Application of preliminary high-pressure processing for improving bioactive characteristics and reducing antigenicity of whey protein hydrolysates.

This study investigated the use of Novo Pro-D® (NPD) and Ficin (FC) as alternative proteases for the production of bioactive peptides with reduced allergenicity from whey protein concentrate (WPC). In addition, the use of high hydrostatic pressure processing as pre-treatment of WPC and its impact on the final characteristics of hydrolysates were also evaluated. NPD treatments generated hydrolysates with a 98% reduction of soluble proteins, greater in vitro antioxidant capacity, and less immunoreactivity when compared to FC ones. However, pre-treatment was an essential tool to improve WPC hydrolysis when FC was used, resulting in hydrolysates with less soluble proteins, enhanced antioxidant capacity, and less allergenicity compared with conventional hydrolysis. As for NPD, the pre-treatment of WPC improved the in vitro antioxidant capacity and resulted in a 100% reduction in immunoreactivity to ß-lactoglobulin in a shorter processing time. Importantly, bioactive peptides generated by FC displayed an improved ability to induce in vitro arterial relaxation, compared with those obtained from NPD process. Therefore, this study provides innovative evidence regarding how the proteases used for production of whey hydrolysates can improve its biological effects, and discloses the use of high hydrostatic pressure combined with enzymatic hydrolysis as a promising alternative to produce hydrolysates with improved properties.

Agmatine improves olfactory and cognitive deficits in Spontaneously Hypertensive Rats (SHR): An animal model of Attention Deficit Hyperactivity Disorder (ADHD).

Attention Deficit Hyperactivity Disorder (ADHD) is a highly prevalent and disabling disorder that frequently persists into adulthood. Many patients are considered nonresponders to typical pharmacological treatments due to insufficient symptoms' reduction or the inability to tolerate the side effects of these medications. Agmatine is an endogenous neuromodulator with emotional- and cognitive-enhancing properties that arises as a promising agent to manage several Central Nervous System disorders. Here, we investigated the effects of chronic treatment with agmatine on behavioral impairments exhibited by adult Spontaneously Hypertensive Rats (SHR), an animal model for the study of ADHD. Adult male Wistar and SHR (3-4 months old) received intraperitoneal (i.p.) treatment with saline (NaCl 0.9%) or agmatine (30 mg/kg/day) during 20 consecutive days and were evaluated in a battery of behavioral tasks. Agmatine treatment improved olfactory and recognition memory impairments of SHR evaluated in the olfactory discrimination, object recognition, and social recognition memory tasks. In addition, agmatine administration improved the cognitive flexibility in the water maze test. Agmatine did not alter SHR's locomotor activity and hedonic-like behaviors observed in the open-field and splash tests, respectively. No changes were observed in SHR's systolic blood pressure following agmatine treatment. This study provides the first evidence that agmatine improves olfactory and cognitive impairments observed in an animal model of ADHD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Involvement of the nitric oxide/soluble guanylate cyclase pathway in the anti-oedematogenic action of Pfaffia glomerata (Spreng) Pedersen in mice.

Pfaffia glomerata is used in southern American countries against inflammatory diseases. We have explored the ability of a crude hydroalcoholic extract of P. glomerata root (HEPG) to prevent the oedematogenic action of several inflammatory agents in mice. We have examined also the duration of its effects and the mechanisms involved. The oral or intraperitoneal treatment of mice with HEPG (1, 10, 30, 100 or 300 mg kg(-1)) reduced, in a dose-dependent manner, carrageenan-induced paw oedema in the early (1-4 h) and late (48 h) periods. In the early period, the ID50 value (the median dose that caused 50% inhibition) of HEPG was 60.5 (28.5-128.71) and 20.4 (14.8-28.3) mg kg(-1) after oral and intraperitoneal administration, respectively. This effect was still evident when HEPG was administered up to 6 h before carrageenan. HEPG inhibited also paw oedema induced by histamine, serotonin, bradykinin, substance P and bacterial lipopolysaccharide. In addition, oral administration of HEPG increased the levels of nitrate and nitrite in the blood of mice. Further, its anti-oedematogenic action against carrageenan was prevented fully by N(G) nitro-L-arginine-methyl-ester (10 mg kg(-1), s.c.), as well as by methylene blue (20 mg kg(-1), s.c.) or 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (2 mg kg(-1), s.c.). The results indicated that stimulation of endogenous production of nitric oxide, followed by soluble guanylate cyclase activation, was implicated in the anti-oedematogenic action of HEPG.

Nitric oxide-dependent vasorelaxation induced by extractive solutions and fractions of Maytenus ilicifolia Mart ex Reissek (Celastraceae) leaves.

This study reveals that an ethanolic supernatant obtained from an aqueous extractive solution prepared from residues of methanolic extracts of ground leaves of Maytenus ilicifolia is able to cause a concentration- and endothelium-dependent relaxation in pre-contract rat aorta rings, with EC(50) of 199.7 (190-210) microg/ml. The non-selective nitric oxide synthase inhibitors l-NAME and l-NMMA abolished this effect, while superoxide dismutase and MnTBAP (a non-enzymatic superoxide dismutase mimetic) enhanced it. Further, relaxation induced by this ethanolic supernatant have been strongly inhibited by the guanylate cyclase inhibitors methylene blue and ODQ, as well as by the potassium channel blockers 4-aminopyridine and tetraethylammonium, but was unchanged by the cyclooxygenase inhibitor indomethacin and the membrane receptor antagonists atropine, HOE-140 and pirilamine. Partition of the ethanolic supernatant between H(2)O and EtOAc generated a fraction several times more potent, able to fully relax endothelium-intact aorta rings with an EC(50) of 4.3 (3.9-4.8) microg/ml. (13)C NMR spectrum of this fraction showed signals typical of catechin. This study reveals that the leaves of M. ilicifolia possess one or more potent substances able to relax endothelium-intact rat aorta rings, an event that appears to involve nitric oxide production, guanylate cyclase activation and potassium channel opening.

Effects of alkaloids of Himatanthus lancifolius (Muell. Arg.) Woodson, Apocynaceae, on smooth muscle responsiveness.

Himatanthus lancifolius, popularly known as "agoniada" in Brazil, is largely used in folk medicine against asthma, dysmenorrhea and as an emenagogue and abortive. This study reveals the effects of an alkaloid rich fraction (AlkF) obtained from the bark of Himatanthus lancifolius in vascular and non-vascular smooth muscle responsiveness. Incubation of AlkF (3-30 microg/ml) during 15 min generates a concentration-related and fully reversible reduction in maximal contractile responses evoked by acetylcholine and phenylephrine in rat jejune and aorta preparations, respectively. Exposition of endothelium-denuded pre-contracted rat aorta rings to AlkF results in a complete relaxation, with EC(50) of 22.2 (16.2-28.2 microg/ml). AlkF is also able to induce a concentration-related rightward shift of cumulative concentration curves for calcium in uterus and aorta rings maintained in depolarizing nutritive solution. Moreover, addition of AlkF in calcium-free solution also reduces, in a concentration-dependent manner, the ability of caffeine and phenylephrine to contract aorta rings. This study reveals that the bark of Himatanthus lancifolius possesses one or more indole alkaloids able to alter non-vascular and vascular smooth muscle responsiveness, an event that may involve the blocking of calcium entry or changes on intracellular calcium utilization or mobilization.

Evaluation of Lewis and SHR rat strains as a genetic model for the study of anxiety and pain.

The study of inbred strains of rodents that differ for specific behaviours can help us to understand the biological mechanisms underlying complex psychological traits. Lewis (LEW) and SHR inbred rat strains, for example, have been recently proposed as a genetic model for the study of anxiety. Our goal was to characterise two Brazilian substrains of LEW and SHR rats, that have never been compared before, behaviourally and/or pharmacologically, in order to evaluate their potential contribution to studies on anxiety and pain. Male and female LEW and SHR rats were submitted after 8 weeks of age to five anxiety/emotionality tests: the open field (7 or 260 lux), the elevated plus-maze, the elevated T-maze and the black/white box. Rats of all groups were also submitted to the formalin test of nociception and measurement of blood pressure. Significant strain differences (P<0.05) were observed in both sexes for all indices of anxiety and also for measures of pain and blood pressure. SHRs, compared with LEWs, explored more the aversive environments of all anxiety tests, showed less nociceptive responses and were hypertensive. All differences in experimental anxiety parameters agree with previous differences reported between two French LEW and SHR substrains, suggesting that LEWs are more anxious than SHRs, thus consolidating these strains as a useful genetic model for the study of anxiety and pain. The possible involvement of tachykinergic mechanisms is discussed.