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Cannabis is a plant that is cultivated worldwide, and its use is internationally regulated, but some countries have been regulating its medicinal, social, and industrial uses. This plant must have arrived in Peru during the Spanish conquest and remains widely cultivated illicitly or informally to this day. However, new regulations are currently being proposed to allow its legal commercialization for medicinal purposes. Cannabis contains specific metabolites known as cannabinoids, some of which have clinically demonstrated therapeutic effects. It is now possible to quantitatively measure the presence of these cannabinoids in dried inflorescences, thus allowing for description of the chemical profile or "chemotype" of cannabinoids in each sample. This study analyzed the chemotypes of eight samples of dried inflorescences from cannabis cultivars in four different regions of Peru, and based on the significant variation in the cannabinoid profiles, we suggest their therapeutic potential. The most important medical areas in which they could be used include the following: they can help manage chronic pain, they have antiemetic, anti-inflammatory, and antipruritic properties, are beneficial in treating duodenal ulcers, can be used in bronchodilators, in muscle relaxants, and in treating refractory epilepsy, have anxiolytic properties, reduce sebum, are effective on Methicillin-resistant Staphylococcus aureus, are proapoptotic in breast cancer, can be used to treat addiction and psychosis, and are effective on MRSA, in controlling psoriasis, and in treating glioblastoma, according to the properties of their concentrations of cannabidiol, cannabigerol, and Δ9-tetrahydrocannabinol, as reviewed in the literature. On the other hand, having obtained concentrations of THC, we were able to suggest the psychotropic capacity of said samples, one of which even fits within the legal category of "non-psychoactive cannabis" according to Peruvian regulations.
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Vitis vinifera L. (grapevine) is a perennial plant of the Vitaceae family that is widely used to produce grapes and wines. Grape seed oil is rich in fatty acids such as linoleic acid (65-75%), vitamin E (50 mg), and phytosterols in addition to phenolic compounds, such as catechins (414 mg), epicatechins (130.4 mg), and gallic acid (77 µg), shows promise as a nutritional compound and is outstanding as a therapeutic substance with active properties for health, detected mainly by in vitro studies, as well as some in vivo studies. The benefits of consuming this oil include modulating the expression of antioxidant enzymes, anti-atherosclerotic and anti-inflammatory effects, and protection against oxidative cell damage and some types of cancer. However, experimental findings confirm that therapeutic functions remain scarce; thus, more studies are needed to determine the mechanisms of action involved in the indicated therapeutic qualities.
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Vitis , Humanos , Antioxidantes/farmacologia , Estresse Oxidativo , Suplementos Nutricionais , Obesidade , Inflamação/tratamento farmacológico , Óleos de Plantas/farmacologia , FrutasRESUMO
Brugmansia suaveolens Bercht. & J. Presl has been widely used due to the presence of different bioactive compounds. This review summarizes the latest advances and perspectives of the B. suaveolens plant species; it is a systematic literature review on aspects of botany, traditional uses, phytochemistry, pharmacology, and toxicology as therapeutic potential. In addition, 120 compounds are described, including alkaloids, flavonoids, terpenoids, steroids, amino acids, aromatics, and aliphatics. As for the therapeutic potential, it is described in extracts and compounds in the antitumor, anti-inflammatory, antioxidant, antimicrobial, antispasmodic, anticoagulant, and analgesic aspects, as well as the effects on the central nervous system. The toxicity of the genus stands out, especially the potential for organ toxicity. Therefore, this review evidenced the knowledge related to the traditional use based on the scientific research of Brugmansia suaveolens, highlighting an overview of bioactive compounds and biological and toxicological activities in order to provide a scientific basis for future studies on the value of this species for the development of new natural products.
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Alcaloides , Brugmansia , Fitoterapia , Medicina Tradicional , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/química , EtnofarmacologiaRESUMO
Brugmansia suaveolens Bercht. & J. Presl represents a promising source of new active molecules. Therefore, the aim of the study is to outline the profile of secondary metabolites and their therapeutic potential and in vitro safety properties. The identification of substances was carried out through the chromatographic profile, while the evaluation of therapeutic use was conducted through in vitro biological assays of antioxidant and antimicrobial activity and quantification of the total phenolic content. The safety of the extracts was evaluated using a cytotoxicity assay. The results found revealed the presence of different secondary metabolites, such as flavonoids and alkaloids. Biological assays showed promising antimicrobial activity in gram-negative strains. Regarding safety, greater cytotoxicity is observed in macrophage cells. The study demonstrated that the extracts are potent for therapeutic use, aiming at the development of a phytoproduct for topical use, providing an innovative, relevant and significant character for future research.
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The economic potential of the cactus species Cereus peruvianus Mill. (syn. C. hildmannianus K. Schum.) has already been demonstrated through the generation of products and patents. However, the phenolic compounds and antioxidant activity have not yet been evaluated. The aim of our study was to determine the total phenolic compounds, evaluate the antioxidant activity and characterize the phenolic compounds of cladode extracts from C. peruvianus grown in the southern region of Brazil, in two collection periods. Higher total content of phenolic compounds and antioxidant activity were detected in the cladode extract collected in 2016 than in the cladode extract collected in 2015. The profile of phenolic compounds identified five flavonoids that had not previously been reported in species of the genus Cereus. The phenolic compounds linked to antioxidant activities identified in the cladode extract from C. peruvianus support the use of this species in human food as a source of natural antioxidants.
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The potential biotechnological and biomedical applications of the animal venom components are widely recognized. Indeed, many components have been used either as drugs or as templates/prototypes for the development of innovative pharmaceutical drugs, among which many are still used for the treatment of human diseases. A specific South American rattlesnake, named Crotalus durissus terrificus, shows a venom composition relatively simpler compared to any viper or other snake species belonging to the Crotalus genus, although presenting a set of toxins with high potential for the treatment of several still unmet human therapeutic needs, as reviewed in this work. In addition to the main toxin named crotoxin, which is under clinical trials studies for antitumoral therapy and which has also anti-inflammatory and immunosuppressive activities, other toxins from the C. d. terrificus venom are also being studied, aiming for a wide variety of therapeutic applications, including as antinociceptive, anti-inflammatory, antimicrobial, antifungal, antitumoral or antiparasitic agent, or as modulator of animal metabolism, fibrin sealant (fibrin glue), gene carrier or theranostic agent. Among these rattlesnake toxins, the most relevant, considering the potential clinical applications, are crotamine, crotalphine and gyroxin. In this narrative revision, we propose to organize and present briefly the updates in the accumulated knowledge on potential therapeutic applications of toxins collectively found exclusively in the venom of this specific South American rattlesnake, with the objective of contributing to increase the chances of success in the discovery of drugs based on toxins.
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Venenos de Crotalídeos , Crotoxina , Animais , Venenos de Crotalídeos/toxicidade , Crotalus , Humanos , Medicina de Precisão , América do SulRESUMO
Mesenchymal stem/stromal cells (MSCs) are remarkable tools for regenerative medicine. Therapeutic approaches using these cells can promote increased activity and viability in several cell types through diverse mechanisms such as paracrine and immunomodulatory activities, contributing substantially to tissue regeneration and functional recovery. However, biological samples of human MSCs, usually obtained from adult tissues, often exhibit variable behavior during in vitro culture, especially with respect to cell population heterogeneity, replicative senescence, and consequent loss of functionality. Accordingly, it is necessary to establish standard protocols to generate high-quality, stable cell cultures, for example, by using pluripotent stem cells (PSCs) in derivation protocols of MSC-like cells since PSCs maintain their characteristics consistently during culture. However, the available protocols seem to generate distinct populations of PSC-derivedMSCs (PSC-MSCs) with peculiar attributes, which do not always resemble bona fide primary MSCs. The present review addresses the developmental basis behind some of these derivation protocols, exposing the differences among them and discussing the functional properties of PSC-MSCs, shedding light on elements that may help determine standard characterizations and criteria to evaluate and define these cells.
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Células-Tronco Pluripotentes Induzidas , Células-Tronco Mesenquimais , Células-Tronco Pluripotentes , Diferenciação Celular , Humanos , Medicina Regenerativa/métodosRESUMO
Osteoporosis (OP), a common systemic metabolic bone disease, is characterized by low bone mass, increasing bone fragility and a high risk of fracture. At present, the clinical treatment of OP mainly involves anti-bone resorption drugs and anabolic agents for bone, but their long-term use can cause serious side effects. The development of stem cell therapy and regenerative medicine has provided a new approach to the clinical treatment of various diseases, even with a hope for cure. Recently, the therapeutic advantages of the therapy have been shown for a variety of orthopedic diseases. However, these stem cell-based researches are currently limited to animal models; the uncertainty regarding the post-transplantation fate of stem cells and their safety in recipients has largely restricted the development of human clinical trials. Nevertheless, the feasibility of mesenchymal stem cells to treat osteoporotic mice has drawn a growing amount of intriguing attention from clinicians to its potential of applying the stem cell-based therapy as a new therapeutic approach to OP in the future clinic. In the current review, therefore, we explored the potential use of mesenchymal stem cells in human OP treatment.
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Reabsorção Óssea , Células-Tronco Mesenquimais , Osteoporose , Animais , Camundongos , Osteoporose/terapiaRESUMO
Huperzine A (HupA), an alkaloid found in the club moss Huperzia serrata, has been used for centuries in Chinese folk medicine to treat dementia. The effects of this alkaloid have been attributed to its ability to inhibit the cholinergic enzyme acetylcholinesterase (AChE), acting as an acetylcholinesterase inhibitor (AChEI). The biological functions of HupA have been studied both in vitro and in vivo, and its role in neuroprotection appears to be a good therapeutic candidate for Alzheimer´s disease (AD). Here, we summarize the neuroprotective effects of HupA on AD, with an emphasis on its interactions with different molecular signaling avenues, such as the Wnt signaling, the pre- and post-synaptic region mechanisms (synaptotagmin, neuroligins), the amyloid precursor protein (APP) processing, the amyloid-ß peptide (Aß) accumulation, and mitochondrial protection. Our goal is to provide an integrated overview of the molecular mechanisms through which HupA affects AD.
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Alcaloides/farmacologia , Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/farmacologia , Fármacos Neuroprotetores/farmacologia , Sesquiterpenos/farmacologia , Acetilcolinesterase/metabolismo , Alcaloides/química , Doença de Alzheimer/metabolismo , Animais , Inibidores da Colinesterase/química , Humanos , Huperzia/química , Estrutura Molecular , Fármacos Neuroprotetores/química , Sesquiterpenos/química , Transdução de Sinais/efeitos dos fármacosRESUMO
Cell-to-cell communication is a broad and complex process associated with regular stimuli to maintain healthy cell interactions. One of the agents capable of cellular communication is known as an exosome, a subset of extracellular vesicles (EVs) released by the cell membrane. The exosome contains a wide range of functional proteins, mRNAs and miRNAs, which have the potential to interact with healthy or diseased cells in the body. On the other hand, melatonin also acts as a cellular communicator, produced and released by the pineal gland in a circadian way and also, non-circadian melatonin is derived from the mitochondria of all normal cells. In addition to exhibiting antioxidant, anti-inflammatory, anti-tumor and anti-aging activities, melatonin has recently been studied by its influence on exosomes. This review summarizes the relationship between exosomes and melatonin in various pathological processes. There is robust evidence that their combination ameliorates inflammation, ischemia-reperfusion injury, hepatic metabolic disturbance, cancer immunosuppression status, degenerative processes like chronic kidney disease, vascular calcification, ageing, ischemic brain injury, neurodegenerative diseases, obesity, colitis, wound healing and even embryonic development. Association of exosomes and melatonin represent a promising therapeutic tool, capable of interfering with basic molecular processes, such as oxidative stress and the inflammatory cascade, which support many pathophysiological aspects of diseases.
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Exossomos/metabolismo , Melatonina/metabolismo , Animais , Encefalopatias/terapia , Colite/terapia , Humanos , Nefropatias/terapia , Hepatopatias/terapia , Neoplasias/terapia , Doenças Neurodegenerativas/terapia , Obesidade/terapia , Traumatismo por Reperfusão/terapia , CicatrizaçãoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Tecoma stans (L.) Juss. ex Kunth (Bignoniaceae) is an attractive evergreen plant known as kusi urakame, koyawari, Palo amarillo, tronadora, yellow-elder, yellow trumpet bush, trumpet-flower, yellow-bells, trumpet bush, ginger-Thomas, esperanza, and timboco. It is widely used in traditional Mexican medicine, to treat hyperglycemia, gastrointestinal and urinary tract disorders, jaundice, toothaches, headaches, colds, skin infections, and scorpion, snake, and rat bites. Current research focusses on evaluating its bioactive components and therapeutic potential. AIM OF THE STUDY: The current article reviewed the information available on Tecoma stans ethnopharmacology, geographical distribution, chemical composition, phytochemistry, therapeutic effects, and toxicology. MATERIAL AND METHODS: Information of botanical description, distribution, traditional uses, chemical composition, bioactive components, and therapeutic investigations was gathered from a comprehensive literature search of electronic databases such as Science Direct, PubMed, Web of Science, Wiley, ACS, Springer, Taylor and Francis, Google Scholar, and SCOPUS until 2020 for publications (peer-reviewed articles, eBooks, short communications, reports from international organizations, and case letters). Information was also included from books, conference proceedings, and thesis. Primary keywords for data collection were "Tecoma stans," and "Ethnopharmacology," followed by secondary keywords such as "Constituents," "Therapeutic effect," and "Toxicity." RESULTS: An exhaustive comparative study of the accessible sources of Tecoma stans confirmed its origin, ethnopharmacological and therapeutic uses. More than 120 chemical compounds have been isolated, and the main active principles are alkaloids, phenolic acids, flavonoids, and fatty acids. The plant possesses vast therapeutic benefits, such as lowering elevated blood sugar levels, anti-inflammatory, anti-cancer, anti-bacterial, anti-fungal, anti-oxidant, hepatoprotective, and wound healing actions. CONCLUSIONS: Comprehensive literature analysis exhibits that many populations have utilized Tecoma stans around the globe with specific reference to different parts of Mexico. The above information shows that the plant holds many hidden potentials and can, therefore, be studied extensively for its phytoconstituents and therapeutic effects. However, while going through the literature, it was observed that incomplete data is reported on in vivo trials, especially concerning its dosage, positive and negative control groups, intervention time, and toxicity studies. Additionally, there is a lack of information on its complete nutritional and phytochemical profiling. We trust that this review will help lay the groundwork for encouraging pharmacological and pharmaceutical studies. It will also direct us to understand the clinical relevance and applications of bioactive compounds from Tecoma stans in the prevention and treatment of diseases.
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Bignoniaceae/química , Medicina Tradicional , Extratos Vegetais/farmacologia , Animais , Etnofarmacologia , Humanos , MéxicoRESUMO
Osteoporosis (OP), a common systemic metabolic bone disease, is characterized by low bone mass, increasing bone fragility and a high risk of fracture. At present, the clinical treatment of OP mainly involves anti-bone resorption drugs and anabolic agents for bone, but their long-term use can cause serious side effects. The development of stem cell therapy and regenerative medicine has provided a new approach to the clinical treatment of various diseases, even with a hope for cure. Recently, the therapeutic advantages of the therapy have been shown for a variety of orthopedic diseases. However, these stem cell-based researches are currently limited to animal models; the uncertainty regarding the post-transplantation fate of stem cells and their safety in recipients has largely restricted the development of human clinical trials. Nevertheless, the feasibility of mesenchymal stem cells to treat osteoporotic mice has drawn a growing amount of intriguing attention from clinicians to its potential of applying the stem cell-based therapy as a new therapeutic approach to OP in the future clinic. In the current review, therefore, we explored the potential use of mesenchymal stem cells in human OP treatment.
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Animais , Camundongos , Osteoporose/terapia , Reabsorção Óssea , Células-Tronco MesenquimaisRESUMO
Acetylcholinesterase (AChE) is the key enzyme responsible for deactivating the ACh neurotransmitter. Irreversible or prolonged inhibition of AChE, therefore, elevates synaptic ACh leading to serious central and peripheral adverse effects which fall under the cholinergic syndrome spectra. To combat the toxic effects of some AChEI, such as organophosphorus (OP) nerve agents, many compounds with reactivator effects have been developed. Within the most outstanding reactivators, the substances denominated oximes stand out, showing good performance for reactivating AChE and restoring the normal synaptic acetylcholine (ACh) levels. This review was developed with the purpose of covering the new advances in AChE reactivation. Over the past years, researchers worldwide have made efforts to identify and develop novel active molecules. These researches have been moving farther into the search for novel agents that possess better effectiveness of reactivation and broad-spectrum reactivation against diverse OP agents. In addition, the discovery of ways to restore AChE in the aged form is also of great importance. This review will allow us to evaluate the major advances made in the discovery of new acetylcholinesterase reactivators by reviewing all patents published between 2016 and 2019. This is an important step in continuing this remarkable research so that new studies can begin.
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Acetilcolinesterase/metabolismo , Reativadores da Colinesterase , Reativadores da Colinesterase/química , Reativadores da Colinesterase/uso terapêutico , Proteínas Ligadas por GPI/metabolismo , Humanos , Oximas/química , Oximas/uso terapêutico , Patentes como AssuntoRESUMO
Flavonoids have aroused much interest in research, since they present a great diversity of biological activities observed in vitro, such as: antioxidant effect, modulation of the enzymatic activity and inhibition of cellular proliferation, exerting beneficial effects on the organism, as well as the use of its therapeutic potential. With wide distribution in the plant kingdom represent a class of phenolic compounds that differ in their chemical structure and particular characteristics. The objective of this review was to describe the relevant aspects of flavonoids, reporting the different known groups, the probable mechanisms by which they act, their pharmacological properties and to gain a better understanding of the reported beneficial health effects of these substances. This systematic review consisted of research using scientific databases such as Scopus, Science Direct, PubMed, SciVerse and SciELO, without time limitation. Some pharmacological properties of some flavonoids and their health benefits have been confirmed by previous studies.
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Flavonoides/farmacologia , Animais , Antioxidantes/farmacologia , Flavonoides/química , Flavonoides/uso terapêutico , Humanos , Fenóis , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
BACKGROUND: Oral cancer is one of the common malignant tumors of the head and neck. However, current treatments have numerous side effects, and drugs from natural sources may have better therapeutic potential. This research investigated the induction of apoptosis by α-hederin (α-HN), a constituent of Pulsatilla chinensis (Bunge) Regel, in the oral cancer cell line SCC-25 and its underlying mechanism. RESULTS: SCC-25 cells were treated with 50, 100, and 200 µmol/L α-HN. Cell proliferation; extent of apoptosis; activities of caspases-3, 8, and 9; and the expression of Bcl-2, Bax, phosphorylated (p)-phosphoinositide 3-kinase (PI3K), p-Akt, and p-mammalian target of rapamycin (mTOR) proteins were determined using the 3-(4,5)-2-thiazole-(2,5)-diphenyl tetrazolium bromide, flow cytometry, caspase activity detection kits, and western blot assays, respectively. The results showed that the proliferation of SCC-25 cells in the α-HN-treated groups decreased significantly, and the inhibitory effect was time and concentration dependent. Compared with cells in the control group, the extent of apoptosis increased significantly, caspase-3 and -9 activities were significantly enhanced, and the Bcl-2 level was lowered and the Bax level was elevated significantly in SCC-25 cells treated with α-HN for 48 h (P b 0.05). The expression of p-PI3K, p-Akt, and p-mTOR was also significantly lower in SCC-25 cells treated with α-HN than that in the control group (P b 0.05). CONCLUSION: These results indicate that α-HN can inhibit proliferation and induce apoptosis of SCC-25 cells and may exert these effects by inhibiting the PI3K/Akt/mTOR signaling pathway.
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Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Neoplasias Bucais/metabolismo , Apoptose/efeitos dos fármacos , Ácido Oleanólico/metabolismo , Ácido Oleanólico/farmacologia , Saponinas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sobrevivência Celular , Western Blotting , Fosfatidilinositol 3-Quinases/metabolismo , Caspases , Pulsatilla , Proliferação de Células/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Citometria de Fluxo , Neoplasias de Cabeça e Pescoço/metabolismoRESUMO
The discovery of animal cloning and subsequent development of cell reprogramming technology were quantum leaps as they led to the achievement of rejuvenation by cell reprogramming and the emerging view that aging is a reversible epigenetic process. Here, we will first summarize the experimental achievements over the last 7 years in cell and animal rejuvenation. Then, a comparison will be made between the principles of the cumulative DNA damage theory of aging and the basic facts underlying the epigenetic model of aging, including Horvath's epigenetic clock. The third part will apply both models to two natural processes, namely, the setting of the aging clock in the mammalian zygote and the changes in the aging clock along successive generations in mammals. The first study demonstrating that skin fibroblasts from healthy centenarians can be rejuvenated by cell reprogramming was published in 2011 and will be discussed in some detail. Other cell rejuvenation studies in old humans and rodents published afterwards will be very briefly mentioned. The only in vivo study reporting that a number of organs of old progeric mice can be rejuvenated by cyclic partial reprogramming will also be described in some detail. The cumulative DNA damage theory of aging postulates that as an animal ages, toxic reactive oxygen species generated as byproducts of the mitochondria during respiration induce a random and progressive damage in genes thus leading cells to a progressive functional decline. The epigenetic model of aging postulates that there are epigenetic marks of aging that increase with age, leading to a progressive derepression of DNA which in turn causes deregulated expression of genes that disrupt cell function. The cumulative DNA damage model of aging fails to explain the resetting of the aging clock at the time of conception as well as the continued vitality of species as millenia go by. In contrast, the epigenetic model of aging straightforwardly explains both biologic phenomena. A plausible initial application of rejuvenation in vivo would be preventing adult individuals from aging thus eliminating a major risk factor for end of life pathologies. Further, it may allow the gradual achievement of whole body rejuvenation.
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Reprogramação Celular/genética , Epigenômica/métodos , Envelhecimento , Animais , Diferenciação Celular , Humanos , CamundongosRESUMO
Snake venoms are sources of molecules with proven and potential therapeutic applications. However, most activities assayed in venoms (or their components) are of hemorrhagic, hypotensive, edematogenic, neurotoxic or myotoxic natures. Thus, other relevant activities might remain unknown. Using functional genomics coupled to the connectivity map (C-map) approach, we undertook a wide range indirect search for biological activities within the venom of the South American pit viper Bothrops jararaca. For that effect, venom was incubated with human breast adenocarcinoma cell line (MCF7) followed by RNA extraction and gene expression analysis. A list of 90 differentially expressed genes was submitted to biosimilar drug discovery based on pattern recognition. Among the 100 highest-ranked positively correlated drugs, only the antihypertensive, antimicrobial (both antibiotic and antiparasitic), and antitumor classes had been previously reported for B. jararaca venom. The majority of drug classes identified were related to (1) antimicrobial activity; (2) treatment of neuropsychiatric illnesses (Parkinson's disease, schizophrenia, depression, and epilepsy); (3) treatment of cardiovascular diseases, and (4) anti-inflammatory action. The C-map results also indicated that B. jararaca venom may have components that target G-protein-coupled receptors (muscarinic, serotonergic, histaminergic, dopaminergic, GABA, and adrenergic) and ion channels. Although validation experiments are still necessary, the C-map correlation to drugs with activities previously linked to snake venoms supports the efficacy of this strategy as a broad-spectrum approach for biological activity screening, and rekindles the snake venom-based search for new therapeutic agents.
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Venenos de Crotalídeos/farmacologia , Descoberta de Drogas , Animais , Bothrops , Venenos de Crotalídeos/uso terapêutico , Humanos , Células MCF-7 , Transcriptoma/efeitos dos fármacosRESUMO
Voltage-gated calcium (CaV) channels are widely expressed and are essential for the completion of multiple physiological processes. Close regulation of their activity by specific inhibitors and agonists become fundamental to understand their role in cellular homeostasis as well as in human tissues and organs. CaV channels are divided into two groups depending on the membrane potential required to activate them: High-voltage activated (HVA, CaV1.1-1.4; CaV2.1-2.3) and Low-voltage activated (LVA, CaV3.1-3.3). HVA channels are highly expressed in brain (neurons), heart, and adrenal medulla (chromaffin cells), among others, and are also classified into subtypes which can be distinguished using pharmacological approaches. Cone snails are marine gastropods that capture their prey by injecting venom, "conopeptides", which cause paralysis in a few seconds. A subset of conopeptides called conotoxins are relatively small polypeptides, rich in disulfide bonds, that target ion channels, transporters and receptors localized at the neuromuscular system of the animal target. In this review, we describe the structure and properties of conotoxins that selectively block HVA calcium channels. We compare their potency on several HVA channel subtypes, emphasizing neuronal calcium channels. Lastly, we analyze recent advances in the therapeutic use of conotoxins for medical treatments.
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Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Conotoxinas/farmacologia , Animais , Bloqueadores dos Canais de Cálcio/química , Bloqueadores dos Canais de Cálcio/uso terapêutico , Canais de Cálcio/metabolismo , Conotoxinas/química , Humanos , Potenciais da Membrana/efeitos dos fármacos , CaramujosRESUMO
INTRODUCTION: There is a great interest in Nitric oxide (NO) within medicinal chemistry since it's involved in human signaling pathways. Prodrugs or hybrid compounds containing NO-donor scaffolds linked to an active compound are valuable, due to their potential for modulating many pathological conditions due to NO's biological properties when released in addition to the native drug. Compounds that selectively inhibit nitric oxide synthase isoforms (NOS) can also increase therapeutic capacity, particularly in the treatment of chronic diseases. However, search for bioactive compounds to efficiently and selectively modulate NO is still a challenge in drug discovery. Areas covered: In this review, the authors highlight the recent advances in the strategies used to discover NO-hybrid derivatives, especially those related to anti-inflammatory, cardiovascular, anticancer and anti-microorganism activities. They also focus on: nitric oxide synthase inhibitors, NO delivery materials and other related activities. Expert opinion: The process of molecular hybridization can be used to obtain NO-releasing compounds that also interact with different targets. The main problem with this approach is to control NO multiple actions in the right biological system. However, the use of NO-releasing groups with many different scaffolds leads to new molecular structures for bioactive compounds, suggesting synergies.
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Desenho de Fármacos , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico/metabolismo , Animais , Química Farmacêutica/métodos , Descoberta de Drogas/métodos , Humanos , Óxido Nítrico Sintase/antagonistas & inibidores , Pró-Fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
The present study reports the evaluation of immunomodulatory and therapeutic potential of a purified Aspergillus panamensis lectin. The immunomodulatory potential of the purified lectin was determined in swiss albino mice by studying its effect on anaphylaxis reaction, arthus reaction, respiratory burst activity, nitric oxide production and quantification of cytokine levels. The therapeutic potential of the lectin was evaluated in male wistar rat models by studying its curative effect on ulcerative colitis. The purified lectin inhibited systemic anaphylaxis and arthus reaction. It enhanced the functional ability of macrophages which was evident from increase in reduction of nitroblue tetrazolium dye and nitric oxide production. It also stimulated the production of Th-1 cytokine IFN-γ and Th-2 cytokine IL-6. Maximum immunomodulatory effect was seen at lectin concentration of 1.5mg/kg body weight. The lectin also showed curative effect against trinitrobenzene sulphonic acid induced ulcerative colitis. The results of this study adequately reflect the role of purified A. panamensis lectin in improving the immune status of mice models. They also show the effect of lectin in reducing the severity of incidence and decrease in clinical symptoms of ulcerative colitis.