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Endopleura uchi bark traditionally used in folk medicine attributed to its anti-inflammatory properties is due to the presence of bergenin. This study aimed to determine the toxicological parameters associated with exposure to a phenolic-enriched extract of E. uchi bark and bergenin a bioactive byproduct of this compound. The total phenolic and flavonoid contents were determined through spectrometric analyses, while phenolic compounds were identified using ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-MS). Antioxidant activity was assessed in vitro using the DPPH assay. Cytotoxicity and genotoxicity were assessed via the MTT assay and comet assay, respectively, whereas mutagenic activity was examined using Salmonella/microsome assay and micronucleus (MN) test. A high content of phenolic (732.22 ± 9.48 mg/g) GAE (gallic acid equivalence) and flavonoid 252.47 ± 5.7 mg/g QE (quercetin) compounds was found in bergenin the phenolic-enriched extract byproduct as well as isomers of gallic acid, epicatechin, isoquercitrin, castalagin, punicalin, and punicalagin. The DPPH value was 23.74 ± 0.45 μg/ml. In MTT assay, the extract exhibited an IC50 of 72.5 ± 2.6 µg/ml. Both extract and bergenin displayed genotoxic activity in L929 fibroblast cells at 50 µg/ml but not mutagenic effects in the Salmonella/microsome assay or MN test. Despite the genotoxic actions, E. uchi bark and bergenin extract did not induce gene or chromosomal mutations, suggesting a low risk of compromising genomic stability. The presence of bioactive compounds such as bergenin and punicalagin in E. uchi bark demonstrates a therapeutic potential of this native tree for treating inflammatory diseases.

Apigenin (APG), a plant-derived flavonoid, has attracted attention as an anti-melanoma agent because of its action on multiple cell signaling pathways and high selectivity for tumor cells. Despite this, extensive metabolism and slow oral absorption are found, which has motivated the development of topical delivery systems. In this context, invasomes were considered, for the first time, for flavonoid incorporation. Given that these vesicles have a more deformable structure than conventional liposomes, greater interaction with the skin is expected. In fact, ATR-FTIR analyses revealed more substantial changes in skin lipid domains with invasomes, which also were more stable to centrifugation and showed lower PDI values. Their reduced particle size (<200 nm), in turn, would allow reaching deeper tumor regions. The APG seems to interact with both polar and apolar domains of invasome lipids, which explains the high encapsulation efficiency (>99 %) and improved vesicle rigidity. Limonene, the terpene selected based on its already described anti-melanoma activity, was crucial for enhancing the retention of APG in the skin (an increase of more than 3.5x when compared to conventional liposomes) as well as vesicle stability. Cholesterol (CHOL) also slightly improved the permeation and retention of this flavonoid in the skin; however, it had a negative effect on the stability of APG-free invasomes. Taking into account the improved distribution of APG in the basal layer of the epidermis (the tumor site) and the advantages in terms of stability and membrane flexibility, invasomes can be considered promising colloidal carriers for the topical delivery of anti-melanoma drugs., 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 © 2025 Elsevier B.V. All rights reserved.)

The bark extract from Endopleura uchi has been widely used in traditional medicine to treat gynecological-related disorders, diabetes, and dyslipidemias albeit without scientific proof. In addition, E. uchi bark extract safety, especially regarding mutagenic activities, is not known. The aim of this study was to determine the chemical composition, antitumor, and toxicological parameters attributed to an E. uchi bark aqueous extract. The phytochemical constitution was assessed by colorimetric and chromatographic analyzes. The antiproliferative effect was determined using sulforhodamine B (SRB) assay using 4 cancer cell lines. Cytotoxic and genotoxic activities were assessed utilizing MTT and comet assays, respectively, while mutagenicity was determined through micronucleus and Salmonella /microsome assays. The chromatographic analysis detected predominantly the presence of gallic acid and isoquercitrin. The antiproliferative effect was more pronounced in human colon adenocarcinoma (HT-29) and human breast cancer (MCF-7) cell lines. In the MTT assay, the extract presented an IC 50  = 39.1 µg/ml and exhibited genotoxic (comet assay) and mutagenic (micronucleus test) activities at 20 and 40 µg/ml in mouse fibroblast cell line (L929) and mutagenicity in the TA102 and TA97a strains in the absence of S9 mix. Data demonstrated that E. uchi bark possesses bioactive compounds which exert cytotoxic and genotoxic effects that might be associated with its antitumor potential. Therefore, E. uchi bark aqueous extract consumption needs to be approached with caution in therapeutic applications.

Ethnopharmacological Relevance: Cecropia pachystachya (CP) Trécul is a medicinal plant native to South and Central America with several pharmacological properties, such as anti-inflammatory and neuroprotective., Aim of the Study: In this study, we investigated the effect of CP extract (200 mg/kg) and its enriched flavonoid fraction (EFF-CP) (50 and 100 mg/kg) in a model of lipopolysaccharide (LPS)-induced neuroinflammation., Material and Methods: CP and EFF-CP were administered intragastrically for 14 days and LPS (250 μg/kg) was administered intraperitoneally from the 8th to the 14th days. LC/DAD/MS analysis showed the presence of isoorientin, orientin, and isovitexin as major compounds., Results: The results demonstrated that CP extract and EFF-CP gave protection against LPS-induced short-term and long-term memory deficits. The treatment with CP and/or EFF-CP protected against LPS-induced increases in reactive species, nitrites, total thiol and lipoperoxidation in the cerebral cortex, hippocampus and striatum. Moreover, CP and EFF-CP restored superoxide dismutase and catalase activities that had been reduced by LPS in the cerebral cortex, hippocampus and striatum. TNF-α levels were increased in the cortex, striatum and hippocampus in the LPS group, while CP treatment prevented this change in the cerebral cortex. EFF-CP decreased the levels of this cytokine in all structures analyzed at both doses., Conclusion: CP extract and its EFF-CP are important therapeutic targets for the management of neuroinflammation observed in neurodegenerative diseases., 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 © 2023 Elsevier B.V. All rights reserved.)

The phloroglucinol eugenial C, eugenial D and eugenial E are the main active compounds in Eugenia umbelliflora fruits. This study aims to evaluate the extraction conditions of E. umbelliflora , using ethanol as solvent, focusing on the phloroglucinol and antimicrobial activity. In order to optimize the extraction conditions, ethanol 50, 70 and 90 o GL was used as a solvent in the proportions of 1:20 (w/v) of drug:solvent ratio (D:S), stirring (330 rpm) at room temperature during 4 h, monitored by LC-UV and antimicrobial assay. The LC-UV method developed was linear over a concentration range of 3.4-68.0, 5.3-106.0 and 5.0-100.8 μg.mL -1 of eugenial C, eugenial D and eugenial E, having LOQ of 1.68, 1.33 and 0.8 μg.mL -1 , respectively. The fruits showed the best herbal raw material and showed the highest phloroglucinol concentration and activity against S. aureus , when extracted with ethanol 90 o GL, during 4 h, at 1:20 of D:S.

Ilex paraguariensis A. St. Hil. (Aquifoliaceae), popularly known as " yerba mate ," has great economic and social significance for the population of Southern Latin America. This study was conducted (1) to investigate the phytochemical composition of four different standardized extracts, (2) to investigate its free radical scavenging properties, and (3) to investigate the anti-inflammatory action of I. paraguariensis and its major chemical markers. The chemical profile was achieved by Folin-Ciocalteu, by LC/DAD, and by LC/MS assays, while the antioxidant and anti-inflammatory properties were investigated, respectively, by DPPH assay and by inhibition of nitric oxide (Griess reaction) and TNF- α (ELISA). Our results demonstrated that the IA (aqueous infusion extract) showed higher amounts of total phenolic contents (266.62 ± 10.85 mg CAE·g -1 DE), the highest amounts of all six chemical markers (theobromine, 5- O -caffeoylquinic acid, 4- O -caffeoylquinic acid, 3- O -caffeoylquinic acid, caffeine, and rutin), and stronger antioxidant activity (EC 50 = 54.4 ± 5.14  μ g · mL -1 ). The IA extract also showed the lowest inhibition of NOx secretion (50.10 ± 8.97%) as well as inhibition of TNF- α (83.33 ± 4.01%). Regarding the chemical markers, all compounds showed strong inhibition of NOx secretion, especially theobromine, which was 200x more potent than dexamethasone. Furthermore, TNF- α secretion was also significantly decreased by THEO at 0.033  μ M (22.15 ± 6.49%), NCA at 1.97  μ M (27.46 ± 3.98%), CCA at 0.35  μ M (39.76 ± 5.73%), CGA at 0.56  μ M (23.58 ± 5.79%), CAF at 0.52  μ M (26.45 ± 5.34%), and RUT at 0.16  μ M (40.18 ± 3.70%). Our results suggest that I. paraguariensis and its major chemical markers have strong free radical scavenging properties as well as showed important anti-inflammatory activity and that these compounds in a plant extract may work based on several different mechanisms synergistically, resulting in moderating the immune system., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 Ingrid Vicente Farias et al.)

The use of medicinal plants concomitantly with conventional drugs can result in herb-drug interactions that cause fluctuations in drug bioavailability and consequent therapeutic failure and/or toxic effects. The CYP superfamily of enzymes plays an important role in herb-drug interactions. Among CYP enzymes, CYP3A4 and CYP2D6 are the most relevant since they metabolize about 50% and 30% of the drugs on the market, respectively. Thus, the main goal of this study was to evaluate the occurrence of in vitro interactions between medicinal plant extracts and drug substrates of CYP3A4 and CYP2D6 enzymes. Standardized extracts from nine medicinal plants ( Bauhinia forficata , Cecropia glaziovii , Cimicifuga racemosa , Cynara scolymus , Echinacea sp., Ginkgo biloba , Glycine max , Ilex paraguariensis , and Matricaria recutita ) were evaluated for their potential interactions mediated by CYP3A4 and CYP2D6 enzymes. Among the extracts tested, C. glaziovii (red embaúba) showed the most relevant inhibitory effects of CYP3A4 and CYP2D6 activity, while I. paraguariensis (yerba mate) inhibited CYP3A4 activity. Both extracts were chemically analyzed by UPLC-MS/MS, and these inhibitory effects could lead to clinically potential and relevant interactions with the drug substrates of these isoenzymes.

The purpose of this study was to synthesize a new magnetic material with antimicrobial properties, incorporated into a biopolymer and containing silver nanoparticles (Ag NP) prepared extract of Eugenia umbelliflora as a reducing agent. Silver nanoparticles incorporated into magnetic nanocomposite O-carboxymethylchitosan/y-Fe 2 O 3 /Ag 0 (CMAgE) composite were synthesized using an extract of E. umbelliflora. The antimicrobial activity of the pathogenic microorganism is reported here. The synthesized nanoparticles were also characterized, and quantified by Ag analysis. The minimum inhibitory concentrations (MIC) of CMAgE against Staphylococcus aureus, Escherichia coli, and Candida albicans were 16.5, 1000 and 500 μg/mL, respectively. The results show that these materials have significant synergistic effect on each other. The potential phytotoxic effect of the nanocomposites was evaluated using Cucumis sativus seeds. The positive values for seedling elongation inhibition (SEI) show that CMAgE and methanol extract of Eugenia umbelliflora (Eug) cause growth inhibition at a concentration of 1000 mg/L. The germination index (GI) values of 40% and 80% at 1000 mg/L, for CMAgE and Eug, respectively, showed inhibition of germination. CMAgE and Eug showed cytotoxic effects against Artemia salina nauplii, with LC 50 values of 72.5 μL/mL and < 5.0 μL/mL respectively, after 48 h., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Vochysia bifalcata is a Brazilian native tree commonly used for economic purpose in the reforestation and in the manufacture of products. However, the potential usage of other parts of the plant is usually wasted. Besides, other species of Vochysia are well known for its anti-inflammatory action., Aim of the Study: In this study we evaluate the possible anti-inflammatory activity of the hydroethanolic extract from the leaves of V. bifalcata in models of mice skin inflammation., Materials and Methods: Effects of V. bifalcata were evaluated in croton oil-induced acute and chronic skin inflammation. The role of glucocorticoid receptors in the extract effect was assessed by using a glucocorticoid receptor antagonist and by a specific binding assay. Possible adverse effects were evaluated after multiple treatments with the extract in a skin atrophy model., Results: Topical application of V. bifalcata reduced ear edema formation, cell infiltration and interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels. In the chronic model, besides edema formation and cell infiltration, the extract inhibited epidermal hyperproliferation and Proliferating Cell Nuclear Antigen expression. V. bifalcata seems to act by biding to corticoid receptors, however it did not induce corticoid related undesirable effects., Conclusion: Hydroethanolic extract from leaves of V. bifalcata could be an interesting tool in the search for new anti-inflammatory and antiproliferative agents for the treatment of skin disorders., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Eugenia umbelliflora fruits are an important source of phloroglucinols, as eugenial C and eugenial D, related to antimicrobial activity against Staphylococcus aureus. However, for the establishment of new antimicrobial substances, it is essential to know their stability profile, in view of driving the administration route and the release system development., Methodology: The in silico approaches, based on the Fukui indices and bond dissociation analysis, were performed. Eugenial C and eugenial D, isolated from the green fruits of E. umbelliflora, with purity > 90%, were submitted to stress degradation including: acid (0.5 mM hydrochloric acid) and alkaline (0.5 mM sodium hydroxide) hydrolysis, and oxidation (0.25% hydrogen peroxide), in different periods, monitoring by high-performance liquid chromatography with ultraviolet detector (HPLC-UV). Eugenial C was also submitted to UV-visible radiation (2,400 lux/h) and dry/humid heating (40°C, 75% relative humidity)., Results: In silico studies indicated that both molecules have regions of high susceptibility to nucleophilic and electrophilic attack as well as sites likely to suffer auto-oxidation. Under in vitro tests, both phloroglucinols proved to be very unstable under hydrolysis (eugenial C and D were degraded 23.8% and 89.0% in acid and 78.4% and 97.8% in alkaline conditions, respectively) and oxidation (eugenial C and D degraded 31.9% and 28.6%, respectively), both during 5 min. Eugenial C degraded 12.6% and 63.8% under dry and humid heat, respectively, without photosensitivity., Conclusion: The in vitro stress tests monitored by HPLC-UV were in agreement with in silico degradation prediction. Phloroglucinols could be unstable if administered by oral route and also under environmental conditions demanding a protective release system., (© 2019 John Wiley & Sons, Ltd.)

Ethnopharmacological Relevance: The leaves of Eugenia species are widely used in popular medicine to treat several diseases, such as arthritis, rheumatism and diabetes. Eugenia umbelliflora O. Berg is popularly known in Brazil as "baguaçu", name also conferred to Eugenia jambolana probably due to their apparent similarity. Although the popular use scientifically proved of E. jambolana as anti-diabetes and also as anti-inflammatory, there are only two scientific studies demonstrating anti-ulcer and bactericide activities of E. umbelliflora leaves extract, without reference to its possible anti-inflammatory activity., Aim of the Study: The aim of this study was to show the anti-oxidant and anti-inflammatory activity of the methanol extract obtained from E. umbelliflora leaves (EuL) using in vitro and in vivo protocols., Materials and Methods: The total phenolic content was evaluated using the folin-Ciocalteu colorimetric method and phloroglucinols content by HPLC. The anti-oxidant activity was evaluated by ORAC, ABTS •+ , DPPH, and metal chelation methods. The anti-inflammatory activity was investigated using carrageenan-induced inflammation in the subcutaneous tissue of male Swiss mice orally pre-treated with the EuL (0.3, 1 or 3 mg/kg). The leukocyte influx (optical microscopy) and secretion of chemical mediators (TNF, IL-6, IL-1β and CXCL1, by enzyme-linked immunosorbent assay) were quantified in the inflamed exudate. Histological analysis of the pouches was also performed. The anti-hypersensitive activity was investigated using carrageenan-induced mechanical hypersensitivity and mice were then evaluated using the von Frey filaments. The Open Field test was used to evaluate possible interference of adverse effect of EuL on locomotor activity that could lead to misinterpretation of the hypersensitivity evaluation., Results: The EuL demonstrated important and moderate reducing capacity on ABTS •+ and DPPH assays, respectively, but with slight activity in ORAC test. It reflects low protection against cell damage. The EuL also presented 30% of phenolic compounds. The phloroglucinols content of EuL was 25.9 mg/g, 18.4 mg/g and 16.6 mg/g of eugenial C, eugenial D and eugenial E, respectively. The in vivo analysis of the inflammatory exudate of EuL-treated mice demonstrated reduction in the polymorphonuclear cells (PMN) migration to the inflamed tissue, as well as the reduction of the pro-inflammatory cytokine IL-1β. Histologically, it was observed evident decrease in the oedema, formed essentially by non-haemorrhagic fibrin exudate, as well as PMN infiltrate, when compared with control mice injected with carrageenan. Furthermore, the extract also presented effective reduction of the mechanical hypersensitivity induced by carrageenan without any interference in animal's locomotor and exploratory activity., Conclusions: Together, the results herein obtained show that EuL presented anti-inflammatory activity by decreasing the influx of PMN to the inflamed tissue, as well as the cytokine IL-1β level. This anti-inflammatory activity was also accompanied by significant anti-hypersensitive effect. The effects presented by EuL seem not to be correlated with an antioxidant activity. However other extract chemical compounds could be responsible for its important anti-inflammatory effects., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Certain members of the genus Eugenia are used as foods. One of these species is Eugenia umbelliflora, which is used for its fruits. The aim of the study was to isolate the constituents of the CH2Cl2 fraction obtained from E. umbelliflora O. Berg (Myrtaceae) and also to evaluate its antimicrobial properties. Two new meroterpenoids, eugenial C (3) and eugenial D (4) were isolated from the unripe fruits of E. umbelliflora and their structures established mainly by extensive NMR spectroscopy. In previous studies, the CH2Cl2 extract showed significant antibacterial activity, which can be attributed to meroterpenoids isolated in this study. The compounds eugenials C and D exhibited potent activity against Bacillus subtilis and Staphylococcus aureus and different strains of MRSA and activity similar to those of the antibiotics used in antimicrobial therapies.