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Pain represents one of the leading causes of suffering and disability worldwide. Currently available drugs cannot treat all types of pain and may have adverse effects. Hence, the use of pharmacological combinations is an alternative treatment strategy. Therefore, this study aimed to evaluate the combination of resveratrol and ketorolac through isobolographic analysis. CD1 mice were used to study the antinociceptive effect of this combination using the formalin test and the study was divided into two phases. In the first phase, four individual doses of each drug were evaluated, totaling eight testing groups. From these data, the median effective doses (ED50) of each drug were calculated. In the second phase, four testing groups were used to evaluate the combination of sub-doses of both drugs and obtain the experimental ED50. To evaluate gastric damage, five groups were employed, including indomethacin, vehicle, resveratrol, ketorolac, and combined resveratrol and ketorolac groups. Stomach samples from the mice were taken after 5 h of treatment, and the area of the ulcers was determined. Resveratrol plus ketorolac elicited a reduction in nociceptive behavior during both phases of the formalin test, and isobologram analysis revealed that the theoretical and experimental ED50 values of resveratrol and ketorolac did not differ significantly, implying an additive interaction between the drugs. Additionally, the drug combination did not generate gastric ulcers, thus enhancing the desired effects without increasing the adverse effects. Consequently, these findings substantiate the efficacy of the resveratrol and ketorolac combination in the formalin test, thereby highlighting its potential as a viable alternative for alleviating pain.
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Nowadays, there is a growing interest in the exploitation of by-products from fruits and vegetables, generated from industrial processing or human feeding. Residues of popularly consumed fruits such as orange, lemon, banana, pomegranate, among others, have been widely described and studied; however, cactus pear (Opuntia spp.) residues, as a locally consumed product, have been forgotten. The whole fruit can be divided into the edible portion (pulp) and the non-edible portion (seeds and peel). Several studies mainly focus on the characteristics of the edible portion or in the whole fruit, ignoring by-products such as peels, which are rich in compounds such as phenols, flavonoids and dietary fiber; they have also been proposed as an alternative source of lipids, carbohydrates and natural colorants. Some uses of the peel have been reported as a food additives, food supplements, as a source of pectins and for wastewater treatment; however, there have not been any deep investigations of the characteristics and potential uses of the cactus pear peel (CPP). The aim of the present paper is to provide an overview of the current research on CPP. CPP has many bio-active compounds that may provide health benefits and may also be useful in pharmaceutical, food and manufacturing industries; however, greater research is needed in order to gain thorough knowledge of the possibilities of this by-product.
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Coronavirus disease 2019 (COVID-19) can directly or indirectly affect the central and peripheral nervous systems, resulting in cognitive impairment, memory problems, and a wide range of neuromuscular involvement, including neuropathies. However, the long-term neurological complications of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection are not clear. The aim this study was to analyze a case report the presence of neurological sequelae due to post-Coronavirus disease 19 in a patient without apparent previous neurological symptoms. Clinical case: A 46-year-old patient, with no relevant history for the described condition, who, after severe COVID-19 infection, started a mixed neuropathy and mental fog syndrome as the main sequel. Multiple laboratory and imaging studies were performed during and after his hospital stay, and it was corroborated by an electromyography that it occurred from a neuropathy triggered by COVID-19 infection. Conclusions: This case provides additional evidence that mixed neuropathy and brain fog syndrome are potential complications of post-coronavirus disease 2019 syndrome. The neurological sequelae that manifest after a COVID-19 episode can be rapidly enhanced as a consequence of another alteration in some systems of the organism. However, future studies are necessary to elucidate the incidence of these neurological complications, their pathophysiological mechanisms and their therapeutic options.
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Pharmacological treatment of pain often causes undesirable effects, so it is necessary to look for natural, safe, and effective alternatives to alleviate painful behavior. In this context, it is known that different parts of pomegranate have been widely consumed and used as preventive and therapeutic agents since ancient times. For example, it has been shown to have an antinociceptive effect, however, there are many varieties. Each part has been found to display unique and attractive pharmacological activities. The content of the active phytochemicals in pomegranate depends on the cultivar, geographical region, the maturity, and the processing method. In this context, the effects of various pomegranate varieties and other parts of the pomegranate (e.g., peel and juice) on pain behavior have not been examined. The aim was to evaluate and compare the antinociceptive effect of ethanolic extracts (PEx) and lyophilized juices (Lj) of three varieties of pomegranate in the formalin test. In addition, computer-aided analysis was performed for determining biological effects and toxicity. Peels were extracted with ethanol and evaporated by rotary evaporation, and juices were filtered and lyophilized. Wistar rats (N = 48) were randomly distributed into 8 groups (n = 6) (Vehicle, Acetylsalicylic Acid, PEx1, PEx2, PEx3, Lj1, Lj2, and Lj3). The formalin test (2%) was carried out, which consists of administering formalin in paw and counting the paw flinches for 1 h, with prior administration of treatments. All samples have an antinociceptive effect (phase 1: 2.8-10%; phase 2: 23.2-45.2%). PEx2 and Lj2 had the greatest antinociceptive effect (57.8-58.9%), and bioactive compounds such as tannins and flavonoids showed promising pharmacodynamic properties that may be involved in the antinociceptive effect, and can be considered as a natural alternative for the treatment of nociceptive and inflammatory pain.
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Several modern drugs, which are derived from traditional herbal medicine are used in contemporary pharmacotherapy. Currently, the study of drug-plant interactions in pain has increased in recent years, looking for greater efficacy of the drug and reduce side effects. The antinociception induced by intragastric co-administration of the combination of pomegranate peel extract (PoPEx) and acetylsalicylic acid (ASA) was assessed using the isobolographic analysis in formalin test (nociceptive and inflammatory pain). The effective dose that produced 30% of antinociception (ED30) was calculated for both drugs from the logarithmic dose-response curves, subsequently generating a curve with the combination on fixed proportions (1:1) of PoPEx and ASA. Through isobolographic analysis, this experimental ED30 was compared with the calculated theoretical additive ED30. The result was a synergistic interaction, the experimental ED30 was significantly smaller (p < 0.05) than the theoretical ED30. The antinociceptive mechanism of the PoPEx-ASA combination involves the l-Arginine/NO/cGMP pathway, antioxidant capacity, and high content of total phenols. These findings suggest that an interaction between PoPEx and ASA could be a novel treatment for inflammatory and nociceptive pain, also diminish the secondary reactions of ASA.
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Analgésicos , Aspirina , Punica granatum , Analgésicos/farmacologia , Animais , Modelos Animais de Doenças , Sinergismo Farmacológico , Dor Nociceptiva , Medição da Dor , Fitoterapia , Ratos , Ratos WistarRESUMO
Neuropathic pain is characterized by the presence of hyperalgesia and allodynia. Pharmacological treatments include the use of antiepileptics such as pregabalin or gabapentin, as well as antidepressants; however, given the role of the sigma-1 receptor in the generation and maintenance of pain, it has been suggested that sigma-1 receptor antagonists may be effective. There are also other alternatives that have been explored, such as the use of flavonoids such as quercetin. Due to the relevance of drug combinations in therapeutics, the objective of this work was to evaluate the effect of the combination of BD-1063 with quercetin in a chronic sciatic nerve constriction model using the "Surface of Synergistic Interaction" analysis method. The combination had preferable additive or synergistic effects, with BD-1063 (17.8 mg/kg) + QUER (5.6 mg/kg) showing the best antinociceptive effects. The required doses were also lower than those used individually to obtain the same level of effect. Our results provide the first evidence that the combination of a sigma-1 receptor antagonist and the flavonoid quercetin may be useful in the treatment of nociceptive behaviors associated with neuropathic pain, suggesting a new therapeutic alternative for this type of pain.
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Analgésicos/administração & dosagem , Antioxidantes/administração & dosagem , Neuralgia/tratamento farmacológico , Piperazinas/administração & dosagem , Quercetina/administração & dosagem , Receptores sigma/antagonistas & inibidores , Animais , Constrição , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Masculino , Neuralgia/metabolismo , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Ratos , Ratos Wistar , Receptores sigma/metabolismo , Receptor Sigma-1RESUMO
Punica protopunica Balf. is one of only two species housed by the Punica genera. Punica protopunica. Balf., known as Socotran pomegranate, is an endemic, isolated species found only in Socotra archipelago in the northwestern Indian Ocean, and is considered to be the ancestor of pomegranate. This review stems from the fact that in many Punica granatum L. articles, Punica protopunica Balf. is mentioned, but just in an informative way, without mentioning their taxonomic and genetic relationship and their medicinal properties. It is there where the need arises to know more about this forgotten species: "the other pomegranate tree." A large part of the human population does not know of its existence, since only its "sister" has spread throughout the world. The present review deals with the taxonomy and origin of Punica protopunica Balf., the morphology of the tree, distribution, cultivation, vulnerability, and as well as its relationship with Punica granatum L. It also discusses its uses in traditional medicine, its antioxidant capacity, and the medicinal properties of this forgotten species.
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The consumption of vegetables in Mexico includes a wide variety of plants that grow naturally as weeds in the fields. The intake of these vegetables is very important in the Mexican diet because these plants supply an important input of nutrients and compounds such as fiber, vitamins, minerals, and antioxidants. Thus, the plants may be universally promoted as healthy. However, there is little information about these vegetables of popular consumption, especially in terms of the nutritional changes caused by boiling. To determine the influence of boiling on five plants of popular consumption in Mexico, the nutritional composition (proximal analysis, dietary fiber, and oxalates), antioxidant compounds (ascorbic acid, phenolics), antioxidant activity (measured by ABTS and DPPH assays), and physicochemical characteristics (water retention capacity, viscosity, color, and SEM) were evaluated. The boiling affected the nutritional composition of plants, mainly soluble compounds as carbohydrates (sugars and soluble fiber), ash, ascorbic acid, and phenolic compounds and caused changes in food hydration and color. Therefore, it is recommended that these plants be consumed raw or with short boiling times and included the cooking water in other preparations to take advantage of the nutrients released in the food matrix. In the future, to complete studies, 3 to 5 min of cooking should be considered to minimize undesirable modifications in terms of the vegetables' composition.
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The use of complementary medicine has recently increased in an attempt to find effective alternative therapies that reduce the adverse effects of drugs. Punica granatum L. (pomegranate) has been used in traditional medicine for different kinds of pain. This review aims to explore the scientific evidence about the antinociceptive effect of pomegranate. A selection of original scientific articles that accomplished the inclusion criteria was carried out. It was found that different parts of pomegranate showed an antinociceptive effect; this effect can be due mainly by the presence of polyphenols, flavonoids, or fatty acids. It is suggested in the literature that the mechanisms of action may be related to the activation of the L-arginine / NO pathway, members of the TRP superfamily (TRPA1 or TRPV1) and the opioid system. The implications for the field are to know the mechanisms of action by which this effect is generated and thus be able to create alternative treatments for specific types of pain, which help alleviate it and reduce the adverse effects produced by drugs. The results propose that pomegranate and secondary metabolites could be considered in the treatment of inflammatory, nociceptive, and neuropathic pain.
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The objective of this study is to evaluate the nutritional composition, antioxidant properties, and functional characteristics of two cultivars of xoconostle Opuntia xoconostle F.A.C. Weber in Diguet cv. Cuaresmeño (XC) and Opuntia matudae Scheinvar cv. Rosa (XR). The samples were frozen (-32 °C, 48 h), lyophilized (96 h, -55 ± 1 °C, vacuum of 0.040 Mbar), and homogenized (size particle 500 µm) to get the xoconostle powder. Both cultivars (XC and XR) had a high content of carbohydrates characterized by soluble sugars (9.8 ± 0.7 and 29.9 ± 0.5 g/100 g dm) and dietary fiber (30.8 ± 0.7 and 36.8 ± 0.9 g/100 g dm), as well as lower proportions of organic acids, mainly citric acid (18.8 ± 0.0 and 13.6 ± 0.0 mg/100 g dm). These samples also had a high content of phenolic compounds (1580.3 ± 33.1 and 1068.5 ± 70.8 mg GAE/100 g dm), vitamin C (723.1 ± 16 and 320.2 ± 7.5 mg/100 g dm), and antioxidant activity ABTS·+ and DPPH· (between 1348.1 ± 74.0 and 3318.7 ± 178.8 µmol TE/100 g dm). Since xoconostle samples had a high content of dietary fiber, they were characterized by the capacity of water retention (water holding capacity 6.00 ± 0.1 and 5.5 ± 0.2 g H2O/g dm) and gel formation (swelling 5.2 ± 0.0 and 5.5 ± 0.0 g H2O/g dm), related with the retention of lipids and glucose in the food matrix similar to other foods. XR was characterized by a higher amount of dietary fiber, sugars and organic acids, while XC had higher phenols content and antioxidant properties, with higher values of functional properties. Then, our data suggest that both xoconostle cultivars in powder can be used as a functional ingredient for its fiber content and antioxidant properties, contributing with sensorial aspects as flavor and color. Therefore, these highly valued products can be used in the pharmaceutical and food industries.
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The negative impact that oxidative stress has on health is currently known. The complex mechanism of free radicals initiates a series of chain reactions that contribute to the evolution or development of different degenerative disorders. Likewise, these disorders are usually accompanied by inflammatory processes and, therefore, pain. In this sense, reactive oxygen species (ROS) have been shown to promote the nociceptive process, but effective treatment of pain and inflammation still represents a challenge. Over time, it has been learned that there is no single way to relieve pain, and as long as there are no other alternatives, the trend will continue to apply multidisciplinary management, such as promote the traditional use of the Erythrina genus to manage pain and inflammation. In this sense, the Erythrina genus produces a wide range of secondary metabolites, including flavanones, isoflavones, isoflavones, and pterocarpans; these compounds are characterized by their antioxidant activity. Phenolic compounds have demonstrated their ability to suppress pro-oxidants and inhibit inflammatory signaling pathways such as MAPK, AP1, and NFκB. Although there is preclinical evidence supporting its use, the pharmacological effect mechanisms are not entirely clear. Nowadays, there is a fast advancement in knowledge of the disciplines related to drug discovery, but most of nature's medicinal potential has not yet been harnessed. This review analyzes the decisive role that the Erythrina genus could play in managing inflammatory pain mediated by its compounds and its uses as an antioxidant.
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Antioxidantes/farmacologia , Terapias Complementares , Erythrina/química , Inflamação/complicações , Dor/etiologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/química , Antioxidantes/uso terapêutico , Terapias Complementares/métodos , Suscetibilidade a Doenças , Avaliação Pré-Clínica de Medicamentos , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/uso terapêutico , Humanos , Medicina Tradicional/métodos , Estresse Oxidativo/efeitos dos fármacos , Dor/tratamento farmacológico , Dor/metabolismo , Manejo da Dor , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
The aim of this study was to evaluate the antioxidant and hepatoprotective activity of Croton hypoleucus (EC). The present work reports the first pharmacological, toxicological, and antioxidant studies of EC extract on liver injury. Liver necrosis was induced by thioacetamide (TAA). Five groups were established: Croton Extract (EC), thioacetamide (TAA), Croton extract with thioacetamide (EC + TAA), vitamin E with thioacetamide (VE + TAA) and the positive control and vehicle (CT). For EC and EC + TAA, Wistar rats (n = 8) were intragastrically pre-administered for 4 days with EC (300 mg/kg.day) and on the last day, EC + TAA received a single dose of TAA (400 mg/kg). At 24 h after damage induction, animals were sacrificed. In vitro activity and gene expression of superoxide dismutase (SOD), catalase (Cat), and Nrf2 nuclear factor were measured. The results show that EC has medium antioxidant properties, with an IC50 of 0.63 mg/mL and a ferric-reducing power of 279.8 µM/mg. Additionally, EC reduced hepatic damage markers at 24 h after TAA intoxication; also, it increased SOD and Cat gene expression against TAA by controlling antioxidant defense levels. Our findings demonstrated the hepatoprotective effect of EC by reducing hepatic damage markers and controlling antioxidant defense levels. Further studies are necessary to identify the mechanism of this protection.
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Antioxidantes , Doença Hepática Induzida por Substâncias e Drogas , Croton/química , Extratos Vegetais , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Catalase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Modelos Animais de Doenças , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Necrose , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Tioacetamida/toxicidadeRESUMO
Geranium schiedeanum has been used in traditional therapies as an antiseptic, antipyretic, and as analgesic. The present study was designed to evaluate the pretreatment with G. schiedeanum total extract (GS) and its active metabolites on stimulating the endogenous antioxidant defense system (EADS): catalase (Cat), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione reduction index (RI GSH/GSSG) in rat liver treated with a sublethal dose (6.6 mmol/Kg) of thioacetamide (TAA) in order to probe the capacity of GS and the active compounds to reduce liver injury. This was assessed by measuring aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (BILT) in rats pretreated or not with TAA, and pretreated or not with GS and its metabolites. The results showed that GS was able to induce the production of EADS enzymes, increasing redox index GSH/GSSG at 24 and 48 h after intoxication, and both the extract and the ellagic acid exhibited a significant reduction of hepatic damage markers. Our data confirmed the hepatoprotective effect of GS and its metabolites, like ellagic acid, support the possible use of this extract in the treatment of liver injury.
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Neuropathic pain has proven to be a difficult condition to treat, so investigational therapy has been sought that may prove useful, such as the use of sigma-1 antagonists. Haloperidol (HAL) is a compound that shows a high affinity with these receptors, acting as an antagonist. Therefore, the objective of this study was to demonstrate its effect in an experimental model of neuropathic pain and corroborate its antagonistic action of the sigma-1 receptors under these conditions. BD-1063 was used as a sigma-1 antagonist control, and gabapentin (Gbp) was used as a positive control. The antihyperalgesic and anti-allodynic effects of the drugs were determined after single-dose trials. In every case, the effects increased in a dose-dependent manner. HAL had the same efficacy as both BD-1063 and Gbp. In the analysis of pharmacological potency, in which the ED50 were compared, HAL was the most potent drug of all. The effect of HAL on chronic constriction injury (CCI) rats was reversed by the sigma-1 agonist (PRE-084). HAL reversed the hyperalgesic and allodynic effects of PRE-084 in naïve rats. The dopamine antagonist, (-)-sulpiride, showed no effect in CCl rats. These results suggest that HAL presents an antinociceptive effect via sigma-1 receptor antagonism at the spinal level in the CCl model.