Relevant Pharmacological Activities Research Articles

Study on Pharmacological Activities and Mechanisms of the Essential Oil of the Flowers of Hemerocallis citrina Baroni (EOFHCB) in the Treatment of Anxiety Disorders by GC-MS, Network Pharmacology, and Molecular Docking.

Hemerocallis citrina Baroni (Huanghuacai), a plant of the genus Hemerocallis in the family Asphodelaceae, is widely planted in China. Based on our survey results, the chemical compounds in the essential oil of the flowers of Hemerocallis citrina Baroni (EOFHCB) and relevant pharmacological activities have never been studied systematically. To preliminarily decipher the pharmacological activities and mechanisms of EOFHCB in the treatment of anxiety disorders by GC-MS, Network Pharmacology, and Molecular docking. EOFHCB compositions were identified using GC-MS, and their targets were predicted using Swiss Target Prediction databases. The targets of anxiety disorders were obtained by GeneCards, DisGeNET, and OMIM databases. The STRING database was used to construct the protein-protein interaction networks, and the DAVID database was used to carry out GO enrichment and KEGG pathway enrichment analysis. The EOFHCB-components-targetspathways- anxiety disorders network was constructed by Cytoscape software (Version 3.10.0). Finally, the result was verified by molecular docking. 28 chemical components were identified by GC-MS, including 3-furanmethanol (28.43%), 2-methyl-1-butanol (27.13%), nerolidol (10.62%), and so on, which correspond to 241 potential targets. Several 2440 biological processes, 187 cellular compositions, and 311 molecular functions were enriched by GO enrichment analysis and 174 pathways by KEGG enrichment analysis. The key targets are PTGS 2, SRC, DRD 2, ESR 1, MAOB, and SLC6A4. The most important pathway is the neuroactive ligand-receptor interaction. EOFHCB exerts its therapeutic effects on anxiety disorders through multicomponents, multi-targets, and multi-pathways, which provided new ideas and methods for the in-depth research of aromatic Chinese medicine in the treatment of anxiety disorders.

Analysis of cassine and spectaline in the Senna spectabilis ethanolic extracts by capillary zone electrophoresis with indirect UV detection.

2,6-Disubstituted piperidin-3-ols are an important group of piperidine alkaloids found in species such as Senna spectabilis, whose main constituents include cassine and spectaline, compounds with relevant pharmacological activity. The analysis of these compounds is challenging due to the complexity of plant extracts and the absence of chromophores capable of absorbing ultraviolet (UV) radiation. This paper presents a new analytical method to separate and quantify the non-UV-absorbing alkaloids present in ethanol extracts from S. spectabilis flowers using capillary zone electrophoresis (CZE) with indirect UV detection. The optimized CZE method employs a background electrolyte containing 60 mM histidine (His), 15 mM α-cyclodextrin, 20% acetonitrile (ACN), and pH-adjusted to 4.7 with acetic acid (AcOH). The limit of detection (LOD) values was 10.2 and 13.9mg L-1 for cassine and spectaline, respectively. For both analytes, the precision data were better than 2% of relative standard deviation (RSD) for migration times and peak areas. To evaluate the applicability of the developed method, ethanolic extracts from S. spectabilis flowers were prepared and analyzed. Thereby, the method proved to be efficient and complementary to conventional techniques, offering a cost-effective alternative in the quantification of the non-UV-absorbing piperidine alkaloids present in plant extracts.

Spectroscopic behavior of bufotenine and bufotenine N-oxide: Solvent and pH effects and interaction with biomembrane models

Bufotenine is a fluorescent analog of Dimethyltryptamine (DMT) that has been widely studied due to its psychedelic properties and biological activity. However, little is known about its spectroscopic properties in different media. Thus, we present in this work, for the first time, the spectroscopic behavior of bufotenine and bufotenine N-oxide by means of their fluorescence properties. Both molecules exhibit changes in optical absorption and emission spectra with variations in pH of the medium and in different solvents. Assays in the presence of biomembranes models, like micelles and liposomes, were also performed. In surfactants titration experiments, the spectral shift observed in fluorescence shows the interaction of both molecules with pre-micellar structures and with micelles. Steady state anisotropy measurements show that both bufotenine and bufotenine N-oxide, in the studied concentration range, interact with liposomes without causing changes in the fluidity of the lipid bilayer. These results can be useful in studies that aim at searching for new compounds, inspired by bufotenine and bufotenine N-oxide, with relevant pharmacological activities and also in studies that use these molecules as markers of psychiatric disorders.

Evobrutinib pathway to its major metabolite M463-2 and insights from a biotransformation and DDI perspective

Evobrutinib is a highly selective, covalent, central nervous system-penetrant Bruton’s tyrosine kinase (BTK) inhibitor, currently in Phase III trials for the treatment of relapsing multiple sclerosis. One major circulating metabolite of evobrutinib has been previously identified as the racemic dihydro-diol M463-2 (MSC2430422) in a Phase I human mass balance study. Phenotyping experiments were conducted to confirm the metabolic pathway of evobrutinib to M463-2. Ratio of the enantiomers was determined by enantioselective liquid chromatography with tandem mass spectrometry analysis of plasma samples from humans and preclinical species. Drug-drug interaction (DDI) characterisation, evaluation of pharmacological activity on BTK, and off-target screening experiments followed assessing safety of the metabolite. The biotransformation of evobrutinib to M463-2 was determined to be a two-step process with a CYP-mediated oxidation acting to form an epoxide intermediate, which was further hydrolysed by soluble and mitochondrial epoxide hydrolase. Only the (S)-enantiomer was determined to be a major metabolite, the (R)-enantiomer was minor. In vitro studies demonstrated the (S)-enantiomer lacked clinically relevant pharmacological activity, off-target effects and DDIs. The biotransformation of evobrutinib to its major metabolite has been elucidated, with the major (S)-enantiomer being shown to pose no on/off target or DDI risks.

Analysis of Pharmacological Activities and Mechanisms of Essential Oil in Leaves of C. grandis 'Tomentosa' by GC-MS/MS and Network Pharmacology.

Citrus grandis 'Tomentosa,' a fruit epicarp of C. grandis 'Tomentosa' or C. grandis (L.) Osbeck is widely used in health food and medicine. Based on our survey results, there are also rich essential oils with bioactivities in leaves, but the chemical compounds in this part and relevant pharmacological activities have never been studied systematically. Therefore, this study was to preliminarily decipher the pharmacological activities and mechanisms of the essential oil in leaves of C. grandis 'Tomentosa' by an integrated network pharmacology approach. Essential oil compositions from leaves ofC. grandis 'Tomentosa' were identified using GC-MS/MS. And then, the targets of these oil compositions were predicted and screened from TCMSP, SwissTargetPrediction, STITCH and SEA databases. STRING database was used to construct the protein-protein interaction networks, and the eligible protein targets were input into WebGestalt 2019 to carry out GO enrichment and KEGG pathway enrichment analysis. Based on the potential targets, disease enrichment information was obtained by TTD databases. Cytoscape software was used to construct the component-target-disease network diagrams. Finally, 61 essential oil chemical components were identified by GC-MS/MS, which correspond to 679 potential targets. Biological function analysis showed 12, 19, and 12 GO entries related to biological processes, cell components and molecular functions, respectively. 43 KEGG pathways were identified, of which the most significant categories were terpenoid backbone biosynthesis, TNF signaling pathway and leishmaniasis. The component-target-disease network diagram revealed that the essential oil compositions in leaves of C. grandis 'Tomentosa' could treat tumors, immune diseases, neurodegenerative diseases and respiratory diseases, which were highly related to CHRM1, PTGS2, CASP3, MAP2K1 and CDC25B. This study may provide new insight into C. grandis 'Tomentosa' or C. grandis (L.) Osbeck and may provide useful information for future utilization and development.

Potentiating-antibiotic activity and absorption, distribution, metabolism, excretion and toxicity properties (ADMET) analysis of synthetic thiadiazines against multi-drug resistant (MDR) strains.

Thiadiazines are heterocyclic compounds that contain two nitrogen atoms and one sulfur atom in their structure. These synthetic molecules have several relevant pharmacological activities, such as antifungal, antibacterial, and antiparasitic. The present study aimed to evaluate the possible in vitro and in silico interactions of compounds derived from thiadiazines. The compounds were initially synthesized, purified, and confirmed through HPLC methodology. Multi-drug resistant bacterial strains of Staphylococcus aureus 10 and Pseudomonas aeruginosa 24 were used to evaluate the direct and modifying antibiotic activity of thiadiazine derivatives. ADMET assays (absorption, distribution, metabolism, excretion, and toxicity) were conducted, which evaluated the influence of the compounds against thousands of macromolecules considered as bioactive targets. There were modifications in the chemical synthesis in carbon 4 or 3 in one of the aromatic rings of the structure where different ions were added, ensuring a variability of products. It was possible to observe results that indicate the possibility of these compounds acting through the cyclooxygenase 2 mechanism, which, in addition to being involved in inflammatory responses, also acts by helping sodium reabsorption. The amine group present in thiadiazine analogs confers hydrophilic characteristics to the substances, but this primary characteristic has been altered due to alterations and insertions of other ligands. The characteristics of the analogs generally allow easy intestinal absorption, reduce possible hepatic toxic effects, and enable possible neurological and anti-inflammatory action. The antibacterial activity tests showed a slight direct action, mainly of the IJ23 analog. Some compounds were able to modify the action of the antibiotics gentamicin and norfloxacin against multi-drug resistant strains, indicating a possible synergistic action. Among all the results obtained in the study, the relevance of thiadiazine analogs as possible coadjuvant drugs in the antibacterial, anti-inflammatory, and neurological action with low toxicity is clear. Need for further studies to verify these effects in living organisms is not ruled out.

A deeper insight into the sialome of male and female Culex quinquefasciatus mosquitoes

IntroductionDuring evolution, blood-feeding arthropods developed a complex salivary mixture that can interfere with host haemostatic and immune response, favoring blood acquisition and pathogen transmission. Therefore, a survey of the salivary gland contents can lead to the identification of molecules with potent pharmacological activity in addition to increase our understanding of the molecular mechanisms underlying the hematophagic behaviour of arthropods. The southern house mosquito, Culex quinquefasciatus, is a vector of several pathogenic agents, including viruses and filarial parasites that can affect humans and wild animals.ResultsPreviously, a Sanger-based transcriptome of the salivary glands (sialome) of adult C. quinquefasciatus females was published based on the sequencing of 503 clones organized into 281 clusters. Here, we revisited the southern mosquito sialome using an Illumina-based RNA-sequencing approach of both male and female salivary glands. Our analysis resulted in the identification of 7,539 coding DNA sequences (CDS) that were functionally annotated into 25 classes, in addition to 159 long non-coding RNA (LncRNA). Additionally, comparison of male and female libraries allowed the identification of female-enriched transcripts that are potentially related to blood acquisition and/or pathogen transmission.ConclusionTogether, these findings represent an extended reference for the identification and characterization of the proteins containing relevant pharmacological activity in the salivary glands of C. quinquefasciatus mosquitoes.

Aurelianolides from Aureliana fasciculata var. fasciculata Trigger Apoptosis With Caspase Activation in Human Leukemia Cells.

Aurelianolide A and B were identified and isolated from Aureliana fasciculata var. fasciculata leaves. Withanolides are naturally occurring C-28 steroidal lactone triterpenoids with cytotoxic and anticancer properties, among other relevant pharmacological activities. Herein we have described, for the first time, the cytotoxic effects of aurelianolides on human cancer cells. Aurelianolide A and B were tested on human leukemia cell lines: THP-1, MOLT-4, Jurkat, K562 and K562-Lucena 1. For aurelianolide A, MOLT-4 had the lower IC50 (1.17 μM) and for aurelianolide B, Jurkat was the most susceptible cell line (IC50 2.25 μM). On the other hand, the multidrug resistant (MDR) cell line K562-Lucena 1 showed higher IC50 for both aurelianolides. Using 293T, a non-tumor embryonic kidney cell line, we observed an excellent selectivity index for both aurelianolides, from 2.24 (aurelianolide B in K562-Lucena 1) to 45.5 (aurelianolide A in MOLT-4). Aurelianolide A and B activated caspase 3/7 with consequent induction of apoptosis on Jurkat and K562-Lucena 1 cell lines. We have not observed induction of necrosis. Aurelianolides A and B have important cytotoxic effects on human leukemia cell lines by the activation of the caspase pathway.

Opuntia ficus-indica Fruit: A Systematic Review of Its Phytochemicals and Pharmacological Activities.

The use of Opuntia ficus-indica fruits in the agro-food sector is increasing for a multiplicity of players. This renewed interest is, in part, due to its organoleptic characteristics, nutritional value and health benefits. Furthermore, industries from different sectors intend to make use of its vast array of metabolites to be used in different fields. This trend represents an economic growth opportunity for several partners who could find new opportunities exploring non-conventional fruits, and such is the case for Opuntia ficus-indica. O. ficus-indica originates from Mexico, belongs to the Cactaceae family and is commonly known as opuntia, prickly pear or cactus pear. The species produces flowers, cladodes and fruits that are consumed either in raw or in processed products. Recent publications described that consumption of the fruit improves human health, exhibiting antioxidant activity and other relevant pharmacological activities through enzymatic and non-enzymatic mechanisms. Thus, we provide a systematic, scientific and rational review for researchers, consumers and other relevant stakeholders regarding the chemical composition and biological activities of O. ficus-indica fruits.

The impact of phyto- and endo-cannabinoids on central nervous system diseases：A review.

Cannabis sativa L. is a medicinal plant with a long history. Phyto-cannabinoids are a class of compounds from C.sativa L. with varieties of structures. Endocannabinoids exist in the human body. This article provides an overview of natural cannabinoids (phyto-cannabinoids and endocannabinoids) with an emphasis on their pharmacology activities. The keywords "Cannabis sativa L″, "cannabinoids", and "central nervous system (CNS) diseases" were used for searching and collecting pieces of literature from PubMed, ScienceDirect, Web of Science, and Google Scholar. The data were extracted and analyzed to explore the effects of cannabinoids on CNS diseases. In this paper, schematic diagrams are used to intuitively show the phyto-cannabinoids skeletons' mutual conversion and pharmacological activities, with special emphasis on their relevant pharmacological activities on central nervous system (CNS) diseases. It was found that the endocannabinoid system and microglia play a crucial role in the treatment of CNS diseases. In the past few years, pharmacological studies focused on Δ9-THC, CBD, and the endocannabinoids system. It is expected to encourage new studies on a more deep exploration of other types of cannabinoids and the mechanism of their pharmacological activities in the future.

Medicinal Plants Used in the Management of Sexual Dysfunction, Infertility and Improving Virility in the East African Community: A Systematic Review.

Sexual disorders such as erectile dysfunction (ED), sterility, and sexual inappetence represent some of the complex reproductive challenges that require addressing the underlying causes. The aim of this paper was to systematically synthesize literature on the ethnobotany, phytochemistry, bioactivities, and safety of plants used as remedies for managing sexual dysfunction and infertility, and improving fertility and virility in the EAC. Through an extensive review conducted in multidisciplinary electronic databases, 171 plant species were identified to have been reported for the management of sexual inappetence (i.e., used as aphrodisiacs, 39.4%), ED (35.9%), infertility (18.7%), and increasing fertility (6.0%). The most used plants are Mondia whitei, Acalypha villicaulis, Combretum illairii, Erythrina abyssinica, Pappea capensis, Rhus vulgaris, and Warburgia ugandensis while roots (44.9%), leaves (21.8%), stem and root barks (16.7%) of shrubs (35%), trees (31%), herbs (26%), and climbers (8%) are the preferred organs for making decoctions (69%). The research strides to date indicate that Citropsis articulata, Cola acuminata, Ekebergia capensis, Plumbago zeylanica, Tarenna graveolens, Urtica massaica, and Zingiber officinale have been assessed for their bioactivity. The majority (71.4%) of the plants either increased testosterone levels and mounting frequency or elicited prosexual stimulatory effects in male rats. More studies investigating the relevant pharmacological activities (aphrodisiac, fertility, and phosphodiesterase-5 inhibitory activities), safety aspects, responsible compounds, and clinical studies are warranted to establish the pharmacological potential of the unstudied species and elucidate the mechanism of action of the bioactive compounds.

Cassia alata, Coriandrum sativum, Curcuma longa and Azadirachta indica: Food Ingredients as Complementary and Alternative Therapies for Atopic Dermatitis-A Comprehensive Review.

Traditional medicine is critical in disease treatment and management. Herbs are gaining popularity for disease management and treatment. Therefore, they can be utilised as complementary and alternative treatment (CAT) ingredients. Atopic dermatitis (AD) is one of the common non-communicable diseases. It is characterised by chronic inflammatory skin disease with intense pruritus and eczematous lesions. AD is associated with oxidative stress, microbial infection, and upregulation of inflammatory cytokines. Both children and adults could be affected by this skin disorder. The prevalence of AD is increasing along with the country’s level of development. This review revisited the literature on four medicinal herbs widely used as complementary medicine to manage AD. These therapeutic herbs are commonly eaten as food and used as spices in Asian cuisine. The four food herbs reviewed are Cassia alata, Coriandrum sativum, Curcuma longa Linn, and Azadirachta indica. Their traditional uses and phytochemical content will be covered. Four relevant pharmacological and biological activities of the plants crucial in AD management have been reviewed and discussed, including anti-inflammatory, anti-microbial, antioxidant, and wound recovery.

A narrative review of the pharmacology of ginsenoside compound K.

Background and ObjectiveThe ginsenoside compound K [20-o-beta-dglucopyranosyl-20 (S)-protopanaxadiol; CK] is the main deglycosylated metabolite of ginsenoside. As a rare ginsenoside converted from the active substance of ginseng by intestinal bacteria, CK has higher biological activity than other ginsenosides. It has demonstrated diverse and intriguing biological activities, including anti-carcinogenic, anti-diabetic, anti-inflammation, anti-allergy, anti-angiogenesis, anti-aging, neuroprotective, and hepatoprotective effects. The purpose of this review was to elucidate the rich pharmacological activities and related mechanisms of ginsenoside CK in vivo and in vitro, as well as the potential therapeutic value of CK as a drug in a variety of systemically related diseases.MethodsThe PubMed database was searched for articles published in English from February 2008 to December 2021 using related keywords such as “Ginsenoside compound K”, “compound K”, and “CK”. About 140 research papers and reports written in English were identified. These papers mainly concentrated on the pharmacological activities of CK in cancer prevention, immune regulation, diabetic improvement, central nervous system (CNS) protection, cardiovascular protection, skin improvement, and hepatoprotection.Key Content and FindingsThis paper describes the synthesis, pharmacokinetics, and adverse reactions of CK, as well as great detailed summarized of the relevant pharmacological activities. Such diverse intriguing biological properties of CK have been found.ConclusionsOn account of CK’s numerous pharmacological activities and anti-carcinogenic, anti-inflammation, antiallergic, anti-diabetic, anti-angiogenesis, anti-aging, neuroprotective, and hepatoprotective effects, strong evidence is available for CK as a preventive or therapeutic agent for various diseases. However, further studies are needed to evaluate the safety and effectiveness of CK as a drug and its application in the medical field.

Insightful Investigative Account on Hydrotropic Solubilization Practice Utilized for Solubility Management of Poorly Dissolvable Drugs

Background: Executing the centralization of medication in the foundational flow for approaching their pharmacological has necessitated studying a vital parameter, i.e. solubility reaction. The poor water dissolvability has an impact on medication adequacy and, consequently, owned poor drugs bioavailability. Aim: The aim of this study is to attain the convergence of medication in an introductory course, a significant parameter, i.e. solvency, has been executed for the pharmacological reactions. On account of revolution and advancement, there is a diversity of new medications, and their subordinates are approachable. Over 40% of lipophilic medication up-and-comers neglect to achieve because of poor bioavailability even though these medications have potential pharmacodynamics activities. Due to high market requirements, lipophilic medication has accomplished the relevant pharmacological activity. Consequently, most strategies are streamlined to improve fluid solvency to upgrade proficiency and lessen the reactions for specific medications. Objectives: The process of hydrotropic solubilization has persisted a novel and promising methodology to improve the solvency of drugs with poor water solvency by ascending the dissolvability to many folds with the involvement of hydrotropes, i.e. Niacinamide, Urea, sodium benzoate, sodium citrate, and so on. The potentiality of hydrotropic solubilization counts on the balance among hydrophobic and hydrophilic parts of hydrotropes. Hence, advancement in hydrotropic updated visualized in novel drug delivery systems and their mechanism of compatibilities and biocompatibilities. Novelty is also reprinted in its usefulness as an extraction agent for bio-active compounds to increase the rate of heterogeneous reactions and in a green synthesis for a substrate. Conclusion: This review focuses on practice utilized for solubility management of drugs with poor solvency, its unmet needs, utilizing the artificial machine learning in the prediction of hydrotropeenhanced solubilization of drugs, practical applicability in drug delivery, interpreted kinetic involved, and various associated mechanisms.

Species selection for nonclinical safety assessment of drug candidates: Examples of current industry practice

In drug development, nonclinical safety assessment is pivotal for human risk assessment and support of clinical development. Selecting the relevant/appropriate animal species for toxicity testing increases the likelihood of detecting potential effects in humans, and although recent regulatory guidelines state the need to justify or dis-qualify animal species for toxicity testing, individual companies have developed decision-processes most appropriate for their molecules, experience and 3Rs policies. These generally revolve around similarity of metabolic profiles between toxicology species/humans and relevant pharmacological activity in at least one species for New Chemical Entities (NCEs), whilst for large molecules (biologics) the key aspect is similarity/presence of the intended human target epitope.To explore current industry practice, a questionnaire was developed to capture relevant information around process, documentation and tools/factors used for species selection. Collated results from 14 companies (Contract Research Organisations and pharmaceutical companies) are presented, along with some case-examples or over-riding principles from individual companies. As the process and justification of species selection is expected to be a topic for continued emphasis, this information could be adapted towards a harmonized approach or best practice for industry consideration.

α-PPP and its derivatives are selective partial releasers at the human norepinephrine transporter: A pharmacological characterization of interactions between pyrrolidinopropiophenones and high and low affinity monoamine transporters

While classical cathinones, such as methcathinone, have been shown to be monoamine releasing agents at human monoamine transporters, the subgroup of α-pyrrolidinophenones has thus far solely been characterized as monoamine transporter reuptake inhibitors. Herein, we report data from previously undescribed α-pyrrolidinopropiophenone (α-PPP) derivatives and compare them with the pharmacologically well-researched α-PVP (α-pyrrolidinovalerophenone). Radiotracer-based in vitro uptake inhibition assays in HEK293 cells show that the investigated α-PPP derivatives inhibit the human high-affinity transporters of dopamine (hDAT) and norepinephrine (hNET) in the low micromolar range, with α-PVP being ten times more potent. Similar to α-PVP, no relevant pharmacological activity was found at the human serotonin transporter (hSERT). Unexpectedly, radiotracer-based in vitro release assays reveal α-PPP, MDPPP and 3Br-PPP, but not α-PVP, to be partial releasing agents at hNET (EC50 values in the low micromolar range). Furthermore, uptake inhibition assays at low-affinity monoamine transporters, i.e., the human organic cation transporters (hOCT) 1–3 and human plasma membrane monoamine transporter (hPMAT), bring to light that all compounds inhibit hOCT1 and 2 (IC50 values in the low micromolar range) while less potently interacting with hPMAT and hOCT3. In conclusion, this study describes (i) three new hybrid compounds that efficaciously block hDAT while being partial releasers at hNET, and (ii) highlights the interactions of α-PPP-derivatives with low-affinity monoamine transporters, giving impetus to further studies investigating the interaction of drugs of abuse with OCT1-3 and PMAT.

Biological and Functional Properties of Wedelolactone in Human Chronic Diseases

Medicinal herbs are well known and studied over the past millennia in most of the developing countries as a rational means of treatment against various diseases and disorders. Wedelolactone (WDL), a major bioactive compound in Eclipta prostrata L (Eclipta alba L), has been reported with potential benefits in human health against chronic diseases. However, a comprehensive study on WDL pharmacological benefits in various ailments, to the best of our knowledge, is not yet reported. Thereof, the present review provides the recent therapeutic applications in reference to biological and functional activities against major human chronic diseases, including cardiovascular, cancer, diabetes mellitus, liver disease, Alzheimer’s disease, and androgenetic alopecia. In this study, we collected all the relevant experimental information on WDL from Scientific databases such as PubMed, Web of Science, Science Direct, and Google Scholar. Conclusively, WDL is recognized as a key anti-oxidant with both specific regulator and inhibitor of major drug targetable proteins in human chronic diseases and disorders. Hence, WDL as a novel therapeutic bioactive molecule is advised to explore further for relevant pharmacological activities.

In Silico Study Examining New Phenylpropanoids Targets with Antidepressant Activity.

Natural products, such as phenylpropanoids, which are found in essential oils derived from aromatic plants, have been explored during non-clinical psychopharmacology studies, to discover new molecules with relevant pharmacological activities in the central nervous system, especially antidepressant and anxiolytic activities. Major depressive disorder is a highly debilitating psychiatric disorder and is considered to be a disabling public health problem, worldwide, as a primary factor associated with suicide. Current clinically administered antidepressants have late-onset therapeutic actions, are associated with several side effects, and clinical studies have reported that some patients do not respond well to treatment or reach complete remission. To review important new targets for antidepressant activity and to select phenylpropanoids with antidepressant activity, using Molegro Virtual Docker and Ossis Data Warris, and to verify substances with more promising antidepressant activity. An in silico molecular modeling study, based on homology, was conducted to determine the three-dimensional structure of the 5-hydroxytryptamine 2A receptor (5- HT2AR), then molecular docking studies were performed and the predisposition for cytotoxicity risk among identified molecules was examined. A model for 5-HT2AR homology, with satisfactory results, was obtained indicating the good stereochemical quality of the model. The phenylpropanoid 4-allyl-2,6-dimethoxyphenol showed the lowest binding energy for 5-HT2AR, with results relevant to the L-arginine/nitric oxide (NO)/cGMP pathway, and showed no toxicity within the parameters of mutagenicity, carcinogenicity, reproductive system toxicity, and skin-tissue irritability, when evaluated in silico; therefore, this molecule can be considered promising for the investigation of antidepressant activity.

Davilla elliptica (Dilleniaceae) a. St.-Hil. Ethnomedicinal, phytochemical, and pharmacological aspects: A review

Abstract Davilla elliptica (Dilleniaceae) is a shrub that occurs naturally in the Brazilian Savannah (Cerrado). This shrub has been widely used in Brazilian folk medicine in tea preparing; infusions; and decoctions from leaves and roots for gastritis, ulcers, and diarrhea treatment. Given the therapeutic potential of this species, the present study provides a comprehensive review on its ethnopharmacological uses, botanical aspects, phytochemistry characterization, and in vivo and in vitro pharmacological studies. The relevant studies on D. elliptica were retrieved from the following scientific databases: Web of Science, Google Scholar, Scopus, SciFinder, PubMed, Scielo, and ScienceDirect. Additional information derived from other literature sources, such as books and Ph.D. and MSc theses, was also considered after a critical review. Ethnopharmacological reports of D. elliptica revealed the use of infusions from roots with tonic and purgative effects, whereas leaves have been used as anti-inflammatory and anti-ulcerative treatments, as well as to treat diarrhea and gastric disorders. Furthermore, fresh leaves have been used in baths to treat swelling. Phytochemical studies have led to the isolation of several compounds, including flavonoids derived from quercetin and myricetin, and tannins, which are known to exhibit relevant pharmacological activities. In vitro assays using crude extracts and/or isolated fractions and chemical constituents from D. elliptica have evidenced antibacterial, cytotoxic activities, while in vivo studies have proven gastroprotective, anti-inflammatory, antihemorrhagic, and antibacterial activities, corroborating ethnomedicinal reports. No relevant side effects has been reported previously, and some studies found a low toxicity and genotoxicity. However, further studies are still needed to ensure the safety of its therapeutic use. Future studies should focused on molecular mechanisms involved in bioactive components’ effects based on both fractions and isolated compounds, creating great opportunities for new investigations.

ChemInform Abstract: Metabolomic Profile of the Genus Inula

AbstractReview: 97 refs.