Papers by Tania Mari Bellé Bresolin
Ethnopharmmacological relevance: Aleurites moluccana is used in folk medicine to treat pain, feve... more Ethnopharmmacological relevance: Aleurites moluccana is used in folk medicine to treat pain, fever, asthma, hepatitis, gastric ulcer and inflammatory process in general, and the nut oil had been topically applied to treat arthritis and other joint pain, however the seeds are classified as toxic for oral use. Aim: Faced with the need for new alternative to treat the symptoms and modify rheumatoid arthritis (RA) the aim of this work was to evaluate the effects of A. moluccanus' leaves dried extract in rats and mice submitted to complete Freund adjuvant (CFA)-induced RA. Material and methods: Wistar Rats and Swiss mice were submitted to CFA-induced RA in the right hindpaw. They received A. moluccanus extract (orally; p.o.), dexamethasone (subcutaneously), 2″-O-rhamnosylswertisin (p.o.) or vehicle (p.o.), from the 14th day after the CFA injection for up to 8 days. The mechanical hypersensitivity was evaluated using the von Frey filaments and the paw-oedema was measured using a plethysmometer. The rats' injected hindpaw was used to perform the histological analysis. Results: A. moluccanus was able to significantly reduce the mechanical hypersensitivity in both ipsi-and contralateral hindpaws of mice injected with CFA, in a dose dependent manner. Furthermore, the paw-oedema was progressively reduced by A. moluccanus. Similar results were obtained for the positive-control drug dexamethasone and the isolated compound 2″-O-rhamnosylswertisin. Besides the effects mentioned above, the extract was also effective to repair the joint damage in CFA-induced RA rats, including reduction of fibrosis, cartilage degradation and bone erosion scores. Conclusion: These results together with the literature data reinforce the anti-hypersensitivity and anti-inflammatory activity of A. moluccanus extract. Part of the observed effects is due to the presence of the compound 2″-O-rhamnosylswertisin. The fact that the extract acted as a disease modifier point this herbal product as a promisor and safe tool to treat RA and other associated chronic diseases.
Chemico-Biological Interactions
Taxifolin (3,5,7,3,4-pentahydroxy flavanone or dihydroquercetin, Tax) was identified as a gastrop... more Taxifolin (3,5,7,3,4-pentahydroxy flavanone or dihydroquercetin, Tax) was identified as a gastroprotective compound and a gastroadhesive formulation was recently developed to prolong its residence time and release in the stomach. So, the gastric healing effectiveness of Tax and gastro-mucoadhesive microparticles containing Tax (MPTax) against the acetic acid induced-gastric ulcer in rats was investigated in this study. Moreover, the interactions between Tax and H+/K+-ATPase were investigated in silico, and its anti- H. pylori activity was determined in vitro. The oral treatment with MPTax (81.37 mg/kg, containing 12.29 % of Tax) twice a day for seven days reduced the ulcer area by 63%, compared to vehicle-treated group (Veh: 91.9 ± 10.3 mm2). Tax (10 mg/kg, p.o) reduced the ulcer by 40% but with a p=0.07 versus Veh group. Histological analysis confirmed these effects. Tax and MPTax increased the gastric mucin amount, reduced the myeloperoxidase activity, and increased the glutathione reduced content at ulcer site. However, only MPTax decreased the lipoperoxide accumulation at ulcer site. Besides, Tax and MPTax normalize the catalase and glutathione S-transferase activity. Tax showed reversible interaction with H+/K+-ATPase in silico and its anti-H. pylori effects was confirmed (MIC = 625 μg/mL). These results suggest that the antiulcer property of Tax involves the strengthening of the gastric protective factors in parallel to its inhibitory interaction with H+/K+-ATPase and H. pylori. Considering that ulcer healing action displayed by Tax was favored by gastroadhesive microparticles, this approach seems to be promising for its oral delivery to treat acid-peptic diseases.
Revista Fitos, 2020
Este trabalho, de parcerias entre uma Universidade Comunitária e empresas farmacêuticas nacionais... more Este trabalho, de parcerias entre uma Universidade Comunitária e empresas farmacêuticas nacionais relata o desenvolvimento de novos e efetivos fitoterápicos obtidos a partir das folhas de Aleurites mollucanus (Euphorbiaceae), uma espécie exótica, proveniente da Ásia, adaptada no Brasil. Este projeto, embora ainda não tenha alcançado o estágio final de estudos clínicos e registro junto à ANVISA, representa uma experiência relevante a ser analisada à luz das dificuldades e superações no decorrer das etapas que compõem a cadeia de estabelecimento de um novo medicamento fitoterápico no Brasil. Com aprovação nas etapas de estudos não clínicos e na etapa clínica-fase I foram desenvolvidos, em escala piloto, comprimidos a base do extrato seco padronizado de A. moluccanus. Além disso, foram estabelecidas formulações como creme tópico e suspensão oral. A superação dos desafios para padronização do extrato em escala industrial, sob boas práticas de fabricação (BPF) e os aspectos de estabilida...
Química Nova, 2014
Polygala cyparissias is a plant widespread in Southern Latin America. Recently, we demonstrated t... more Polygala cyparissias is a plant widespread in Southern Latin America. Recently, we demonstrated the gastroprotective activity of the extract, as well as for one of the isolated metabolites-1,7-dihydroxy-2,3-methylenedioxyxanthone (MDX). In this study, a HPLC method for the quantification of MDX was validated. The HPLC method was linear (0.5-24 µg mL-1 of MDX) with good accuracy, precision and robustness. The content of MDX in the extracts from whole and different parts of the plant ranged from 0 to 5.4 mg g-1 and the gastroprotective index ranged from 72.1 to 99.1%. Thus, the method might be used for the standardization of the extracts based on the MDX marker.
Acne affects most young people and its topical treatment with antibacterials is associated with i... more Acne affects most young people and its topical treatment with antibacterials is associated with increased bacterial resistance to antibiotics and adverse effects. As an alternative, ozone therapy stands out through the application of ozonized oils. The objective of this work was to raise the scientific evidence about the effectiveness in the treatment of acne, in addition to the techniques of characterization and stability of ozonated oils. This is an exploratory, descriptive study with a quantitative approach, based on the analysis of scientific references in a bibliographic review of the expository type, of the last 20 years. Among the selected references, only four manuscripts reporting clinical studies of ozone therapy, with controversial results. Seven articles with the physicochemical characterization of ozonated oils were found. The major part of manuscripts reported the use of sunflower, sesame and olive oil. The more common techniques used to characterize the ozonation proc...
Natural Product Communications, 2019
Stability tests are essential to assuring herbal derivative quality, especially because of the co... more Stability tests are essential to assuring herbal derivative quality, especially because of the complexity of the herbal matrix. To monitor the stability of Sambucus nigra L. flower tincture, a practical liquid chromatography (LC)-UV method was developed and validated. Rutin, the flower's pharmacopeial marker, in addition to other markers, isoquercitrin and quercetin, were quantified. The last two represent the degradation products of glycosylated flavonoids. In addition, other chromatographic peaks exhibiting typical flavonoid UV absorption profiles (total flavonoids) were also quantified and expressed in rutin equivalents. The method was developed with a reverse phase C18 column, using a gradient mobile phase at 0.7 mL min -1 at 30°C. The herbal drug and tincture obtained by percolation at 60 °C with ethanol 25% (v/v) were submitted to accelerated (40°C/75% RH, 2 months) and long duration (15–30°C, 6 months) studies. The LC-UV method was linear in the ranges of 1–200 μg mL-1 (r...
Journal of Pharmaceutical Analysis, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Biomedicine & Pharmacotherapy, 2018
The increase in fructose consumption in the last decades has an important correlation with the gr... more The increase in fructose consumption in the last decades has an important correlation with the growth of overweight population. Fructose is a monosaccharide found in fruits, vegetables and honey, however, it is widely used in processed food and beverages such as sweeteners. This monosaccharide is metabolized in the liver, so it can produce glucose, lactate, triglycerides, free fatty acids and uric acid, which are responsible for negative effects on the liver and extrahepatic tissues. One effect of the high consumption of fructose is the resistance to Insulin, which appears to be an important issue in the development of metabolic abnormalities observed in animals that were subjected to a high fructose diet. The population and, consequently, the market search for natural sources to manage metabolic abnormalities is increasing, but, adequate scientific proof still is necessary. The Passiflora edulis peel flour (PEPF) is a byproduct of the juice industry, and, represents an important source of fiber and bioactive compounds. The present study investigates the PEPF supplementation (30%) effects on insulin sensitivity, adiposity and metabolic parameters in young rats that were given beverages enriched with 10% of fructose for 8 weeks. Fructose intake induced insulin resistance, increased serum triglycerides levels, growth of fat deposits in the liver and widening of the diameter of adipocytes. In contrast, the group that received PEPF did not present such abnormalities, which could be related to the presence of fiber or bioactive compounds (phenolics compounds, e.g., caffeic acid and isoorientin) in its composition, as identified by analytical methods. Thus, for the first time, it has been demonstrated that PEPF supplementation prevents insulin resistance and hepatic steatosis induced by low-fructose-diet in young rats.
Revista Brasileira de Farmacognosia, 2019
Solvents play important and critical role in natural product chemistry and could generate artefac... more Solvents play important and critical role in natural product chemistry and could generate artefacts during the extraction and purification of metabolites from a biological matrix. This study aimed to correlate the chromatographic profile with biological activity of Ipomoea pes-caprae (L.) R. Br., Convolvulaceae, extracts obtained with hydroethanolic extraction. Thus, aerial parts of I. pes-caprae were extracted with different concentration of ethanol (50, 70 and 90 • GL) and the obtained extracts were analysed by HPLC-UV. HPLC data were studied employing chemometrics to discriminate the samples. Moreover these samples were further characterized by using UPLC-QTOF/MS data. The extracts were also biomonitored through the paw-oedema and spontaneous nociception induced by trypsin in mice. Different chromatographic profiles were obtained and the exploratory analysis clearly revealed higher level of ethyl caffeate in extracts of lower strength of ethanol (50 • GL). This compound was suggested to be an artefact formed by transesterification of caffeoylquinic acid derivatives present in the plant, once it was not observed when other solvents were employed. During the biological assay, only the extract obtained with ethanol 50 • GL presented significant inhibition of inflammation (45 ± 9%) and nociception (24 ± 3%). Ethyl caffeate seems to be linked to the anti-inflammatory effect since it reduced 86 ± 5% of paw-oedema induced by trypsin. Artefacts could contribute to the biological activity of herbal preparations and consequently lead to misinterpretation of the results.
Photodermatology, Photoimmunology & Photomedicine, 2019
Natural products, such as plant-derived extracts and mineral clays, have gained considerable atte... more Natural products, such as plant-derived extracts and mineral clays, have gained considerable attention as skin care agents, especially because of their broad spectrum biological activities, such as ultraviolet radiation (UVR) absorption, and antioxidant, anti-inflammatory, and antiseptic properties. In this sense, the Litchi chinensis leaf ethanolic extract (LC) has been studied by in vitro models, which show a high sun protection factor (SPF), antioxidant properties, and safety. In contrast, mineral clays are natural materials that have been used as potential candidates for association with natural source UVR filters and provide several skin health benefits. This article is protected by copyright. All rights reserved.
Carbohydrate Polymers, 2019
Highlights Taxifolin is better absorbed in the stomach then in the small intestine Taxifolin ... more Highlights Taxifolin is better absorbed in the stomach then in the small intestine Taxifolin loaded into Syloid was amorphous and showed solubility increase Taxifolin-Syloid complex was successfully loaded in chitosan microparticle Chitosan microparticles released taxifolin for 5h in simulated gastric fluid Microparticles adhered to gastric mucosa for 5h avoiding intestinal degradation
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2018
Various medicinal plants are traditionally used in a hepatoprotective manner, like, for example, ... more Various medicinal plants are traditionally used in a hepatoprotective manner, like, for example, the Litchi chinensis leaf infusion that is employed in Chinese medicine as liver tonics to strengthen hepatic functioning. In this context, the present study was designed to evaluate the hepatoprotective and acute toxicological effects of hydroethanolic L. chinensis leaf extract in HepG2 cells and mice. Specifically, the cytotoxicity and hepatoprotective activities of L. chinensis leaf extract were evaluated in HepG2 cells and in vivo against carbon tetrachloride (CCl)-induced acute liver injury. The administration of CCl in mice provokes cell swelling, loss of sinusoid capillary spaces and structural disarrangement of the hepatic lobe, apoptosis and leukocyte infiltration. Further, CCl evokes an increase in serum alanine aminotransferase (ALT), tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels in hepatic tissue. However, Silymarin, the positive control, and the L. chinensis ex...
Talanta, Jan 15, 2017
As the temperature of extraction and processing could impact the biological effects of herbal ext... more As the temperature of extraction and processing could impact the biological effects of herbal extracts, which have wide chemical diversity, the aim of this work were to investigate the thermostability of herbal derivatives of the aerial parts of Sphagneticola trilobata, a reputed medicinal plant; to biomonitor its oral anti-hyperalgesic effect; and to elucidate the degradation pathways of the major components by UHPLC-ESI-QTOF-MS. The lipophilic markers (kaurenoic acid-KA) and hydrophilic markers [chlorogenic acids; measured as total phenolic compounds (PC), expressed in caffeic acid] were also monitored through a validated HPLC-UV methodology, suitable for quality control and stability studies. The soft extract (drug:solvent ratio of 1:10, ethanol 60% v/v) was exposed to high temperatures (50-180°C). PC showed high thermolability (27.4% of degradation at 150°C), compared to KA (16.5%, at 180°C). These results suggest that the loss of oral anti-hyperalgesic activity observed in the ...
Regulatory toxicology and pharmacology : RTP, Jan 28, 2017
We investigated the hepatoprotective effect of methanolic extract from Maytenus robusta leaves in... more We investigated the hepatoprotective effect of methanolic extract from Maytenus robusta leaves in mice and HepG2 cells. The administration of CCl4 in mice promoted a deep destruction of the histological lobular structure and increased the alanine aminotransferase (ALT) serum levels by 46.25% compared with the control group (p < 0.05). The M. robusta extract reduced the hepatic histological changes and normalization the ALT levels. The antioxidant effect of M. robusta in liver tissue promoted the reduction in 31.5% on lipoperoxides levels (p < 0.05), increased by 101.5% the reduced glutathione content (p < 0.05) and increased the activity of superoxide dismutase, catalase, and glutathione-S-transferase by 21.3% (p < 0.05), 49.3%…
Journal of Photochemistry and Photobiology B: Biology, 2017
Actually, there has been an increase in the use of natural products as skin photoprotective agent... more Actually, there has been an increase in the use of natural products as skin photoprotective agents. In this way, the aim of present study was to investigate the L. chinensis leaves extract photochemoprotection potential and photosafety using in vitro methods. The extract cytotoxicity, cytoprotection and photochemoprotection against UVA and UVB radiation were assayed in L929 cells. The DNA damage was evaluated by comet assay. DCFH-DA, SOD, CAT and GSH assays were employed to verify the oxidative stress. We also determined the spectrophotometric Solar Protection Factor (SPF) of the extract. The photosafety was evaluated in red blood cells (RBC). In addition, the HET-CAM and agarose overlay tests were employed to evaluate the irritant potential. The results obtained show that extract is not cytotoxic and present cytoprotective activity against H 2 O 2 and is able to protect the cells against DNA damage induced by UVA and UVB radiation. The extract was able to reduce the ROS production. The SPF obtained was 18.9 at 1 mg/mL. We demonstrate that L. chinensis extract is photosafe and protect RBCs against oxidative damage, and did not induce irritation. Data herein obtained pointed out the potential of L. chinensis extract for photochemoprotection against UVA/UVB radiation and its damaging effects on human skin.
Phytomedicine, 2016
Background: Ethnobotanical studies of the Sapium genus reveal that many species are widely used i... more Background: Ethnobotanical studies of the Sapium genus reveal that many species are widely used in several countries as therapeutic drugs and they are widely used in folk medicine for treatment of different diseases, including skin inflammation. This raises interest in the study of the pharmacological properties and phytochemical composition of these plants. The biological properties of Sapium glandulatum , a native species of southern Brazil, has not been reported in the literature. Purpose: The aim of the present study was to investigate the anti-inflammatory action of the hydroalcoholic extract of Sapium glandulatum (EHSG) leaves in mouse models of acute or chronic skin inflammation. Study design/methods: Topical effects of EHSG were evaluated in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema in the ear. Systemic effects of the extract were studied in a TPA-induced ear edema model, as well as in a carrageenan-induced paw edema model. To gain insight into the mechanism by which EHSG blocked inflammation, we evaluated the role of glucocorticoid receptors (GR) using the TPA-induced ear edema model and also measured specific binding in a glucocorticoid assay. Possible adverse effects of EHSG were evaluated after multiple treatments with the extract in the skin atrophy model on the ear and with the alkaline comet assay. Results: EHSG presented potent anti-inflammatory activity when applied topically in acute and chronic models, inhibiting edema formation and leukocyte migration as well as expression pro-inflammatory cytokines IL-1 β, IL-6 and TNF-α in the tissue. Similar anti-inflammatory effects were found following oral treatment in both ear and paw edema models. Strikingly, the EHSG-induced blockade of leukocyte migration was reversed by mifepristone, a GR antagonist. Additionally, a specific binding assay revealed that ESGH interacts with GR. Multiple treatments with EHSG failed to induce adverse effects when evaluated in the skin atrophy model and bone marrow genotoxicity test. Conclusion: Taken together, our data suggest that EHSG is a potential source of anti-inflammatory tool compounds for the treatment of pro-inflammatory-derived skin diseases, and its mechanism of action may be, at least in part, via the GR pathway.
Pharmaceutical Biology, 2016
Context: The aerial parts of Sphagneticola trilobata (L.) Pruski (Asteraceae) are popularly used ... more Context: The aerial parts of Sphagneticola trilobata (L.) Pruski (Asteraceae) are popularly used to treat topical inflammation, but have not been fully investigated. Objective: To identify polar compounds in S. trilobata extracts and develop a new topical phytomedicine based on the kaurenoic acid (KA) content while monitoring and demonstrating its topical anti-inflammatory activity. Materials and methods: Ethanol spray-dried extract of S. trilobata was analysed by LC-MS while the KA content from semisolid was analysed by LC-UV. The extent of ear edema induced by applying 20 lL of croton oil (2.5%), arachidonic acid (AA; 2 mg/ear) and decanoylphorbol-13-acetate (TPA; 2.5 mg/ear) in mice was used to evaluate the biological activity of the semisolids, which were applied 30 min before the phlogistic agents. Results: Eight phenylpropanoids and four oleanane-type triterpenoid saponins were identified, majority of them reported for the first time in this species, in addition to KA. The semisolid containing 1.0% of dried extract reduced the ear edema induced by croton oil [77.2 6 4.5%; ID50 ¼ 0.49 (0.28-0.87%)], TPA (81.5 6 2.4%) and AA (39.1 6 6.9%), with decreasing effect at higher KA concentrations. This was accompanied by neutrophil migration inhibition as investigated by biochemical and histological assays. Discussion and conclusion: The anti-inflammatory effects were (at least in part) due to the interference in protein kinase C (PKC) activation, AA-cascade products and neutrophil migration inhibition, demonstrating the efficacy of the folk topical usage of this plant. The results support the development of a novel topical anti-inflammatory phytomedicine properly standardized to treat inflammatory dermatological diseases.
Revista Brasileira de Farmacognosia, 2016
The fruits of Litchi chinensis Sonn., Sapindaceae, are renowned for their biological activities. ... more The fruits of Litchi chinensis Sonn., Sapindaceae, are renowned for their biological activities. However, their leaves are poorly explored, although they represent an important source of vegetable raw material with biological properties as antioxidant, anti-inflammatory and antinociceptive. An HPLC method was developed and validated for the simultaneous quantification of epicatechin and procyanidin A2 in the leaf hydroethanolic extract of L. chinensis. The markers and other unidentified components were separated on a Luna Phenomenex C 18 column (250 mm × 4.6 mm, 5 m) with mobile phase composed of acetonitrile: water pH 3.0 (with sulfuric acid), in a gradient run; at 1.0 ml min −1 , 30 • C and 278 nm for detection. The method was linear over an epicatechin and procyanidin A2 concentration range of 10-100 g ml −1. The Limit of Quantification for epicatechin and procyanidin A2 were 1.7 and 2 g ml −1 , respectively. The Relative Standard Deviation (%) values for markers (intra-and inter-day precision studies) were <4.0% and the accuracy was 100 ± 5%. The method was applied to ten samples collected in the state of Santa Catarina (Brazil), which showed 14.8-44.5 and 44.8-69.6 mg g −1 of epicatechin and procyanidin A2, respectively. The proposed method could be a valuable tool for quality assessment of L. chinenis leaves as well as their herbal derivatives.
Revista Brasileira de Farmacognosia, 2016
Aleurites moluccanus L. (Willd.), Euphorbiaceae, is a tree that is native to Indonesia and India.... more Aleurites moluccanus L. (Willd.), Euphorbiaceae, is a tree that is native to Indonesia and India. Various parts of this tree are commonly used in traditional medicine to treat pain, fever, inflammation, hepatitis, gastric ulcer and other ailments. An oral suspension containing dried extract of A. moluccanus was developed and in vivo anti-inflammatory activity was evaluated. Extract 100 and 50 mg/ml loaded oral suspensions were prepared using different suspending agents. The formulations were analysed by their appearance, pH, density, redispersion time, rate of settling, rheological behaviour, distribution of particle size and zeta potential. The dose uniformity was determined by measuring the content of total phenolic compounds expressed in swertisin by a validated HPLC method, as well as the dissolution profile. The stability of oral suspensions was analysed in accelerated studies (40 • C for 6 months). The anti-inflammatory activity was analysed using an in vivo paw oedema model. The taste and odour of the suspensions were shown to be characteristic of the extract. Carmellose sodium (CS; 0.5%) and microcrystalline cellulose and carmellose sodium mixture (MCCS; 1%) showed better physical behaviour. The content of total phenolic compounds was 1.6 mg/ml and approximately 100% of the total phenolic compounds dissolved within 10 min. During the stability study, the formulations were approved by their physical-chemical properties and were shown to lose 12-14% of total phenolic compounds at 40 • C after 6 months. Suspensions containing 50 mg/ml of standardised dried extract inhibited around 35 ± 7.6% of paw oedema. Formulations containing CS showed more anti-inflammatory activity. Suspensions containing dry extract of A. moluccanus were successfully obtained and showed physical and physical-chemistry properties that were appropriate and characteristic of this dosage form, suitable for administration in paediatric and elderly populations, making this an alternative to tablets.
Journal of Medicinal Plants Research, 2014
Gel formulations containing I. pes-caprae spray dried extract (SDE) at 0.11 and 0.18%, were devel... more Gel formulations containing I. pes-caprae spray dried extract (SDE) at 0.11 and 0.18%, were developed with three types of polymers Ce = Cellosize ® QP 100, Ca = Carbopol ® ultrez, and Ar = Aristoflex ® AVC. The pH, sensory characteristics, weight loss and the viscosity profile of gels were analyzed at times (t) t 0 , t 90 and t 180 (24 h, 90 and 180 days after their production, respectively), in ambient temperature (AT = 25 2 C), in the fridge (F = 5 2 C) and in the oven (OV = 40 2 C). Isoquercitrin assay were analyzed by High-performance liquid chromatography (HPLC), after 24h and 360 days (in AT and in the F). None of these formulations nor the spray dried extract (SDE) showed any level of cutaneous irritation in agarose overlay test. The greatest polymers were Ca and Ar in relation to their sensory characteristics and viscosity.
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Papers by Tania Mari Bellé Bresolin