RESUMO

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,ß-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.

Assuntos

RESUMO

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)-1ß, 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-1ß, 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.

Assuntos

RESUMO

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.

Assuntos

RESUMO

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.

Assuntos

RESUMO

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)

Assuntos

RESUMO

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)

Assuntos

RESUMO

The objective of this study was to evaluate the ingestive behavior and the displacement patterns of cutting steers kept in millet or sorghum pastures. The treatments consisted of: millet pasture (Pennisetum americanum Leeke) and sorghum (Sorghum bicolor L. Moench), both undergoing continuous stocking. Eighteen steers Charolais × Nellore breeding cross, with initial age of 14 months, and initial body weight of 195 kg, were used. The experimental design was randomized blocks, with 3 replicates and plots subdivide in time and by periods, and the data were submitted to variance analysis through the MIXED proc with P≤0,05. Grazing time was not inÁ uenced by forage species. The animals grazed longer in the third evaluation period (613.3 minutes) than the À rst period (555.5 minutes), both of which did not differ from the grazing time presented in the second period (568.9 minutes). The rumination and idle times were similar among the pastures evaluated, however, leisure time decreased and rumination increased with the advancement of the periods. Forage species did not influence the variables related to the displacement strategies. As the pasture cycle progressed, the time for 10 seasons and the time of rumination per cake increased, while the number of seasons per minute and per day, and the number of times animals water decreased. The use of millet or sorghum pastures does not alter the ingestive behavior and the displacement and feeding patterns of beef steers. The structural variation of the pastures throughout the vegetative cycle, alter the strategies of feeding and consumption, which are closely associated with the productive characteristics of the pasture.

Objetivou-se com este estudo avaliar o comportamento ingestivo e os padrões de deslocamento de novilhos de corte mantidos em pastagens de milheto ou de sorgo. Os tratamentos consistiam em: pastagem de milheto ( Penniselum americanum Leeke) ou pastagem de sorgo ( Sorghum bicolor L. Moench), ambos submetidos à lotação contínua. Foram utilizados 18 novilhos, oriundos do cruzamento entre as raças Charolês e Nelore, com idade média inicial de 14 meses, e peso corporal inicial de 195 kg. O delineamento experimental foi blocos ao acaso com 3 repetições e parcelas subdivididas no tempo em 3 períodos, sendo os dados submetidos a análise de variância através do proc MIXED com P≤0,05. O tempo de pastejo não foi inÁ uenciado pelas espécies forrageiras. Os animais pastejaram por mais tempo no terceiro período de avaliação (613,3 minutos) em relação ao primeiro (555,5 minutos), sendo que ambos não diferiram do tempo de pastejo apresentado no segundo período (568,9 minutos). Os tempos de ruminação e ócio foram semelhantes entre as pastagens avaliadas, no entanto, o tempo de ócio diminuiu e o de ruminação aumentou com o avanço dos períodos. As espécies forrageiras não inÁ uenciaram as variáveis relacionadas às estratégias de deslocamento. Com o avanço do ciclo das pastagens, o tempo para 10 estações e o tempo de ruminação por bolo regurgitado aumentaram, enquanto que o número de estações por minuto e por dia, e o número de vezes que os animais ingeriram água diminuíram. O uso de pastagens de milheto ou de sorgo não altera o comportamento ingestivo e os padrões de deslocamento e alimentação de novilhos de corte. A variação estrutural das pastagens ao longo do ciclo vegetativo, alteram as estratégias de alimentação e consumo, as quais, estão intimamente associadas às características produtivas da pastagem.

Assuntos

RESUMO

The objective of this study was to evaluate the ingestive behavior and the displacement patterns of cutting steers kept in millet or sorghum pastures. The treatments consisted of: millet pasture (Pennisetum americanum Leeke) and sorghum (Sorghum bicolor L. Moench), both undergoing continuous stocking. Eighteen steers Charolais × Nellore breeding cross, with initial age of 14 months, and initial body weight of 195 kg, were used. The experimental design was randomized blocks, with 3 replicates and plots subdivide in time and by periods, and the data were submitted to variance analysis through the MIXED proc with P≤0,05. Grazing time was not inÁ uenced by forage species. The animals grazed longer in the third evaluation period (613.3 minutes) than the À rst period (555.5 minutes), both of which did not differ from the grazing time presented in the second period (568.9 minutes). The rumination and idle times were similar among the pastures evaluated, however, leisure time decreased and rumination increased with the advancement of the periods. Forage species did not influence the variables related to the displacement strategies. As the pasture cycle progressed, the time for 10 seasons and the time of rumination per cake increased, while the number of seasons per minute and per day, and the number of times animals water decreased. The use of millet or sorghum pastures does not alter the ingestive behavior and the displacement and feeding patterns of beef steers. The structural variation of the pastures throughout the vegetative cycle, alter the strategies of feeding and consumption, which are closely associated with the productive characteristics of the pasture.

Objetivou-se com este estudo avaliar o comportamento ingestivo e os padrões de deslocamento de novilhos de corte mantidos em pastagens de milheto ou de sorgo. Os tratamentos consistiam em: pastagem de milheto ( Penniselum americanum Leeke) ou pastagem de sorgo ( Sorghum bicolor L. Moench), ambos submetidos à lotação contínua. Foram utilizados 18 novilhos, oriundos do cruzamento entre as raças Charolês e Nelore, com idade média inicial de 14 meses, e peso corporal inicial de 195 kg. O delineamento experimental foi blocos ao acaso com 3 repetições e parcelas subdivididas no tempo em 3 períodos, sendo os dados submetidos a análise de variância através do proc MIXED com P≤0,05. O tempo de pastejo não foi inÁ uenciado pelas espécies forrageiras. Os animais pastejaram por mais tempo no terceiro período de avaliação (613,3 minutos) em relação ao primeiro (555,5 minutos), sendo que ambos não diferiram do tempo de pastejo apresentado no segundo período (568,9 minutos). Os tempos de ruminação e ócio foram semelhantes entre as pastagens avaliadas, no entanto, o tempo de ócio diminuiu e o de ruminação aumentou com o avanço dos períodos. As espécies forrageiras não inÁ uenciaram as variáveis relacionadas às estratégias de deslocamento. Com o avanço do ciclo das pastagens, o tempo para 10 estações e o tempo de ruminação por bolo regurgitado aumentaram, enquanto que o número de estações por minuto e por dia, e o número de vezes que os animais ingeriram água diminuíram. O uso de pastagens de milheto ou de sorgo não altera o comportamento ingestivo e os padrões de deslocamento e alimentação de novilhos de corte. A variação estrutural das pastagens ao longo do ciclo vegetativo, alteram as estratégias de alimentação e consumo, as quais, estão intimamente associadas às características produtivas da pastagem.(AU)

Assuntos

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cenostigma macrophyllum Tul. var. acuminata Teles Freire (Leguminosae-Caesalpinioideae), popularly known in Brazil as "caneleiro", is widely used in folk medicine against gastrointestinal diseases. In previous studies, the ethanol extract of leaves from Cenostigma macrophyllum Tul. var. acuminata Teles Freire had shown antinociceptive, anti-inflammatory, antibacterial, antioxidant and antiulcerogenic activities. AIM OF THE STUDY: The aim of this study was to assess the gastroprotective effect of the hydroalcoholic fraction of leaves of Cenostigma macrophyllum Tul. var. acuminata Teles Freire (Cm-FHA), as well as to elucidate the possible underlying mechanisms of action. MATERIALS AND METHODS: Mice were used for the evaluation of the acute toxicity, and mice and rats to study the gastroprotective activity. The potential gastroprotective of Cm-FHA was assessed on different gastric ulcer models in rodents, such as absolute ethanol, HCl/ethanol, ischemia-reperfusion, cold restraint stress and indomethacin. The participation of prostaglandins, NO-synthase pathway and ATP-sensitive potassium channels (KATP) in gastroprotective activity of Cm-FHA were evaluated after treatment with a cyclooxygenase inhibitor (indomethacin), a NO-synthase inhibitor (L-NAME) and a KATP channel blocker (glibenclamide 5mg/kg), respectively. Likewise, the catalase activity was determinated in order to assess the possible participation of antioxidant mechanisms. RESULTS: No signs of acute toxicity was observed after oral acute administration of Cm-FHA, considering the analyzed parameters. Likewise, Cm-FHA promoted a protective effect against gastric ulcers induced by absolute ethanol (lesion inhibition by 40% at both 100 and 200mg/kg), HCl/ethanol (lesion inhibition by 50 or 48% at 100 or 200mg/kg, respectively), ischemia-reperfusion (lesion inhibition by 49 or 90% at 100 or 200mg/kg, respectively) and cold restraint stress (lesion inhibition by 63 or 76% at 100 or 200mg/kg, respectively), as well as a increase of catalase activity was observed. Otherwise, Cm-FHA was not able to protect gastric mucosa against indomethacin-induced lesions. Nitric oxide release, the of KATP channels opening and antioxidant activity are the possibly involved in the Cm-FHA-induced gastroprotective activity. CONCLUSION: This study corroborates the folk medicine use of Cenostigma macrophyllum for treatment of gastric ulcers, as well as reinforces this species as a valuable source of promising natural drugs with gastroprotective activity.

Assuntos

RESUMO

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.

Assuntos

RESUMO

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

Assuntos

RESUMO

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

Assuntos

RESUMO

Dopamine constitutes about 80% 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.

Assuntos

RESUMO

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%, MET po = 39%, CH ip = 27%, CH po = 50%, POL ip = 74%, and POL po = 49% 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.

Assuntos