Alzheimer’s and Parkinson’s diseases are considered the most common neurodegenerative disorders, representing a major focus of neuroscience research to understanding the cellular alterations and ...pathophysiological mechanisms involved. Several natural products, including flavonoids, are considered able to cross the blood-brain barrier and are known for their central nervous system-related activity. Therefore, studies are being conducted with these chemical constituents to analyze their activities in slowing down the progression of neurodegenerative diseases. The present systematic review summarizes the pharmacological effects of flavonoids in animal models for Alzheimer’s and Parkinson’s diseases. A PRISMA model for systematic review was utilized for this search. The research was conducted in the following databases: PubMed, Web of Science, BIREME, and Science Direct. Based on the inclusion criteria, 31 articles were selected and discussed in this review. The studies listed revealed that the main targets of action for Alzheimer’s disease therapy were reduction of reactive oxygen species and amyloid beta-protein production, while for Parkinson’s disease reduction of the cellular oxidative potential and the activation of mechanisms of neuronal death. Results showed that a variety of flavonoids is being studied and can be promising for the development of new drugs to treat neurodegenerative diseases. Moreover, it was possible to verify that there is a lack of translational research and clinical evidence of these promising compounds.
Pain and inflammation are unpleasant experiences that usually occur as a result of tissue damage. Despite the number of existing analgesic drugs, side effects limit their use, stimulating the search ...for new therapeutic agents. In this sense, five hydrazone derivatives (H1, H2, H3, H4, and H5), with general structure R1R2C = NNR3R4, were synthesized with molecular modification strategies. In this paper, we describe the ability of hydrazone derivatives to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In both experimental models, the hydrazone with the greatest potency (H5) significantly (p < 0.05) reduced nociceptive behavior. Additionally, methods of acute and chronic inflammation induced by different chemicals (carrageenan and histamine) were performed to evaluate the anti-inflammatory effect of H5. Moreover, molecular docking analysis revealed that H5 can block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. H5 also changes locomotor activity. In summary, H5 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug.
Rationale
Solanum paniculatum L., popularly known as jurubeba, has traditionally been used in Brazilian folk medicine for liver diseases. However, there is a lack of knowledge about the chemical ...characterization of 3‐aminospirostane alkaloids, an important class related to pharmacological activities. This work aimed to characterize the alkaloids using liquid chromatography with tandem mass spectrometry (LC/MS/MS) supported by molecular networking and theoretical calculations as well as to evaluate the contribution to hepatoprotective activity.
Methods
S. paniculatum roots were collected and macerated with MeOH/H2O (8:2) obtaining the crude extract (SP‐CE). From this, partition using EtOAc with pH variation yielded the alkaloidic fraction (SP‐AF). Both were evaluated in an acute liver injury model (100 and 200 mg/kg), after intraperitoneal administration of carbon tetrachloride (CCl4) in mice. AST (aspartate transaminase) and ALT (alanine transaminase) serum levels were investigated, as well as the histopathological characteristics. The SP‐CE and SP‐AF were analyzed by LC/MS/MS, using quadrupole/time‐of‐flight and ion‐trap systems. The alkaloids annotated by the GNPS molecular network had their structures defined using gas‐phase ionization and fragmentation reaction supported by theoretical calculations.
Results
The SP‐CE and SP‐AF decreased the ALT serum levels compared with the negative control. The group treated with the SP‐CE (at the highest dose) demonstrated a significant decrease of ALT. Hepatic cell degeneration decrease was observed mainly at the highest dose of the treatment. Detailed electrospray ionization MS/MS data allowed us to identify alkaloids not previously reported, to propose their gas‐phase reactions and to redefine the initial open ring fragmentation mechanism of the steroidal alkaloids with the jurubidine moiety.
Conclusions
The results allowed us to identify seven steroidal alkaloids from jurubeba and redefine the initial mechanism of fragmentation. A significant hepatoprotective effect was also demonstrated, corroborating its traditional use.
Pain and inflammation are complex clinical conditions that are present in a wide variety of disorders. Most drugs used to treat pain and inflammation have potential side effects, which makes it ...necessary to search for new sources of bioactive molecules. In this paper, we describe the ability of LASSBio-1586, an N-acylhydrazone derivative, to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In these experimental models, LASSBio-1586 significantly (p<0.05) reduced nociceptive behavior. Several methods of acute and chronic inflammation induced by different chemical (carrageenan, histamine, croton oil, arachidonic acid) and physical (cotton pellet) agents were used to evaluate the anti-inflammatory effect of LASSBio-1586. LASSBio-1586 exhibited potent anti-inflammatory activity in all tests (p<0.05). Study of the mechanism of action demonstrated the possible involvement of the nitrergic, serotonergic and histamine signaling pathways. In addition, a molecular docking study was performed, indicating that LASSBio-1586 is able to block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. In summary, LASSBio-1586 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug.
Most anti-inflammatory drugs used nowadays have an excessive cost and their prolonged use has been connected with several injurious effects. Thus, the search for new anti-inflammatory agents is ...increasing. Lectins are carbohydrate-interacting proteins that can modulate immune response and the release of inflammation mediators. The
frond lectin (MvFL) was previously reported to be an immunomodulatory agent in vitro. This work aimed to evaluate the effects of MvFL on the in vivo inflammatory status in the carrageenan-induced peritonitis and paw edema, using female Swiss mice. The animals were pretreated intraperitoneally with MvFL (5 and 10 mg/kg). In the peritonitis assay, the total and differential migration of white blood cells was evaluated, as well as the levels of cytokines, nitric oxide (NO), and total proteins in the peritoneal fluid. In the paw edema evaluation, the paw volume was measured in the early (from 30 min-2 h) and late (3-4 h) phases of edema formation. MvFL (5 and 10 mg/kg) was efficient in reducing neutrophil infiltration, pro-inflammatory cytokines (IL-6, IL-17, and TNF-α), NO, and protein content in the peritoneal fluid. It also repressed the edema formation in the late phase of the assay. In conclusion, MvFL showed inhibitory effects in in vivo acute inflammation, which encouraged future studies exploiting its immunomodulatory ability.
Medicinal plants have been widely used in the treatment of chronic pain. In this study, we describe the antinociceptive effect of the essential oil from
(the EO 25, 50, and 100 mg/kg, i.p.), a ...medicinal plant native to Brazil. Antinociceptive activity was investigated by measuring the nociception induced by acetic acid, formalin, hot plate and carrageenan. A docking study was performed with the major constituents of the EO (
-caryophyllene, caryophyllene oxide, and camphor). The EO reduced nociceptive behavior at all doses tested in the acetic acid-induced nociception test (
< 0.05). The same was observed in both phases (neurogenic and inflammatory) of the formalin test. When the hot-plate test was conducted, the EO (50 mg/kg) extended the latency time after 60 min of treatment. The EO also reduced leukocyte migration at all doses, suggesting that its antinociceptive effect involves both central and peripheral mechanisms. Pretreatment with glibenclamide and atropine reversed the antinociceptive effect of the EO on the formalin test, suggesting the involvement of K
channels and muscarinic receptors. The docking study revealed a satisfactory interaction profile between the major components of the EO and the different muscarinic receptor subtypes (M2, M3, and M4). These results corroborate the medicinal use of
in folk medicine.
Inflammatory diseases result from the body’s response to tissue damage, and if the resolution is not adequate or the stimulus persists, there will be progression from acute inflammation to chronic ...inflammation, leading to the development of cancer and neurodegenerative and autoimmune diseases. Due to the complexity of events that occur in inflammation associated with the adverse effects of drugs used in clinical practice, it is necessary to search for new biologically active compounds with anti-inflammatory activity. Among natural products, essential oils (EOs) present promising results in preclinical studies, with action in the main mechanisms involved in the pathology of inflammation. The present systematic review summarizes the pharmacological effects of EOs and their compounds in in vitro and in vivo models for inflammation. The research was conducted in the following databases: PubMed, Scopus, BIREME, Scielo, Open Grey, and Science Direct. Based on the inclusion criteria, 30 articles were selected and discussed in this review. The studies listed revealed a potential activity of EOs and their compounds for the treatment of inflammatory diseases, especially in chronic inflammatory conditions, with the main mechanism involving reduction of reactive oxygen and nitrogen species associated with an elevation of antioxidant enzymes as well as the reduction of the nuclear factor kappa B (NF-κB), reducing the expression of proinflammatory cytokines. Thus, this review suggests that EOs and their major compounds are promising tools for the treatment of chronic inflammation.
Schinus terebinthifolia Raddi is a plant broadly used in folk medicine and the use of its leaf extract as an antitumor agent has been reported.
To evaluate the antitumor potential and the toxicity of ...saline extract (SE) and lectin (SteLL) from S. terebinthifolia leaves in sarcoma 180-bearing mice.
Cytotoxicity to sarcoma 180 cells was tested in vitro, and antitumor assay was performed using Swiss female mice. The treatments (0.15 M NaCl, negative control; methotrexate 1.5 mg/kg, positive control; SE 100 mg/kg; SteLL 1 and 5 mg/kg) by intraperitoneal injections started on the 8th day after tumor inoculation and lasted 7 days. It was analyzed: tumor weight; number and gauge of tumor vessels; hematological and biochemical parameters; histopathological changes; and occurrence of micronuclei in bone marrow cells.
SE and SteLL showed IC50 values (concentrations that reduced cell viability to 50%) of 301.65 and 8.30 μg/mL, respectively. The lectin was able to induce apoptosis. Treatments with the extract and lectin caused a 57.6–73.6% reduction in tumor weight, which was not significantly different from the reduction in the methotrexate group. Tumors of animals treated with SteLL at 5 mg/kg showed reduced number of secondary vessels while the gauge was lower in all treated groups. In the groups treated with SteLL, tumors showed reduced and slightly vascularized parenchyma, with necrosis in the center and at the periphery. No alterations in the blood levels of urea, creatine, and glucose were detected while serum AST level was moderately increased in the SE group. Histopathological analysis revealed vacuolization and steatosis in the liver of animals treated with the extract and lectin. In addition, the treatments with SE and SteLL resulted in the reduction of filtration space and alterations in tubular architecture in kidneys. In respect to hematological parameters, it was only detected increase in the number of monocytes in SE group. The extract and lectin did not induce the formation of micronuclei in the bone marrow cells.
SE and SteLL had antitumor effect against sarcoma 180 without inducing hematological changes and genotoxic effects in mice; however, some degree of hepatic and renal toxicity was observed, suggesting the evaluation of drug delivery strategies in the future.
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Schinus terebinthifolia Raddi leaves have been used in folk medicine due to several properties, including antitumor and analgesic effects. The variable efficacy and adverse effects of analgesic drugs ...have motivated the search for novel antinociceptive agents. It has been reported that the S. terebinthifolia leaf lectin (SteLL) has antitumor activity against sarcoma 180 in mice.
This work aimed to evaluate whether SteLL would reduce cancer pain using an orthotopic tumor model.
A sarcoma 180 cell suspension was inoculated into the right hind paws of mice, and the treatments (150 mM NaCl, negative control; 10 mg/kg morphine, positive control; or SteLL at 1 and 2 mg/kg) were administered intraperitoneally 24 h after cell inoculation up to 14 days. Spontaneous nociception, mechanical hyperalgesia, and hot-plate tests were performed. Further, the volume and weight of the tumor-bearing paws were measured.
SteLL (2 mg/kg) improved limb use during ambulation. The lectin (1 and 2 mg/kg) also inhibited mechanical hyperalgesia and increased the latency time during the hot-plate test. Naloxone was found to reverse this effect, indicating the involvement of opioid receptors. The tumor-bearing paws of mice treated with SteLL exhibited lower volume and weight.
SteLL reduced hyperalgesia due to sarcoma 180 in the paws of mice, and this effect can be related to its antitumor action.
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•The lectin SteLL was evaluated for antinociceptive activity on orthotopic tumor model.•In the spontaneous nociception assay, SteLL improved limb use during ambulation.•The lectin also inhibited mechanical hyperalgesia.•SteLL increased the latency time during the hot-plate test.•SteLL reduced hyperalgesia due to sarcoma 180 in the paws of mice.
In recent decades, public policies of the Unified Health System (SUS) in Brazil have structured a community mental health care network (RAPS) based on various community actions and services. This ...study carried out evaluative research on the implementation of the structure and process dimensions of this care network in Minas Gerais, the second most populous state of Brazil, generating indicators that can enhance the strategic management of the public health system in the strengthening the psychosocial care in the state. The application of a multidimensional instrument, previously validated (IMAI-RAPS), in 795 of the 853 municipalities in Minas Gerais was carried out between June and August 2020. Regarding the structural dimension, we noticed an adequate implementation of services like 'Family Health Strategy,' 'Expanded Family Health Center,' and 'Psychosocial Care Centers' but a lack of 'Beds in General Hospitals' destinated to mental health care, 'Unified Electronic Medical Records' and 'Mental Health Training Activities for Professionals.' In the process dimension, adequate implementation of actions such as 'Multidisciplinary and Joint Care,' 'Assistance to Common Mental Disorders by Primary Health Care,' 'Management of Psychiatric Crises in Psychosocial Care Centers,' 'Offer of Health Promotion Actions,' and 'Discussion of Cases by Mental Health Teams' point to a form of work consistent with the guidelines. However, we detected difficulties in the implementation of 'Psychosocial Rehabilitation Actions,' 'Productive Inclusion,' 'User Protagonism,' 'Network Integration,' and practical activities for the effectiveness of collaborative care. We found a better implementation of the mental health care network in more populous, demographically dense, and socioeconomically developed cities, which shows the importance of regional sharing of services that are not possible for small cities. The evaluation practices of mental health care networks are scarce throughout the Brazilian territory, a fact also found in Minas Gerais, highlighting the need for its expansion not only in the scientific sphere but also in the daily life of the various levels of management.
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