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According to the available ethnobotanical data, the Bouvardia ternifolia plant has long been used in Mexican traditional medicine to relieve the symptoms of inflammation. In the present study, the cytotoxic effect of extracts obtained from the flowers, leaves and stems of B. ternifolia using hexane, ethyl acetate (AcOEt) and methanol (MeOH) was evaluated by applying them to the SiHa and MDA-MB-231 cancer cell lines. An MTT reduction assay was carried out along with = biological activity assessments, and the content of total phenols, tannins, anthocyanins, betalains and saponins was quantified. According to the obtained results, nine extracts exhibited a cytotoxic effect against both the SiHa and MDA lines. The highest cytotoxicity was measured for leaves treated with the AcOEt (ID50 of 75 µg/mL was obtained for MDA and 58.75 µg/mL for SiHa) as well as inhibition on ABTSâ¢+ against DPPH⢠radical, while MeOH treatment of stems and AcOEt of flowers yielded the most significant antioxidant capacity (90.29% and 90.11% ABTSâ¢+ radical trapping). Moreover, the highest phenolic compound content was measured in the stems (134.971 ± 0.294 mg EAG/g), while tannins were more abundant in the leaves (257.646 mg eq cat/g) and saponins were most prevalent in the flowers (20 ± 0 HU/mg). Screening tests indicated the presence of flavonoids, steroids, terpenes and coumarins, as well as ursolic acid, in all the studied extracts. These results demonstrate the biological potential of B. ternifolia.
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Acute kidney injury and impaired kidney function is associated with reduced survival and increased morbidity. Porophyllum ruderale is an edible plant endemic to Mexico used in Mexican traditional medicine. The aim of this study was to evaluate the nephroprotective effect of a hydroalcoholic extract (MeOH:water 70:30, v/v) from the aerial parts of P. ruderale (HEPr). Firstly, in vitro the antioxidant and anti-inflammatory activity of HEPr was determined; after the in vivo nephroprotective activity of HEPr was evaluated using a thioacetamide-induced injury model in rats. HEPr showed a slight effect on LPS-NO production in macrophages (15% INO at 40 µg/mL) and high antioxidant activity in the ferric reducing antioxidant power (FRAP) test, followed by the activity on DPPH and ABTS radicals test (69.04, 63.06 and 32.96% of inhibition, respectively). In addition, values of kidney injury biomarkers in urine (urobilinogen, hemoglobin, bilirubin, ketones, glucose, protein, pH, nitrites, leukocytes, specific gravity, and the microalbumin/creatinine) and serum (creatinine, urea, and urea nitrogen) of rats treated with HEPr were maintained in normal ranges. Finally, 5-O-caffeoylquinic, 4-O-caffeoylquinic and ferulic acids; as well as 3-O-quercetin glucoside and 3-O-kaempferol glucoside were identified by HPLC as major components of HEPr. In conclusion, Porophyllum ruderale constitutes a source of compounds for the treatment of acute kidney injury.
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Amaranth seeds, although a valuable food in Mexico, contain anti-nutritional compounds that can affect food quality. As a part of this work, the proximate composition, fatty acid profile, protein digestibility, and the effect of germination and popping of Amaranthus hypochondriacus seeds was analyzed with the aim of eliminating anti-nutritional compounds. Untreated seeds comprised of 11.35-18.8% protein and 0.27-13.39% lipids, including omega 3, 6, and 9 fatty acids such as oleic, linoleic, linolenic, and arachidonic acid. The main minerals detected were Ca+2, K+1, and Mg+2. Nevertheless in vitro studies indicate that germination significantly improved digestibility, whereby treatments aimed at reducing anti-nutritional compounds decreased lectin concentration, while significantly increasing tannins and completely eliminating trypsins and saponins.
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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
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 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 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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It has been known for years that, after chemical damage or surgical removal of its tissue, the liver initiates a series of changes that, taken together, are known as regeneration, which are focused on the recovery of lost or affected tissue in terms of the anatomical or functional aspect. The Nuclear factor-erythroid 2-related factor (Nrf-2) is a reduction-oxidation reaction (redox)-sensitive transcriptional factor, with the basic leucine Zipper domain (bZIP) motif, encoding the NFE2L2 gene. The Keap1-Nrf2-ARE pathway is transcendental in the regulation of various cellular processes, such as antioxidant defenses, redox equilibrium, the inflammatory process, the apoptotic processes, intermediate metabolism, detoxification, and cellular proliferation. Some reports have demonstrated the regulator role of Nrf-2 in the cellular cycle of the hepatocyte, as well as in the modulation of the antioxidant response and of apoptotic processes during liver regeneration. It has been reported that there is a delay in liver regeneration after Partial hepatectomy (PH) in the absence of Nrf-2, and similarly as a regulator of hepatic cytoprotection due to diverse chemical or biological agents, and in diseases such as hepatitis, fibrosis, cirrhosis, and liver cancer. This regulator/protector capacity is due to the modulation of the Antioxidant response elements (ARE). It is postulated that oxidative stress (OS) can participate in the initial stages of liver regeneration and that Nrf-2 can probably participate. Studies are lacking on the different initiation stages, maintenance, and the termination of liver regeneration alone or with ethanol.
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One of the major components of some geraniums is geraniin, described by its discoverer as crystallizable tannin, well known as an excellent antioxidant, and also found in fruits such as pomegranate. Recently, natural antioxidants have attracted great attention from consumers over the world due to their lower toxicity than synthetics. But geraniin is not a stable compound, and also is difficult to obtain, that is why in the present study we obtained acetonylgeraniin from Geranium schideanum (Gs), a stable acetone condensate of geraniin. In the present study the effect of Gs acetone-water extract was studied in reference to postnecrotic liver regeneration induced by thioacetamide (TA) in rats. Two months male rats were pretreated with daily dose of Gs extract for 4 days (300 mg/kg) and the last day also were intraperitoneally injected with TA (6.6 mmol/kg). Samples of blood were obtained from rats at 0, 24, 48, 72 and 96 h following TA intoxication. The pre-treatment with the crude extract in the model of thioacetamide-induced hepatotoxicity in rats decreased and delayed liver injury by 66% at 24 h. This result suggests that Gs extract may be used as an alternative for reduction of liver damage. On the other hand, acute toxicity study revealed that the LD50 value of the Gs extract is more than the dose 5000 mg/kg in rats, according to the Lorke method.
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For many years, several studies have been employing lectin from vegetables in order to prove its toxic effect on various cell lines. In this work, we analyzed the cytotoxic, antiproliferative, and post-incubatory effect of pure tepary bean lectins on four lines of malignant cells: C33-A; MCF-7; SKNSH, and SW480. The tests were carried out employing MTT and 3[H]-thymidine assays. The results showed that after 24 h of lectin exposure, the cells lines showed a dose-dependent cytotoxic effect, the effect being higher on MCF-7, while C33-A showed the highest resistance. Cell proliferation studies showed that the toxic effect induced by lectins is higher even when lectins are removed, and in fact, the inhibition of proliferation continues after 48 h. Due to the use of two techniques to analyze the cytotoxic and antiproliferative effect, differences were observed in the results, which can be explained by the fact that one technique is based on metabolic reactions, while the other is based on the 3[H]-thymidine incorporated in DNA by cells under division. These results allow concluding that lectins exert a cytotoxic effect after 24 h of exposure, exhibiting a dose-dependent effect. In some cases, the cytotoxic effect is higher even when the lectins are eliminated, however, in other cases, the cells showed a proliferative effect.
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Antineoplásicos Fitogênicos/farmacologia , Phaseolus/química , Lectinas de Plantas/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/toxicidade , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Lectinas de Plantas/isolamento & purificação , Lectinas de Plantas/toxicidade , Fatores de TempoRESUMO
It is well known that gadolinium chloride (GD) attenuates drug-induced hepatotoxicity by selectively inactivating Kupffer cells. In the present study the effect of GD in reference to cell cycle and postnecrotic liver regeneration induced by thioacetamide (TA) in rats was studied. Two months male rats, intraveously pretreated with a single dose of GD (0.1 mmol/Kg), were intraperitoneally injected with TA (6.6 mmol/Kg). Samples of blood and liver were obtained from rats at 0, 12, 24, 48, 72 and 96 h following TA intoxication. Parameters related to liver damage were determined in blood. In order to evaluate the mechanisms involved in the post-necrotic regenerative state, the levels of cyclin D and cyclin E as well as protein p27 and Proliferating Cell Nuclear Antigen (PCNA) were determined in liver extracts because of their roles in the control of cell cycle check-points. The results showed that GD significantly reduced the extent of necrosis. Noticeable changes were detected in the levels of cyclin D1, cyclin E, p27 and PCNA when compared to those induced by thioacetamide. Thus GD pre-treatment reduced TA-induced liver injury and accelerated the postnecrotic liver regeneration. These results demonstrate that Kupffer cells are involved in TA-induced liver and also in the postnecrotic proliferative liver states.
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Ciclo Celular/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Gadolínio/farmacologia , Células de Kupffer/efeitos dos fármacos , Células de Kupffer/metabolismo , Regeneração Hepática/efeitos dos fármacos , Animais , Pontos de Checagem do Ciclo Celular , Proliferação de Células/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Ciclina D/sangue , Ciclina E/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Necrose/tratamento farmacológico , Antígeno Nuclear de Célula em Proliferação/sangue , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Wistar , Tioacetamida/toxicidadeRESUMO
Lectins comprise a heterogeneous class of proteins that recognize the carbohydrate moieties of glycoconjugates with high specificity. Numerous studies have shown that lectins are capable of recognizing specific carbohydrate moieties displayed by malignant cells or tissues. The present work was performed to investigate the effects of tepary bean (Phaseolus acutifolius) lectins on proliferation, colony formation, and alteration of DNA synthesis of human malignant cells. Tepary bean lectin showed dose dependent effects on the inhibition of viability as well as on colony formation in two human malignant cells lines (C33-A, Sw480); By contrast, tepary bean lectin only showed significant effects on DNA synthesis on Sw480 cells. Our results provide evidence of the anti- proliferative and cytotoxic effects of the tepary bean lectins on C33-A and Sw480 cells lines.