The Polyphenols α-Mangostin and Nordihydroguaiaretic Acid Induce Oxidative Stress, Cell Cycle Arrest, and Apoptosis in a Cellular Model of Medulloblastoma

Medulloblastoma is a common malignant brain tumor in the pediatric age. The current therapeutics present serious collateral effects. Polyphenols α-mangostin and nordihydroguaiaretic acid (NDGA) exert potent antitumoral activity in different cancer models, although their antitumoral effects have not been described in medulloblastoma cells yet. This study aimed to examine the proapoptotic effects of these polyphenols on human medulloblastoma cells. Medulloblastoma cell line Daoy was incubated with increasing concentrations of α-mangostin or NDGA for 24 h. The cell viability was analyzed using crystal violet and trypan blue dyes. Determination of the glutathione (GSH)/glutathione disulfide (GSSG) ratio and levels of carbonylated proteins was performed to evaluate the oxidative stress. Cell cycle progression and induction of cell death by fluorochrome-couple and TUNEL assays were evaluated using flow cytometry assays. Individual treatments with α-mangostin or NDGA decreased the viability of Daoy cells in a dose-dependent manner, inducing G2/M and S-G2/M cell cycle arrest, respectively. Both polyphenols induced cell death and increased oxidative stress. Very interestingly, α-mangostin showed more potent effects than NDGA. Our results indicate that α-mangostin and NDGA exert important cytostatic and cytotoxic effects in the Daoy cell line. These data highlight the potential usefulness of these compounds as an alternative strategy in medulloblastoma treatment.

Evaluation of the Antioxidant and Antiradical Properties of Some Phyto and Mammalian Lignans

In this study, the antioxidant and antiradical properties of some phyto lignans (nordihydroguaiaretic acid, secoisolariciresinol, secoisolariciresinol diglycoside, and α-(-)-conidendrin) and mammalian lignans (enterodiol and enterolactone) were examined by different antioxidant assays. For this purpose, radical scavenging activities of phyto and mammalian lignans were realized by 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical (ABTS•+) scavenging assay and 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging assay. Additionally, the reducing ability of phyto and mammalian lignans were evaluated by cupric ions (Cu2+) reducing (CUPRAC) ability, and ferric ions (Fe3+) and [Fe3+-(TPTZ)2]3+ complex reducing (FRAP) abilities. Also, half maximal inhibitory concentration (IC50) values were determined and reported for DPPH• and ABTS•+ scavenging influences of all of the lignan molecules. The absorbances of the lignans were found in the range of 0.150–2.320 for Fe3+ reducing, in the range of 0.040–2.090 for Cu2+ reducing, and in the range of 0.360–1.810 for the FRAP assay. On the other hand, the IC50 values of phyto and mammalian lignans were determined in the ranges of 6.601–932.167 µg/mL for DPPH• scavenging and 13.007–27.829 µg/mL for ABTS•+ scavenging. In all of the used bioanalytical methods, phyto lignans, as secondary metabolites in plants, demonstrated considerably higher antioxidant activity compared to that of mammalian lignans. In addition, it was observed that enterodiol and enterolactone exhibited relatively weaker antioxidant activities when compared to phyto lignans or standard antioxidants, including butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), Trolox, and α-tocopherol.

Antioxidants green tea extract and nordihydroguaiaretic acid confer species and strain specific lifespan and health effects in Caenorhabditis nematodes

The Caenorhabditis Intervention Testing Program (CITP) is an NIH–funded research consortium of investigators who conduct analyses at three independent sites to identify chemical interventions that reproducibly promote health and lifespan in a robust manner. The founding principle of the CITP is that compounds with positive effects across a genetically diverse panel of Caenorhabditis species and strains are likely engaging conserved biochemical pathways to exert their effects. As such, interventions that are broadly efficacious might be considered prominent compounds for translation for pre-clinical research and human clinical applications. Here, we report results generated using a recently streamlined pipeline approach for the evaluation of the effects of chemical compounds on lifespan and health. We studied five compounds previously shown to extend C. elegans lifespan or thought to promote mammalian health: 17α–estradiol, acarbose, green tea extract, nordihydroguaiaretic acid, and rapamycin. We found that green tea extract and nordihydroguaiaretic acid extend Caenorhabditis lifespan in a species-specific manner. Additionally, these two antioxidants conferred assay-specific effects in some studies–for example, decreasing survival for certain genetic backgrounds in manual survival assays in contrast with extended lifespan as assayed using automated C. elegans Lifespan Machines. We also observed that GTE and NDGA impact on older adult mobility capacity is dependent on genetic background, and that GTE reduces oxidative stress resistance in some Caenorhabditis strains. Overall, our analysis of the five compounds supports the general idea that genetic background and assay type can influence lifespan and health effects of compounds, and underscores that lifespan and health can be uncoupled by chemical interventions.

Canopy Spraying of Abscisic Acid to Improve Fruit Quality of Different Sweet Cherry Cultivars

Abscisic acid (ABA) plays a major role in promoting ripening in sweet cherry, a non-climacteric fruit. Exogenous application of ABA has been performed to study fruit ripening and cracking, but this growth regulator is not used for commercial production. To determine the potential of this growth regulator to improve sweet cherry fruit quality, ABA canopy spraying was assayed in four cultivars. Canopy spraying of S-ABA significantly: (1) enhanced sweet cherry fruit color in ‘Glenred’, ‘Lapins’ and ‘Bing’ cultivars, but not in ‘Royal Rainier’ (a bi-colored cultivar), and (2) decreased fruit size and firmness in ‘Lapins’, ‘Bing’ and ‘Royal Rainier’. Seasonally reproducible effects were seen in ‘Lapins’ (mid/late-maturing) but not in ‘Glenred’ (early-maturing). Canopy spraying of nordihydroguaiaretic acid (NDGA) decreased color and increased fruit size in ‘Lapins’, but not in ‘Glenred’. Direct application of ABA on fruits attached to the tree, without application to the foliage, increased ‘Lapins’ fruit color without reducing size. These results suggest a localized fruit response to exogenous ABA application on fruit color development, but that a decrease in fruit size may be due to the effects of exogenous ABA on the tree canopy foliage.

Canopy Spraying of Abscisic Acid to Improve Fruit Quality of Different Sweet Cherry Cultivars

Abscisic acid (ABA) plays a major role in promoting ripening in sweet cherry, a non-climateric fruit. Exogenous application of ABA has been performed to study fruit ripening and cracking, but this growth regulator is not used for commercial production. To determine the potential of this growth regulator to improve sweet cherry fruit quality, ABA canopy spraying was assayed in four cultivars. Canopy spraying of S-ABA significantly: 1) enhanced sweet cherry fruit color in ‘Glenred’, ‘Lapins’ and 'Bing' cultivars, but not in ‘Royal Rainier’ (a bi-colored cultivar), and 2) decreased fruit size and firmness in ‘Lapins’, ‘Bing’ and ‘Royal Rainier’. Seasonally reproducible effects were seen in ‘Lapins’ (mid/late-maturing) but not in ‘Glenred’ (early-maturing). Canopy spraying of nordihydroguaiaretic acid (NDGA) decreased color and increased fruit size in ‘Lapins’, but not in ‘Glenred’. Direct application of ABA on fruits attached to the tree, without application to the foliage, increased Lapins' fruit color without reducing size. These results suggest a localized fruit response to exogenous ABA application on fruit color development, but that a decrease in fruit size may be due to the effects of exogenous ABA on the tree canopy foliage.

Larrea tridentata and its biological activities

Background: Larrea tridentata is a dominant shrub in the deserts of North America and is recognized for its various traditional uses. More than 50 traditional uses have been recorded. Regarding its chemical composition, the products of the mevalonate, shikimate, and malonate pathways are predominant. L. tridentata has nordihydroguaiaretic acid (NDGA), one of its most studied secondary metabolites that exhibited remarkable different biological activities: sequestration of reactive oxygen species, inhibition of lipoxygenases (LOX) and activation of the endogenous antioxidant response mediated by nuclear factor erythroid 2–related factor 2 (NRF2). Objective and Methods: This review seeks to draw attention to metabolites other than NDGA and which also contribute to the various biological activities of L. tridentata. Therefore, the present review includes those reports focused on the pharmacological properties of the organic extracts of L. tridentata and its natural products with promising values. Results and Conclusion: Among the most promising and widely reported metabolites from L. tridentata, are: 3’-demethoxy-6-O-demethylisoguaiacin, 3’-O-methylnordihydroguiaretic acid, meso-dihydroguaiaretic acid, and tetra-O-methylnorhydroguiaretic acid. These have been reported to exhibit antibacterial, antiprotozoal, anthelmintic, antifungal, antiviral, anticancer, and antioxidant activities.

Targeting Mammalian 5-Lipoxygenase by Dietary Phenolics as an Anti-Inflammatory Mechanism: A Systematic Review

5-Lipoxygenase (5-LOX) plays a key role in inflammation through the biosynthesis of leukotrienes and other lipid mediators. Current evidence suggests that dietary (poly)phenols exert a beneficial impact on human health through anti-inflammatory activities. Their mechanisms of action have mostly been associated with the modulation of pro-inflammatory cytokines (TNF-α, IL-1β), prostaglandins (PGE2), and the interaction with NF-κB and cyclooxygenase 2 (COX-2) pathways. Much less is known about the 5-lipoxygenase (5-LOX) pathway as a target of dietary (poly)phenols. This systematic review aimed to summarize how dietary (poly)phenols target the 5-LOX pathway in preclinical and human studies. The number of studies identified is low (5, 24, and 127 human, animal, and cellular studies, respectively) compared to the thousands of studies focusing on the COX-2 pathway. Some (poly)phenolics such as caffeic acid, hydroxytyrosol, resveratrol, curcumin, nordihydroguaiaretic acid (NDGA), and quercetin have been reported to reduce the formation of 5-LOX eicosanoids in vitro. However, the in vivo evidence is inconclusive because of the low number of studies and the difficulty of attributing effects to (poly)phenols. Therefore, increasing the number of studies targeting the 5-LOX pathway would largely expand our knowledge on the anti-inflammatory mechanisms of (poly)phenols.

Creosote Bush (Larrea tridentata) Phytochemical Traits and its Different uses: A Review

Creosote bush (Larrea tridentata) is a perennial shrub present in Chihuahuan, Sonoran and Mojave deserts it contains diverse metabolites; among them lignans are the most important, one of the most studied is nordihydroguaiaretic acid (NDGA), this shrub has been studied for more than seventy years due to its great variety uses. The bactericidal effect of creosote bush has been well documented, as the fungicide, nematicide, protozoa and viral effect. It has been used as an antioxidant to preserve meat in canned food. Recently research has been done on NDGA effects on anti-carcinogenic cells. There is scarce information about the use of creosote bush in livestock production. Some studies in sheep and broilers are available. The results of these research indicate that creosote bush could be used to improve productive variables in livestock and have an intestinal effect on bacteria.