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Passiflora cincinnata is a Passifloraceae typical of the Caatinga, a biome unique to Brazil. It has various pharmacological properties associated with its high flavonoid content. Vitexin, isovitexin, orientin, isoorientin and derivatives are the main chemical and pharmacological markers for this plant. Although flavonoids enriched-extracts have been widely applied in phytocosmetics, especially in sunscreen formulations, the use of P. cincinnata as a photoprotective ingredient remains unexplored. Different hydro-alcoholic extracts were prepared and their antioxidant and photoprotective activities were evaluated by in vitro assays. The most promising extract (Pc-1) was analyzed by HPLC-DAD-ESI-MS/MS. Nine flavonoids were identified as major compounds: isovitexin-7-O-glucoside, isoorientin-2"O-hexoside, orientin, isoorientin, isovitexin-2"-O-glucoside, isovitexin-6"-O-glucoside, isoscoparin and isoquercitrin. Finally, Pc-1 (5 and 10 %, v/v) was incorporated into gel formulations, alone or combined to commercial chemical filters (benzophenone-3 and octyl methoxycinnamate). Formulations containing Pc-1 showed high SPF spectrophotometric values. When combined to commercial filters, Pc-1 (5 %) potentiated their photoprotective efficacy (p<0.05). A physicochemical characterization indicated no incompatibility or signs of instability after extract incorporation. Altogether, these findings encourage the use of Pc-1 as a photoprotective ingredient or co-adjuvant in sunscreens formulations., (© 2024 The Author(s). Chemistry & Biodiversity published by Wiley-VHCA AG.)

Brown seaweeds of the Fucus genus represent a rich source of natural antiviral products. In this study, a Fucus ceranoides hydroalcoholic extract (FCHE) was found to inhibit 74.2 ± 1.3% of the proteolytic activity of the free SARS-CoV-2 3CL protease (3CLpro), an enzyme that plays a pivotal role in polyprotein processing during coronavirus replication and has been identified as a relevant drug discovery target for SARS- and MERS-CoVs infections. To purify and identify 3CLpro ligands with potential inhibitory activity using a one-step approach, we immobilized the enzyme onto magnetic microbeads (3CLpro-MPs), checked that the enzymatic activity was maintained after grafting, and used this bait for a ligand-fishing strategy followed by a high-resolution mass spectrometry analysis of the fished-out molecules. Proof of concept for the ligand-fishing capacity of the 3CLpro-MPs was demonstrated by doping the FCHE extract with the substrate peptide TSAVLQ-pNA, resulting in the preferential capture of this high-affinity peptide within the macroalgal complex matrix. Ligand fishing in the FCHE alone led to the purification and identification via high-resolution mass spectrometry (HRMS) of seven hepta-, octa-, and decapeptides in an eluate mix that significantly inhibited the free 3CLpro more than the starting FCHE (82.7 ± 2.2% inhibition). Molecular docking simulations of the interaction between each of the seven peptides and the 3CLpro demonstrated a high affinity for the enzyme's proteolytic active site surpassing that of the most affine peptide ligand identified so far (a co-crystallographic peptide). Testing of the corresponding synthetic peptides demonstrated that four out of seven significantly inhibited the free 3CLpro (from 46.9 ± 6.4 to 76.8 ± 3.6% inhibition at 10 µM). This study is the first report identifying peptides from Fucus ceranoides with high inhibitory activity against the SARS-CoV-2 3CLprotease which bind with high affinity to the protease's active site. It also confirms the effectiveness of the ligand-fishing strategy for the single-step purification of enzyme inhibitors from complex seaweed matrices.

Passiflora cincinnata Mast. is described as a native Caatinga species, used by nutritional and medicinal purposes, although there are still few studies and pharmacological data related to this species. This paper aims to evaluate the safety profile and hypolipidemic potential of the fruit peel of this species in mice. It was analyzed the chemical composition of ethanolic extract (EtOH-Pc) by HPLC-DAD-MS/MS, and the organic and inorganic composition of flour (MF-Pc). Also were evaluated the acute toxicity, the lipid-lowering potential of these samples, through of a pretreatment (oral: 100 and 200 mg/kg), and a single treatment with the same doses, after hyperlipidemic induction with triton WR-1339, using as animal model Swiss Mus musculus mice, besides histopathological analysis. The presence of flavonoids in the extract was confirmed, mainly C -glycosides, and antioxidant minerals and pectin, in flour. No clinical signs of toxicity or death were reported in the study. In the hyperlipidemia study model used, the analyzed substances, at all doses, notably decreased the lipid levels of TC, TG, LDL-c and VLDL-c and increase the HDL-c levels in the induced hyperlipidemic mice ( p  < 0.05). The results of the histopathological analysis showed that in the group only induced was identified the discrete presence of hepatic steatosis, in 2 animals at the analysis of 24 h, not being visualized in the groups treated with the substances evaluated. The results obtained in the present study suggest a hypolipidemic potential of the extract and flour, obtained from the fruit peel of Passiflora cincinnata Mast.

A new nor- ent -kaurene diterpene and ten other compounds were isolated from Annona vepretorum stems, including four kaurene diterpenes, three alkamides, one sesquiterpene and two steroids. Their chemical structures were elucidated using spectroscopic methods, including 1D-, 2D-NMR, and HRESIMS. The absolute configuration of compounds 1 , 5 , 8 , 9 and 10 was confirmed by CD experiments. Compounds 1-5 and 8-10 were evaluated for cytotoxic activity using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT method, against three human carcinoma cell lines: human colon (HCT-116), glioblastoma (SF295) and prostate (PC3). However, all isolated compounds exhibited low cytotoxic activity.

Lobularia maritima ( Alyssum maritimum , Brassicaceae), commonly known as sweet alyssum, is an annual ornamental halophyte widely spread along the Tunisian seashore. Lobularia maritima leaf ethanol extract was tested in an experimental model of hepatotoxicity induced by carbon tetrachloride (CCl 4 ). L. maritima extract was found to possess in vitro antioxidant activity by scavenging the DPPH radical (IC 50 = 45 μg/mL), reducing/chelating iron ions and inhibiting liver lipid peroxidation induced by FeSO 4 . The levels of total phenolics and flavonoids were 175 ± 2.66 mg GAE/g, and 35 ± 2.88 mg QE/g respectively. Moreover, HPLC analysis revealed six compounds, namely gallic, salicylic, ellagic and ferulic acids as well as catechin and quercetin. A mice model of acute liver injury was successfully established after a single intraperitoneal injection of CCl 4 , as evidenced by histological analysis, Masson trichrome and Sirius red staining. Compared with the CCl 4 intoxicated group, the L. maritima treatment resulted to reduce the liver serum marker enzymes, lipid peroxidation and increased the activities of antioxidant enzymes with further amelioration in the oxidative stress. The present findings discover the therapeutic potentials of L. maritima empowered with promising natural leads for the treatment of oxidative stress associated health disorders by attenuating free radicals, inhibiting lipid peroxidation, and upregulating the tissue-specific antioxidant enzymes.

A phytochemical investigation of cytotoxic extract and fractions of Cnidoscolus quercifolius Pohl led to isolation of five terpenoids, including three lupane-type triterpenes (1-3) and two bis-nor-diterpenes (4-5). Compounds 4 (phyllacanthone) and 5 (favelanone) are commonly found in this species and have unique chemical structure. Although their cytotoxic activity against cancer cells has been previously reported, the anticancer potential of these molecules remains poorly explored. In this paper, the antimelanoma potential of phyllacanthone (PHY) was described for the first time. Cell viability assay showed a promising cytotoxic activity (IC 50  = 40.9 μM) against chemoresistant human melanoma cells expressing the BRAF oncogenic mutation (A2058 cell line). After 72 h of treatment, PHY inhibited cell migration and induced apoptosis and cell cycle arrest (p < 0.05). Immunofluorescence assay showed that the pro-apoptotic effect of PHY is probably associated with tubulin depolymerization, resulting in cytoskeleton disruption of melanoma cells. Molecular docking investigation confirmed this hypothesis given that satisfactory interaction between PHY and tubulin was observed, particularly at the colchicine binding site. These results suggest PHY from C. quercifolius could be potential leader for the design of new antimelanoma drugs., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Saponins are glycosides which, after acid hydrolysis, liberate sugar(s) and an aglycone (sapogenin) which can be triterpenoid or steroidal in nature. Steroidal saponins and sapogenins have attracted significant attention as important natural anti-inflammatory compounds capable of acting on the activity of several inflammatory cytokines in various inflammatory models., Purpose: The aim of this review is to collect preclinical in vivo studies on the anti-inflammatory activity of steroidal saponins through the modulation of inflammatory cytokines., Study Design and Methods: This review was carried out through a specialized search in three databases, that were accessed between September and October, 2021, and the publication period of the articles was not limited. Information about the name of the steroidal saponins, the animals used, the dose and route of administration, the model of pain or inflammation used, the tissue and experimental method used in the measurement of the cytokines, and the results observed on the levels of cytokines was retrieved., Results: Forty-five (45) articles met the inclusion criteria, involving the saponins cantalasaponin-1, α-chaconine, dioscin, DT-13, lycoperoside H, protodioscin, α-solanine, timosaponin AIII and BII, trillin, and the sapogenins diosgenin, hecogenin, and ruscogenin. The surveys were carried out in seven different countries and only articles between 2007 and 2021 were found. The studies included in the review showed that the saponins and sapogenins were anti-inflammatory, antinociceptive and antioxidant and they modulate inflammatory cytokines mainly through the Nf-κB, TLR4 and MAPKs pathways., Conclusion: Steroidal saponins and sapogenins are promising compounds in handling of pain and inflammation for the development of natural product-derived drugs. However, it is necessary to increase the methodological quality of preclinical studies, mainly blinding and sample size calculation., (Copyright © 2021. Published by Elsevier GmbH.)

Background: Chronic orofacial pain is a serious public health problem with a prevalence of 7-11% in the population. This disorder has different etiologies and characteristics that make pharmacological treatment difficult. Natural products have been shown to be a promising source of treatments for the management of chronic pain, as an example the terpenes., Purpose: The aim of this study was to evaluate the anti-nociceptive and anti-inflammatory effects of one of these terpenes, d-limonene (LIM - a common monoterpene found in citrus fruits) alone and complexed with hydroxypropyl-β-cyclodextrin (LIM/HPβCD) in preclinical animal models., Methods: Orofacial pain was induced by the administration of hypertonic saline on the corneal surface, the injection of formalin into the temporomandibular joint (TMJ), or chronic constriction injury of the infraorbital nerve (CCI-IoN). The study used male Wistar rats and Swiss mice treated with LIM (50 mg/kg), LIM/HPβCD (50 mg/kg), vehicle (control), gabapentin or morphine, and eyes wiping (induced by hypertonic saline), face rubbing (formalin-induced in TMJ) or mechanical hyperalgesia (provoked by CCI-IoN) were assessed. Additionally, ELISA was used to measure TNF-α, and western blot analysis to assess levels of PKAcα, NFκB, p38MAPK and phosphorylated PKC substrates. Serum levels of aspartate aminotransferase (AST) and alanine transferase (ALT) were also evaluated., Results: LIM and LIM/HPβCD significantly reduced (p < 0.001) corneal nociception and formalin-induced TMJ nociception. In addition, both substances attenuated (p < 0.001) mechanical hyperalgesia in the CCI-IoN model. The antinociceptive effect induced by LIM and HPβCD/LIM was associated with decreased TNF-α levels, downregulation of the NFκB and p38MAPK signalling pathways and reduced PKC substrate phosphorylation and PKA immunocontent. Moreover, the results demonstrated that complexation with HPβCD was able to decrease the therapeutic dose of LIM., Conclusion: LIM was found to be a promising molecule for the treatment of orofacial pain due to its capacity to modulate some important mediators essential to the establishment of pain, and HPβCD can be a key tool to improve the profile of LIM., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist.

Morus nigra, popularly known as mulberry, has been traditionally used as anti-diabetic herbal medication. This study focused on hexane fraction from Brazilian M. nigra leaves (Hex-Mn) effects on digestion and absorption of carbohydrate in diabetic mice. The high-performance liquid chromatography (HPLC) analysis was performed, and showed the presence of flavonoids isoquercetin and kaempferol-3- O -rhamnoside. Hex-Mn did not alter oral glucose tolerance test; however, it prevented hyperglycemia in oral sucrose and starch tolerance test in diabetic mice. Also, Hex-Mn was more efficient to inhibit the α-glucosidase, showing lower inhibitory effect on α-amylase activity in vitro . The results suggest that Hex-Mn may delay the carbohydrate digestion, but not glucose transport through brush border membrane of the intestine, which contribute with reduction in postprandial hyperglycemia in mice. Hex-Mn has antihyperglycemic effect by attenuating the carbohydrate digestion in diabetic mice, which could be explained, at least in part, by the presence of isoquercetin and kaempferol-3- O -rhamnoside.

Neoglaziovia variegata (Arruda) Mez (Bromeliaceae) is a medicinal plant popularly known as "caroá." The leaves are made up of highly resistant fibers, which is of great commercial value to the handicraft and textile industry. Some studies have demonstrated that ethanolic extract of N. variegata have gastroprotective properties. This study aimed to investigate the gastroprotective activity and cytoprotective mechanisms of ethyl acetate (Nv-AcOEt), hexane (Nv-Hex), and chloroform (Nv-CHCl 3 ) fractions of N. variegata leaves. The gastroprotective activity of Nv-AcOEt, Nv-Hex, and Nv-CHCl 3 was evaluated using the ethanol and ethanol/HCl-induced gastric injury model. To elucidate the gastroprotective mechanisms, the functions of prostaglandins (PGs), nitric oxide (NO), and K ATP channels were evaluated. In addition, the nonprotein sulfhydryl groups and the mucus content in the gastric tissues were analyzed. All fractions of N. variegata leaves at oral doses of 100, 200, and 400 mg/kg significantly decreased ethanol and ethanol/HCl-induced gastric lesions, leading to gastroprotection, accompanied by an increase in reduced glutathione (GSH) and gastric mucus. Gastroprotective activity of Nv-AcOEt was inhibited after pretreatment with ibuprofen and N(G)-nitro-L-arginine (L-NOARG). Gastroprotective effect of Nv-Hex and Nv-CHCl 3 was also inhibited after pretreatment with L-NOARG and with glibenclamide. The results indicate that N. variegata (Arruda) Mez exhibits promising gastroprotective activity with the possible participation of NO, PGs, mucus, sulfhydryl groups, and K ATP .

Ethnopharmacological Relevance: The genus Triplaris (Polygonaceae) comprises approximately 25 species distributed throughout South and Central America. Some species have been used in folk medicine, mainly, to treat malaria, leishmaniasis, diarrheia, dysenteria, pain and inflammation., Aim of the Study: The purpose of this review is to provide information on the traditional uses, phytochemistry and known biological activities of Triplaris, an important genus for South America research groups on medicinal plants, in order to explore its therapeutic potential to direct future research in the search for new bioactive molecules., Materials and Methods: The available information on the genus Triplaris was gathered from scientific databases (LILACS, Pubmed, SciELO, Science Direct, Scopus, CAPES Periodicals Portal and Theses and Dissertations Catalog) before March 2020 using the keyword "Triplaris". Works related to traditional uses, phytochemistry and biological activities of plants were included in this review., Results: Most of the studies involving Triplaris were conducted by research groups located in Brazil, Peru e Bolivia. Probably, because the genus has been used in folk medicine only by these countries. Regarding the annual evolution of the publications, a larger number of articles published in 2010 were observed. Flavonols represent the main classe of secondary metabolites from Triplaris. In terms of the pharmacological investigations, T. americana and T. gardneriana are considered the most studied species, with extensive promising biological activities. The pharmacological activities can be attributed to bioactive phytochemicals., Conclusions: All findings indicate that Triplaris is an important genus of the Polygonaceae family. However, considering its chemical and pharmacological importance, the studies developed with Triplaris species are still limited, representing an opportunity to investigate new bioactive molecules and extracts. The review shows that little pre-clinical or in vivo research is available to prove the ethnopharmacological records in the genre. Therefore, this review encourages further studies on Triplaris in the search for a wide range of therapeutic products., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Hymenaea martiana is a native tree known in Brazil as 'jatobá' and used in folk medicine to treat pain and inflammation. The aim of this work was to identify the flavonoids present in the crude ethanolic extract and ethyl acetate fraction using HPLC-DAD and LC-MS n analysis. The ethanolic extract was partitioned to obtain the ethyl acetate fraction. The analysis of astilbin content also was carried out by HPLC analysis. HPLC-DAD-ESI/MS n analysis of the ethanolic extract and ethyl acetate fraction revealed the presence of eleven peaks in the chromatograms, and all these peaks were identified: taxifolin, eucryphin, astilbin and 3 diastereoisomers, engeletin and 2 diastereoisomers, quercitrin and 2,6,3',4'-tetrahydroxy-2-benzylcoumaran-3-one. The ethyl acetate fraction had a higher astilbin concentration (151.87 µg/mL) than the ethanolic extract (40.13 µg/mL). In conclusion, the species could be considered a good source of flavonoids, which can be related to the main chemotaxonomic markers for the genus Hymenaea .

Annona coriacea Mart., popularly known as "marolo", "araticum" and "araticum-liso" is a species distributed in Paraguay and Brazil, and easily found in Caatinga, Cerrado, and Pantanal biomes. The araticum has been used in folk medicine to treat stomatitis, neuralgia, rheumatism, headaches, furuncle, ulcers, and dermatitis. This systematic review aimed to provide a comprehensive overview of the ethnomedicinal use, phytochemistry, and pharmacological activity of A. coriacea. A search for scientific articles of electronic databases (Science Direct, PubMed, Lilacs, Scopus, Google Scholar, Scielo, and Web of Science) was performed identifying studies published until November 2020. All papers considering traditional medicinal uses, phytochemistry, and pharmacological properties were included. Forty-six articles (n = 212 subjects) met the inclusion criteria set for this review. Of the 46 articles reviewed, 34 were focused on biological activity investigations, while 12 were limited to phytochemical studies. These studies showed the presence of a diversity of secondary metabolites such as acetogenins, sesquiterpenes, alkaloids, flavonoids, and diterpenes. To date, pharmacological tests have demonstrated significant biological activities of this plant, being the most promising anticancer, anti-inflammatory, antiulcer, and insecticide activities. Additionally, the medicinal utilization of A. coriacea appears to be promising, supporting its possible uses for human health with antioxidant, anxiolytic, antiulcer, insecticide, and antiparasitic activities. Ultimately, comprehensive studies involving clinical trials are required to validate the existing traditional practices and their related health benefits scientifically., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Fat burners are a category of nutritional supplements that are claimed to increase the metabolism and promote greater energy expenditure, leading to weight loss. However, little is known about the side effects on gastrointestinal motility. In this study, we evaluated the effect of ingestion with a fat burner named Thermbuterol® (THERM) on the gastric motility and food behavior of mice. THERM compounds were identified using nuclear magnetic resonance (NMR). Mice received variable doses of THERM (10, 50, 100 or 300 ​mg/kg, p.o.) or NaCl 0.15 ​M (control). Gastric emptying (GE) was assessed using the phenol red technique. Another set of mice was pretreated with intraperitoneal administration of hexamethonium (HEXA, 10 ​mg/kg), prazosin (PRAZ, 0.25 ​mg/kg), propranolol (PROP, 2 ​mg/kg), parachlorophenylalanine (PCPA, 300 ​mg/kg) or ondansetron (ONDA, 50 ​μg/kg) 30 ​min before THERM treatment for evaluation of GE. We assessed the gastrointestinal responsiveness in vitro as well as THERM's effects on food behavior. Caffeine was the major compound of THERM, identified by NMR. THERM 100 and 300 ​mg/kg decreased GE compared to the respective controls. Pretreatment with PRAZ or PROP did not prevent gastric dysmotility induced by THERM 100 ​mg/kg. However, the pretreatment with HEXA, ONDA or PCPA prevented GE delay induced by THERM. In vitro , THERM relaxed contractions in strips of longitudinal gastric fundus and duodenum. THERM also increased food intake, which was prevented by PCPA and ONDA treatments. THERM decreased GE of a liquid and increased food intake in mice, a phenomenon mediated by the autonomic nicotinic receptors and serotoninergic receptor., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

This work aimed to investigate the chemical composition, antimicrobial, antinociceptive, acute toxicity and antioxidant activity of the essential oil of Algrizea minor (EOAm). The essential oil presented as the major constituents β-Pinene (56.99%), α-Pinene (16.57%), Germacrene D (4.67%), Bicyclogermacrene (4.66%), (E)-Caryophyllene (3.76%) and Limonene (1.71%). It was verified that the essential oil did not show acute toxicity in the maximum dose of 5,000 mg/kg. In the evaluation of the antinociceptive activity it was verified that the essential oil reduced in 65.84% the number of writhing in the mice, reducing the pain in 59.17%, and the mechanism of action in pain reduction was opioid, similar to morphine. The essential oil also presented significant antimicrobial against Gram positive and Gram-negative bacteria and fungi, and the antioxidant activity was relevant. Therefore, these results demonstrate the great potential for the future development of pharmaceutical products with the essential oil of Algrizea minor (EOAm) .[Figure: see text].

Harman, a natural β-carboline alkaloid, has recently gained considerable interest due to its anticancer properties. However, its physicochemical characteristics and poor oral bioavailability have been limiting factors for its pharmaceutical development. In this paper, we described the complexation of harman (HAR) with β-cyclodextrin (βCD) as a promising alternative to improve its solubility and consequently its cytotoxic effect in chemoresistant melanoma cells (A2058 cell line). Inclusion complexes (βCD-HAR) were prepared using a simple method and then characterized by FTIR, NMR and SEM techniques. Through in silico studies, the mechanism of complexation of HAR with βCD was elucidated in detail. Both HAR and βCD-HAR promoted cytotoxicity, apoptosis, cell cycle arrest and inhibition of cell migration in melanoma cells. Interestingly, complexation of HAR with βCD enhanced its pro-apoptotic effect by increasing of caspase-3 activity (p < 0.05), probably due to an improvement in HAR solubility. In addition, HAR and βCD-HAR sensitized A2058 cells to vemurafenib, dacarbazine and 5FU treatments, potentializing their cytotoxic activity. These findings suggest that complexation of HAR with natural polymers such as βCD can be useful to improve its bioavailability and antimelanoma activity., Competing Interests: Declaration of Competing Interest There are no conflict of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Croton rhamnifolioides is used in popular medicine for the treatment of inflammatory diseases. The objective of this study was to characterize and evaluate the anti-inflammatory effect of C. rhamnifolioides essential oil complexed in β-cyclodextrin (COEFC). The physicochemical characterization of the complexes was performed using different physical methods. The anti-inflammatory activity was evaluated in vivo by ear edema, paw edema, cotton pellet-induced granuloma, and vascular permeability by Evans blue extravasation. The mechanism of action was validated by molecular docking of the major constituent into the cyclooxygenase-2 (COX-2 enzyme). All doses of the COEFC reduced acute paw edema induced by carrageenan and dextran, as well as vascular permeability. Our results suggest the lowest effective dose of all samples inhibited the response induced by histamine or arachidonic acid as well as the granuloma formation. The complexation process showed that the pharmacological effects were maintained, however, showing similar results using much lower doses. The results demonstrated an involvement of the inhibition of pathways dependent on eicosanoids and histamine. Complexation of β-cyclodextrin/Essential oil (β-CD/EO) may present an important tool in the study of new compounds for the development of anti-inflammatory drugs., Competing Interests: All authors declare that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome;

Ethanol extracts of different parts of P assiflora cincinnata were obtained by maceration. The total phenolic and flavonoid contents were evaluated. The antioxidant activities were determined by β-carotene-linoleic acid bleaching test, 2,2-diphenyl-1-picrylhydrazil (DPPH), and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging. The crude ethanol stem extract showed the highest amount of total polyphenols (45.53 mg gallic acid equivalent/g) while the highest total flavonoid contents (1.42 mg of quercetin equivalent/g) were observed in the leaf extract. The lowest IC 50 (25.65 μg/ml) by the DPPH method was observed for the stem extract. The ABTS method showed a significant antioxidant activity for all investigated extracts. The secondary metabolite composition of ethanol extracts was assessed by HPLC-DAD-MS/MS analysis, leading to the identification of fourteen secondary metabolites in P. cincinnata extracts. These results showed the potentiality of this species as a source of phenolic compounds and antioxidants.

The relevance of oxidative stress in the pathogenesis of several diseases (including inflammatory disorders) has traditionally led to the search for new sources of antioxidant compounds. In this work, we report the selection of fractions with high antioxidant action from B. tetraphylla (BT) leaf extracts. In vitro methods (DPPH and ABTS assays; determination of phenolic and flavonoid contents) were used to select products derived from B. tetraphylla with high antioxidant action. Then, the samples with the highest potentials were evaluated in a model of injury based on the inoculation of a lethal dose of heat-inactivated Escherichia coli in Tenebrio molitor larvae. Due to its higher antioxidant properties, the methanolic extract (BTME) was chosen to be fractionated using Sephadex LH-20 column-based chromatography. Two fractions from BTME (BTFC and BTFD) were the most active fractions. Pre-treatment with these fractions protected larvae of T. molitor from the stress induced by inoculation of heat-inactivated E. coli . Similarly, BTFC and BTFD increased the lifespan of larvae infected with a lethal dose of enteroaggregative E. coli 042. NMR data indicated the presence of aliphatic compounds (terpenes, fatty acids, carbohydrates) and aromatic compounds (phenolic compounds). These findings suggested that products derived from B. tetraphylla leaves are promising candidates for the development of antioxidant and anti-infective agents able to treat oxidative-related dysfunctions.

Background: D-limonene (DL) is a monoterpene and is the major component in the essential oil of citrus fruit. It presents antihyperglycemic and vasodilatation activities., Objectives: This study evaluated the cardiovascular effects and potential antiarrhythmic of DL in rats., Methods: Hemodynamic and electrocardiographic (ECG) parameters were measured in male Wistar rats, which under anesthesia had been cannulated in the abdominal aorta and lower vena cava and had electrodes subcutaneously implanted. In the in vitro approach, the heart was removed and perfused using the Langendorff technique. The significance level adopted was 5% (p < 0.05)., Results: DL, in doses of 10, 20, and 40 mg/kg (i.v), produced intense and persistent bradycardia associated with hypotension. Bradycardia with prolonged QTc was observed in the ECG in vivo recording. In the in vivo model of arrhythmia induced by Bay K8644, DL (10 mg/kg) decreased the arrhythmia score from 15.33 ± 3.52 to 4.0 ± 2.64 u.a (p < 0.05, n = 4). In isolated perfused hearts, DL (10-3 M) promoted significant reductions in heart rate (from 228.6 ± 8.5 ms to 196.0 ± 9.3 bpm; p < 0.05) and left ventricular development pressure (from 25.2 ± 3.4 to 5.9 ± 1.8 mmHg; n = 5, p < 0.05)., Conclusions: DL produces bradycardia and antiarrhythmic activity in rat heart.

This study refers to the impact of the use of pesticides on human health in the São Francisco River Valley region, in which, through semi-structured interviews, the objective was to analyze the influence of social, cultural and economic determinants on the health-disease process of workers exposed to agrochemicals. For data collection, 339 rural workers from irrigated perimeters of the cities of Juazeiro, in the State of Bahia, and Petrolina, in the State of Pernambuco, were interviewed. All were male, of which 182 (53,7%) were rural owners and 157 (46,3%) were employees, predominantly between 40 and 59 years of age among owners and under 39 among workers. Over 50% have a low level of schooling and 55.2% of them have monthly incomes less than or equal to 2 minimum wages. Many of them know about the importance of wearing personal protective equipment (PPE) and the mandatory license for the use and purchase of agrochemicals. However, about 40% do not use PPE or use it inadequately and 28.9% do not have a license to purchase. More than 9% of participants reported cases of intoxication, however, less than 7% sought specialized care. Workers are aware of the risks that the use of agrochemicals expose them to risk situations, but this does not encourage them to change their worksite behavior.

Morin is a flavonoid has been reported with several pharmacological effects such as, antioxidant, anti-inflammatory, anticancer, antidiabetic, etc. However, morin has low solubility in water, which decreases the bioavailability and limits its clinical application. In this way, to improve the pharmaceutical properties, morin was complexed in hydroxypropyl-β-cyclodextrin (HP-β-CD) and its oral bioavailability and anti-inflammatory effects were evaluated. Initially, a phase solubility study was performed, which showed that HP-β-CD would be the better cyclodextrin for the formation of complexes with morin. The morin/HP-β-CD inclusion complex (1:1) was prepared by freeze-drying method. The sample obtained was characterized by DSC, FTIR, PXRD, SEM and 1 H NMR techniques, evidencing the formation of morin/HP-β-CD inclusion complex. In addition, complexation efficiency (98.3%) and loading content (17.63%), determined by HPLC demonstrated that morin was efficiently complexed in HP-β-CD. In vitro dissolution study confirmed that morin/HP-β-CD inclusion complex increased the solubility and dissolution rate of morin. The oral bioavailability of the morin/HP-β-CD complex and free morin were evaluated through a pharmacokinetic study in rat plasma. The oral bioavailability of morin complexed with HP-β-CD was increased by 4.20 times compared with the free morin. Hyperalgesia induced by carrageenan and carrageenan-induced pleurisy were carried out in mice to evaluate the antihyperalgesic and anti-inflammatory activities of free morin and inclusion complex. Morin/HP-β-CD inclusion complex showed antihyperalgesic effect in inflammatory pain model and anti-inflammatory effect decreasing leukocyte migration and TNF-α levels at a lower dose than free morin. Therefore, the morin/HP-β-CD inclusion complex improved the solubility, dissolution rate, oral bioavailability, antihyperalgesic and anti-inflammatory effects of morin. In this way, the morin/HP-β-CD inclusion complex exhibits potential for development of new pharmaceutical product for future clinical applications., (Copyright © 2019. Published by Elsevier Ltd.)

Neoglaziovia variegata is endemic to northeastern Brazil. The drought resistant plant produces edible fruits and is used as a fibre plant by rural communities in the Caatinga region where a variety of products are made from the white, soft and flexible fibres. Extracts of N. variegata have been reported to be of low toxicity and to exhibit antinociceptive effect, photoprotective potential, antioxidant effect, gastroprotective effects and antibacterial effect against both Gram-positive and Gram-negative bacteria, however, the chemical constituents of this species are mainly unknown. The novel poly-oxygenated flavone glucoside 5,6,7,4'-tetrahydroxy-3',5'-dimethoxy-flavone 7- O - β -glucopyranoside in addition to the rare poly-oxygenated flavone 5,4'-dihydroxy-6,7,3'-trimethoxyflavone 4'-O-β-glucopyranoside and the flavonol quercetin 3- O -(6''-rhamnopyranosyl- β -glucopyranoside) have been characterised from the leaves of N. variegata . 5,6,7,4'-tetrahydroxy-3',5'-dimethoxy-flavone, which comprises the core structure of the novel compound, is a new flavonoid aglycone in nature. The structure determinations were based on extensive use of 2D NMR spectroscopic techniques and high-resolution mass spectrometry. Both substances exhibited toxicity towards MOLM-13 acute myeloid leukaemia cells.

Background: Bothropic venoms cause intense local damage, pain, edema, and myonecrosis. Morus nigra L. (Moraceae) has several uses in folk medicine and can be a promising candidate for the treatment of several inflammatory disorders., Hypothesis/purpose: The present study aims to evaluate the anti-inflammatory and antinociceptive effects of the ethanolic extract of Morus nigra L. (Mn-EtOH) on paw lesions induced by Bothrops jararacussu snake venom (BjcuV) in mice., Methods: UV-vis absorption of BjcuV was evaluated. A phytochemical study was performed, which led to the isolation and characterization of three compounds. These compounds were identified using spectrometric methods, namely LC-MS and NMR (1D and 2D), followed by the validation of their spectra with the data available in the literature. Further, the flavonoids i.e. rutin and quercetin (chemical markers of M. nigra), Mn-EtOH or Mn-EtOH-encapsulated electrospun fibers of Eudragit L100 (FB/Mn-EtOH), and Mn-EtOH-encapsulated microparticles of Eudragit L100 (MP/Mn-EtOH) were evaluated, in paw edema test induced by BjcuV., Results: UV-vis spectra showed the presence of phospholipases A 2 as component of BjcuV. The chemical examination resulted in the isolation of β-sitosterol, quercetin-3-O-glucopyranoside, and kaempferol-3-O-glucopyranoside. Mn-EtOH, FB/Mn-EtOH, MP/Mn-EtOH, rutin, and quercetin reduced the local edema induced by BjcuV. The Mn-EtOH also prevented edema provoked by serotonin and bradykinin. Moreover, it reduced paw edema and peritoneal leukocyte infiltration induced by carrageenan, and decreased the mechanical hypernociception of BjcuV. Mn-EtOH exerted anti-inflammatory and antinociceptive effects, possibly by the inhibition of leukocyte migration and the modulation of serotonin and bradykinin actions. This anti-inflammatory activity was maintained even upon incorporation of the M. nigra extract into the drug delivery systems (i.e., Mn-EtOH-encapsulated FBs and MPs of Eudragit L100)., Conclusion: These results reinforce the therapeutic potential of M. nigra in the treatment of inflammatory conditions, in addition to, its role as a complementary treatment of snakebites., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Leonotis nepetifolia (Family Lamiaceae) is a medicinal plant from which the flavonoid cirsiliol with sedative, hypnotic, anti-inflammatory and cytotoxic activity has been extracted., Methods: Seedlings were cultivated under different levels of shade in native or fertilized modes. The content of cirsiliol was measured monthly by high-performance liquid chromatography and the total phenolic content by the Folin-Ciocalteu method. Monitoring of growth was carried out with the weekly measurement of height until the stabilization of growth., Results: The application of fertilizing and/or shading does not alter significantly the cirsiliol content. However, this content varies throughout the year, reaching the peak production in the summer, independently of the treatment applied. This same profile, with production in the summer, was also verified for phenolic compounds, reaching 58.15 ± 9.35 mg of equivalents of gallic acid per g of extract in the summer, content 1.84 times greater than the content verified in winter (31.56 ± 4.09 mg of gallic acid/g of extract). Although shading and fertilizing had no effect on cirsiliol content, the results also showed a positive influence on the height and biomass of the plant, which can causes a higher yield of extractable material., Discussion: Biotic and abiotic stresses are able to increase or decrease the production of secondary metabolites, including phenolic compounds in medicinal plants and, as the stress response is peculiar to each species, cultivation studies become necessary. The present study reports by the first time the influence of shading, fertilizing and seasons in cirsiliol content in L. nepetifolia . Among analyzed variables, the seasons showed a larger influence in expression of cirsiliol and among seasons, our results showed that the summer is the ideal season for collections. In summer, the photoperiod is larger than in other seasons of the year and due to that, the plants need greater protection against the long photoperiod. For this, the plants increase the production of phenolic compounds as observed in this study. Although they do not influence the production of cirsiliol, the shading and nutrients in soil favor growth and leaf area of several plants, explaining, thus, the higher height and biomass obtained., Competing Interests: The authors declare there are no competing interests.

Inflammatory response can be driven by cytokine production and is a pivotal target in the management of inflammatory diseases. Monoterpenes have shown that promising profile as agents which reduce the inflammatory process and also modulate the key chemical mediators of inflammation, such as pro and anti-inflammatory cytokines. The main interest focused on monoterpenes were to develop the analgesic and anti-inflammatory drugs. In this review, we summarized current knowledge on monoterpenes that produce anti-inflammatory effects by modulating the release of cytokines, as well as suggesting that which monoterpenoid molecules may be most effective in the treatment of inflammatory disease. Several different inflammatory markers were evaluated as a target of monoterpenes. The proinflammatory and anti-inflammatory cytokines were found TNF-α, IL-1β, IL-2, IL-5, IL-4, IL-6, IL-8, IL-10, IL-12 IL-13, IL-17A, IFNγ, TGF-β1 and IFN-γ. Our review found evidence that NF-κB and MAPK signaling are important pathways for the anti-inflammatory action of monoterpenes. We found 24 monoterpenes that modulate the production of cytokines, which appears to be the major pharmacological mechanism these compounds possess in relation to the attenuation of inflammatory response. Despite the compelling evidence supporting the anti-inflammatory effect of monoterpenes, further studies are necessary to fully explore their potential as anti-inflammatory compounds., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Cnidoscolus is a genus belonging to the Euphorbiaceae family, distributed in South American countries, such as Mexico and Brazil, which includes several species widely used in folk medicine. However, the genus is not sufficiently exploited from a chemical and pharmacological point of view., Hypothesis/purpose: This paper aims to present a systematic review of known pharmacological and chemical aspects from Cnidoscolus, an important genus for South America research groups on medicinal plants. In this article, we highlight the importance of Cnidoscolus species in the search for new bioactive molecules., Study Design: A systematic review was conducted in order to collect chemical and pharmacological information on species of this genus in the last 25 years., Methods: Literature search was performed through specialized databases (PUBMED, LILACS, SCIELO, Science Direct and Web of Science) using different combinations of the following keywords: Cnidoscolus, phytochemistry, pharmacological activity. For the selection of the manuscripts, two independent investigators (RGOJ and CAAF) first selected the articles according to the title, then to the abstract and finally through an analysis of the full-text publication. All selected manuscripts were analyzed for year of publication, country where the research was performed, reported plant species, isolated chemical compounds and evaluated biological activities., Results: Most of the studies involving Cnidoscolus were conducted by research groups located in Brazil, Nigeria and Mexico. Regarding the annual evolution of the publications, a larger number of articles published in 2014 were observed. Flavonoids, triterpenes and diterpenes represent the main classes of secondary metabolites that have been isolated from Cnidoscolus. In terms of the pharmacological investigations, C. aconitifolius, C. chayamansa and C. quercifolius are considered the most studied species, with different pharmacological activities., Conclusion: All findings indicate that Cnidoscolus is an important genus of the Euphorbiaceae family. However, considering its chemical and pharmacological importance, the studies developed with Cnidoscolus species are still limited, representing an opportunity to investigate new bioactive molecules., (Copyright © 2017. Published by Elsevier GmbH.)

In this study, we report the effects of arbuscular mycorrhizal fungi (AMF) and increasing doses of phosphorus (P) on the growth and production of secondary metabolites in Mimosa tenuiflora, a medicinal species native to Brazil. We used a completely randomized design with four inoculation treatments: Control not inoculated (1); Claroideoglomus etunicatum (2); Gigaspora albida (3); and C. etunicatum + G. albida (4) and four doses of P; P0 - baseline dose, P8, P16 and P32. After 70 d in a greenhouse, growth, mycorrhizal variables, biochemical and phytochemical parameters were evaluated. Compared to non-mycorrhizal plants, mycorrhized M. tenuiflora seedlings showed greater: growth, greater photosynthetic performance and content of soluble carbohydrates and secondary metabolites, with the most significant benefits occurring in soil with low to moderate P content (up to 16 mg kg -1 ). The plant growth is severely restricted at low P levels, but the addition of AMF appears to remove this limiting factor. Although M. tenuiflora responds to levels of phosphate fertilization, it responds well to mycorrhizal inoculation, especially with G. albida, which promotes benefits for the initial growth and secondary metabolite content in this plant species of medical and potential commercial interest and may be used instead of phosphate fertilizer., (Copyright © 2018 British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

Background: Passiflora cincinnata Mast. is described as a native species from the Caatinga biome, and used by traditional medicine for several pharmacological purposes, such as inflammatory disorders. However, studies that prove its biological activities are scarce., Hypothesis/purpose: This paper aims to evaluate the antinociceptive and anti-inflammatory activities of the aerial parts of Passiflora cincinnata (Pc-EtOH) in mice., Methods: The chemical composition of Pc-EtOH was assessed by high-performance liquid chromatography coupled to diode array detector (HPLC-DAD). The antinociceptive profile of the extract (given orally: 100, 200 and 400 mg/kg) was established using the in vivo chemical models (acetic acid-induced abdominal constriction and formalin-induced paw licking test) and thermal (hot plate test) of nociception. The role of opioid, potassium channels, TRPV-1, muscarinic, serotoninergic (5-HT 3 ) receptors and the participation of the nitric oxide pathway also was determined. The rota-rod test was used to verify the possible interference of the extract treatment in motor performance. Paw edema induced by carrageenan or histamine, and leukocyte migration, determination of total protein and nitric oxide to the peritoneal cavity were used for anti-inflammatory profile., Results: The presence of flavonoids in the extract was confirmed using HPLC-DAD. At all doses tested the Pc-EtOH significantly reduced the number of writhing and decreased the paw licking time in both phases of the formalin test (p < 0.05). In the hot plate test, the extract increased the reaction time, reducing painful behavior. The antinociceptive mechanism probably involves central and peripheral pathways, involving the pathway of opioid and muscarinic receptors with influence of potassium channels and the nitric oxide pathway. However, the motor coordination test indicated that in the time of 120 min the extract decreases the stay time of the animal in the rota-rod. Pc-EtOH inhibited significantly (p < 0.05) the increase of the edema volume after administration of carrageenan and histamine. In the peritonitis test, acute pre-treatment with Pc-EtOH inhibited leukocyte migration, with a reduction in the number of neutrophils and concentration of total proteins and nitric oxide., Conclusion: The present study suggests that Pc-EtOH possesses peripheral and central antinociceptive action, and showed potential in inhibition of release of mediators of the inflammatory process., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist.

Ethnopharmacological Relevance: Croton conduplicatus Kunth (Euphorbiaceae) is a Brazilian aromatic medicinal plant, widely known as "quebra-faca". In folk medicine, its leaves and stem-barks are used as a natural analgesic for the treatment of headaches., Aim of the Study: In this study, we describe for the first time the neuropharmacological potential of the essential oil obtained from the leaves of Croton conduplicatus (EO) in experimental models of pain, anxiety and insomnia. The mechanisms of action involved in these activities were also investigated., Material and Methods: Different experimental models were used to evaluate the antinociceptive (acetic acid, formalin-induced nociception and hot plate tests), anxiolytic (elevated plus maze and hole board tests) and sedative (thiopental-induced sleeping time) effects of EO in mice. EO was evaluated in three different doses (25, 50 and 100 mg/kg, i.p.) and compared with positive and negative controls in all experimental protocols. When appropriate, animals were pretreated with pharmacological antagonists (naloxone, atropine and flumazenil) in order to evaluate the mechanisms of action involved. A docking study also was performed to identify possible targets involved., Results: EO (25, 50 and 100 mg/kg, i.p.) demonstrated a significant antinociceptive activity in all experimental models. Pretreatment with naloxone or atropine reversed the antinociceptive response (p < 0.05), suggesting the involvement of opioid and muscarinic receptors, respectively. A docking study was performed with the major components identified in EO (1,8 cineole - 21.42%, spathulenol - 15.47%, p-cymene - 12.41% and caryophyllene oxide - 12.15%), demonstrating favorable interaction profile with different subtypes of muscarinic (M2, M3 and M4) and opioids (delta and mu) receptors. EO also showed anxiolytic (mainly at doses of 25 and 50 mg/kg, i.p.) and sedative (only at the dose of 100 mg/kg, i.p.) effects in mice. These pharmacological responses were reversed by flumazenil (p < 0.05), indicating possible involvement of GABA A receptors., Conclusion: Our findings support the traditional use of this plant as a natural analgesic and suggest that EO is a multi-target natural product, presenting not only antinociceptive effect but also anxiolytic and sedative activities depending on the dose used., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Ximenia americana L. (Olacaceae) is used in ethnomedicine as cicatrizant and for the treatment of gastric disorders. This study identified the chemical constituents of the aqueous extract of X. americana (XaAE) and evaluated its antiulcerogenic activity. After lyophilization, XaAE was analyzed by liquid chromatography-mass spectrometry (LC-MS) and its antiulcerogenic effect was evaluated in acute gastric lesions induced by ethanol, acidified ethanol, and indomethacin. Antisecretory action, mucus production and the participation of sulfhydryl groups (-SH) and nitric oxide (NO) were also investigated. The chromatographic analysis identified procyanidins B and C and catechin/epicatechin as major compounds. Oral administration of XaAE (100, 200 and 400 mg/kg) inhibited the gastric lesions induced by ethanol (76.1%, 77.5% and 100%, respectively), acidified ethanol (44.9%, 80.6% and 94.9%, respectively) and indomethacin (56.4%, 52.7% and 64.9%, respectively). XaAE reduced gastric contents and acidity (51.4% and 67.7%, respectively) but did not alter the production of gastric mucus. The reduction of the -SH and NO groups promoted by N -ethylmaleimide (NEM) and N ω-nitro-l-arginine-methyl-ester (L-NAME) respectively, reduced the gastroprotective effect of XaAE. In conclusion, XaAE has gastroprotective activity mediated in part by -SH, NO and antisecretory activity. This antiulcer action was initially correlated to its major constituents, procyanidins B and C and catechin/epicatechin., Competing Interests: The authors declare no conflict of interest.

Introduction: Depression is a serious mood disorder and is one of the most common mental illnesses. Despite the availability of several classes of antidepressants, a substantial percentage of patients are unresponsive to these drugs, which have a slow onset of action in addition to producing undesirable side effects. Some scientific evidence suggests that cyclodextrins (CDs) can improve the physicochemical and pharmacological profile of antidepressant drugs (ADDs). The purpose of this paper is to disclose current data technology prospects involving antidepressant drugs and cyclodextrins., Areas Covered: We conducted a patent review to evaluate the antidepressive activity of the compounds complexed in CDs, and we analyzed whether these complexes improved their physicochemical properties and pharmacological action. The present review used 8 specialized patent databases for patent research, using the term 'cyclodextrin' combined with 'antidepressive agents' and its related terms. We found 608 patents. In the end, considering the inclusion criteria, 27 patents reporting the benefits of complexation of ADDs with CDs were included., Expert Opinion: The use of CDs can be considered an important tool for the optimization of physicochemical and pharmacological properties of ADDs, such as stability, solubility and bioavailability.

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 Croton conduplicatus (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 ( E -caryophyllene, caryophyllene oxide, and camphor). The EO reduced nociceptive behavior at all doses tested in the acetic acid-induced nociception test ( p < 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 ATP 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 C. conduplicatus in folk medicine., Competing Interests: The authors declare no conflict of interest.

Purpose:: To realize a morphological examination of the musculoskeletal tissue, assessing the effect of a contusion method for the production in rat gastrocnemius, comparing the inflammatory responses generated by different impacts., Methods:: For the analysis of a contusion method, twelve female Wistar rats were distributed into four groups. The lesion was generated by 324 g of mass that was dropped from different predetermined heights for each group (30, 45, 60 and 70 cm)., Results:: In the analysis of musculoskeletal tissue, the response to injury varied according to the mass of the height drop onto the muscle. Only the group that was injured from 70 cm responded with uniform and severe inflammation, whereas the groups 30, 45 and 60 cm showed inflammation in some regions of the tissue with mild and moderate infiltrates., Conclusion:: The method with the 324-gram mass dropped from a 70-cm height onto the gastrocnemius muscle of rats seems to be the most suitable for the production of muscle injury in these animals after 72 hours, showing an important inflammatory infiltrate.

Schinopsis brasiliensis Engl. is a native plant of Caatinga which has high concentrations of compounds capable of absorbing ultraviolet light, suggesting its potential application for the development of sunscreen preparations. After its identification and collection, this vegetable drug was submitted to a physicochemical analysis through the preparation of ethanolic extract. The phytochemical screening and analysis of extracts were carried out by high-performance liquid chromatography (HPLC) evaluation. The antioxidant activity of the extract was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) method and β -carotene bleaching test. Inhibitory hemolytic activity and morphological deformation of erythrocytes induced by H 2 O 2 were also demonstrated and the antimicrobial activity was analyzed by the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) method. For the in vitro determination of the sun protection factor (SPF), the spectrophotometric method was used. From the analyses carried out with this species, this plant showed significant results for the antioxidant and antimicrobial activities, as well as sunscreen action. Important flavonoids were identified. These data are an important step for the development of new photoprotective cosmetic with Caatinga species, revealing importance and representing another incentive for the preservation of the species involved and analyzed in the study.

Morus nigra has been used popularly for several proposes, including diabetic. In an attempt to support medicinal value, the acute hypoglycemic, hypolipidemic, and antioxidant effects of the ethanolic extract of Morus nigra (EEMn 200 or 400 mg/kg b.w.) were evaluated in normal and alloxan-induced diabetic treated for 14 days. Serum biochemical and antioxidant analysis were performed at the end of experiment. Oral glucose tolerance test was performed at 10th and 15th days. Chromatographic analysis by HPLC-DAD of EEMn was performed. Insulin was used as positive control to glycemic metabolism as well as fenofibrate to lipid metabolism. EEMn (400 mg/kg/day) reduced fasting and postprandial glycaemia, improved oral glucose tolerance, and reduced lipolysis and proteolysis in diabetic rats. EEMn decreased the blood levels of total cholesterol and increased HDL level when compared to the diabetic control rats. At higher levels, EEMn reduced triglycerides and VLDL levels in diabetic rats. Also, EEMn reduced malondialdehyde and increased the reduced glutathione levels in liver of diabetic rats. Chromatographic analysis identified the presence of the flavonoids rutin, isoquercetin, and kaempferitrin. Acute EEMn treatment reduced hyperglycemia, improved oral glucose tolerance, and minimized dyslipidemia and oxidative stress leading to a reduction in atherogenic index in alloxan-induced diabetic rats.

Neoglaziovia variegata is a Bromeliaceae plant species widely found in Brazil with several pharmacological properties, including photoprotective activity. Although herbal-based active ingredients have been applied in cosmetic products, especially for skin treatment, its application in sunscreen formulations remains unexplored. The aim of this work is to evaluate the photoprotective effect of cosmetic formulations containing hydroalcoholic extract of N. variegata (Nv-HA). Initially, the phenolic and flavonoid total content of Nv-HA were determined. The photoprotective activity of Nv-HA was subsequently assessed using a spectrophotometric method. Nv-HA was incorporated in O/W emulsions in the presence or absence of synthetic filters and their photoprotective efficacy was evaluated by spectrophotometric SPF determination. Finally, the stability study of the formulations was performed through the freezing/defrosting method. Nv-HA showed significant phenolic and flavonoids content (61.66 ± 5.14 mg GAE/g and 90.27 ± 5.03 mg CE/g, resp.). Nv-HA showed SPF values of 5.43 ± 0.07 and 11.73 ± 0.04 for the concentrations of 0.5 and 1.0% (v/v), respectively. It was verified that Nv-HA potentiated the photoprotective effect of formulations containing only synthetic filters. Furthermore, the formulations have remained stable at the end of the preliminary stability study. According to the results, it was concluded that Nv-HA can be used as a chemical filter in cosmetic formulations.