α, ß-Amyrin prevents steatosis and insulin resistance in a high-fat diet-induced mouse model of NAFLD via the AMPK-mTORC1-SREBP1 signaling mechanism

Nonalcoholic fatty liver disease (NAFLD), characterized by hepatosteatosis and steatohepatitis, is intrinsically related to obesity. Our previous study reported on the anti-obese activity of α,β-amyrin (AMY), a pentacyclic triterpene isolated from Protium heptaphyllum. This study investigated its ability to prevent fatty liver and the underlying mechanism using the mouse model of NAFLD. NAFLD was induced in male Swiss mice fed a high fat diet (HFD) for 15 weeks. The controls were fed a normal chow diet (ND). The mice were simultaneously treated with AMY at 10 and 20 mg/kg or fenofibrate at 50 mg/kg. Lipid levels along with metabolic and inflammatory parameters were assessed in liver and serum. The liver sections were histologically examined using H&E staining. RT-qPCR and western blotting assays were performed to analyze signaling mechanisms. Mice fed HFD developed severe hepatic steatosis with elevated triglycerides and lipid droplets compared with ND controls. This was associated with a decrease in AMP-activated protein kinase (AMPK) activity, an increase of mechanistic target of rapamycin complex 1 (mTORC1) signaling, and enhanced sterol regulatory element binding protein 1 (SREBP1) expression, which have roles in lipogenesis, inhibition of lipolysis, and inflammatory response. AMY treatment reversed these signaling activities and decreased the severity of hepatic steatosis and inflammatory response, evidenced by serum and liver parameters as well as histological findings. AMY-induced reduction in hepatic steatosis seemed to involve AMPK-mTORC1-SREBP1 signaling pathways, which supported its beneficial role in the prevention and treatment of NAFLD.

Acute blockade of endogenous melatonin by Luzindole, with or without peripheral LPS injection, induces jejunal inflammation and morphological alterations in Swiss mice

This study investigated the acute blockade of endogenous melatonin (MLT) using Luzindole with or without systemic lipopolysaccharide (LPS) challenge and evaluated changes in inflammatory and oxidative stress markers in the mouse jejunum. Luzindole is an MT1/MT2 MLT receptor antagonist. Both receptors occur in the small intestine. Swiss mice were treated with either saline (0.35 mg/kg, ip), Luzindole (0.35 mg/kg, ip), LPS (1.25 mg/kg, ip), or Luzindole+LPS (0.35 and 1.25 mg/kg, ip, respectively). Jejunum samples were evaluated regarding intestinal morphometry, histopathological crypt scoring, and PAS-positive villus goblet cell counting. Inflammatory Iba-1, interleukin (IL)-1β, tumor necrosis factor (TNF)-α, nuclear factor (NF)-kB, myeloperoxidase (MPO), and oxidative stress (NP-SHs, catalase, MDA, nitrate/nitrite) markers were assessed. Mice treated with Luzindole, LPS, and Luzindole+LPS showed villus height shortening. Crypt damage was worse in the LPS group. Luzindole, LPS, and Luzindole+LPS reduced the PAS-goblet cell labeling and increased Iba-1-immunolabelled cells compared to the saline group. Immunoblotting for IL-1β, TNF-α, and NF-kB was greater in the Luzindole group. The LPS-challenged group showed higher MPO activity than the saline and Luzindole groups. Catalase was reduced in the Luzindole and Luzindole+LPS groups compared to saline. The Luzindole group showed an increase in NP-SHs, an effect related to compensatory GSH activity. The acute blockade of endogenous MLT with Luzindole induced early changes in inflammatory markers with altered intestinal morphology. The other non-detectable deleterious effects of Luzindole may be balanced by the unopposed direct action of MLT in immune cells bypassing the MT1/MT2 receptors.

Características de carcaça e carne de novilhos Aberdeen Angus submetidos à castração cirúrgica ou imunológica / Carcass characteristics and meat of Aberdeen Angus steers submitted to surgical or immunological castration

Objetivou-se avaliar as características de carcaça e carne de novilhos Aberdeen Angus castrados cirurgicamente em duas idades ou imunocastrados com dois protocolos. Foram utilizados 48 bezerros, monitorados a partir do nascimento e desmamados, com idade e peso médio inicial de seis meses e de 160±16,54kg, respectivamente. Os animais foram distribuídos aleatoriamente nos seguintes tratamentos: castração cirúrgica ao nascer; castração cirúrgica ao desmame; imunocastração com três doses da vacina Bopriva® e imunocastração com quatro doses da vacina Bopriva®. O delineamento experimental utilizado foi o inteiramente ao acaso. Novilhos imunocastrados com três doses apresentaram maior quebra ao resfriamento e menor espessura de gordura ajustada para 100kg de carcaça fria que castrados cirurgicamente ao nascer (P<0,05). A imunocastração com três doses proporcionou incremento na participação de músculo, em relação às castrações cirúrgicas, mas reduziu a gordura em relação à castração cirúrgica ao nascimento (P<0,05). A relação músculo:osso foi superior nos imunocastrados com três doses em relação a castrados cirurgicamente no desmame (P<0,05). Apesar de variações na participação tecidual na carcaça, a castração imunológica mostrou-se viável em substituição à castração cirúrgica, não alterando os padrões qualitativos da carne.(AU)

The objective of this study was to evaluate the carcass and meat characteristics of Aberdeen Angus steers surgically castrated at two ages or immunocastrated with two protocols. Forty-eight calves we used, monitored from birth and weaned, with age and initial mean weight of six months and 160±16.54kg, respectively. The animals were randomly assigned to the following treatments: surgical castration at birth; surgical castration at weaning; immunocastration with three doses of the Bopriva ® vaccine and immunocastration with four doses of the Bopriva ® vaccine. The experimental design was completely randomized. Immunocastrated steers with three doses had a greater cooling break and lower fat thickness adjusted for 100kg of cold carcass than surgically castrated at birth (P< 0.05). Immunocastration with three doses provided an increase in muscle participation in relation to surgical castration but reduced fat in relation to surgical castration at birth (P< 0.05). The muscle:bone ratio was higher in the immunocastrated with three doses compared to surgically castrated at weaning (P< 0.05). Despite variations in tissue involvement in the carcass, the immunological castration proved to be viable to replace surgical castration, not changing the quality of the meat standards.(AU)

Atividade antiulcerogênica do extrato aquoso da Bryophyllum pinnatum (Lam. ) Kurz / Antiulcerogenic activity of aqueous extract from Bryophyllum pinnatum (Lam. ) Kurz

Bryophyllum pinnatum (Lam.) Kurz pertence a família Crassulaceae e é conhecida vulgarmente como coirama, folha-da-fortuna, ou folha-do-ar, sendo usada popularmente como antifúngico, no tratamento da hipertensão, em úlceras e em inflamações. O presente estudo objetivou analisar a atividade antiulcerogênica do extrato aquoso das folhas de Bryophyllum pinnatum (Lam.) Kurz em modelo de úlcera gástrica induzida por indometacina em Rattus norvegicus, machos (150 a 250 g) com idade de 70 dias. Os animais receberam por via oral: água, extrato aquoso de Bryophyllum pinnatum (Lam.) Kurz (1 e 2 g Kg-1 ) ou ranitidina (60 mg Kg-1 ), fármaco com ação gastroprotetora conhecida que atua bloqueando os receptores de histamina H2. Após uma hora dos tratamentos, todos animais receberam indometacina via intraperitoneal. Os resultados demonstraram que o extrato aquoso da Bryophyllum pinnatum (Lam.) Kurz possui ação gastroprotetora; na dose de 1 g Kg-1 inibiu 45,49% o índice de ulceração induzido pela indometacina, e, na dose de 2 g Kg-1, inibiu 49,50%. Sugere-se o envolvimento de vários mecanismos na ação gastroprotetora dessa planta e não somente uma possível participação das prostaglandinas nesse efeito. Estudos futuros com diferentes modelos de indução de úlcera gástrica tornam-se necessários para melhor avaliar a atividade antiulcerogênica do extrato aquoso de Bryophyllum pinnatum (Lam.) Kurz.

Bryophyllum pinnatum (Lam.) Kurz belongs to the family Crassulaceae, is popularly known as "coirama", "folha-da-fortuna", or "folha-do-ar" and has been commonly used as antifungal, in the treatment of hypertension, ulcers and inflammation. The present study aimed to analyze the antiulcerogenic activity of aqueous extract from the leaves of Bryophyllum pinnatum (Lam.) Kurz using indomethacin-induced gastric ulcer models in Rattus norvegicus, males (150-250 g) aged 70 days old. The animals received by the oral route: water, aqueous extract from Bryophyllum pinnatum (Lam.) Kurz (1 and 2 g Kg-1) or ranitidine (60 mg Kg-1), a drug with known gastroprotective action, blocking histamine H2-receptors. After one hour of treatments, all animals received indomethacin by the intraperitoneal route. Results demonstrated that the aqueous extract from Bryophyllum pinnatum (Lam.) Kurz has gastroprotective action; at 1g kg-1 it inhibited 45.49% of the indomethacin-induced ulcer index, while at 2g Kg-1 it inhibited 49.50%. Several mechanisms of actions are suggested to be involved in the gastroprotective action of this plant, besides the possible participation of prostaglandins in this effect. Further studies using different gastric ulcer-induction models are needed to better evaluate the antiulcerogenic activity of aqueous extract from Bryophyllum pinnatum (Lam.) Kurz.

Dopaminergic profile of new heterocyclic N-phenylpiperazine derivatives

Dopamine constitutes about 80 percent of the content of central catecholamines and has a crucial role in the etiology of several neuropsychiatric disorders, including Parkinson's disease, depression and schizophrenia. Several dopaminergic drugs are used to treat these pathologies, but many problems are attributed to these therapies. Within this context, the search for new more efficient dopaminergic agents with less adverse effects represents a vast research field. The aim of the present study was to report the structural design of two N-phenylpiperazine derivatives, compound 4: 1-[1-(4-chlorophenyl)-1H-4-pyrazolylmethyl]-4-phenylhexahydropyrazine and compound 5: 1-[1-(4-chlorophenyl)-1H-1,2,3-triazol-4-ylmethyl]-4-phenylhexahydropyrazine, planned to be dopamine ligands, and their dopaminergic action profile. The two compounds were assayed (dose range of 15-40 mg/kg) in three experimental models: 1) blockade of amphetamine (30 mg/kg, ip)-induced stereotypy in rats; 2) the catalepsy test in mice, and 3) apomorphine (1 mg/kg, ip)-induced hypothermia in mice. Both derivatives induced cataleptic behavior (40 mg/kg, ip) and a hypothermic response (30 mg/kg, ip) which was not prevented by haloperidol (0.5 mg/kg, ip). Compound 5 (30 mg/kg, ip) also presented a synergistic hypothermic effect with apomorphine (1 mg/kg, ip). Only compound 4 (30 mg/kg, ip) significantly blocked the amphetamine-induced stereotypy in rats. The N-phenylpiperazine derivatives 4 and 5 seem to have a peculiar profile of action on dopaminergic functions. On the basis of the results of catalepsy and amphetamine-induced stereotypy, the compounds demonstrated an inhibitory effect on dopaminergic behaviors. However, their hypothermic effect is compatible with the stimulation of dopaminergic function which seems not to be mediated by D2/D3 receptors

Antinociceptive activity of Hypericum caprifoliatum and Hypericum polyanthemum (Guttiferae)

The aim of the present study was to assess the analgesic activity of the aerial parts of two Hypericum species native to Southern Brazil, H. caprifoliatum and H. polyanthemum. The antinociceptive effect of the H. polyanthemum cyclohexane extract (POL; 180 mg/kg) and of the H. caprifoliatum methanol (MET) and cyclohexane (CH) extracts (90 mg/kg) was evaluated in the hot-plate (ip and po) and writhing (po) tests using male Swiss CF1 mice weighing 22-27 g (N = 10 per group). All extracts displayed antinociceptive effects in the hot-plate test (MET ip = 48 percent, MET po = 39 percent, CH ip = 27 percent, CH po = 50 percent, POL ip = 74 percent, and POL po = 49 percent compared to control). Pretreatment with naloxone (2.5 mg/kg, sc) abolished the effects of CH and POL, and partially prevented the analgesia induced by MET administered by the ip (but not by the po) route. POL and CH (po) significantly reduced the number of writhes induced by acetic acid, while MET was ineffective in this regard. We conclude that the antinociceptive effects of the H. caprifoliatum (CH) and H. polyanthemum (POL) hexane extracts seem to be mediated by the opioid system. Moreover, the antinociceptive activity of the H. caprifoliatum MET extract seems to depend on at least two chemical substances (or groups of substances) with distinct pharmacokinetic profiles and mechanisms of action. Only the naloxone-insensitive component of MET activity showed good bioavailability following oral administration