.18 (no wash) µmol QE/100 g of raw pistachios and 115.62 ± 3.02 (wash) and 216.76 ± 6.6 (no wash) µmol QE/100 g of roasted pistachios. Roasted pistachios contained more vitamin E when compared with raw pistachios, while raw pistachios contained more carotenoids than the roasted pistachios. Additionally, the free form of roasted pistachios extracts exhibited superior antiproliferation activity against HepG2, Caco-2 and MDA-MB-231 cancer cells in a dose-dependent manner, with EC50 34.73 ± 1.64, 36.66 ± 3.3 and 7.41 ± 0.82 mg per mL, respectively. These results provided new knowledge about the phytochemical profiles, antioxidant activity, cellular antioxidant activity and antiproliferative activity of raw and roasted pistachios.

DAF-16 is involved in colonic metabolites of ferulic acid-promoted longevity and stress resistance of Caenorhabditis elegans.

BACKGROUND: Ferulic acid (FA) is a dietary polyphenol widely found in plant tissues. It has long been considered to have health-promoting qualities. However, the biological properties of dietary polyphenols depend largely on their absorption during digestion, and the effects of their intestinal metabolites on human health have attracted the interest of researchers. This study evaluated the effects of three main colonic metabolites of FA - 3-(3,4-dihydroxyphenyl)propionic acid (3,4diOHPPA), 3-(3-hydroxyphenyl)propionic acid (3OHPPA) and 3-phenylpropionic acid (3PPA) - on longevity and stress resistance in Caenorhabditis elegans. RESULTS: Our results showed that 3,4diOHPPA, 3OHPPA and 3PPA extended the lifespan under normal conditions in C. elegans whereas FA did not. High doses of 3,4diOHPPA (0.5 mmol L-1 ), 3OHPPA (2.5 mmol L-1 ) and 3PPA (2.5 mmol L-1 ) prolonged the mean lifespan by 11.2%, 13.0% and 10.6%, respectively. Moreover, 3,4diOHPPA, 3OHPPA and 3PPA treatments promoted stress tolerance against heat, UV irradiation and paraquat. Furthermore, three metabolites ameliorated physical functions, including reactive oxygen species and malondialdehyde levels, motility and pharyngeal pumping rate. The anti-aging activities mediated by 3,4diOHPPA, 3OHPPA and 3PPA depend on the HSF-1 and JNK-1 linked insulin/IGF-1 signaling pathway, which converge onto DAF-16. CONCLUSION: The current findings suggest that colonic metabolites of FA have the potential for use as anti-aging bioactivate compounds. © 2022 Society of Chemical Industry.

Molecular regulation of phenolic compounds on IGF-1 signaling cascade in breast cancer.

Breast cancer is a highly aggressive and heterogeneous disease with complex features that remains a major health problem and undermines the span and quality of life of women worldwide. Primary literature has shown the role of phenolic compounds in controlling the onset of breast cancer. The mechanism of action of phenolic compounds can be explained by their interaction with signal transduction pathways that regulate cell proliferation and induction of apoptosis. One of the targets of phenolic compounds is the insulin like growth factor 1 (IGF-1) signaling cascade, which plays a significant role in the growth and development of mammary tissues by leading proliferative and anti-apoptotic events. Increasing research evidence points to the function of the IGF-1 cascade system in the commencement, progression, and metastasis of breast tissue malignancy. In this review, we mainly discuss the function of the IGF-1 system, and the role of phenolic compounds in regulating the IGF-1 signaling cascade and curbing breast malignancies.

Identification of key phenolic compounds responsible for antioxidant activities of free and bound fractions of blackberry varieties' extracts by boosted regression trees.

BACKGROUND: Free fractions of different blackberry varieties' extracts are high in phenolic compounds with antioxidant activities. However, the phenolic profiles and antioxidant activities against peroxyl radicals of bound fractions of different blackberry varieties' extracts have not been previously reported. In addition, what the key antioxidant phenolic compounds are in free and bound fractions of blackberry extracts remain unknown. This study aimed to investigate the phenolic profiles and antioxidant activities of free and bound fractions of eight blackberry varieties' extracts and reveal the key antioxidant phenolic compounds by boosted regression trees. RESULTS: Fifteen phenolics (three anthocyanins, four flavonols, three phenolic acids, two proanthocyanidins, and three ellagitannins) were identified in blackberry by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Ferulic acid, ellagic acid, procyanidin C1, kaempferol-O-hexoside, ellagitannins hex, and gallic acid were major bound phenolics. Bound fractions of eight blackberry varieties' extracts were high in phenolics and showed great antioxidant activity. Boosted regression trees analysis showed that cyanidin-3-O-glucoside and chlorogenic acid were the most significant compounds, contributing 48.4% and 15.9% respectively to the antioxidant activity of free fraction. Ferulic acid was the most significant antioxidant compound in bound fraction, with a contribution of 61.5%. Principal component analysis showed that Kiowa was the best among the eight varieties due to its phenolic profile and antioxidant activity. CONCLUSION: It was concluded that blackberry varieties contained high amounts of bound phenolics, which confer health benefits through reducing oxidative stress. Ferulic acid was the key compound to explain the antioxidant activities of bound fractions. © 2021 Society of Chemical Industry.

Comparison of phytochemical profiles, antioxidant and antiproliferative activities in Chinese bayberry (Myrica rubra Sieb. et Zucc.) fruits.

Here, we examined the phytochemical profiles, antioxidant activity (AA), and antiproliferative activity (APA) of four Chinese bayberry (Myrica rubra Sieb. et Zucc.) pulp extracts. They were found to be rich in total phenolics content (TPC; 186.45 ± 5.42 to 498.94 ± 8.25 mg of gallic acid equiv./100 g FW) and total flavonoids content (TFC; 126.28 ± 4.18 to 194.35 ± 12.03 mg of catechin equiv./100 g FW). For all varieties, the free flavonoid/phenolic/anthocyanin contents were higher than that the bound fractions. Wild pink bayberry (WPB) displayed the highest values of TPC and TFC, and also showed the highest total antioxidant activity (TAA) as revealed by peroxyl radical scavenging capacity (PSC) (451.47 ± 8.01 µmol Vit. C equiv./100 g FW), and free cellular antioxidant activity (CAA) (184.99 ± 6.11 µmol quercetin equiv./100 g FW, no PBS wash; 117.78 ± 2.34 µmol quercetin equiv./100 g FW, PBS wash) assays. Bayberry extracts had a marked reduction in the APA of HepG2 cells, and WPB exhibited the lowest EC50 (8.50 ± 0.83 mg/ml) value, which was probably associated with cell cycle arrest and apoptosis induction. PRACTICAL APPLICATION: Chinese bayberry (Myrica rubra Sieb. et Zucc.) fruit is rich in natural phenolic compounds, which might be a functional ingredient in food and nutraceutical products. Our findings would provide a logical strategy to promote the comprehensive utilization of phenolics in bayberry fruit with both health and economy benefits.

HSF-1 and SIR-2.1 linked insulin-like signaling is involved in goji berry (Lycium spp.) extracts promoting lifespan extension of Caenorhabditis elegans.

The anti-cancer, vision-improving, and reproduction-enhancing effects of goji berry have been generally recognized, but its role in anti-aging is rarely studied in depth. Therefore, two widely-circulated goji berries, Lycium ruthenicum Murr. (LRM) and Lycium Barbarum. L (LB), were selected to explore their effects on extending lifespan and enhancing defense against extrinsic stress and to uncover the mechanism of action through genetic study. The results showed that supplementation with high-dose LRM (10 mg mL-1) and LB (100 mg mL-1) extracts significantly extended the lifespan of Caenorhabditis elegans (C. elegans) by 25.19% and 51.38%, respectively, accompanied by the improved stress tolerance of C. elegans to paraquat-induced oxidation, UV-B irradiation and heat shock. Furthermore, LRM and LB extracts remarkably enhanced the activities of antioxidant enzymes including SOD and CAT in C. elegans, while notably decreased the lipofuscin level. Further genetic research demonstrated that the expression levels of key genes daf-16, sod-2, sod-3, sir-2.1 and hsp-16.2 in C. elegans were up-regulated by the intervention with LRM and LB, while that of the age-1 level was down-regulated. Moreover, the daf-16 (mu86) I, sir-2.1 (ok434) IV and hsf-1 (sy441) I mutants reversed the longevity effect brought about by LRM or LB, which confirmed that these genes were required in goji berry-mediated lifespan extension. Therefore, we conclude that HSF-1 and SIR-2.1 act collaboratively with the insulin/IGF signaling pathway (IIS) in a daf-16-independent mode. The present study indicated goji berry as a potential functional food to alleviate the symptoms of aging.

Goji berry (Lycium spp.) extracts exhibit antiproliferative activity via modulating cell cycle arrest, cell apoptosis, and the p53 signaling pathway.

The phytochemical profiles, antioxidant activity and antiproliferative mechanism of two goji berry varieties were investigated in the present study. In contrast to Lycium barbarum L. (LB), Lycium ruthenicum Murr. (LRM) showed stronger antioxidant activity evaluated by ORAC, PSC and CAA assays, which might be attributed to its higher total phenolics and total flavonoids. However, LB contains greater contents of VE and carotenoids compared to LRM, which may endow LB with other unique functions instead of antioxidant activity. Additionally, high dose LRM showed a stronger capability in terms of cell cycle arrest and cell apoptosis induction of MDA cells with increments of 17.85% cells blocked at the G1 phase and 50.49% cells achieving early apoptosis compared with the control group. Although supplementation with LB increased the number of cells in the G1 phase by 10%, its effect on inducing cell apoptosis was not ideal. Furthermore, both LRM and LB activated the proliferation-related p53 signaling pathway including p53, p21, CDK4, Cyclin E, Bax and Caspase3, but LB failed to downregulate bcl-2 and CDK2 levels, indicating the weaker antiproliferative effect of LB. The present findings indicated LRM and LB as potential candidates for managing the proliferation of cancer cells and improving human health.

Methionine restriction alleviates age-associated cognitive decline via fibroblast growth factor 21.

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.

Effects of high hydrostatic pressure and thermal processing on anthocyanin content, polyphenol oxidase and ß-glucosidase activities, color, and antioxidant activities of blueberry (Vaccinium Spp.) puree.

Thermal processing (TP) and high hydrostatic pressure (HHP) are two important puree processing methods. In this study, the polyphenol oxidase (PPO) and ß-glucosidase activities, chromatic values, peroxide radical scavenging capacities (PSCs), cellular antioxidant activities (CAAs), and anthocyanin profiles were evaluated in blueberry puree following TP and HHP treatments. Nine anthocyanins were identified and cyanidin glycosides were the most abundant compounds in the blueberry puree sample. Petunidin-3-O-arabinoside, malvidin-3-O-galactoside, and malvidin-3-O-glucoside concentrations increased at temperatures of 70-90 °C (TP) and a pressure of 300 MPa (HHP). The highest total anthocyanin concentration (503.5 µg/mL) and PSC (13.45 µg VCE/mL) were observed following the TP (90 °C) treatment. Furthermore, a positive correlation was observed between the anthocyanin content and PSC (R2 = 0.655, P < 0.05). Finally, HHP treatment resulted in better puree color retention than TP treatment. The results of this study could provide valuable information for optimizing the processing methods for anthocyanin-rich products.

IRS-1/PI3K/Akt pathway and miRNAs are involved in whole grain highland barley (Hordeum vulgare L.) ameliorating hyperglycemia of db/db mice.

The effects of whole grain highland barley (WGH) with rich phenolics on glucose metabolism, the insulin pathway, and microRNA (miRNA) expression in db/db mice were explored in the present study. Supplementation with WGH decreased the levels of blood glucose, glycosylated serum protein (GSP), insulin, and inflammatory cytokines in db/db mice. Furthermore, WGH administration triggered a remarkable amelioration of glucose intolerance and insulin resistance. The hepatic glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxylase (PEPCK) activities and the G6PC, PEPCK, and forkhead transcription factor 1 (FOXO1) mRNA levels in the WGH-treated group were also reduced. Moreover, WGH promoted the glycogen storage in the liver via up-regulating the activities of hexokinase (HK) and glycogen synthase (GS) and the phosphorylation of glycogen synthase kinase 3ß (GSK3ß) protein, while down-regulating the GSK3ß mRNA level. The protein expression of phosphatidylinositol 3-kinase (PI3K), the phosphorylation of protein kinase B (Akt), and the mRNA levels of insulin receptor substrate-1 (IRS-1), PI3K and Akt were also up-regulated by WGH treatment. Moreover, WGH significantly augmented the expression of miRNA-26a and miRNA-451, but reduced those of miRNA-126a and miRNA-29a. These results demonstrated that WGH exhibits a hypoglycemic effect through regulating the IRS-1/PI3K/Akt pathway and related miRNAs, further modulating the expression of G6PC, PEPCK, and FOXO1 mRNAs and p-GSK3ß protein, thus inhibiting hepatic gluconeogenesis, improving glycogen synthesis and alleviating insulin resistance. Therefore, this study suggested WGH as an effective candidate to ameliorate the hyperglycemia of type 2 diabetes mellitus.

Effects of ethyl acetate fractional extract from Portulaca oleracea L. (PO-EA) on lifespan and healthspan in Caenorhabditis elegans.

Portulaca oleracea L. (PO), with abundant natural bioactive phytochemicals, exhibits potential bioactivities and pharmacological activities. However, the mechanisms of action of PO on anti-aging effect remain unclear. In this study, the ethyl acetate fractional extract from PO (PO-EA) was obtained by fractionation of solvent extractions, and its effect on lifespan was assessed using the Caenorhabditis elegans (C. elegans). Results showed that PO-EA could significantly increase the lifespan of C. elegans by 5.31, 12.67, and 16.47% at the doses of 250, 500, and 1,000 µg/mL, respectively. Moreover, PO-EA significantly promoted the mobility of C. elegans without obvious side effects such as changing body length or decreasing fecundity of the nematodes. Further study demonstrated that PO-EA could enhance the stress resistance in C. elegans via improving the activities of superoxide dismutase and catalase, and diminishing the contents of reactive oxygen species and malondialdehyde. The gene expression of daf-12, daf-16, sod-3, skn-1, cat-1, mev-1, akt-1, and sek-1 were upregulated in C. elegans after administrated by PO-EA. This study indicated that PO-EA plays a vital role in extending lifespan and healthspan in C. elegans, and the underlying mechanism of action might be attributed to Insulin/IGF-1-like signaling pathways. Therefore, PO-EA could be served as a potential candidate for anti-aging functional food. PRACTICAL APPLICATION: Portulaca oleracea L. (PO) is an edible vegetable that could be used as functional food to exert health benefits for humans such as neuroprotective, antioxidant, anticancer, and anti-aging effects. Therefore, our findings would provide a strategy to promote the comprehensive utilization of ethyl acetate extract from PO with additional health benefits.

Phenolic profiles, antioxidant, antiproliferative, and hypoglycemic activities of Ehretia macrophyla Wall. (EMW) fruit.

Phenolic profiles, antioxidant, antiproliferative, and hypoglycemic activities of the whole Ehretia macrophylla Wall. (EMW) fruit were investigated in the present study. Catechin (CE), o-methoxy benzoic acid (o-MBA), and rosmarinic acid (RA) were the predominant phenolics in free extract, while CE, vanillic acid (VA), and o-MBA were for bound extract. These extracts exhibited potential antioxidant capacity measured by peroxyl radical scavenging capacity (PSC), oxygen radical absorbance capacity (ORAC), and cellular antioxidant activity (CAA) assays. This fruit also possessed dose-dependently antiproliferative activity, and this may be due to the synergistic and additive effects of individual phenolics. Furthermore, EMW fruit showed favorable hypoglycemic activity via inhibition of activities of α-glucosidase and α-amylase, enhancement of glucose consumption, glycogen accumulation, and glycogen synthase 2 (GYS2) activity, and downregulation of activities of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK). Therefore, EMW fruit has the potential as an ingredient of functional foods to improve human health and shows promising applications with additional health and economical benefits. PRACTICAL APPLICATION: EMW fruit is a plant-based food rich in natural phenolic compounds, which suggesting its potential bioactivities for humans such as antioxidant, antiproliferative, and hypoglycemic activities. Our findings would provide a logical strategy to promote the comprehensive utilization of phenolics in EMW fruit with both health and economical benefits.

Antiproliferative Activity of Ursolic Acid in MDA-MB-231 Human Breast Cancer Cells through Nrf2 Pathway Regulation.

The potential mechanisms of action of ursolic acid (UA) in regulating cell proliferation in MDA-MB-231 human breast cancer cells through Nrf2 pathway were investigated. UA significantly inhibited the proliferation of MDA-MB-231 cells at a dose ≥10 µM in a dose-dependent manner, and no cytotoxicity was observed at concentrations below 29.87 ± 2.60 µM. The expressions of Nrf2 and p-Nrf2, in whole cell and nucleus, and NQO1 were inhibited by UA treatment, whereas the Keap1 expression was upregulated. No significant difference was observed in the Nrf2 mRNA levels, indicating that UA reduced Nrf2 expression not through mRNA but through a post-translational mechanism. Additionally, EGF-induced p-Nrf2 and its downstream NQO1 and SOD1 enzymes were abolished by UA. However, EGF or p-EGFR had no effect on the expressions of Keap1. These results suggested that the proliferative inhibitory effect of UA might be partially through downregulating Nrf2 via the Keap1/Nrf2 pathway and EGFR/Nrf2 pathway in MDA-MB-231 cells.

Comparison of phenolics, antioxidant, and antiproliferative activities of two Hypsizygus marmoreus varieties.

Phenolics, antioxidant activities, and antiproliferative properties of brown Hypsizygus marmoreus (brown HM) and white Hypsizygus marmoreus (white HM) were compared. The results showed that the contents of (+)-catechin, gallic acid, and protocatechuic acid of brown HM were higher than those of white HM. Moreover, brown HM had greater cellular antioxidant activity (CAA), peroxyl radical scavenging capacity (PSC), and oxygen radical absorbance capacity (ORAC) values than white HM, which demonstrated that brown HM presented a stronger antioxidant capacity. Both of brown HM and white HM showed remarkable antiproliferative activities against HepG2 cells and brown HM was proven to be the more effective. The flow cytometry results revealed that both of brown HM and white HM could induce G1 arrest and cell apoptotics in a dose-dependent manner. In addition, CyclinD1, CDK4, and Bcl-2 mRNA expression levels were downregulated with the treatment of brown HM or white HM. Taken together, our study revealed that brown HM afforded better antioxidant and antiproliferative activities than white HM and laid the foundation for potential application of Hypsizygus marmoreus as source of nutraceuticals and functional food products. PRACTICAL APPLICATION: A systematic assessment of the potential differences of phenolics, antioxidant, and antiproliferative activities between different Hypsizygus marmoreus varieties was carried out in the present study. Furthermore, our findings would present possible antiproliferative mechanism of extracts of different Hypsizygus marmoreus varieties, which may provide theoretical basis for further development and utilization of Hypsizygus marmoreus.

Phytochemical profiles of rice and their cellular antioxidant activity against ABAP induced oxidative stress in human hepatocellular carcinoma HepG2 cells.

The phytochemical contents, peroxyl radical scavenging capacities (PSCs) and cellular antioxidant activities (CAAs) of free and bound fractions of rice were reported. Black rice had the highest total phenolic content and total flavonoid content in free and bound fractions, followed by red rice, brown rice, and polished rice. Black rice contained much more free phenolic compounds than other rice samples, such as cyanidin-3-O-glucoside, protocatechuic acid, and vanillic acid. Tocopherols and tocotrienols contents were highest in red rice, then in black rice, brown rice, and polished rice. PSCs and CAAs of free and bound fractions were in the order: black rice > red rice > brown rice > polished rice, except that bound CAA of red rice was higher than that of black rice. The cellular uptake rate of free phenolics was highest in red rice, while cellular uptake rates of bound phenolics were highest in brown rice and polished rice.