A polyphenol-enriched fraction from Annona crassiflora fruit peel (Ac-Pef) containing chlorogenic acid, (epi)catechin, procyanidin B2, and caffeoyl-glucoside was investigated against hepatic oxidative and nitrosative stress in streptozotocin-induced diabetic rats. Serum biochemical parameters, hepatic oxidative and nitrosative status, glutathione defense system analysis, and in silico assessment of absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the main compounds of Ac-Pef were carried out. Ac-Pef treatment during 30 days decreased serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase activities, as well as hepatic lipid peroxidation, protein carbonylation and nitration, inducible nitric oxide synthase level, and activities and expressions of glutathione peroxidase, superoxide dismutase, and catalase. There were increases in antioxidant capacity, glutathione reductase activity, and reduced glutathione level. ADMET predictions of Ac-Pef compounds showed favorable absorption and distribution, with no hepatotoxicity. A. crassiflora fruit peel showed hepatoprotective properties, indicating a promising natural source of bioactive molecules for prevention and therapy of diabetes complications.

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Jararhagin, a metalloprotease from Bothrops jararaca snake venom, is a toxin containing the metalloproteinase, disintegrin-like and cysteine-rich domains; it causes acute inflammation and damage to vascular tissue. However, the actions of these domains on key components of chronic inflammation have not been determined. Our aim was to investigate the effects of jararhagin (Jar), jararhagin-C (Jar-C) and o-phenantrolin-treated jararhagin (Jar-Phe), on inflammatory response, blood vessel formation and extracellular matrix deposition in the murine sponge model. The polyether-polyurethane sponge matrix was implanted into Balb/c mice and injected daily with Jar (400 ng), Jar-Phe (400 ng), Jar-C (200 ng) or saline (control). Nine days after implantation, the sponge discs were removed and processed. In the Jar-treated implants, some of inflammatory markers (N-acetyl-β-d-glucosaminidase activity, CCL2 and TNF-α) and TGF-β1 levels were higher compared with the control group. In the Jar-C group, the inflammatory markers myeloperoxidase activity and CXCL1 were higher compared with the control. In this group, VEGF levels and collagen deposition were also higher. Jar-Phe treatment was able to inhibit the activity and/or production of MPO, CXCL1, CCL2 and TGF-β. The differential effects of these proteins in modulating the main components of fibrovascular tissue may be exploited in the management fibroproliferative diseases.

A polyphenol-enriched fraction from Annona crassiflora fruit peel (PEF-Ac) containing chlorogenic acid, epi-catechin, procyanidins B2 and C1, quercetin-glucoside, kaempferol, and caffeoyl-glucoside was investigated for its anti-inflammatory, pro-angiogenic, and profibrogenic potential in the healing of cutaneous wounds. Four wounds were performed on the back of C57 mice and the lesions were treated with the vehicle (Vaseline and lanolin) and PEF-Ac at concentrations of 2%, 4%, and 6% for 4 and 7 d. Neutrophils and macrophages activities were evaluated indirectly by the activity of myeloperoxidase and N-acetyl-β-D-glycosaminidase, angiogenesis was evaluated by hemoglobin dosing and vessel count in histological sections, and collagen deposition was assessed from histological sections stained with picrosirius red. PEF-Ac demonstrated anti-inflammatory activity, with reduced activities of neutrophil and macrophage in the cutaneous wounds. In addition, there was an increase in the synthesis of types I and III collagen, as well as in the percentage of wound closure, mainly after 4 d of treatment. On the other hand, PEF-Ac did not present an effective pro-angiogenic activity. A. crassiflora fruit peel showed anti-inflammatory and profibrogenic properties, indicating a promising natural source of bioactive molecules for treatment of cutaneous wounds.

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Cardiotoxicity is one of the most significant adverse effects of the oncologic treatment with doxorubicin, which is responsible for a substantial morbid and mortality. The occurrence of heart failure with ventricular dysfunction may lead to severe cardiomyopathy and ultimately to death. Studies have focused on the effects of leucine supplementation as a strategy to minimize or revert the clinical condition of induced proteolysis by several clinical onsets. However, the impact of leucine supplementation in heart failure induced by doxorubicin is unknown. Therefore, the objective of this work is to evaluate the effects of leucine supplementation on the cardiotoxicity in the heart of rats treated with doxorubicin. Rats treated with a 7.5 mg/kg cumulative dose of doxorubicin for 14 days presented a dilatation of the left ventricle (LV), and a reduction of the ejection fraction (FE). The 5% supplementation of leucine in the rats' food prevented the malfunctioning of the LV when administered with doxorubicin. Some alterations in the extracellular matrix remodeling were confirmed by the increase of collagen fibers in the doxorubicin group, which did not increase when the treatment was associated with leucine supplementation. Leucine attenuates heart failure in this experimental model with doxorubicin. Such protection is followed by the maintenance of interstitial collagen fibers.

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