Improving in vitro bioaccessibility and bioactivity of carnosic acid using a lecithin-based nanoemulsion system.

As a phenolic terpenoid, carnosic acid (CA) mainly exists in rosemary, which can be effectively used for the treatment of degenerative and chronic diseases by taking advantage of its health-promoting bioactivities. However, the low solubility and dissolution of CA in aqueous solutions at ambient and body temperatures result in low stability and bioaccessibility during the digestion process, which limits its application scope in the functional foods industry. In this regard, a lecithin based nanoemulsion system (CA-NE) is employed in the present work to enhance the bioaccessibility and bioactivities of CA. It is revealed that the CA-NE under investigation exhibits high loading capacity (2.80 ± 0.15%), small particle size (172.0 ± 3.5 nm) with homogeneous particle distribution (polydispersity index (PDI) of 0.231± 0.025) and high repulsive force (zeta potential = -57.2 ± 0.24 mV). More importantly, the bioaccessibility of CA-NE is improved by 2.8-fold compared to that of CA in MCT oil. In addition, the cellular antioxidant assay (CAA) and cellular uptake study of the CA-NE in HepG2 cell models demonstrate a longer endocytosis process, suggesting the well-controlled release of CA from CA-NE. Furthermore, an improved anti-inflammatory activity was evaluated via the inhibition of the pro-inflammatory cytokines, nitric oxide (NO) and TNF-α production in LPS-stimulated RAW 264.7 macrophage cells. The results clearly demonstrated a promising application of CA-NE as a functional food.

Antistress and anti-aging activities of Caenorhabditis elegans were enhanced by Momordica saponin extract.

BACKGROUND: Momordica saponin extract (MSE) was found to not only improve longevity and neuroprotection but also alleviate fat accumulation in Caenorhabditis elegans in our previous study. However, the lipid-lowering activity of MSE alone could not fully explain its ability to improve health, so the antistress effects of MSE were further studied. METHODS: Using C. elegans as an in vivo animal, the lifespan of MSE-treated C. elegans under various stressors (H2O2, paraquat and heat) and normal conditions was studied. Furthermore, the antioxidant activities of MSE were discussed. To study the underlying mechanisms, the expression of stress resistance genes and the resistance of related mutants to H2O2 stress were tested. RESULTS: MSE significantly improved the lifespan of C. elegans under stress and normal conditions. Meanwhile, the mobility of C. elegans was also improved. Moreover, the activities of SOD and CAT and the ratio of GSH/GSSG were elevated. Consistently, the levels of ROS and lipid oxidation (the NEFA and MDA content) were reduced. Furthermore, MSE treatment upregulated the expression of the sod-3, sod-5, clt-1, clt-2, hsp-16.1 and hsp-16.2 genes. All biomarkers indicated that the antistress and anti-aging activities of MSE were due to its strong antioxidant activities. Finally, MSE induced nuclear DAF-16::GFP localization. Studies with mutants revealed that skn-1 and hsf-1 were involved in the activity of MSE, which might upregulate the expression of downstream stress-responsive genes. CONCLUSIONS: Therefore, in addition to its lipid-lowering property, the ability of MSE to improve healthspan was also attributed to the stress resistance effect. Together, MSE might serve as a lead nutraceutical in geriatric research.

Effect of Momordica saponin- and Cyclocarya paliurus polysaccharide-enriched beverages on oxidative stress and fat accumulation in Caenorhabditis elegans.

BACKGROUND: As an edible and medicinal herb in Chinese folk medicine, Cyclocarya paliurus (Batal.) Iljinskaja leaves are traditionally widely used in the treatment of metabolic disorders. The vegetable Momordica charantia L. has been consumed worldwide for thousands of years as a traditional drug due to its activities against obesity and diabetes. In view of the therapeutic value of Momordica saponins (MSs) and C. paliurus polysaccharides (CPPs), an independently developed MSs- and CPPs-containing beverage (MC) was evaluated for its efficacy in controlling oxidative stress and obesity in Caenorhabditis elegans. RESULTS: First, we found that MC could promote the nuclear localization of DAF-16 and the translation of SOD-3. Further exploring its antioxidant properties, the oxidative stress by-products reactive oxygen species, malondialdehyde, and nonesterified fatty acids were significantly inhibited in C. elegans. Moreover, damage due to diseases related to oxidative stress (age pigments and neurodegenerative diseases) was alleviated. Furthermore, fat accumulation was significantly reduced in normal and high-fat models. Finally, the lipid-lowering effects of MC might involve reductions in the size and number of lipid droplets without impairing basic physiological functions in C. elegans. CONCLUSION: These results provide promising data indicating MC as an innovative health beverage for the pharmacological management of oxidative stress and obesity. © 2020 Society of Chemical Industry.

In vitro and in vivo antioxidant activity of eucalyptus leaf polyphenols extract and its effect on chicken meat quality and cecum microbiota.

While eucalyptus leaf polyphenols extract (EPE) has been evaluated for its various bioactivities, few studies thus far have focused on its systemic antioxidant activity or its effects in chickens in relation to meat quality or the intestinal microbiome. Therefore, the goal of this study was to investigate the antioxidant activity of EPE in vitro and in vivo, and to evaluate its effect on chicken meat quality and cecum microbiota. In this study, EPE scavenged DPPH free radical, ABTS free radical, and superoxide radical, and showed strong reducing power in chemical-based assay. EPE protected RAW264.7 cells from H2O2-induced oxidative damage by improving total superoxide dismutase (T-SOD) activity, catalase (CAT) activity and glutathione (GSH) content, decreasing malondialdehyde (MDA) content. Additionally, EPE dietary supplementation was found to increase chicken meat antioxidant levels and quality. Furthermore, chickens fed a diet supplemented with EPE had differentially changed cecal microbial compositions when compared to controls. EPE supplementation notably improved the α-diversity of the cecum. The Firmicutes/Bacteroidetes ratio and the relative abundance of Verrucomicrobia at the phylum level were clearly enhanced in the cecum with EPE supplementation (p < 0.05), with the relative abundance of Subdivision 5 genera incertae sedis and Aminivibrio enriched at genus level (p < 0.05). Therefore, these findings indicate that EPE is a good source of natural antioxidants and could be used as antioxidant supplements in animal feed and other foods, contributing to gut health improvement.

Dietary citrus peel essential oil ameliorates hypercholesterolemia and hepatic steatosis by modulating lipid and cholesterol homeostasis.

Citrus peel essential oil (CPEO) contains abundant volatile compounds and exhibits fragrance properties and beneficial pharmacological effects on humans. Herein, we aimed to investigate the effects of CPEO on the prevention of hypercholesterolemia and hepatic steatosis in high-fat diet-fed rats and identify its possible regulatory mechanisms in lipid metabolism by combining lipidomics with gene expression analysis. CPEO at effective supplementation levels of 0.5% and 0.75% significantly ameliorated hypercholesterolemia and hepatic steatosis, including decreased serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), hepatic TC and triglyceride (TG) levels, and hepatic lipid droplet accumulation. Lipidomics analysis revealed that the total levels of fatty acid (FFA), TG and cholesteryl ester (CE) classes in the liver tissue were remarkably decreased after 0.75% CPEO supplementation some of which (3 TGs and 4 CEs) might emerge as potential lipid biomarkers in response to the effects of CPEO. Furthermore, these lipidomics findings were associated with downregulation of lipogenesis-related genes SREBP-1c, ACC and FAS and upregulation of bile acid biosynthesis-related genes LXRα, CYP7A1 and CYP27A1 in the liver. This study indicated that CPEO could effectively prevent hypercholesterolemia and hepatic steatosis, possibly because of its mediation of lipid and cholesterol homeostasis by altering liver lipid metabolites and regulating lipid metabolism-related genes.

Proteome and Transcriptome Analysis of the Antioxidant Mechanism in Chicken Regulated by Eucalyptus Leaf Polyphenols Extract.

Eucalyptus leaf polyphenols extract (EPE) has been proved to have various bioactivities, but few reports focus on its antioxidant mechanism in vivo. The purpose of this study was to elucidate the effect and mechanism of EPE dietary supplements on antioxidant capacity in chicken. A total of 216 chickens were randomly selected for a 40-day experiment. Four treatment groups received diets including the control diet only, the control diet + low EPE (0.6 g/kg), the control diet + moderate EPE (0.9 g/kg), and the control diet + high EPE (1.2 g/kg). Compared with control group, the glutathione peroxidase (GSH-Px) activity and glutathione (GSH) content in the breast muscle of the moderate EPE treatment group was significantly higher (p < 0.05), while the malonaldehyde (MDA) content in the moderate EPE group was reduced (p < 0.05). Moreover, proteomic and transcriptomic analyses of the breast muscle revealed that glutathione metabolism and the peroxisome were the two crucial metabolic pathways responsible for increased antioxidant capacity of the muscle. Accordingly, nine candidate genes and two candidate proteins were identified related to improved antioxidant status induced by EPE supplements. This research provides new insights into the molecular mechanism of antioxidant capacity in chickens treated with EPE dietary supplements.

Oxyresveratrol extracted from Artocarpus heterophyllus Lam. inhibits tyrosinase and age pigments in vitro and in vivo.

We extracted and purified oxyresveratrol (OXY) from Artocarpus heterophyllus Lam. and identified its structure. The kinetics and mechanisms of OXY-induced mushroom tyrosinase inhibition were studied using fluorescence spectroscopy, copper ion chelation, and circular dichroism (CD). We found that OXY significantly inhibited tyrosinase with a half maximal inhibitory concentration (IC50) of 0.03 mM. The inhibitory effect of OXY on tyrosinase was almost 25 times that of kojic acid, which had an IC50 of 0.78 mM. Additionally, OXY and the tyrosinase substrate L-dopa did not have a competitive relationship; OXY is a non-competitive inhibitor. Using a fluorescence quenching experiment, we determined the corresponding rate constant (Kq) values at 298, 303, and 310 K to be 2.24 × 1012, 1.08 × 1012 and 1.44 × 1012 L mol-1 s-1, respectively. The OXY and tyrosinase interaction occured mainly through van der Waals forces and a hydrogen bond between the -OH group and its amino acid residue. Furthermore, we investigated the effects of OXY on murine melanoma B16 cells and on age pigments in Caenorhabditis elegans (C. elegans). OXY decreased melanin production by inhibiting the tyrosinase activity in murine melanoma B16 cells, which decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH) and increased catalase (CAT), leading to apoptosis. The lifespan of nematodes in the 50 ml resveratrol-treated group was significantly longer than that in the blank group by 5%. The mean lifespan of nematodes in the 50 µM OXY-treated group was significantly longer than that in the blank group by 6.82%.The fluorescence intensity of C. elegans pigments decreased by 30.43%, 47.35% and 64.42% after the treatment with a low, middle, and high OXY dose, respectively, showing that OXY has a significant inhibitory effect on melanin and age pigment production.

Bioactivity-guided isolation of anti-inflammatory components from Phyllanthus emblica.

Phyllanthus emblica (P. emblica) is a traditionally edible fruit that is good for treatment of biliary diseases, bronchitis, etc. It has obvious anti-inflammatory activity, but few studies focus on its anti-inflammatory active substance basis. The purpose of this study was to explore the material basis of anti-inflammatory activity of P. emblica, purify, and identify anti-inflammatory active monomers. Fisetin and gallic acid, which were identified after separation from ethanol extract components of P. emblica, exhibited the best anti-inflammatory effects, markedly inhibiting nitric oxide and proinflammatory cytokine levels in LPS-stimulated macrophages. In particular, fisetin with significant anti-inflammatory activity was firstly identified from P. emblica. For the first time, our research systematically revealed the material basis of the anti-inflammatory effects of P. emblica from the perspective of the composition of the bioactive substances and provided scientific research methods and ideas for researching bioactive monomers in other plant extracts.

Anti-fat effect and mechanism of polysaccharide-enriched extract from Cyclocarya paliurus (Batal.) Iljinskaja in Caenorhabditis elegans.

Obesity is a global epidemic. Recent studies have shown that Cyclocarya paliurus (C. paliurus) leaves have the potential to alleviate fat deposits. However, the fat-reducing mechanism of it remains unclear. Using Caenorhabditis elegans (C. elegans) as a model, we found that C. paliurus polysaccharide (CPP) significantly decreased fat storage in both normal and high-fat worms without affecting the movement. Moreover, the size and number of lipid droplets were reduced in CPP-treated ZXW618 worms. In energy metabolism, CPP decreased Escherichia coli (E. coli) OP50 growth and pharyngeal pumping and increased the expression of vit-2. In lipid metabolism, CPP down-regulated the expression of the sbp-1 and nhr-49 genes by modulating mdt-15 to prevent the expression of the Δ9-desaturase genes (fat-5, fat-6 and fat-7). Meanwhile, the expression of the acs-2 genes, the downstream of nhr-49, was suppressed by CPP. These findings provided insights into the CPP-induced anti-fat mechanisms, which contributed to the application of CPP in anti-obesity drugs.

Hepatic Lipidomics Analysis Reveals the Antiobesity and Cholesterol-Lowering Effects of Tangeretin in High-Fat Diet-Fed Rats.

Tangeretin (TAN) exhibited antilipogenic, antidiabetic, and lipid-lowering effects. However, the lipid biomarkers and the underlying mechanisms for antiobesity and cholesterol-lowering effects of TAN have not been sufficiently investigated. Herein, we integrated biochemical analysis with lipidomics to elucidate its efficacy and mechanisms in high-fat diet-fed rats. TAN at supplementation levels of 0.04 and 0.08% not only significantly decreased body weight gain, serum total cholesterol, and low-density lipoprotein cholesterol levels but also ameliorated hepatic steatosis. These beneficial effects were associated with the declining levels of fatty acids, diacylglycerols (DGs), triacylglycerols, ceramides, and cholesteryl esters by hepatic lipidomics analysis, which were attributed to downregulating lipogenesis-related genes and upregulating lipid oxidation- and bile acid biosynthesis-related genes. Additionally, 21 lipids were identified as potential lipid biomarkers, such as DGs and phosphatidylethanolamines. These findings indicated that the modulation of lipid homeostasis might be the key pathways for the mechanisms of TAN in the antiobesity and cholesterol-lowering effects.

Engineering water-induced ceramide/lecithin oleogels: understanding the influence of water added upon pre- and post-nucleation.

A mixture of ceramide (CER) and lecithin (LEC) at specific ratios was capable of forming oleogels in sunflower oil triggered by adding a trace amount of water. It was noted that the addition of water at different temperatures (TW) resulted in different gelation behaviors and microstructures. To better illuminate the assembly mechanism at different TW, samples with water added at different TW (20 °C, 45 °C, 70 °C and 95 °C) were prepared. The viscoelastic properties, microstructures, and the crystal packing of these samples were investigated. It was observed that all samples prepared at TW of 20 °C and 95 °C formed gels, while most samples prepared at TW of 45 °C and 70 °C were too weak to form gels. Gels prepared at 95 °C were stronger but more fragile in texture compared to gels produced at 20 °C. The crystal morphology of gels drastically changed with TW. Spindle-shaped crystals were observed in gels prepared at low TW (20 °C), while gels prepared at high TW (95 °C) exhibited a network with packed oil droplets stabilized by lamellar shells together with fibrillar crystals in the bulk phase. X-ray diffractograms showed a different reflection peak (d-spacing of 14.5 Å) in gel prepared at 20 °C, compared to the d-spacing in oleogels with a single gelator (13.14 Å and 15.33 Å, respectively, for CER and LEC). Gel prepared at 95 °C showed two long-spacing characteristic peaks, which correspond to the characteristic peaks of CER gel (∼13 Å) and LEC gel (∼12 Å). Fourier transform infrared spectroscopy results indicated that the different gelation behaviors at different TW were mainly caused by vibrational changes in the amide bond of CER. Our hypothesized assembly mechanism can be concluded as: increasing TW resulted in the conversion of CER and LEC crystallization from co-assembly (TW = 20 °C) to self-sorting by individual gelators (TW = 95 °C). In this study, novel water-induced oleogels were produced by manipulating TW, and such information further assists the rational design of lipid-based healthy fat products.

HPLC fingerprint analysis of Phyllanthus emblica ethanol extract and their antioxidant and anti-inflammatory properties.

ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthus emblica L. (P. emblica) as a medical plant has been used to treat diseases in Asia. It is famous for a wide range of biological activities, especially for its antioxidant and anti-inflammatory activity. However, quality control underlying the bioactivity of P. emblica fruits remains to be studied. MATERIALS AND METHODS: In this study, we evaluated the HPLC fingerprint and bioactivity of polyphenols extracted from P. emblica fruits grown in different habitats. RESULTS: P. emblica fruits collected from 10 different habitats in Guangdong, Fujian, Yunnan, and Guangxi provinces in China were used to establish a simple and reliable HPLC fingerprint assay. Simultaneous quantification of three monophenols was also performed to determine assay quality and consistency. Additionally, chemical assessment of the different ethanolic extract (PEEE) from 10 P. emblica fruits demonstrated that they exhibited antioxidant activity by enhancing reducing power and total antioxidant capacity, scavenging hydroxyl radical and superoxide anion. PEEE protected RAW264.7 cells from oxidative damage by increasing glutathione content and total superoxide dismutase activity, suppressing MDA content. PEPE also alleviated lipopolysaccharide-induced inflammation in RAW 264.7 cells by decreasing release of pro-inflammatory mediators. Notably, the PEEE samples from Yunnan province showed the optimal antioxidant and anti-inflammatory effects among all the PEEE samples. CONCLUSION: In conclusion, The PEEE HPLC fingerprint may help improve P. emblica quality control, and P. emblica with antioxidant and anti-inflammatory activities may be potentially applied in functional foods or in adjuvant therapy for medicinal development.

RNA-seq-based quanitative transcriptome analysis of meat color and taste from chickens administered by eucalyptus leaf polyphenols extract.

To evaluate how eucalyptus leaf polyphenol extract (EPE) affects chicken meat color and taste, we added different levels of EPE (0%, 0.06%, 0.09%, and 0.12%) to chicken feed. The redness (a* value) and the myoglobin content of breast muscle in EPE group were remarkably higher. Furthermore, the guanosine monophosphate, histidine, and glycine muscle contents were also enhanced. Transcriptome analysis showed that 10 candidate genes related to meat quality were affected by EPE treatment. The identified genes, with functions critical to chicken meat color and taste, will help to determine the molecular mechanisms of EPE.

Healthspan Improvements in Caenorhabditis elegans with Traditional Chinese Herbal Tea.

Searching for natural and safe herbal tea with health benefits has attracted more and more attention, which is of great significance for reducing disease risk. A Chinese traditional herbal tea (HT) is rich in active ingredients extracted from natural plants. Numerous pharmacological studies showed that HT had the potential to improve health, including antidepression and antioxidant effects. In this study, we proposed a strategy to explore the role and underlying mechanism of HT in improving healthspan of a Caenorhabditis elegans model. First, we found that HT significantly prolonged the lifespan without reducing fertility in worms. Second, stress resistance (oxidative stress and heat stress) was enhanced and Aß- and polyQ-induced toxicity was relieved significantly by HT treatment. Both fat deposition and age pigment accumulation were found to be significantly reduced in HT-treated worms. The locomotion in mid-late stages was improved, indicating that behavioral mobility was also significantly enhanced. Furthermore, the main components of HT were eighteen polyphenols and two terpenoids. Finally, it was found that this protective mechanism was positively correlated with the insulin/insulin-like growth factor signaling- (IIS-) dependent manner, which went through promoting the nuclear localization of DAF-16 and its downstream SOD-3 expression. These results suggested that HT had an important role in improving health, which might serve as a promising healthy tea.

Polysaccharide extracted from the leaves of Cyclocarya paliurus (Batal.) Iljinskaja enhanced stress resistance in Caenorhabditis elegans via skn-1 and hsf-1.

Cyclocarya paliurus polysaccharide (CPP) has many beneficial biological activities. Although the antioxidant activity of CPP is well-known, the stress tolerance and underlying mechanism of the activities of CPP have not been determined in vivo. In this study, we applied the emerging model of Caenorhabditis elegans (C. elegans) to observe that CPP imparted stronger resistance to stress than the positive control Astragalus polysaccharide (H2O2- and paraquat-induced oxidative stress, as well as heat stress) without threatening the growth and reproduction of worms. Further studies found that CPP-treated worms had a strong antioxidant defense system that downregulated peroxidation products (ROS, MDA, NEFAs and GSSG) and upregulated antioxidant enzymes and nonenzymatic activities (SOD, CAT, GSH-Px and GSH). The CPP-treated worms also exhibited improved physiological functions, such as inhibition of age pigment and improvement of lifespan, mobility and neuroprotection. Further exploration of the mechanism of action of CPP treatment suggested that increased resistance to CPP might activate stress-inducible genes (sod-3, sod-5, ctl-1, ctl-2, hsp-16.1 and hsp-16.2) via skn-1 and hsf-1, rather than daf-16. These findings suggest that CPP may have health benefits for humans.

Effects of Momordica saponin extract on alleviating fat accumulation in Caenorhabditis elegans.

Momordica saponins have diverse biological activities and are widely used to improve obesity. Here, we investigated the alleviation of fat accumulation and mechanism of action of the saponin-enriched ethanol extract from Momordica charantia (MSE) in Caenorhabditis elegans (C. elegans). First, MSE had a strong fat-reduction capacity in normal and high-fat worms. Second, MSE significantly increased the proportion of small lipid droplets and reduced the average particle size in ZXW618. Meanwhile, it improved lifespan and healthspan and physiological functions, such as age pigmentation and neuroprotection. Furthermore, MSE mediated fat reduction gets involved neither in energy intake nor in energy expenditure. Finally, MSE might down-regulate sbp-1 and nhr-49 via mdt-15, and up regulate age-1 via daf-2. And these targets genes together down-regulated the expression of fat-5, fat-6 and fat-7 to decrease fat accumulation. Our results provided new insights into the inhibition of fat accumulation and underlying mechanisms of Momordica saponins in C. elegans, which might be developed into a nutraceutical to ameliorate obesity.

The effect of dietary magnesium and caseinphosphopeptides on bone metabolism in rats.

The effect of dietary magnesium (Mg) or caseinphosphopeptides (CPPs) on bone metabolism has been reported. However, few studies have investigated the effects of simultaneous supplementation of Mg and CPPs. Sixty-three 3-week-old Sprague-Dawley male rats were divided into seven groups and fed a specified diet for 45 days. Body characteristics, bone physicochemical indicators, and bone metabolism indicators relative to bone metabolism were analyzed. We found that, first, a dietary Mg deficiency resulted in increased bone formation and decreased bone resorption. Second, dietary Mg or CPP supplementation promoted bone formation and prevented bone resorption. Third, dietary Mg supplementation with CPPs also functioned to enhance bone formation and prevent bone resorption. There were synergistic effects on femur length, serum parathyroid hormone level and urinary deoxypyridinoline of the HS-Mg-CPP group (0.2% Mg, 0.1% CPPs). The increase in the femur length of the HS-Mg-CPP group compared with the control group was 6% which was much higher than that of HS-Mg (1%) or CPPs (5%). The induction in serum parathyroid hormone content in the HS-Mg-CPP group was 33% compared with the control group which was higher than that of the induction of the HS-Mg (19%) or CPP (23%) group. The induction in the deoxypyridinoline content of the HS-Mg-CPP (43%) group compared with the control group was remarkably higher than that of HS-Mg (8%) or CPPs (16%). Overall our results demonstrated that high doses of Mg (0.2%) and CPPs (0.1%) in combination produced synergistic effects on femur length, serum parathyroid hormone level and urinary deoxypyridinoline in rats, which is important for a better understanding of the effect of Mg and CPPs on bone metabolism.

Novel ent-Kaurane Diterpenoid from Rubus corchorifolius L. f. Inhibits Human Colon Cancer Cell Growth via Inducing Cell Cycle Arrest and Apoptosis.

The tender leaves of Rubus corchorifolius L. f. have been consumed as tea for drinking in China since ancient times. In this study, a novel ent-kaurane diterpenoid was isolated and identified from R. corchorifolius L. f. leaves as ent-kaur-2-one-16ß,17-dihydroxy-acetone-ketal (DEK). DEK suppressed the growth of HCT116 human colon cancer cells with an IC50 value of 40 ± 0.21 µM, while it did not cause significant growth inhibition on CCD-18Co human colonic myofibroblasts at up to100 µM. Moreover, DEK induced extensive apoptosis and S phase cell cycle arrest in the colon cancer cells. Accordingly, DEK caused profound effects on multiple signaling proteins associated with cell proliferation, cell death, and inflammation. DEK significantly upregulated the expression levels of pro-apoptotic proteins such as cleaved caspase-3, cleaved caspase-9, cleaved PARP, p53, Bax, and tumor suppressor p21Cip1/Waf1, downregulated the levels of cell cycle regulating proteins such as cyclinD1, CDK2, and CDK4 and carcinogenic proteins such as EGFR and COX-2, and suppressed the activation of Akt. Overall, our results provide a basis for using DEK as a potential chemopreventive agent against colon carcinogenesis.

Identification of terpenoids from Rubus corchorifolius L. f. leaves and their anti-proliferative effects on human cancer cells.

The leaves of Rubus corchorifolius L. f. have been consumed as a herbal tea for a long time. In this study, two novel (1 and 5) and four known (2, 3, 4 and 6) terpenoids were isolated from the leaves of Rubus corchorifolius L. f. Structural analysis was performed using various spectroscopic methods (1H NMR, 13C NMR and MS) to identify the following six compounds: (16α)-16,17,18-trihydroxy-ent-kauran-18-O-ß-d-glucoside (1), ent-16ß,17-dialkyl-3-oxygen-kaurane (2), ent-kaurane-3α,16ß,17-triol (3), ent-kaurane(5R,8S,9R,10R,13R,16R)-2-one-16α,17-diol (4), (16R)-16ß,17,19-trihydroxy-ent-kaur-3-one (5) and ent-16α,17-dihydroxy-kauran-19-oic-acid (6). These compounds showed different inhibitory effects on various human cancer cells. Compounds 3 and 6 exhibited stronger inhibitory effects on human colon cancer HCT116 cells than the other 4 compounds. Flow cytometry analysis demonstrated that both compounds 3 and 6 caused cell cycle arrest at the G0/G1 phase and induced cellular apoptosis in HCT116 cells. Compounds 3 and 6 modulated the expression levels of key signaling proteins closely related to cell proliferation and apoptosis, i.e., increasing the levels of poly(ADP-ribose) polymerase, p53, and p27, and decreasing the levels of EGFR, cyclin D1, CDK2 and CDK4. Overall, our findings provided insight into the anticancer components of Rubus corchorifolius L. f. leaves, which could facilitate their utilization as functional food ingredients.

Mechanism of longevity extension of Caenorhabditis elegans induced by pentagalloyl glucose isolated from eucalyptus leaves.

The multicellular model organism Caenorhabditis elegans (C. elegans) was used to identify the anti-aging effect of pentagalloyl glucose (PGG) isolated from Eucalyptus leaves at four different concentrations. For 160 µM PGG, the median lifespan of C. elegans was found to increase by 18%, and the thermal stress resistance was also increased. The anti-aging effect of PGG did not cause side effects on the physiological functions including the reproduction, pharyngeal pumping rate, age pigments accumulation, and locomotion ability. The life extension induced by PGG was found to rely on genes daf-16, age-1, eat-2, sir-2.1, and isp-1 but did not rely on genes mev-1 and clk-1. These findings suggested that the insulin/IGF-1 signaling pathway, dietary restriction, Sir-2.1 signaling, and mitochondrial electron transport chain became partly involved with the mechanism of lifespan extension mediated by PGG. Our results provided an insight into the mechanism of longevity extension mediated by PGG in C. elegans, which might be developed into a new generation of multitarget drug to prolong lifespan.