James L. Hargrove

Nutritional Significance and Metabolism of Very Long Chain Fatty Alcohols and Acids from Dietary Waxes

Very long chain fatty alcohols obtained from plant waxes and beeswax have been reported to lower plasma cholesterol in humans. This review discusses nutritional or regulatory effects produced by wax esters or aliphatic acids and alcohols found in unrefined cereal grains, beeswax, and many plant-derived foods. Reports suggest that 5–20 mg per day of mixed C24–C34 alcohols, including octacosanol and triacontanol, lower low-density lipoprotein (LDL) cholesterol by 21%–29% and raise high-density lipoprotein cholesterol by 8%–15%. Wax esters are hydrolyzed by a bile salt–dependent pancreatic carboxyl esterase, releasing long chain alcohols and fatty acids that are absorbed in the gastrointestinal tract. Studies of fatty alcohol metabolism in fibroblasts suggest that very long chain fatty alcohols, fatty aldehydes, and fatty acids are reversibly inter-converted in a fatty alcohol cycle. The metabolism of these compounds is impaired in several inherited human peroxisomal disorders, including adrenoleukodystrophy and Sjögren-Larsson syndrome. Reports on dietary management of these diseases confirm that very long chain fatty acids (VLCFA) are normal constituents of the human diet and are synthesized endogenously. Concentrations of VLCFA in blood plasma increase during fasting and when children are placed on ketogenic diets to suppress seizures. Existing data support the hypothesis that VLCFA exert regulatory roles in cholesterol metabolism in the peroxisome and also alter LDL uptake and metabolism.

Inhibition of TNF-α induced ICAM-1, VCAM-1 and E-selectin expression by selenium

Abstract The initiation of an atherosclerotic lesion involves an endothelial cell pro-inflammatory state that recruits leukocytes and promotes their movement across the endothelium. These processes require endothelial expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial-leukocyte adhesion molecule-1 (E-selectin). Tumor necrosis factor-α (TNF-α) is a powerful inducer of these adhesion molecules. Selenium status is known to affect the rate of atherosclerosis. These experiments tested whether selenium alters cytokine-induced expression of these adhesion molecules. Human umbilical vein endothelial cells (HUVECs) were pretreated for 24 h with sodium selenite (0–2 μM) and then treated with 0 or 50 U/ml TNF-α in the presence of 0–2 μM selenite. ICAM-1, VCAM-1 and E-selectin were detected by ELISA and their mRNAs were evaluated by Northern blots. Selenite significantly inhibited TNF-α-induced expression of each adhesion molecule in a dose-dependent manner and reduced the level of the respective mRNAs. Nuclear factor-κB (NF-κB) is required for transcription of these adhesion molecule genes. Western blot analysis revealed that selenite did not inhibit the translocation of the p65 subunit of NF-κB to the nucleus. In conclusion, these data indicate selenium can modulate cytokine-induced expression of ICAM-1, VCAM-1 and E-selectin in HUVECs without interfering with translocation of NF-κB.

Topical anti-inflammatory activity of Polygonum cuspidatum extract in the TPA model of mouse ear inflammation.

BackgroundThis study tested the ability of a characterized extract of Polygonum cuspidatum (PCE) to inhibit mouse ear inflammation in response to topical application of 12-O- tetradecanoylphorbol-13-acetate (TPA).MethodsA 50% (wt:vol) ethanolic solution of commercial 200:1 PCE was applied to both ears of female Swiss mice (n = 8) at 0.075, 0.15, 0.3, 1.25 and 2.5 mg/ear 30 min after TPA administration (2 μg/ear). For comparison, 3 other groups were treated with TPA and either 1) the vehicle (50% ethanol) alone, 2) indomethacin (0.5 mg/ear), or 3) trans-resveratrol (0.62 mg/ear). Ear thickness was measured before TPA and at 4 and 24 h post-TPA administration to assess ear edema. Ear punch biopsies were collected at 24 h and weighed as a second index of edema. Myeloperoxidase activity was measured in each ear punch biopsy to assess neutrophil infiltration.ResultsPCE treatment at all doses significantly reduced ear edema compared to the TPA control. The PCE response was dose-dependent and 2.5 mg PCE significantly inhibited all markers of inflammation to a greater extent than indomethacin (0.5 mg). MPO activity was inhibited at PCE doses ≥ 1.25 mg/ear. Trans- resveratrol inhibited inflammation at comparable doses.ConclusionPCE inhibits development of edema and neutrophil infiltration in the TPA-treated mouse ear model of topical inflammation.

Inhibition of protein glycation by extracts of culinary herbs and spices.

We tested whether polyphenolic substances in extracts of commercial culinary herbs and spices would inhibit fructose-mediated protein glycation. Extracts of 24 herbs and spices from a local supermarket were tested for the ability to inhibit glycation of albumin. Dry samples were ground and extracted with 10 volumes of 50% ethanol, and total phenolic content and ferric reducing antioxidant potential (FRAP) were measured. Aliquots were incubated in triplicate at pH 7.4 with 0.25 M fructose and 10 mg/mL fatty acid-free bovine albumin. Fluorescence at 370 nm/440 nm was used as an index of albumin glycation. In general, spice extracts inhibited glycation more than herb extracts, but inhibition was correlated with total phenolic content (R(2) = 0.89). The most potent inhibitors included extracts of cloves, ground Jamaican allspice, and cinnamon. Potent herbs tested included sage, marjoram, tarragon, and rosemary. Total phenolics were highly correlated with FRAP values (R(2) = 0.93). The concentration of phenolics that inhibited glycation by 50% was typically 4-12 microg/mL. Relative to total phenolic concentration, extracts of powdered ginger and bay leaf were less effective than expected, and black pepper was more effective. Prevention of protein glycation is an example of the antidiabetic potential for bioactive compounds in culinary herbs and spices.

Anti-inflammatory activity of select sorghum (Sorghum bicolor) brans.

The bran fractions of certain varieties of sorghum (Sorghum bicolor) grain are rich sources of phytochemicals and antioxidants. In this article, the anti-inflammatory actions of extracts of select sorghum brans were evaluated in two experimental inflammatory systems: (1) the release of cytokines by lipopolysaccharide-activated peripheral blood mononuclear cells and (2) 12-O-tetradecanoylphorbol acetate (TPA)-induced ear edema in mice. A 1:200 dilution of a 10% (wt/vol) ethanol extract of black sorghum bran significantly inhibited the secretion of the pro-inflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha. Ethanolic extracts of both black and sumac varieties of sorghum bran significantly reduced edema in inflamed ears as measured by ear thickness and ear punch weight 6 hours following TPA application. The degree of inhibition was similar to that observed with indomethacin. Black sorghum bran significantly diminished the increase in myeloperoxidase activity 24 hours following the application of TPA. No anti-inflammatory activity was observed with white and Mycogen sorghum bran varieties or with oat, wheat, or rice brans in the mouse ear model. The anti-inflammatory activity observed with these brans correlated with their phenolic content and antioxidant activity. These results demonstrate that select sorghum bran varieties possess significant anti-inflammatory activity.

Inhibition of aromatase and α-amylase by flavonoids and proanthocyanidins from Sorghum bicolor bran extracts.

We compared the ability of simple flavonoids and proanthocyanidins in Sorghum bicolor bran extracts to inhibit enzymes in vitro. In particular, aromatase is a target for breast cancer therapy, and inhibition of α-amylase can reduce the glycemic effect of dietary starches. Proanthocyanidin-rich sumac sorghum bran extract inhibited α-amylase at a lower concentration (50% inhibitory concentration [IC₅₀]=1.4 μg/mL) than did proanthocyanidin-free black sorghum bran extract (IC₅₀=11.4 μg/mL). Sumac sorghum bran extract inhibited aromatase activity more strongly than black sorghum bran extract (IC₅₀=12.1 μg/mL vs. 18.8 μg/mL, respectively). Bovine serum albumin (BSA), which binds proanthocyanidins, reduced inhibition by sumac but not black sorghum bran extract. When separated on Sephadex LH-20, sumac sorghum proanthocyanidins inhibited both enzymes but showed reduced inhibition with BSA. Flavonoids from either cultivar had higher IC₅₀ values than proanthocyanidins, and BSA had little effect on their inhibition. Proanthocyanidins and simple flavonoids in LH-20 fractions both inhibited aromatase with mixed kinetics and affected K(m) and V(max). The results show that potential health benefits of sorghum bran may include actions of monomeric flavanoids as well as proanthocyanidins.

Inhibition of Hyaluronidase Activity by Select Sorghum Brans

Hyaluronidase hydrolyzes glycosaminoglycans, including hyaluronan, in the extracellular matrix during tissue remodeling. Hyaluronidase activity increases in chronic inflammatory conditions, e.g., inflammatory joint disease. In this study, we tested the ability of ethanolic extracts (1:9 [wt/vol] of 50% ethanol) of bran from six cultivated varieties of Sorghum bicolor to inhibit hyaluronidase activity in vitro in comparison to extracts of wheat and rice bran. Each extract inhibited hyaluronidase activity with this order of potency: Sumac > Shanqui Red > Black > Mycogen > Fontanelle > White sorghum. Extracts of wheat and rice bran had weak inhibitory activities relative to the high phenolic sorghum brans. Hyaluronidase inhibition correlated positively with total phenolic content and ferric reducing antioxidant power values for each bran extract. Inhibition was not only due to condensed tannins (proanthocyanidins) because the Black sorghum cultivar lacks condensed tannins but has abundant anthocyanins and other polyphenols. Since hyaluronidase activity is important in conditions such as osteoarthritis and skin aging, these sorghum varieties deserve consideration for functional foods and beverages, and for nutraceutical and cosmeceutical ingredients.

Microcomputer-assisted kinetic modeling of mammalian gene expression.

New software for microcomputers enables predictive, quantitative models of genetic systems to be produced that can account for the elements of time, scale, and feedback control of hierarchical systems. The flow of genetic information during protein synthesis can be addressed by treating each intermediate as a kinetic element in a linked series of reactions. When the rate of transcription changes, the time required to achieve a new level of the encoded protein is expected to be a function of the conversion rates or half‐lives of all intermediates. Kinetic modeling may be used to make predictions and integrate primary data concerning rates of transcription, nuclear mRNA dynamics, nucleocytoplasmic transport, translational control, and other processes that govern the rate of synthesis for specific proteins.—Hargrove, J. L., Microcomputer‐assisted kinetic modeling of mammalian gene expression. FASEB J. 7: 1163‐1170; 1993.

Nutrition and Health Education Intervention for Whole Grain Foods in the Georgia Older Americans Nutrition Program

Abstract This study examined the effects of a nutrition education intervention on improving the intake and behaviors related to whole grain foods in congregate meal recipients in senior centers in north Georgia. Participants were a convenience sample and completed a pretest, an educational intervention, and a posttest (N = 84, mean age = 77 years, 88% female, 76% Caucasian, and 24% African American). At the pretest, most participants agreed that eating more whole grain foods would help reduce their risk of cancer (69%), heart disease (76%), type 2 diabetes (65%), and bowel disorders (82%), but consumption of 11 whole grain foods was low (10.5 times/week). Following the intervention, participants were more likely to suggest one or more correct ways to identify whole grain foods (45 vs. 62%, P ⩽0.05), and to report an increased intake of whole grain bread, cereal, and crackers (5.8 vs. 6.9 times/week, P ⩽0.05). While awareness of the health benefits of whole grain foods was high, the intakes were low. As a first step, this intervention improved several aspects of the consumption of whole grain foods; however, additional interventions that target the individual and the congregate meal program are needed to increase intakes to the recommended three servings daily.

A novel nutraceutical property of select sorghum (Sorghum bicolor) brans: inhibition of protein glycation

Despite the high levels of polyphenolic phytochemicals in grain sorghum and its position as a major food staple, there has been a lack of research on its effects on both animal and human health and disease prevention. These phenolic compounds, mainly located in the bran fraction, result in the plant having substantial antioxidant properties. This study examined the effect of ethanol extracts of several varieties of sorghum (S. bicolor) bran on albumin glycation, a non‐enzymatic process thought to be important in the pathogenesis of many diabetic complications. Sorghum brans with a high phenolic content and high antioxidant properties inhibited protein glycation, whereas sorghum brans that are low in these properties did not inhibit this process. Ethanol extracts of wheat, rice or oat bran did not inhibit protein glycation. Although one high phenolic sorghum bran variety (sumac) inhibited protein glycation by approximately 60%, it produced only a 20% decrease in methylglyoxal mediated albumin glycation. These results suggest that certain varieties of sorghum bran may affect critical biological processes that are important in diabetes and insulin resistance. These results distinguish select sorghum brans from the common food brans and suggest a nutraceutical rationale for its human consumption. Copyright