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The Euphorbiaceae family is a rich source of bioactive terpenoids. Among its genera, Jatropha is a conspicuous producer of diterpenes and includes approximately 175 species, many of which have medicinal uses. To date, 140 diterpenes from Jatropha (JTDs) have been reported. Given their structural diversity and notable biological activities, this work aims to highlight the pharmaceutical potential of JTDs. To achieve this goal, an extensive literature review was conducted, encompassing studies on structural elucidation through NMR and pharmacological assays, both in vitro and in vivo. Based on 132 selected papers, a thorough discussion is presented on the biosynthesis, extraction, isolation, and structural characterization of JTDs, including a compilation of their 13 C NMR chemical shifts. The review also covers their synthetic production and biological effects. Additionally, an in silico analysis predicting the drug-likeness of 141 JTDs was carried out. Notably, the occurrence of macrocyclic diterpenes has doubled in the past decade, and the summary of their NMR data provides a useful resource for future research. Furthermore, 21 distinct pharmacological activities were identified, with potent cytotoxic effects targeting new molecular pathways being particularly significant. Recent advances highlight the contributions of modern approaches in organic synthesis and the pharmacological evaluation of natural products. The drug-likeness analysis identified JTD classes and compounds with favorable physicochemical and ADMET features for pharmaceutical development. In light of these findings, the use of nanotechnology is proposed as a future direction for continued research on JTDs, a fascinating class of natural compounds. This work opens up new avenues for the study of Euphorbiaceae species, particularly the Jatropha genus and its bioactive compounds.

Monnieriside A (MoA) is a chromone isolated from Evolvulus linarioides . This study investigated the antinociceptive potential of MoA in mice. MoA (0.01-100 mg/kg, i.p.) inhibited nociception in the inflammatory phase of the formalin test without causing motor impairment. MoA (0.1-100 mg/kg, i.p.) also reduced hindpaw mechanical allodynia caused by either intraplantar injection of Complete Freund's Adjuvant (CFA) or surgical paw incision to simulate postoperative pain. Postoperative antinociception was accompanied by reduced IL-1β levels in the incised paw, assessed by ELISA. The antinociceptive action of MoA (100 mg/kg, i.p.) was preserved in IL-10 knockout mice submitted to paw incision, indicating that IL-10 is not essential to the antinociceptive effect. Interestingly, MoA (100 mg/kg, i.p.) increased the expression of TGF-β in IL-10 knockout mice, which could be a compensation mechanism leading to an antinociceptive effect in the absence of IL-10.

The content of chemical constituents in Eugenia uniflora leaf extracts correlates positively with biological activities. The experimental objective was to carry out the phytochemical screening and purification of the major polyphenols from the leaves of E. uniflora . In addition, the anti- Candida activity of the hydroalcoholic extract, fraction, subfractions and polyphenols purified were evaluated. After partitioning of the extract with ethyl acetate, the fractions were chromatographed on Sephadex ® LH-20 gel followed by RP-flash chromatography and monitored by TLC and RP-HPLC. The samples were characterized by mass spectrometry (LC-ESI-QTOF-MS 2 ) and subjected to the microdilution method in 96-well plates against strains of C. albicans , C. auris, and C. glabrata . Myricitrin (93.89%; w / w ; m / z 463.0876), gallic acid (99.9%; w / w ; m / z 169.0142), and ellagic acid (94.2%; w / w ; m / z 300.9988) were recovered. The polyphenolic fraction (62.67% ( w / w ) myricitrin) and the ellagic fraction (67.86% ( w / w ) ellagic acid) showed the best antifungal performance (MIC between 62.50 and 500 μg/mL), suggesting an association between the majority constituents and the antifungal response of E. uniflora derivatives. However, there is a clear dependence on the presence of the complex chemical mixture. In conclusion, chromatographic strategies were effectively employed to recover the major polyphenols from the leaves of the species.

Seven new abietane diterpenoids, comprising medusanthol A-G ( 1 - 3 , 5 , 7 - 9 ) and two previously identified analogs ( 4 and 6 ), were isolated from the hexane extract of the aerial parts of Medusantha martiusii. The structures of the compounds were elucidated by HRESIMS, 1D/2D NMR spectroscopic data, IR spectroscopy, NMR calculations with DP4+ probability analysis, and ECD calculations. The anti-neuroinflammatory potential of compounds 1 - 7 was evaluated by determining their ability to inhibit the production of nitric oxide (NO) and the proinflammatory cytokine TNF-α in BV2 microglia stimulated with LPS and IFN-γ. Compounds 1 - 4 and 7 exhibited decreased NO levels at a concentration of 12.5 µM. Compound 1 demonstrated strong activity with an IC 50 of 3.12 µM, and compound 2 had an IC 50 of 15.53 µM; both compounds effectively reduced NO levels compared to the positive control quercetin (IC 50 11.8 µM). Additionally, both compounds significantly decreased TNF-α levels, indicating their potential as promising anti-neuroinflammatory agents.

Cervical cancer is a specific type of cancer that affects women around the world, with an incidence of 604 thousand new cases per year and 341 thousand deaths. There is a high demand for new effective antineoplastic drugs with few side effects. In this sense, recent research highlights the potential of compounds of natural origin in treating and preventing different types of cancer. Myrciaria glazioviana is a Brazilian native species belonging to the Myrtaceae family, which has previously described biological activities such as antimicrobial, anti-inflammatory, and antioxidant properties. This study aims to evaluate the anticancer activity of the dichloromethane extract (MGD) and ethyl acetate extract (MGA) of M. glazioviana leaves against human cervical cancer cell line (HeLa), as well as to identify their bioactive compounds. Using HPLC-HRESIMS technique, ten compounds were characterized in both samples: quinic acid, ellagic acid, Tri-O-methyl ellagic acid, two derivatives of Tetra-O-methyl flavellagic acid, quercetrin, Di-O-methyl ellagic acid, and three derivatives of pentamethyl coruleoellagic acid. Through MTT assays using HeLa cells and NIH/3T3 cells, it was observed that MGD and MGA were selective against tumor cells, with IC 50 values of 24.31 and 12.62 μg/mL, respectively. The samples induced the tumor cell death by apoptosis, as evidenced by the activation of caspases 3/7, cell shrinkage, and pyknotic nuclei. Both samples were also able to inhibit the migration of HeLa cells after 24 hours of treatment, indicating a potential antimetastatic effect. Therefore, the present research highlights the antiproliferative and antimigratory potential of this species against HeLa cells., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Ethnopharmacological Relevance: Ayahuasca (AYA) is a psychedelic brew used in religious ceremonies. It is broadly used as a sacred medicine for treating several ailments, including pain of various origins., Aim of the Study: To investigate the antinociceptive effects of AYA and its mechanisms in preclinical models of acute and chronic pain in mice, in particular during experimental neuropathy., Materials and Methods: The antinociceptive effects of AYA administered orally were assessed in the following models of pain: formalin test, Complete Freund's Adjuvant (CFA)-induced inflammation, tail flick test, and partial sciatic nerve ligation model of neuropathic pain. Antagonism assays and Fos immunohistochemistry in the brain were performed. AYA-induced toxicity was investigated. AYA was chemically characterized. The antinociceptive effect of harmine, the major component present in AYA, was investigated., Results: AYA (24-3000 μL/kg) dose-dependently reduced formalin-induced pain-like behaviors and CFA-induced mechanical allodynia but did not affect CFA-induced paw edema or tail flick latency. During experimental neuropathy, single treatments with AYA (24-3000 μL/kg) reduced mechanical allodynia; daily treatments once or twice a day for 14 days promoted consistent and sustained antinociception. The antinociceptive effect of AYA (600 μL/kg) was reverted by bicuculline (1 mg/kg) and methysergide (5 mg/kg), but not by naloxone (5 mg/kg), phaclofen (2 mg/kg), and rimonabant (10 mg/kg), suggesting the roles of GABA A and serotonergic receptors. AYA increased Fos expression in the ventrolateral periaqueductal gray and nucleus raphe magnus after 1 h, but not after 6 h or 14 days of daily treatments. AYA (600 μL/kg) twice a day for 14 days did not alter mice's motor function, spontaneous locomotion, body weight, food and water intake, hematological, biochemical, and histopathological parameters. Harmine (3.5 mg/kg) promoted consistent antinociception during experimental neuropathy., Conclusions: AYA promotes consistent antinociceptive effects in different mouse models of pain without inducing detectable toxic effects. Harmine is at least partially accountable for the antinociceptive properties of AYA., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Tonantzitlolone B (TZL-B) is a diterpene isolated from the roots of Stillingia loranthacea . Its antinociceptive effects were investigated in male Swiss mice using the following models of pain: formalin test, inflammation induced by Complete Freund's Adjuvant (CFA), tail flick test, and cold plate test. The influence of TZL-B on the opioid system was assessed in vivo , using opioid antagonists; in silico , investigating the chemical similarity among TZL-B and opioid agonists; and ex vivo , measuring preproenkephalin (PENK) gene expression in the spinal cord by RT-qPCR. TZL-B (10-1000 μg/kg) promoted antinociception in the four experimental models without impairing mice's motor function. TZL-B did not alter paw edema during CFA-induced inflammation. The antinociceptive effects of TZL-B in the tail flick and cold plate tests were diminished by the opioid antagonists naloxone (5 mg/kg), NOR-BNI (0.5 mg/kg), naltrindole (3 mg/kg), and CTOP (1 mg/kg), indicating the involvement of κ-, δ-, and μ-opioid receptors. TZL-B showed no significant chemical similarity to opioid agonists, but the treatment with TZL-B (1000 μg/kg) increased PENK gene expression in the spinal cord of mice. These data suggest that TZL-B promotes antinociception by enhancing the transcription of PENK, hence modulating the endogenous opioid system.

Rationale: Tropane alkaloids represent an important class of secondary metabolites, but many of these compounds are already described in the scientific literature, so the use of guided identification and isolation strategies, such as dereplication, represent a fast and safe alternative., Methods: For the annotation of the tropane alkaloids the chloroform phases of the four Erythroxylum species were analyzed by high-performance liquid chromatography coupled to mass spectrometry with positive-mode electrospray ionization, then the ions of their protonated molecules, molecular formulas and fragmentation patterns were observed and a comparison of the obtained data with those present in the scientific literature was performed. The compounds not fully annotated were isolated and characterized by 1 H and 13 C nuclear magnetic resonance spectroscopy., Results: The annotation of 29 tropane alkaloids was performed, some being described for the first time in the family Erythroxylaceae. The chemical profiles of these secondary metabolites in the four Erythroxylum species analyzed were traced and compared. Isolation of three compounds whose mass spectral data were not sufficient for their full annotation was performed. They were 6-(benzoyloxy)-3-(3,5-dimethoxy-4-hydroxybenzoyloxy)tropane, 6-(benzoyloxy)-3-(3,4,5-trimethoxybenzoyloxy)tropane and 6-(benzoyloxy)-3-(3,4,5-trimethoxycinamoyloxy)tropane, first reported in the species Erythroxylum revolutum Mart., Conclusions: This work contributes to the phytochemical knowledge of the genus Erythroxylum, and demonstrates the efficiency and importance of using guided isolation methodologies of secondary metabolites in natural products research. Since safe results were presented in the annotation of the compounds evidenced, employing small quantities of organic solvents, when compared to classical methodologies, besides promoting an optimization in the research time., (© 2023 John Wiley & Sons Ltd.)

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.

The use of agrochemicals has become a standard practice worldwide to ensure the productivity and quality of sugarcane crops. This study aimed to analyze the metabolic changes in sugarcane culms treated with five different nematicides. The experimental design was randomized in blocks, and agro-industrial and biometric variables were evaluated. The samples were extracted and then analyzed using LC-MS, LC-MS/MS, and LC-HRMS. The data obtained were submitted to statistical methods (PCA and PLS). Fragmentation patterns, retention time, and UV absorptions of the main features were analyzed. The plantations treated with carbosulfan (T4) obtained higher agricultural productivity and total recoverable sugar (TRS), while the use of benfuracarb (T3) was associated with lower growth and lower TRS. Statistical analysis revealed the contribution of the features at m / z 353 and m / z 515, assigned as chlorogenic acids, which discriminated the groups. The MS profile also supported the occurrence of flavonoids (C-glycosides and O-glycosides) in the samples.

Nopalea cochenillifera (Cactaceae), popularly known as "palma" or "palma doce", is from Mexico, but it was widely introduced in Brazil through crops. It has been used as food and in traditional medicine and is a good source of phenolic compounds. In this study the phytochemical profile and gastroprotective activity of phenolic-rich extract of N. cochenillifera in acute gastric lesion models induced by ethanol and indomethacin were evaluated. High-performance liquid chromatography coupled with mass spectrometry (HPLC/ESI/MS n ) allowed the characterization of 12 compounds such as sugars, phenolics and flavonoids. Among polyphenols, the main peak was assigned to isorhamnetin-3- O -(2'',3''- O -di-rhamnose)-glucoside. The TPC and TFC in the dry extract were 67.85 mg of gallic acid equivalent per g/extract and 46.16 mg quercetin equivalent per g/extract, respectively. In the in vitro MTT assay, the extract showed no cytotoxicity and suppressed ROS levels in LPS-treated RAW 264.7 cells. Preclinical models in rats showed that a dose of 100 mg kg -1 ( p < 0.0001) in the ethanol model and doses of 100 mg kg -1 ( p < 0.5) and 200 mg kg -1 ( p < 0.01) in the indomethacin model reduced the gastric lesions. Also, the extract reduced the MPO, MDA, TNF-α and IL-1β levels and increased the GSH and IL-10 levels. The pre-treatment with the extract led to the upregulation of SOD and the downregulation of COX-2 by immunohistochemical analysis. It also showed a cytoprotective effect in the histopathological analysis and stimulated the restoration of the mucus content as observed in the periodic acid-Schiff analysis without modifying the pH, volume or total acidity of the gastric juice. Taken together, N. cochenillifera extract can be applied as a novel gastroprotective ingredient for food or pharmaceutical products.

Oral squamous cell carcinoma (OSCC) is a worldwide public health problem, accounting for approximately 90% of all oral cancers, and is the eighth most common cancer in men. Cisplatin and carboplatin are the main chemotherapy drugs used in the clinic. However, in addition to their serious side effects, such as damage to the nervous system and kidneys, there is also drug resistance. Thus, the development of new drugs becomes of great importance. Naphthoquinones have been described with antitumor activity. Some of them are found in nature, but semi synthesis has been used as strategy to find new chemical entities for the treatment of cancer. In the present study, we promote a multiple component reaction (MCR) among lawsone, arylaldehydes, and benzylamine to produce sixteen chemoselectively derivated Mannich adducts of 1,4-naphthoquinones in good yield (up to 97%). The antitumor activities and molecular mechanisms of action of these compounds were investigated in OSCC models and the compound 6a induced cytotoxicity in three different tumor cell lines (OSCC4, OSCC9, and OSCC25) and was more selective (IS > 2) for tumor cells than the chemotropic drug carboplatin and the controls lapachol and shikonin, which are chemically similar compounds with cytotoxic effects. The 6a selectively and significantly reduced the amount of cell colony growth, was not hemolytic, and tolerable in mice with no serious side effects at a concentration of 100 mg/kg with a LD50 of 150 mg/kg. The new compound is biologically stable with a profile similar to carboplatin. Morphologically, 6a does not induce cell retraction or membrane blebs, but it does induce intense vesicle formation and late emergence of membrane bubbles. Exploring the mechanism of cell death induction, compound 6a does not induce ROS formation, and cell viability was not affected by inhibitors of apoptosis (ZVAD) and necroptosis (necrostatin 1). Autophagy followed by a late apoptosis process appears to be the death-inducing pathway of 6a, as observed by increased viability by the autophagy inhibitor (3-MA) and by the appearance of autophagosomes, later triggering a process of late apoptosis with the presence of caspase 3/7 and DNA fragmentation. Molecular modeling suggests the ability of the compound to bind to topoisomerase I and II and with greater affinity to hPKM2 enzyme than controls, which could explain the mechanism of cell death by autophagy. Finally, the in-silico prediction of drug-relevant properties showed that compound 6a has a good pharmacokinetic profile when compared to carboplatin and doxorubicin. Among the sixteen naphthoquinones tested, compound 6a was the most effective and is highly selective and well tolerated in animals. The induction of cell death in OSCC through autophagy followed by late apoptosis possibly via inhibition of the PKM2 enzyme points to a promising potential of 6a as a new preclinical anticancer candidate.

Nordine was reported to be an unusual humulene-type macrocyclic sesquiterpenoid that contains an ether-bridged bicyclic ring between C-10 and C-6 with a hydroxy group at position 2. Here, we report the structure revision of nordine based on incongruities found for carbon chemical shifts in the originally proposed structure, in addition to formation of a diacetylated derivative. As expected, a single-crystal X-ray diffraction analysis unambiguously confirmed our proposal that the nordine ( 1 ) structure contains an ether-bridged bicyclic ring between C-10 and C-7 and hydroxy groups at C-2 and C-6. Furthermore, the absolute configuration was determined by ECD spectroscopic analysis.

Herein, the isolation of secondary metabolites from the aerial parts of Justicia aequilabris guided by HPLC-MS n and molecular networking analyses is reported. Twenty-two known compounds were dereplicated. Three new lignans (aequilabrines A-C ( 1 - 3 )) and three known compounds (lariciresinol-4'- O- β-glucose ( 4 ), roseoside ( 5 ), and allantoin ( 6 )) were obtained. The anti-inflammatory activity of compounds 1 - 3 was evaluated in vitro by inhibiting the nitric oxide production (NO) and pro-inflammatory activity on the cytokine IL-1β. Compounds 2 and 3 showed significant inhibitory activity against NO production, with IC 50 values of 9.1 and 7.3 μM, respectively. The maximum inhibition of IL-1β production was 23.5% ( 1 ), 27.3% ( 2 ), and 32.5% ( 3 ).

Mandevilla Lindl. is an important genus of the Apocynaceae family, not only as ornamental plants but also for its medicinal uses. In Brazil, Mandevilla species are indicated to treat asthma and skin infections, their anti-inflammatory potential and wound healing properties are also reported in the literature. Concerning their chemical composition, this group of plants is a conspicuous producer of pregnane glycosides. Mandevilla dardanoi is an endemic species from the Brazilian semiarid region not studied by any phytochemical methods. In view of the medicinal potential of Mandevilla species, this study aimed to isolate new pregnane glycosides from M. dardanoi . To achieve this main goal, modern chromatography techniques were employed. Five new pregnane glycosides, dardanols A-E, were isolated from the roots of M. dardanoi by HPLC. Their structures were determined using extensive 1D and 2D-NMR and mass spectrometry (MS n and HRESIMS) data. The cytotoxicity and the anti-inflammatory potential of these compounds were evaluated. The first was evaluated by measuring proinflammatory cytokines and nitric oxide production by stimulated macrophages. Dardanols were able to inhibit the production of nitric oxide and reduce IL-1β and TNF-α. The current work demonstrates the chemodiversity of Brazilian semiarid species and contributes to amplifying knowledge about the biological potential of the Mandevilla genus.

Background: The relationship between spirituality and health has been the object of growing discussion. There is a lack of data on spiritual needs assessments in Brazil., Objective: This study aimed to assess the spiritual needs of patients admitted to a public tertiary hospital and perform a comparative analysis between patients with and without indications for palliative care., Design and Setting: A cross-sectional observational study included patients hospitalized between August and December 2020 in Hospital do Servidor Publico Municipal, Sao Paulo, Brazil., Methods: The included patients answered a questionnaire consisting of sociodemographic data, the Duke religiosity scale, and the Spiritual Needs Assessment for Patients (SNAP) tool for a spiritual needs assessment. The World Health Organization Palliative Needs tool (NECPAL) was used to evaluate the indications for palliative care. The level of significance adopted was 5%., Results: A total of 66 patients were included in this study. Most participants (97%) declared themselves as belonging to a religion. The group without indication for palliative care by the NECPAL showed greater spiritual (P = 0.043) and psychosocial needs (P = 0.004). No statistically significant difference was observed in the religious needs domain (P = 0.176). There were no statistically significant differences in the Duke scale scores between the two groups., Conclusion: Spiritual, psychosocial, and religious needs are prevalent among hospitalized patients, and multidisciplinary teams must consider these needs in their management approach. In addition, this study suggests that psychosocial and spiritual needs can be even higher in patients who do not receive palliative care.

Hypertension is a chronic disease and a global health problem. Due to its high prevalence, it constitutes the most important risk factor for cardiovascular disease. Fruit peels from Passiflora edulis fo. flavicarpa are rich in bioactive natural compounds that may have action in hypertension. This study aimed to perform a fingerprinting analysis of Passiflora edulis fruit peel extract and evaluate its actions on the cardiovascular system in an in vivo model. The extract was obtained from the dried and powdered fruit peels of Passiflora edulis . Glycoside flavonoids were identified in the extract by HPLC-ESI-MS n . The extract showed a significant hypotensive effect after 28 days of treatment and improved vascular function in the mesenteric artery. This effect was verified by decreased vascular hypercontractility and increased vasorelaxant in response to sodium nitroprusside and acetylcholine. There was also a decrease in endothelial dysfunction, which can be attributed to nitric oxide's increased bioavailability. Thus, we hypothesize that all these effects contributed to a reduction in peripheral vascular resistance, leading to a significant hypotensive effect. These results are novel for fruit peels from P. edulis . Also, there was a decrease in plasma and cardiac malondialdehyde levels and an increase in glutathione, suggesting a reduction in oxidative stress, as well as an increase of anti-inflammatory cytokines such as IL-10 in the plasma. This study demonstrated that the extract can be a new source of raw material to be applied as food or medicine adjuvant for treating hypertension., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Natural products have played a pivotal role for the discovery of anticancer drugs. Tonantzitlolones are flexibilan-type diterpenes rare in nature; therefore, few reports have shown antiviral and cytotoxic activities. This study aimed to investigate the in vivo antitumor action of Tonantzitlolone B (TNZ-B) and its toxicity. Toxicity was evaluated in mice (acute and micronucleus assays). Antitumor activity of TNZ-B (1.5 or 3 mg/kg intraperitoneally - i.p.) was assessed in Ehrlich ascites carcinoma model. Angiogenesis and reactive oxygen species (ROS) and nitric oxide (NO) production were also investigated, in addition to toxicological effects after 7-day treatment. The LD 50 (lethal dose 50%) was estimated at around 25 mg/kg (i.p.), and no genotoxicity was recorded. TNZ-B reduced the Ehrlich tumor's volume and total viable cancer cell count (p < 0.001 for both). Additionally, TNZ-B reduced peritumoral microvessel density (p < 0.01), suggesting antiangiogenic action. Moreover, a decrease was observed on ROS (p < 0.05) and nitric oxide (p < 0.001) levels. No significant clinical findings were observed in the analysis of biochemical, hematological, and histological (liver and kidney) parameters. In conclusion, TNZ-B exerts antitumor and antiangiogenic effects by reducing ROS and NO levels and has weak in vivo dose-repeated toxicity. These data contribute to elucidate the antitumor action of TNZ-B and point the way for further studies with this natural compound as an anticancer drug., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Quillaja saponins have an intrinsic capacity to interact with membrane lipids that self-assembles in nanoparticles (immunostimulating complexes or ISCOM-matrices) with outstanding immunoadjuvant activity and low toxicity profile. However, the expensive and laborious purification processes applied to purify Quillaja saponins used to assemble ISCOM-matrices show an important drawback in the large-scale use of this vaccine adjuvant. Thus, in this study, we describe a protocol to appropriately formulate ISCOM-matrices using the raw aqueous extract (AE) of Quillaja lancifolia leaves. In the presence of lipids, AE was able to self-assemble in nanostructures that resembles immunostimulating complexes (ISCOM). These negatively charged nanoparticles of approximately 40 nm were characterized by transmission electron microscopy and dynamic light scattering. In addition, well-known saponins with remarkable immunoadjuvant activity, as QS-21, were detected into nanoparticles. Thus, the easier, robust, cheaper, and environmentally friendly method developed here may be an alternative to the classical methods for ISCOM-matrices production that use high-purified saponins., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: Given the diversity of secondary metabolites produced by species of the genus Erythroxylum, in addition to the many methods that have already been described in the literature, modern screening and identification methodologies, such as dereplication, represent an efficient and quick strategy compared to the classic techniques linked to natural product research., Objective: The objective of the present study was to determine the phenolic profiles obtained from three species of Erythroxylum (Erythroxylum pauferrense Plowman, Erythroxylum pulchrum A.St.-Hil. and Erythroxylum simonis Plowman) by dereplication using liquid chromatography coupled with ESI-MS n and HRESIMS., Material and Methods: Ethyl acetate and n-butanolic fractions from crude ethanolic extract of Erythroxylum species were analyzed by HPLC-ESI-MS n and HPLC-HRESIMS, in order to identify its corresponding compounds. Experiments were performed in negative ionization mode, and the metabolites were provisionally identified based on deprotonated molecules, molecular formulas, fragmentation patterns and literature data. The corresponding isolated compounds were characterized by 1 H and 13 C NMR spectroscopy., Results: According to the dereplication method, it was possible to establish and compare the phenolic profile of the corresponding species by the assignment of 55 compounds, most of which were first described in these species and among which some were also new to the Erytroxylum genus. Additionally, nine compounds were isolated, including biphenyl-3,3',4,4'-tetraol, where the mass spectral data were not sufficient for their identification, and reported for the first time in the Erythroxylaceae family., Conclusion: This research contributes to the phytochemical knowledge of the Erythroxylum genus and demonstrates the importance of the dereplication method regarding the investigation of natural products, enabling accurate identification of the metabolites while avoiding the efforts and material expenses involved in the isolation of known compounds., (© 2021 John Wiley & Sons, Ltd.)

Hundreds of millions of people worldwide are affected by Chagas' disease caused by Trypanosoma cruzi. Since the current treatment lack efficacy, specificity, and suffers from several side-effects, novel therapeutics are mandatory. Natural products from endophytic fungi have been useful sources of lead compounds. In this study, three lactones isolated from an endophytic strain culture were in silico evaluated for rational guidance of their bioassay screening. All lactones displayed in vitro activity against T. cruzi epimastigote and trypomastigote forms. Notably, the IC 50 values of (+)-phomolactone were lower than benznidazole (0.86 vs. 30.78 μM against epimastigotes and 0.41 vs. 4.88 μM against trypomastigotes). Target-based studies suggested that lactones displayed their trypanocidal activities due to T. cruzi glyceraldehyde-3-phosphate dehydrogenase (TcGAPDH) inhibition, and the binding free energy for all three TcGAPDH-lactone complexes suggested that (+)-phomolactone has a lower score value (-3.38), corroborating with IC 50 assays. These results highlight the potential of these lactones for further anti-T. cruzi drug development., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

The proper pharmacological control of pain is a continuous challenge for patients and health care providers. Even the most widely used medications for pain treatment are still ineffective or unsafe for some patients, especially for those who suffer from chronic pain. Substances containing the chromone scaffold have shown a variety of biological activities, including analgesic effects. This work presents for the first time the centrally mediated antinociceptive activity of 5-O-methylcneorumchromone K (5-CK). Cold plate and tail flick tests in mice showed that the 5-CK-induced antinociception was dose-dependent, longer-lasting, and more efficacious than that induced by morphine. The 5-CK-induced antinociception was not reversed by the opioid antagonist naloxone. Topological descriptors (fingerprints) were employed to narrow the antagonist selection to further investigate 5-CK's mechanism of action. Next, based on the results of fingerprints analysis, functional antagonist assays were conducted on nociceptive tests. The effect of 5-CK was completely reversed in both cold plate and tail-flick tests by GABA A receptor antagonist bicuculline, but not by atropine or glibenclamide. Molecular docking studies suggest that 5-CK binds to the orthosteric binding site, with a similar binding profile to that observed for bicuculline and GABA. These results evidence that 5-CK has a centrally mediated antinociceptive effect, probably involving the activation of GABAergic pathways.

Background: Natural products are useful agents for the discovery of new lead- compounds and effective drugs to combat coronaviruses (CoV)., Objective: The present work provides an overview of natural substances, plant extracts, and essential oils as potential anti-SARS-CoV agents. In addition, this work evaluates their drug-like properties which are essential in the selection of compounds in order to accelerate the drug development process., Methods: The search was carried out using PubMed, ScienceDirect and SciFinder. Articles addressing plant-based natural products as potential SARS-CoV or SARS-CoV-2 agents within the last seventeen years were analyzed and selected. The descriptors for Chemometrics analysis were obtained in alvaDesc and the principal component analysis (PCA) was carried out in SIMCA version 13.0., Results: Based on in vitro assays and computational analyses, this review covers twentynine medicinal plant species and more than 300 isolated substances as potential anti-coronavirus agents. Among them, flavonoids and terpenes are the most promising compound classes. In silico analyses of drug-like properties corroborate these findings and indicate promising candidates for in vitro and in vivo studies to validate their activity., Conclusion: This paper highlights the role of ethnopharmacology in drug discovery and suggests the use of integrative (in silico/ in vitro) and chemocentric approaches to strengthen current studies and guide future research in the field of antiviral agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This current study presents the phytochemical analysis of Croton velutinus, describing phenylpropanoids obtained from this species. The fractionation of the roots hexane extract led to the isolation of four new phenylpropanoids derivatives, velutines A-D (1-4) and three known (5-7). Their structures were established based on spectroscopic (1D-2D NMR; HRMS and IR) analysis. Cytotoxic, trypanocidal and anti-inflammatory activities of compounds 1-7 were evaluated. Only compounds 2 and 5 showed cytotoxic activity against cancer cell lines (B16F10, HL-60, HCT116, MCF-7 and HepG2), with IC 50 values ranging from 6.8 to 18.3 μM and 11.1 to 18.3 μM, respectively. Compounds 2 and 5 also showed trypanocidal activity against bloodstream trypomastigotes with EC 50 values of 9.0 and 9.58 μM, respectively. Finally, the anti-inflammatory potential of these compounds was evaluated on cultures of activated macrophages. All compounds exhibited concentration-dependent suppressive activity on the production of nitrite and IL-1β by macrophages stimulated with LPS and IFN-γ. These results indicate phenylpropanoids esters (2 and 5) from C. velutinus as promising cytotoxic, trypanocidal and anti-inflammatory candidates that warrants further studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: South American rattlesnakes are represented in Brazil by a single species, Crotalus durissus , which has public health importance due to the severity of its envenomation and to its wide geographical distribution. The species is subdivided into several subspecies, but the current classification is controversial. In Brazil, the venoms of C. d. terrificus and C. d. collilineatus are used for hyperimmunization of horses for antivenom production, even though the distinction of these two subspecies are mostly by their geographical distribution. In this context, we described a comparative compositional and functional characterization of individual C. d. collilineatus and C. d. terrificus venoms from three Brazilian states., Methods: We compared the compositional patterns of C. d. terrificus and C. d. collilineatus individual venoms by 1-DE and RP-HPLC. For functional analyzes, the enzymatic activities of PLA 2 , LAAO, and coagulant activity were evaluated. Finally, the immunorecognition of venom toxins by the crotalic antivenom produced at Butantan Institute was evaluated using Western blotting., Results: The protein profile of individual venoms from C. d. collilineatus and C. d. terrificus showed a comparable overall composition, despite some intraspecific variation, especially regarding crotamine and LAAO. Interestingly, HPLC analysis showed a geographic pattern concerning PLA 2 . In addition, a remarkable intraspecific variation was also observed in PLA 2 , LAAO and coagulant activities. The immunorecognition pattern of individual venoms from C. d. collilineatus and C. d. terrificus by crotalic antivenom produced at Butantan Institute was similar., Conclusions: The results highlighted the individual variability among the venoms of C. durissus ssp. specimens. Importantly, our data point to a geographical variation of C. durissus ssp. venom profile, regardless of the subspecies, as evidenced by PLA 2 isoforms complexity, which may explain the increase in venom neurotoxicity from Northeastern through Southern Brazil reported for the species., Competing Interests: Competing interests: The authors declare that they have no competing interests.

Ethnopharmacological Relevance: Miconia albicans (Sw) Triana (Melastomataceae), a medicinal plant widely used by practitioners of folk medicine in the northeast of Brazil, has been used to treat chronic inflammatory disorders, such as rheumatoid arthritis (RA) and other joint conditions. Oddly, there is little research on the species., Aim of the Study: We aimed to evaluate the anti-arthritic and anti-inflammatory profile of the ethanolic leaf extract of M. albicans (EEMA), as well as to perform dereplication and quantification by HPLC-DAD-ESI-/MS/MS., Materials and Methods: The compounds present in the extracts were identified by HPLC-DAD-ESI-MS/MS. The possible anti-inflammatory effect of EEMA (50 and 100 mg/kg, p.o) was evaluated using the pleurisy model induced by carrageenan and its action on IL-1β and TNF-α levels was also evaluated. The RA model was induced through the intra-articular injection of complete Freund's adjuvant (CFA)., Results: HPLC-DAD-ESI-MS/MS analysis identified 23 compounds, with glycoside flavonoids mainly derived from quercetin, and rutin being the main compounds. EEMA significantly reduced (p < 0.001) leukocyte migration in the pleurisy model and reduced TNF-α and IL-1β levels in pleural lavage (p < 0.001). In the CFA animal model, EEMA significantly reduced the nociceptive and hyperalgesic behaviors demonstrated by the rearing test (p < 0.01 or p < 0.05) and decreased mechanical hyperalgesia (p < 0.001). EEMA produced a significant improvement in mobility in the open-field test (only at the higher dose, p < 0.05). EEMA significantly (p < 0.01) increased hindpaw grip strength. The diameter of CFA-induced ipsilateral knee edema was significantly reduced (p < 0.001) by EEMA, which was related to reduced levels of IL-6 and TNF-α in the joint knee (p < 0.01). No indication of hepatic injury after chronic treatment was found., Conclusion: Taken together, these results contribute to the chemical and pharmacological knowledge of M. albicans and demonstrated that this medicinal plant appears to be able to mitigate deleterious symptoms of RA, which supports its use in folk medicine., Competing Interests: Declaration of competing interest All authors report no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Six sesquiterpenoids with unprecedented macrocyclic humulene-type structures, namely, dolichocarpols A-E ( 1 - 5 ) with ether-bridged bicyclic rings between C-10 and C-2, C-10 and C-7, C-10 and C-6 (×2), and C-6 and C-3 and dolichocarpol F ( 6 ) cyclized between C-7 and C-2 and with an ether bridge between C-10 and C-3, were isolated from Anaxagorea dolichocarpa roots. The structures of the compounds were elucidated by NMR, MS, and IR data. Absolute configurations of compounds 1 - 3 and 6 were established on the basis of data from electronic circular dichroism, whereas relative configurations of compounds 4 and 5 were suggested by the NOESY spectrum. In addition, a putative biosynthetic pathway of the compounds is proposed. Furthermore, the cytotoxicity of 3 , 4 , and 6 against HCT-116 (human colorectal carcinoma) and L929 (murine fibroblast) was evaluated., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Three new caryophyllane-type sesquiterpenoids, linariophyllenes A-C ( 1 - 3 ), two new hamamelitol derivatives, linaritols A ( 4) and B ( 5 ), two new chromones, linariosides A ( 6 ) and B ( 7 ), and three known chromones, cnidimol C ( 8 ), monnieriside A ( 9 ), and undulatoside A ( 10 ), were identified from the aerial parts of Evolvulus linarioides . The structures of these compounds were elucidated by NMR, MS, and IR data. The absolute configurations of compounds 1 - 5 and 7 were established via electronic circular dichroism data. The anti-inflammatory potential of compounds 1 - 5 and 7 - 10 was evaluated by determining their ability to inhibit the production of nitric oxide (NO) and proinflammatory cytokine IL-1β by stimulated J774 macrophages. Compounds tested at noncytotoxic concentrations inhibited NO production by macrophages, exhibiting IC 50 values between 17.8 and 66.2 μM, and inhibited IL-1β production by stimulated macrophages by 72.7-96.2%.

One new diterpene (4 R ,7 R ,14 S )-4α,7α-diacetoxy-10-one-14α-hydroxydolasta-1(15),8-diene ( 1 ), and five known compounds (4 R ,7 R ,14 S )-4α,7α-diacetoxy-14α-hydroxydolasta-1(15),8-diene ( 2 ), (4 R ,14 S )-4α,14α-dihydroxydolasta-1(15),8-diene ( 3 ), (4 S ,9 R ,14 S )-4α-acetoxy-9β,14α-dihydroxydolasta-1(15),7-diene ( 4 ), 4-acetoxy-14-hydroxydolasta-1(15),7,9-triene ( 5 ) and isolinearol ( 6 ), were isolated from Canistrocarpus cervicornis . In this study, dolastane diterpenes were isolated from the alga C. cervicornis and evaluated as modifiers of antibiotic activity in Staphylococcus aureus : SA-1199B, which overexpresses the norA gene RN-4220, which encodes for the protein efflux of macrolides (MRSA), and IS-58 which has the gene encoding the protein TetK. The minimum inhibitory concentrations (MICs) for norfloxacin, tetracycline and erythromycin were determined by the microdilution broth nutrient in the absence and presence of diterpenes at a sub-inhibitory concentration (MIC/4). The extracts of C. cervicornis and isolated diterpenes showed no antibacterial activity, but showed modulatory activity, decreasing the MIC of antibiotics by 4-256 fold. The results indicate that seaweed extracts and diterpenes are potential sources of antibiotic adjuvant, acting as potential inhibitors of efflux pump.

Limonoids, quinolone alkaloids and chromones have been reported as constituents of Dictyoloma vandellianum Adr. Juss. (Rutaceae). Although those compounds are known for their biological activities, only the anti-inflammatory activity of chromones isolated from the underground parts has been evaluated. There are no studies of the pharmacological properties of the aerial parts of D. vandellianum. The present study was carried out to determine the phytochemical profile and antinociceptive activity of the methanol extract, fractions and isolated compounds of leaves of D. vandellianum. The phytochemical profile was performed by HLPC-DAD-ESIMSn and pure substances obtained were characterized by MS and NMR spectroscopy. The antinociceptive activity was assessed using the formalin assay in mice, and the motor function in the rotarod test. ME and all the fractions obtained from ME produced antinociceptive effects. Among them, the ethyl ether fraction was the most active. Data from HPLC-DAD-ESIMSn showed that the ethyl ether fraction presented 42 compounds. The major compounds isolated from this fraction-gallic acid, methyl gallate and 1,2,6-tri-O-galloyl-β-d-glucopyranose-were tested and produced antinociceptive effects. Gallic acid, methyl gallate and 1,2,6-tri-O-galloyl-β-d-glucopyranose at antinociceptive doses did not affect the motor performance in mice in the rotarod test. This work is the first report of the occurrence of gallotanins in D. vandellianum. In addition, the pharmacological study showed that D. vandellianum leaves present antinociceptive activity, probably induced by gallic acid, methyl gallate and 1,2,6-tri-O-galloyl-β-d-glucopyranose., Competing Interests: The authors have declared that no competing interests exist.

This study represents the first phytochemical analysis of Stillingia loranthacea ( S. loranthacea ) and describes new terpenoids obtained from the root bark of this species. The fractionation of the hexane extract from the root bark led to the isolation of two new 28-nor-taraxarenes derivatives, loranthones A and B ( 1 and 2 ), four new tigliane diterpenes ( 5 - 8 ), three known tigliane diterpenes ( 9 - 11 ), and three known flexibilene diterpenes, tonantzitlolones A-C ( 12 - 14 ). The investigation of these compounds and the use of a molecular networking-based prioritization approach afforded two other new 28-nor-taraxarenes, loranthones C and D ( 3 and 4 ). The cytotoxicity of compounds 1 , 2 , and 5 - 14 was evaluated against Vero cells, and their 20% cytotoxic concentration (CC 20 ) values varied from 8.7 to 328 μM; antiviral activity was tested against an epidemic Zika virus (ZIKV) strain circulating in Brazil. Six out of 12 compounds ( 2 , 5 , 9 - 11 , and 14 ) exhibited significant antiviral effects against ZIKV. Specifically, compounds 2 and 5 offered the most promise as lead compounds as they had a 1.7 and 1.8 log 10 TCID 50 /mL reduction in ZIKV replication, respectively. Together, the present findings have identified S. loranthacea terpenoids as potent anti-ZIKV inhibitors and pave the way to the development of possible new treatments against this devastating pathogen.

Zornia brasiliensis Vogel (Leguminosae) is a species popularly known in Brazil as "urinária", "urinana", and "carrapicho", it is popularly used as a diuretic and in the treatment of venereal diseases. A specific methodology to obtain a saponin-enriched fraction and high-performance liquid chromatography coupled with diode array detection, ion trap mass spectrometry, and TOF-MS (HPLC-DAD-ESI-MS/MS) was applied for the analysis of triterpene saponins. The MS and MS/MS experiments were carried out by ionization in negative mode. Molecular mass and fragmentation data were used to support the structural characterization of the saponins. Based on retention times, high-resolution mass determination and fragmentation, 35 oleanane-triterpene saponins were tentatively identified in Z. brasiliensis .

Chromones are a group of natural substances with a diversity of biological activities. Herein we assessed the pharmacological potential of three chromones (1, 2 and 3) isolated from Dictyoloma vandellianum as anti-inflammatory agents using in vitro and in vivo approaches. During in vitro screening, the production of NO and cytokines by macrophages stimulated with LPS and IFN-γ was inhibited by all chromones at concentrations (5-20 μM) that did not induce cytotoxicity. Analysis of pharmacokinetic parameters (in vitro half-life and intrinsic clearance) using human liver microsomes revealed that 3 has a superior pharmacokinetic profile, compared to 1 and 2. Treatment with 3 (100 mg/kg, ip) did not affect the mice motor performance, while 1 and 2 induced motor deficit. Taking into account the pharmacokinetic profile and absence of motor impairment, 3 was selected for further pharmacological characterization. Corroborating the data from in vitro screening, treatment of cell cultures with 3 (5-20 μM) reduced TNF-α, IL-6 and IL-1β production by stimulated macrophages. In the complete Freund's adjuvant-induced paw inflammation model in mice, 3 (25 and 50 mg/kg, ip) inhibited mechanical hyperalgesia, edema and cytokine production/release (IL-1β, IL-6 and TNF-α). 3 (5-20 μM) also reduced the transcriptional activity of NF-κB in stimulated macrophages. Furthermore, treatment with RU486, a glucocorticoid receptor (GR) antagonist, partially prevented the inhibitory effect of 3 on macrophages, indicating that this chromone exerts its anti-inflammatory effects in part through the activation of GR. The results presented herein demonstrate the pharmacological potential of natural chromones, highlighting 3 as a possible candidate for the drug discovery process targeting new anti-inflammatory drugs., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Canthin-6-one alkaloids, which are present in plants of the genus Simaba, are natural compounds that are capable of acting as fluorescent probes. However, the chemical composition and fluorescent properties of most species of this genus have not been analyzed. The objective of this study was to characterize the fluorescent properties of an extract of S. bahiensis and identify the chemical entities responsible for these properties. In addition, the cell-labeling properties of the fluorescent dye from A and of the isolated compounds were characterized by confocal fluorescence microscopy and flow cytometry. One quassinoid and three fluorescent alkaloids were isolated from S. bahiensis, all compounds were identified by using NMR spectroscopy and high-resolution mass spectrometry. Staining experiments and HPLC-FL analysis shown that canthin-6-one alkaloids are the main green fluorescent compounds in the analyzed dyes. All compounds evaluated showed a cytoplasmic marker with a residence time of 24 h. The present study is the first to describe the presence of canthin-6-one alkaloids in S. bahiensis, in addition to demonstrating promising cell-labeling properties of fluorescent compounds from S. bahiensis with broad emission wavelengths., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Genipa americana is a medicinal plant popularly known as "jenipapo", which occurs in Brazil and belongs to the Rubiaceae family. It is a species widely distributed in the tropical Central and South America, especially in the Cerrado biome. Their leaves and fruits are used as food and popularly in folk medicine to treat anemias, as an antidiarrheal, and anti-syphilitic. Iridoids are the main secondary metabolites described from G. americana , but few studies have been conducted with their leaves. In this study, the aim was to chemical approach for identify the main compounds present at the extract of G. americana leaves. The powdered leaves were extracted by maceration with EtOH: water (70:30, v / v ), following liquid-liquid partition with petroleum ether, chloroform, ethyl acetate and n -butanol. A total of 13 compounds were identified. In addition three flavonoids were isolated from the ethyl acetate fraction: quercetin-3-O-robinoside ( GAF 1 ), kaempferol-3-O-robinoside ( GAF 2 ) and isorhamnetin-3-O-robinoside ( GAF 3 ) and, from n -butanol fraction more two flavonoids were isolated, kaempferol-3-O-robinoside-7-O-rhamnoside (robinin) ( GAF 4 ) and isorhamnetin-3-O-robinoside-7-rhamnoside ( GAF 5 ). Chemical structures of these five flavonoids were elucidated using spectroscopic methods (MS, ¹H and 13 C-NMR 1D and 2D). These flavonoids glycosides were described for the first time in G. americana ., Competing Interests: The authors declare no conflict of interest.

Introduction: Although culturally food and physical activity restriction are part of the routine postoperative care of many Brazilian surgeons, current evidences from other countries support no such recommendations., Objective: To determine whether dietary and physical restriction effectively lead to a decrease on postoperative complications of adenotonsillectomy in children when compared to no restriction., Methods: We have designed a randomized clinical trial comparing two intervention: no specific counseling on diet or activity (Group A), and restriction recommendations on diet and physical activities (Group B). Caregivers completed a questionnaire on observed pain, diet and activity patterns, and medications administered. Parameters were compared at the 3rd and at the 7th postoperative day between intervention groups., Results: We have enrolled a total of 95 patients, 50 in Group A and 45 in Group B. Fourteen patients were lost to follow up. Eventually, 41 patients in group A and 40 in Group B were available for final analysis. Mean age in months (A=79.5; SD=33.9/B=81.1; SD=32.6) and sex (A=58% male; B=64.4% male) were equivalent between groups. Pain, evaluated through visual analog scale in the 3rd (A=2.0; IQR 1-6/B=4.5; IQR 2-6; p=0.18) and in the 7th (A=1.0; IQR 1.0-4.5/B=2.0; IQR 1.0-4.7; p=0.29) postoperative days, was not different between groups, as was the amount of analgesics administered. Dietary and physical activity patterns also showed no statistically significant differences between groups., Conclusion: Dietary and activity restriction after adenotonsillectomy does not seem to affect patients' recovery. Such information may impact considerably on the social aspects that involve a tonsillectomy, reducing the working days lost by parents and accelerating the return of children to school., (Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

One new chromone 3,3-dimethylallylspatheliachromene methyl ether (1), as well as five known chromones, 6-(3-methylbut-2-enyl) allopteroxylin methyl ether (2), 6-(3-methylbut-2-enyl) allopteroxylin (3), 3,3-dimethylallylspatheliachromene (4), 5-O-methylcneorumchromone K (5) and spatheliabischromene (6), two alkaloids, 8-methoxy-N-methylflindersine (7) and 8-methoxyflindersine (8), and two limonoids, limonin diosphenol (9) and rutaevin (10), were isolated from Dictyoloma vandellianum A. Juss (Rutaceae). Cytotoxic activities towards tumor cell lines B16-F10, HepG2, K562 and HL60 and non-tumor cells PBMC were evaluated for compounds 1 - 6. Compound 1 was the most active showing IC 50 values ranging from 6.26 to 14.82 μg/ml in B16-F10 and K562 cell lines, respectively, and presented IC 50 value of 11.65 μg/ml in PBMC cell line., (© 2017 Wiley-VHCA AG, Zurich, Switzerland.)

Purpose: Trachoma, caused by the bacterium Chlamydia trachomatis, is a chronic, recurrent inflammatory disease that affects the cornea and conjunctiva. Trachoma is the leading infectious cause of avoidable blindness worldwide. Its prevalence is higher among individuals of low socioeconomic status, and trachoma is common in indigenous communities. The present study presents aspects of the epidemiological profile of trachoma in indigenous communities in Brazil., Methods: We analyzed data from two databases collected during trachoma screening activities among the population of indigenous settlements in Brazil between 2000 and 2008. Trachoma cases were detected by ocular examination in accordance with the World Health Organization simplified trachoma grading system., Results: According to the surveillance database, a total of 9582 individuals in six different states were examined. Among children aged 1-9 years, the prevalence of follicular trachomatous inflammation (TF) was 35.2%. In individuals aged ≥15 years, the prevalence of trachomatous trichiasis (TT) was 1.2% in individuals and the sex-specific prevalence was 0.8% in males and 1.6% in females (p = 0.02). In a survey of two states, 2301 indigenous schoolchildren were examined. In the age bracket 5-9 years, the prevalence of TF was 4.9 (95% confidence interval 3.8-6.0%)., Conclusion: In Brazil, trachoma appears to be a serious public health problem in indigenous settlements, which should therefore be given priority in programs aimed at the elimination of trachoma in the country.

We report two similarly affected cousins (children of monozygotic twin sisters) with phenotypic features consistent with 9p deletion syndrome, including dysmorphic craniofacial features (trigonocephaly, midface hypoplasia, upward-slanting palpebral fissures and long philtrum), intellectual disability and disorders of sex development. Initial cytogenetic examination showed normal karyotypes in the probands and their respective parents, though multiplex ligation probe amplification revealed a 1q terminal duplication and a 9p terminal deletion in both affected children. Further analysis by fluorescence in situ hybridization, identified a familial balanced cryptic translocation t(1;9)(q44;p23) in the mothers, showing the importance of the association of molecular cytogenetic techniques in clinical genetics, given the implications for the care of patients and for genetic counseling.

This article discusses the social representations of women living in common-law marriage in terms of their vulnerability to becoming infected with HIV/AIDS. Data were obtained through the free association of words, and consisted of an excerpt of a study founded on the Social Representations Theory developed with HIV-negative women living in the state capital and cities in the interior of Bahia. The correspondence factor analysis showed significance for the variables: origin, education level and time spent in common-law marriage. Their acceptance of marital affairs emerged as a vulnerability factor for respondents with one to five years spent in common-law marriage, living in cities in the interior. Women from the capital, with 6-10 years spent in common-law marriage, reported monogamy as a form of prevention. Women with a longer common-law marriage who had completed only a primary education reported feeling invulnerable, which was the opposite of those with one to five years in common-law marriage with a secondary education. Results show there is a need for more interventions aiming to denaturalize the socio-cultural coercions that generate representations and make women in common-law marriages more vulnerable to AIDS.

Objective: Estimate cataract surgical rates (CSR) for Brazil and each federal unit in 2006 and 2007 based on the number of surgeries performed by the Unified Health System to help plan a comprehensive ophthalmology network in order to eliminate cataract blindness in compliance with the target set by the World Health Organization (WHO) of 3,000 cataract surgeries per million inhabitants per year., Methods: This descriptive study calculates CSR by using the number of cataract surgeries carried out by the Brazilian Unified Health System for each federal unit and estimates the need for cataract surgery in Brazil for 2006-2007, with official population data provided by the Brazilian Institute of Geography and Statistics. The number of cataract surgeries was compared with the WHO target., Results: To reach the WHO goal for eliminating age-related cataract blindness in Brazil, 560,312 cataract surgeries in 2006 and 568,006 surgeries in 2007 needed to be done. In 2006, 179,121 cataract surgeries were done by the Unified Health System, corresponding to a CSR of 959 per million population; in 2007, 223,317 were performed, with a CSR of 1,179. With the Brazilian Council of Ophthalmology estimation of 165,000 surgeries each year by the non-public services, the CSR for Brazil would be 1,842 for 2006 and 2,051 for 2007. The proportions needed to achieve the proposed target were 38.6% in 2006 and 31.6% in 2007., Conclusions: Human resources, technical expertise, and equipment are crucial to reach the WHO goal. Brazil has enough ophthalmologists but needs improved planning and infrastructure in order to eliminate the problem, aspects that require greater financial investment and stronger political commitment.

Purpose: To estimate the prevalence and severity of trachoma among preschool children and to identify the risk factors., Methods: Cross-sectional study involving preschool children up to seven years of age residing in a neighborhood of the city of São Paulo, Brazil., Results: A total of 1128 children were studied. Although most were of low socioeconomic status, access to good sanitary services was virtually universal. The prevalence of inflammatory trachoma was 4.7%. In the bivariate analysis, being 4-7 years of age and having classroom contact with a trachoma case were associated with the disease. Multivariate logistic regression showed that contact with trachoma in the classroom was an independent predictor of trachoma., Conclusions: Trachoma persists among children in low-income families, even in urban areas with good sanitation. To eliminate trachoma in a low endemic community, a sensitive surveillance system should be implemented to identify residual sources of infection.

Objective: To assess the prevalence of trachoma among preschool and school children of public schools to give new focus to control programs., Methods: An epidemiological survey was carried out in São Paulo City in 1999. Children between four and 14 years old were selected by a cluster sampling where school shift was the sampling unit. External eye examination was conducted to detect trachoma., Results: A total of 27,091 children were examined and 597 cases of trachoma were found (2.2%; 95% CI: 1.86-2.55). The prevalence ranged from 0.4% to 4.2% in 10 city areas. The trachoma detection rate in the household contacts examined was 8.7%. Follicular trachoma was found in 99% of the cases and intense trachoma in 1.0%. It was observed that 21.8% of the cases were asymptomatic., Conclusions: Though the trachoma prevalence was low, the occurrence of severe cases points out to the likelihood of cicatricial trachoma cases in the future if they are not adequately treated and controlled. The great difference in the prevalences in different city areas indicates the need for strengthening epidemiological surveillance activities.