Investigation of mechanisms of action involved in the antidepressant-like effect of Trans,trans-farnesol in mice.

This study aimed to investigate, through in vivo and biochemical methodologies, the effect of trans,trans-farnesol (12.5, 25, 50 or 100 mg/kg, p.o.) acute administration, adopting different behavioral and neurochemical parameters associated with an acute induced-depression model in mice. The initial results showed that, the oral treatment with trans,trans-farnesol, at the dose of 100 mg/kg induced a possible antidepressant-like effect in animals subjected to forced swim test (FST) and reserpine-induced akinesia. In addition, it was observed that the compound in question has an effect size and properties similar to imipramine (prototype of tricyclic antidepressants), but devoid of proconvulsant adverse effect. In biochemical assays, the pretreatment with trans,trans-farnesol, at a dose of 100 mg/kg (p.o.), decreased the hippocampal concentration of thiobarbituric acid reactive substances (TBARS) and restored striatal levels of noradrenaline and serotonin in mice subjected to FST. Altogether, these results suggest that trans,trans-farnesol showed a significant antidepressant-like effect, which seems to be mediated by the antagonism of muscarinic cholinergic receptors, reduction of oxidative stress and the modulation of noradrenaline and serotonin content in the central nervous system.

Plectranthus Species with Anti-Inflammatory and Analgesic Potential: A Systematic Review on Ethnobotanical and Pharmacological Findings.

The use of medicinal plants to treat inflammatory conditions and painful processes has attracted the attention of scientists and health professionals due to the evidence that natural products can promote significant therapeutic benefits associated with fewer adverse effects compared to conventional anti-inflammatory drugs. The genus Plectranthus is composed of various plants with pharmacological potential, which are used to treat various diseases in traditional communities worldwide. The present study systematically reviewed Plectranthus species with anti-inflammatory and analgesic potential. To this end, a systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The search was conducted on the following databases: PubMed, ScienceDirect, SciVerse Scopus, and Web of Science. Different combinations of search terms were used to ensure more excellent article coverage. After the selection, a total of 45 articles were included in this review. This study identified twelve Plectranthus species indicated for the treatment of different inflammatory conditions, such as wounds, fever, bronchitis, abscess, asthma, hepatitis, labyrinthitis, tonsillitis, and uterine inflammation. The indications for pain conditions included headache, sore throat, heartburn, menstrual cramp, colic, toothache, stomachache, migraine, chest pain, abdominal pain, local pain, labor pain, and recurring pain. Among the listed species, ten plants were found to be used according to traditional knowledge, although only four of them have been experimentally studied. When assessing the methodological quality of preclinical in vivo assays, most items presented a risk of bias. The SR results revealed the existence of different Plectranthus species used to treat inflammation and pain. The results of this systematic review indicate that Plectranthus species have the potential to be used in the treatment of diseases with an inflammatory component, as well as in the management of pain. However, given the risk of biases, the experimental analysis of these species through preclinical testing is crucial for their safe and effective use.

Vasodilation promoted by (E,E)-farnesol involving ion channels in human umbilical arteries.

Background: (E,E)-farnesol is a sesquiterpene alcohol derived from plants and animals that exhibits pharmacological properties in the cardiovascular system. However, its effects on human umbilical vessels remain unknown. Purpose: Thus, this study aims to characterize the vasodilatory effect of (E,E)-farnesol in human umbilical arteries (HUA). Study design: The tissue is obtained from pregnant women over 18 years of age, normotensive, and without prepartum complications. After collected, the tissue was segmented and dissected to remove Wharton's jelly and obtain the umbilical arteries segments. Methods: HUA segments were isolated and sectioned into rings that were subjected to isometric tension recordings in an organ bath. Results: (E,E)-farnesol (1 µmol/L to 1 mmol/L) promoted vasodilatory effect in HUA preparations, affecting basal tone, and inhibiting the electromechanical coupling induced by KCl 60 mmol/L with greater potency (EC50 225.3 µmol/L) than the pharmacomechanical coupling induced by 5-HT 10 µmol/L (EC50 363.5 µmol/L). In the absence of extracellular calcium, pharmacomechanical coupling was also abolished, and contractions induced by CaCl2 or BaCl2 were attenuated by (E,E)-farnesol indicating a possible direct inhibition of L-type VOCC as a mechanism of the vasodilatory effect. The vasodilator efficacy of (E,E)-farnesol on reduction of vasocontraction induced by the presence of tetraethylammonium (1 or 10 mmol/L), 4-aminopyridine (1 mmol/L) and glibenclamide (10 µmol/L) suggesting a possible influence of different potassium channels (BKCa, KV and KATP). Conclusion: These results suggest that (E,E)-farnesol may be a promising pharmacological candidate for obstetric hypertensive disorders.

Mechanisms of Actions Involved in The Antinociceptive Effect of Estragole and its ß-Cyclodextrin Inclusion Complex in Animal Models.

(1) Background: estragole is a monoterpene found in the essential oils of several aromatic plants, which can be used for several pharmacological activities. The aim of this study was to evaluate the antinociceptive effect of estragole (Es) and its ß-cyclodextrins inclusion complex (Es/ß-CD). (2) Methods: the effects of Es and Es/ß-CD on the central nervous system (CNS) were evaluated through open field and rota-rod assays, and the antinociceptive effect in formalin models, abdominal writhing induced by acetic acid, hot plate, tail flick test and plantar mechanical hyperalgesia. (3) Results: Es and Es/ß-CD showed no alterations on the CNS evaluated parameters and the results suggested there was an antinociceptive action in the formalin, abdominal writhing, hot plate, tail flick tests and plantar mechanical hyperalgesia, proposing the involvement of the nitric oxide, glutamatergic signaling pathways, cyclic guanosine monophosphate and vanilloid pathways. (4) Conclusion: the results suggest that Es and Es/ß-CD have a promising antinociceptive potential as a possible alternative for the pharmacological treatment of pain, also showing that the encapsulation of Es in ß-cyclodextrins probably improves its pharmacological properties, since the complexation process involves much lower amounts of the compound, contributing to better bioavailability and a lower probability of adverse effect development.

Evidence for the beneficial effect of ketamine in the treatment of patients with post-traumatic stress disorder: A systematic review and meta-analysis.

Post-traumatic stress disorder (PTSD) is an anxiety disorder with manifestations somatic resulting from reliving the trauma. The therapy for the treatment of PTSD has limitations, between reduced efficacy and "PTSD pharmacotherapeutic crisis". Scientific evidence has shown that the use of ketamine has benefits for the treatment of depressive disorders and other symptoms present in PTSD compared to other conventional therapies. Therefore, this study aims to analyze the available evidence on the effect of ketamine in the treatment of post-traumatic stress. The systematic review and the meta-analysis were conducted following PRISMA guidelines and RevManager software, using randomized controlled trials and eligible studies of quality criteria for data extraction and analysis. The sample design evaluated included the last ten years, whose search resulted in 594 articles. After applying the exclusion criteria, 35 articles were selected, of which 14 articles were part of the sample, however, only six articles were selected the meta-analysis. The results showed that the ketamine is a promising drug in the management of PTSD with effect more evident performed after 24 h evaluated by MADRS scale. However, the main limitations of the present review demonstrate that more high-quality studies are needed to investigate the influence of therapy, safety, and efficacy.

The Protein-Rich Fraction from Spirulina platensis Exerts Neuroprotection in Hemiparkinsonian Rats by Decreasing Brain Inflammatory-Related Enzymes and Glial Fibrillary Acidic Protein Expressions.

Spirulina platensis is a cyanobacterium with high protein content and presenting neuroprotective effects. Now, we studied a protein-enriched fraction (SPF), on behavior, neurochemical and immunohistochemical (IHC) assays in hemiparkinsonian rats, distributed into the groups: SO (sham-operated), 6-hydroxydopamine (6-OHDA), and 6-OHDA (treated with SPF, 5 and 10 mg/kg, p.o., 15 days). Afterward, animals were subjected to behavioral tests and euthanized, and brain areas used for neurochemical and IHC assays. SPF partly reversed the changes in the apomorphine-induced rotations, open field and forced swim tests, and also the decrease in striatal dopamine and 3,4-dihydroxyphenylacetic acid contents seen in hemiparkinsonian rats. Furthermore, SPF reduced brain oxidative stress and increased striatal expressions of tyrosine hydroxylase and dopamine transporter and significantly reduced hippocampal inducible nitric oxide synthase, cyclooxygenase-2 and glial fibrillary acidic protein expressions. The data suggest that the protein fraction from S. platensis, through its brain anti-inflammatory and antioxidative actions, exerts neuroprotective effects that could benefit patients affected by neurodegenerative diseases, like Parkinson's disease.

UPLC-MS-ESI-QTOF Analysis and Antifungal Activity of Aqueous Extracts of Spondias tuberosa.

This study aimed to identify the chemical composition of the Spondias tuberosa aqueous leaf and root extracts (EALST and EARST) and to evaluate their effect, comparatively, against opportunistic pathogenic fungi. Ultra-Performance Liquid Chromatography Coupled to a Quadrupole/Time of Flight System (UPLC-MS-ESI-QTOF) was employed for chemical analysis. Candida albicans and C. tropicalis standard strains and clinical isolates were used (CA INCQS 40006, CT INCQS 40042, CA URM 5974, and CT URM 4262). The 50% Inhibitory Concentration for the fungal population (IC50) was determined for both the intrinsic action of the extracts and the extract/fluconazole (FCZ) associations. The determination of the Minimum Fungicidal Concentration (MFC) and the verification of effects over fungal morphological transitions were performed by subculture in Petri dishes and humid chambers, respectively, both based on micro-dilution. UPLC-MS-ESI-QTOF analysis revealed the presence of phenolic and flavonoid compounds. The association of the extracts with fluconazole, resulted in IC50 values from 2.62 µg/mL to 308.96 µg/mL. The MFC of the extracts was ≥16,384 µg/mL for all tested strains, while fluconazole obtained an MFC of 8192 µg/mL against C. albicans strains. A reduction in MFC against CA URM 5974 (EALST: 2048 µg/mL and EARST: 1024 µg/mL) occurred in the extract/fluconazole association.

Chemical Constituents and Biological Activities of Croton heliotropiifolius Kunth.

Croton heliotropiifolius Kunth (Euphorbiaceae), whose occurrence has already been registered in the most varied Brazilian biomes, is commonly found in the Chapada do Araripe, Ceará. The species is traditionally used to treat fungal, parasitic, and degenerative diseases. This study investigated the chemical composition and pharmacological potential (antioxidant, antifungal, antiparasitic, and cytotoxic) of an aqueous extract obtained from the roots of C. heliotropiifolius. Following a qualitative phytochemical screening, the chemical constituents were identified by ultra-efficiency liquid chromatography coupled witha quadrupole/time-of-flight system (UPLC-QTOF). The antioxidant potential was verified by thin-layer chromatography (TLC). The direct and combined antifungal activity of the extract against opportunistic Candida strains was investigated using the microdilution method. The minimal fungicidal concentration (MFC) was determined by subculture, while the modulation of the morphological transition (fungal virulence) was evaluated by light microscopy. The in vitro antiparasitic activity was analyzed using epimastigotes of Trypanosoma cruzi and promastigotes of Leishmania braziliensis and Leishmania infantum, while cytotoxicity was determined in cultures of mouse fibroblasts. The phytochemical analysis identified the presence of acids, terpenes, flavonoids, lignans, and alkaloids. Among these constituents, the presence of polar and non-polar phenolic compounds with known antioxidant action was highlighted. While the extract showed clinically ineffective antifungal effects, it could enhance the effectiveness of fluconazole, in addition to inhibiting the morphological transition associated with increased virulence in Candida strains. Although the extract showed low cytotoxicity against fibroblasts, it also had weak antiparasitic effects. In conclusion, Croton heliotropiifolius is a source of natural products with antifungal and antioxidant potential.

Concepts, Beliefs, and Traditional Treatment for Childhood Seizures in a Quilombola Community in Northeastern Brazil: Analysis by the Discourse of the Collective Speech.

BACKGROUND: Non-pharmacological therapy related to traditional, magical, and/or religious treatments for managing recurrent and non-recurrent seizures in children persists in several traditional communities. The research aims to investigate the concepts, beliefs, and types of traditional treatments used for cases of seizures in children reported by residents of a quilombola community. METHODS: The research took place in the quilombo community Sítio Arruda, Ceará, northeastern Brazil. The study population consisted of 19 participants, including healers, prayers, and midwives. Applied a socioeconomic form and a semi-structured interview script. For data analysis, the Discourse of the Collective Speech (DCS) technique was used. RESULTS: For the questions asked, a total of 14 central ideas were found. The most prevalent was seizure is the most common type of disease in children (50.0%); The seizure occurs because of the fever (42.0%); In the community, we treat and prevent seizures with the use of plants (63.2%). CONCLUSIONS: The present study's results addressed relevant issues that include valuing and understanding the traditional knowledge of the community, access to health services, and the need for clarification actions about seizures.

Pharmacological applications of farnesol (C15H26O): a patent review.

Introduction: Farnesol (C15H26O) is a sesquiterpene alcohol found in essential oils. This substance is reported to have different pharmacological activities such as antimicrobial, antitumor and antioxidant effects, as well as actions in different body systems.Areas covered: This study aimed to analyze pharmaceutical patents containing this substance in their formulations. Patent search was carried out through the WIPO (World Intellectual Property Organization), LatiPat and INPI (National Institute of Industrial Property) electronic banks using the following descriptors and combinations: 'farnesol', 'pharmaceutical product', 'pharmacology' and 'pharmacy'.Expert opinion: Primary research identified 54 patents, from which 17 were selected for the final analysis after applying the inclusion criteria. The selected patents referred to products presenting different pharmaceutical activities of interest such as the prevention and treatment of diseases affecting the dermis, central nervous and cardiovascular systems, diseases caused by different microorganisms and cancers, among others. A minority of the articles included in this review reported the type of farnesol isomer that was investigated, this becoming a major limitation for the development of future pharmaceutical products. With the completion of this study, farnesol presents itself as a potential agent with pharmacological application both in the prevention and treatment of different diseases.

Antiparasitic Activity and Essential Oil Chemical Analysis of the Piper Tuberculatum Jacq Fruit.

With the increase of neglected diseases such as leishmaniasis and Chagas disease, there was a need for the search for new therapeutic alternatives that reduce the harm caused by medicine available for treatment. Thus, this study was performed to investigate the antiparasitic activity of the essential oil from the fruits of Piper tuberculatum Jacq, against lines of Leishmania braziliensis (MHOM/CO/88/UA301), Leishmania infantum (MHOM/ES/92/BCN83) and Trypanosoma cruzi (LC-B5 clone). Before running protocols, an analysis of the chemical composition of essential oil was conducted, which presented monoterpenes and sesquiterpenes. As major constituents, ß-pinene and α-pinene were identified. Regarding to antiparasitic activity, the essential oil had an EC50 values of 133.97 µg/mL and 143.59 µg/mL against variations promastigotes of L. infantum and L. braziliensis, respectively. As for trypanocidal activity, the oil showed EC50 value of 140.31 µg/mL against epimastigote form of T. cruzi. Moreover, it showed moderate cytotoxicity in fibroblasts with LC50 value of 204.71 µg/mL. The observed effect may be related to the presence of terpenes contained in the essential oil, since it has its antiparasitic activity proven in the literature.

ETHNOBIOLOGICAL SURVEY OF PLANTS AND ANIMALS USED FOR THE TREATMENT OF ACUTE RESPIRATORY INFECTIONS IN CHILDREN OF A TRADITIONAL COMMUNITY IN THE MUNICIPALITY OF BARBALHA, CEARÁ, BRAZIL.

BACKGROUND: The use of natural resources for the treatment of acute respiratory infections in children is a widespread practice within traditional communities, especially by women by being the primary caregivers. This study aimed to perform ethnobiological survey of plants and animals used for the treatment of acute respiratory infections in children of a traditional community in the municipality of Barbalha, Ceará, Brazil. METHODS: It is a descriptive exploratory study with a quantitative approach, developed in Sitio Santo Antonio, in the municipality of Barbalha, Ceará, Brazil. As a tool for data collection, was applied a questionnaire and a semi-structured interview. Data analysis used descriptive statistics (simple and percentage rate) and the Relative Frequency of Citation. RESULTS: The research included a total of 54 informants. In total, there were 38 species cited. According to the Relative Frequency of Citation the following species were the most cited: Ocimum basilicum L. (0.59), Eucalyptus globulus Labili (0.59), Plectranthus amboinicus (L.) Spreng (0.42), Hyptis suaveolens (L.) Poit. (0.24), Allium aescalonicum L. (0.22) and Mentha arvensis L. (0.18). Among the symptoms mentioned by the research subjects to treat the acute respiratory infections in childhood, there were: fever; cough; coughing with secretions; sore throat; hoarseness; tiredness; nasal congestion. CONCLUSIONS: It is important the knowledge about the usefulness of natural resources as alternative practices in diseases treatment, seeking to rescue popular knowledge used in the traditional community and fomenting the need to consider cultural aspects in the full practice to children's health care.