In the present study, we appraise the anti-inflammatory efficacy of lutein oxidative degradation derivatives mediated through UV-irradiation over lutein in counteracting the inflammation induced by lipopolysaccharide (LPS) in rats (n = 5 per group). UV-irradiated lutein fragments were identified as anhydrolutein (B, C40H54O), 2,6,6-trimethylcyclohexa-1,4-dienylium (M1, C9H13), (2E,4E,6E,8E)-9-(4-hydroxy-2,6,6-trimethylcyclohex-1-1en-1-yl)-3,7-dimethylnona-2,4,6,8-tetraen-1-ylium (M2, C20H29O), 4-[(1E,3E,5E,7E)-3,7,-dimethyldeca-1,3,5,7-tetraen-1-yl]-3,5,5-methylcyclohex-3-en-1-ol (M3, C21H30O) and zeaxanthin (M4, C40H56O) and its isomers as 13'-Z zeaxanthin, 13'-Z lutein, all-trans zeaxanthin, and 9-Z lutein. Induction of inflammation by LPS significantly increased the production of nitrites (3.3 fold in the serum and 2.6 fold in the liver), prostaglandin E2 (26 fold in the serum), and pro-inflammatory cytokines like tumor necrosis factor-α (6.6 fold in the serum), and interleukin-6 (4.8 fold in the serum). Oxidative derivatives of lutein, especially M1, M2 and M3, ameliorated acute inflammation in rats by inhibiting the production of nitrites, malondialdehyde (MDA), PGE2, TNF-α, and IL-6 cytokines more efficiently than lutein in rats. The anti-inflammatory mechanism of derivatives might be related to the decrease of inflammatory cytokines and the increase of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione S transferase, glutathione reductase), which would result in the reduction of iNOS, COX-2 and MDA and subsequently inflammatory responses.

Dipeptidyl peptidase-4 (DPP-4) is a proteolytic enzyme responsible for the rapid degradation of Glucagon-like peptide 1 (GLP-1) that is required for the secretion of insulin. DPP-4 also influences activation of node like receptor family, pyrin domain containing 3 (NLRP3) inflammasome under diabetic conditions. Although several polyphenols are reported for various bioactivities, they are consumed as part of the food matrix and not in isolation. Horsegram (Macrotyloma uniflorum) is a rich source of myricetin (Myr) (35 μg/g flour), reported for its anti-hyperglycemic effect. In this investigation, we aimed to study the effect of Myr, singly, and in the presence of co-nutrient horsegram protein (HP) on DPP-4 activity and its consequential impact on GLP-1, insulin, and NLRP3 inflammasome in high-fat diet and single low dose streptozotocin (STZ)-induced diabetic male Wistar rats. In diabetic control (DC), the activity of DPP-4 and its expression were higher compared to treated groups. The consequential decrease in the circulating GLP-1 levels in the DC group, but not treated groups, further indicated the effectiveness of our test molecules under diabetic conditions. Specifically, Myr decreased DPP-4 activity and its expression levels with enhanced circulating GLP-1 and insulin levels. Myr administration also resulted in a lessening of diabetes-induced NLRP3 inflammasome activation and enhanced antioxidant enzyme activities. HP also proved to be efficient in reducing elevated blood glucose levels and enhancing antioxidant enzyme activities. However, Myr, in the presence of HP as a co-nutrient, had diminished capacity to inhibit DPP-4 and, consequently, reduced potential in ameliorating diabetic conditions. Myr proved to be a potent inhibitor of DPP-4 in vitro and in vivo, resulting in enhanced circulating GLP-1 and insulin levels, thereby improving diabetic conditions. Though Myr and HP, individually ameliorate diabetic conditions, their dietary combination had reduced efficiency.

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Spray-dried milk enriched with n-3 fatty acids from linseed oil or fish oil were fed to rats to study its influence on liver lipid peroxides, hepatic antioxidant enzyme activities, serum prostaglandins and platelet aggregation. Significant level of alpha linolenic acid, eicosapentaenoic acid and docosahexaenoic acid were accumulated at the expense of arachidonic acid in the liver of rats fed n-3 fatty acid enriched formulation. The linseed oil and fish oil enriched formulation fed group had 44 and 112% higher level of lipid peroxides in liver homogenate compared to control rats fed groundnut oil enriched formulation. Catalase activity in liver homogenate was increased by 37 and 183% respectively in linseed oil and fish oil formulation fed rats. The glutathione peroxidase activity decreased to an extent of 25-36% and glutathione transferase activity increased to an extent of 34-39% in rats fed n-3 fatty acids enriched formulation. Feeding n-3 fatty acid enriched formulation significantly elevated the n-3 fatty acids in platelets and increased the lipid peroxide level to an extent of 4.2-4.5 fold compared to control. The serum thromboxane B2 level was decreased by 35 and 42% respectively in linseed oil and fish oil enriched formulation fed rats, whereas, 6-keto- prostaglandin F1alpha level was decreased by 17 and 23% respectively in linseed oil and fish oil enriched formulation fed rats. The extent and rate of platelet aggregation was decreased significantly in n-3 fatty acids enriched formulation fed rats. This indicated that n-3 fatty acids enriched formulation beneficially reduces platelet aggregation and also enhances the activities of hepatic antioxidant enzymes such as catalase and glutathione transferase.

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The effects of feeding rats with groundnut oil (GNO), rice bran oil (RBO), and sesame oil (SESO) on serum lipids, liver lipids, and inflammatory markers were evaluated in rats. Male Wistar rats were fed with AIN-93 diet supplemented with 10 wt% of GNO, RBO, and SESO in the form of native (N) and minor constituent-removed (MCR) oils. Rats given RBO and SESO showed significant reduction in serum and liver lipids, 8-hydroxy-2-deoxyguanosine, cytokines in liver, and eicosanoids in leukocytes as compared with the rats given GNO and MCR oils. The rats fed with native oils of RBO and SESO showed an upregulation of sterol regulatory element-binding protein (SREBP)-2 and peroxisome proliferator-activated receptor gamma (PPARγ) and downregulation of nuclear factor-kappa B (NF-κB) p65. These effects of native oil were significantly compromised when rats were given MCR oils. In conclusion, the minor constituents significantly support the hypolipidemic and anti-inflammatory properties of RBO and SESO.

Indian diets comprising staples such as cereals, millets, and pulses provide 4.8 energy % from linoleic acid (18:2n-6) but fail to deliver adequate amounts of n-3 FA. Consumption of long-chain n-3 PUFA such as EPA (20:5n-3) and DHA (22:6n-3) is restricted to those who consume fish. The majority of the Indian population, however, are vegetarians needing additional dietary sources of n-3 PUFA. The present work was designed to use n-3 FA-enriched spray-dried milk powder to provide n-3 FA. Whole milk was supplemented with linseed oil to provide alpha-linolenic acid (LNA, 18:3n-3), with fish oil to provide EPA and DHA, or with groundnut oil (GNO), which is devoid of n-3 PUFA, and then spray-dried. Male Wistar rats were fed the spray-dried milk formulations for 60 d. The rats given formulations containing n-3 FA showed significant increases (P < 0.001) in the levels of LNA or EPA/DHA in the serum and in tissue lipids as compared with those fed the GNO control formulation. Rats fed formulations containing n-3 FA had 30-35% lower levels of serum total cholesterol and 25-30% lower levels of serum TAG than control animals. Total cholesterol and TAG in the livers of rats fed the formulations containing n-3 FA were lower by 18-30% and 11-18%, respectively, compared with control animals. This study showed that spray-dried milk formulations supplemented with n-3 FA are an effective means of improving dietary n-3 FA intake, which may decrease the risk factors associated with cardiovascular disease.

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