In Vitro and In Vivo Antiurolithic Effect of Betulinic Acid Obtained from Citharexylum mirianthum.

The study aimed to investigate the potential antiurolithic effects of extracts, fractions, and betulinic acid (BA) from Citharexylum mirianthum. In vitro analysis involved precipitating calcium oxalate (CaOx) crystals in urine. For in vivo studies, rats were divided into four groups: naive; vehicle; potassium citrate (KC); and BA. Urolithiasis was induced using ethylene glycol and ammonium chloride. After seven days, urine, blood, and kidney tissues were evaluated. The results showed that methanolic extract, hexane, dichloromethane, and ethyl acetate fractions, as well as BA, reduced CaOx crystal formation. In vivo, the vehicle-treated group exhibited reduced urinary volume and Na+ excretion, while the BA-treated group showed restored urinary volume and Na+ excretion similar to the naive group. BA also significantly reduced urinary monohydrate and dihydrate crystal formation, comparable to the KC group. Other urinary parameters remained unchanged, but plasma analysis revealed decreased Na+, K+, and Ca2+ in the KC group. Renal tissue analysis indicated reduced lipid hydroperoxides and increased reduced glutathione in all urolithiasis groups, with unchanged nitrite levels. BA treatment also improved renal corpuscle morphology. Overall, our findings demonstrate that treatment with BA effectively prevented kidney damage induced by EG+AC ingestion, thereby improving renal function in the urolithiasis model.

Cytogenotoxic screening of the natural compound niga-ichigoside F1 from Rubus imperialis (Rosaceae).

Rubus imperialis Chum. Schl. (Rosaceae) have demonstrated some pharmacological activities, including gastroprotective action. However, genotoxic effects of R. imperialis extract was also reported. Since niga-ichigoside F1 (NIF1) is a major compound of this plant species, and which has proven pharmacological properties, it is essential to investigate whether this compound is responsible for the observed toxicity. Therefore, the objective of this study was to analyze the effects of NIF1 on HepG2/C3A cells for possible cytogenotoxicity, cell cycle and apoptosis influence, and expression of genes linked to the DNA damage, cell cycle, cell death, and xenobiotic metabolism. The results showed no cytogenotoxic effects of NIF1 at concentrations between 0.1 and 20 µg/ml. Flow cytometry also showed no cell cycle or apoptosis disturbance. In the gene expression analysis, none of the seven genes investigated showed altered expression. The data indicate that NIF1 has no cytogenotoxic effects, and no interruption of the cell cycle, or induction of apoptosis, apparently not being responsible for the cytotoxic effects observed in the crude extract of R. imperialis.

Vasodilation and Blood Pressure-Lowering Effect of 3-Demethyl-2-Geranyl-4-Prenylbellidifoline, a Xanthone Obtained from Garcinia achachairu, in Hypertensive Rats.

3-demethyl-2-geranyl-4-prenylbellidifoline (DGP), a natural xanthone isolated from Garcinia achachairu, has previously demonstrated remarkable diuretic and renal protective actions. The present study expands its actions on the cardiovascular system by evaluating its vasorelaxant and blood pressure-lowering effects in spontaneously hypertensive rats (SHRs). Aortic endothelium-intact (E+) preparations of SHRs pre-contracted by phenylephrine and exposed to cumulative concentrations of G. achachairu extract, fractions, and DGP exhibited a significant relaxation compared to vehicle-only exposed rings. The non-selective muscarinic receptor antagonist (atropine), the non-selective inhibitor of nitric oxide synthase (L-NAME), as well as the inhibitor of soluble guanylate cyclase (ODQ) altogether avoided DGP-induced relaxation. Tetraethylammonium (small conductance Ca2+-activated K+ channel blocker), 4-aminopyridine (a voltage-dependent K+ channel blocker), and barium chloride (an influx-rectifying K+ channel blocker) significantly reduced DGP capacity to induce relaxation without the interference of glibenclamide (an ATP-sensitive inward rectifier 6.1 and 6.2 K+ channel blocker). Additionally, administration of DGP, 1 mg/kg i.v., decreased the mean, systolic, and diastolic arterial pressures, and the heart rate of SHRs. The natural xanthone DGP showed promising potential as an endothelium-dependent vasorelaxant, operating through the nitric oxide pathway and potassium channels, ultimately significantly reducing blood pressure in hypertensive rats.

Naringen's Effects on Diuresis and Prevention of Urolithiasis in Hypertensive Rats.

This research demonstrates the diuretic effect of naringenin, a flavanone aglycone found in citrus, on spontaneously hypertensive female and male rats (SHR). The data reinforces existing literature findings that male SHR exhibits higher systolic blood pressure than age-matched females. Urine volume assessed over 8 hours was lower when obtained from SHR males than females. When these animals were orally treated with different doses of naringenin (0.1-1 mg/kg), this increased urinary volume in both genders at the highest dose tested. In contrast, the lowest dose promoted a significant natriuretic effect. The other electrolytes analyzed in urine were not significantly altered, except potassium excretion, which was shown to be increased in the urine of SHR males. Furthermore, naringenin showed promise in reducing calcium oxalate (CaOx) crystal formation in an in vitro model, presenting potential advantages in lithiasis prevention.

Dimethyl Cardamonin from Fruits of Campomanesia reitziana D. Legrand Promotes Gastroprotection and Gastric Healing Effects in Rodents.

Campomanesia reitziana D. Legrand (Myrtaceae) displays antiulcer properties when given to rodents. The major active chemical components of C. reitziana are chalcones, including 4',6'-dihydroxy-2'-methoxy-3',5'-dimethylchalcone or dimethyl cardamonin (DMC); therefore, we hypothesized that this compound could have antiulcer effects and the present study aimed to evaluate its gastroprotective and gastric healing properties. DMC was isolated from the fruits of C. reitziana, and its gastroprotective effect was evaluated by ethanol and indomethacin-induced gastric ulcer models in mice (0.1 mg/kg, i.p. and 1 and 3 mg/kg, p.o.). Oxidative stress and inflammatory parameters were analyzed in the gastric tissue. Moreover, its gastric healing effect was evaluated in rats. In addition, the compound's mode of action was evaluated in vivo and in vitro by measuring H+ -K+ -ATPase activity. Finally, the cytotoxic potential of DMC was tested in fibroblasts and human gastric adenocarcinoma cells. The DMC reduced the ethanol-induced gastric ulcer in mice by 77 %, increased the adhered mucus, and reduced lipoperoxides levels. The block of nonprotein sulfhydryls (NP-SH) compounds by pretreatment with N-ethylmaleimide (NEM), the inhibition of nitric oxide synthase with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), or the antagonism of α2 receptor using yohimbine reversed the gastroprotective effects of DMC. Furthermore, DMC reduced the acidity of gastric content in pylorus-ligated rats but did not change H+ , K+ -ATPase (isolated from rabbit) activity in vitro. DMC reduced the lesion area in acetic acid-induced ulcers and decreased myeloperoxidase activity. DMC did not change the viability of fibroblast cells (L929) but reduced the viability of human gastric adenocarcinoma cells (AGS). The results confirmed that DMC could significantly enhance the gastric healing process and prevent ulcers due to improving protective factors on the gastric mucosa and reducing gastric acid secretion.

Cytotoxicity, antinociceptive and gastroproiltective potential of the Abuta selloana Eichler: a fruit plant from Catarinense flora, Brazil.

This study evaluated some biological activities of extracts from Abuta selloana. The gastroprotective potential was determined against ethanol/HCl- and indomethacin-induced gastric ulcers, whereas the antinociceptive effect was evaluated by acetic acid-induced abdominal contortions in mice. The cytotoxicity activity was measured against human cancer cell lines: U251 (glioma), MCF-7 (breast cancer) and NCI-H460 (lung cancer). The radical scavenger potential was verified; and preliminary phytochemical analyses were performed. The phytochemical screening revealed higher levels of phenolic compounds in all extracts. Moreover, the methanolic extract from pulp fruit (MEPu), peel fruit (MEPe), branches (MEB) and leaves (MEL) scavenged the DPPH radical at 100 µg/mL. Besides, only MEL presented GI50 < 30 µg/mL in all tested cells. Besides, MEPu, MEPe, MEB or MEL at 10 mg/kg (i.p) reduced the abdominal contortions at 47.22%, 63.31%, 84.59% and 37.76%, respectively. The MEPu, MEPe, MEB and MEL reduced the ethanol/HCl- and indomethacin- induced ulcer at 250 mg/kg (p.o). In conclusion, A. selloana had interesting biological activities; presenting the leaves as a promising source for compounds with cytotoxic potential, however, further studies should be performed to confirm its antitumoral activity. Besides, the whole plant can be an important source of bioactive compounds associated with gastroprotective and antinociceptive properties.

BChE inhibitors from marine organisms - A review.

Acetylcholine is a key neurotransmitter for brain and muscle function, that has its levels decreased in the brain of people with Alzheimer's Disease (AD). Cholinesterase inhibitors are medicines that decrease the breakdown of acetylcholine, through the inhibition of acetyl- and butyrylcholinesterase enzymes. Despite the fact that butyrylcholinesterase activity rises with the disease, while acetylcholinesterase activity declines, the cholinesterase inhibitors that are currently commercialized inhibit either acetylcholinesterase or both enzymes. The development of selective butyrylcholinesterase inhibitors is a promising strategy in the search for new drugs acting against AD. The marine environment is a rich source of molecules with therapeutic potential, which can provide compounds more easily than traditional methods, with reduced toxicity risks compared to synthetic molecules. This review comprises articles from 2003 to 2020, that assessed the butyrylcholinesterase inhibitory activities from marine organisms, considering their crude extracts and isolated compounds. Part of the articles reported a multi-target activity, inhibiting also other AD-related enzymes. Some of the marine compounds reported here have shown an excellent potential for butyrylcholinesterase inhibition compared to standard inhibitors. Further studies of some compounds reported here may lead to the development of a new treatment for AD.

Diuretic and Antiurolithic Effect of Garcinia humilis (Vahl) C.D. Adams Leaves, a Medicinal Plant Native to South American Countries.

This study evaluated the diuretic and antiurolithic effect of methanolic extract (MEGHL), dichloromethane (DCM), and ethyl acetate (EtA) fractions obtained from the leaves of Garcinia humilis, a medicinal plant known as achachairu and native to South American countries such as Bolivia, Peru, and Brazil. For the analysis of diuretic effect, the female rats received the treatment with MEGHL (3, 10, and 30 mg/kg), DCM (1, 3 and 10 mg/kg), EtA (1, 3, and 10 mg/kg), hydrochlorothiazide (HCTZ; 10 mg/kg), or vehicle (VEH) after an overload of saline solution. At the end 8 h of the experiment, the urinary parameters were measured. Additionally, the antiurolithic effect was analyzed, in which sodium oxalate was added in synthetic urine in the presence or absence of MEGHL, DCM, and EtA in different concentrations (0.1, 0.3, and 1 mg/mL). MEGHL, DCM, and EtA were able to promote 8-h diuresis in rats. MEGHL treatment at dose 30 mg/kg was accompanied by increased urinary Na+ , K+ and Cl- excretion. Moreover, the DCM and EtA fractions treatment increased K+ and Cl- excretion in the urine, although it does not cause any change in Na+ elimination. All the preparations were able to exert an antiurolithic effect in vitro, decreasing the number of calcium oxalate crystals of the monohydrate and dihydrate types. Taking together, the results presented herein showed that the preparations of G. humilis leaves are promising strategies to induce diuresis and antiurolithic effects.

Novel one-pot synthesis of a library of 2-aryloxy-1,4-naphthoquinone derivatives. Determination of antifungal and antibacterial activity.

The development of new antibiotics and inexpensive antifungals is an important field of research. Based on the privileged pharmacophore of lawsone, a series of phenolic ether derivatives of 1,4-naphthoquinone were synthesized easily in one step in reasonable yields. All the new compounds were characterized and tested as potential antifungal and antibacterial agents against Candida albicans, Escherichia coli and Staphylococcus aureus. Compound 55 has significant antibacterial action (as good as or better than the controls) against E. coli and S. aureus. Against C. albicans, compounds 38, 46, 47 and 60 were the best candidates as antifungals. Using a qualitative structure-activity analysis, a correlation between molar mass and antimicrobial activity was identified, regardless of the substituent group on the phenolic moiety, except for 55 and 63, where electronic effects seem more important. An in silico evaluation of the absorption, distribution, metabolism and excretion (ADME) for 37, 50, 55 and 63 was made, indicating that the classic Lipinski's rule of five applies in all cases.

Exotic Medicinal Plants Used in Brazil with Diuretic Properties: A Review.

Several exotic plants (non-native) are used in Brazilian traditional medicine and are known worldwide for their possible diuretic actions. Among the wide variety of plants, standing out Achillea millefolium L., Camellia sinensis L. Kuntze, Crocus sativus L., Hibiscus sabdariffa Linn., Petroselinum crispum (Mill.) A.W. Hill, Taraxacum officinale (L.) Weber, and Urtica dioica L., whose effects have already been the subject of some scientific study. In addition, we also discussed other exotic species in Brazil used popularly, but that still lack scientific studies, like the species Arctium lappa L., Carica papaya L., Catharanthus roseus (L.) G. Don, Centella asiatica (L.) Urb, Citrus aurantium L., and Persea americana Mill. However, generally, clinical studies on these plants are scarce. In this context, different plant species can be designated for further comprehensive studies, therefore, promoting support for developing an effective medicine to induce diuresis.

Diuretic and Natriuretic Effects of Hesperidin, a Flavanone Glycoside, in Female and Male Hypertensive Rats.

Hesperidin (HSP) is a major flavanone glycoside in citrus fruits, including sweet oranges and lemons. It demonstrates numerous pharmacological activities, such as antihypertensive effects and cardiac and kidney tissue protection. However, its effect on modulating renal function has yet to be properly explored. Female and male Wistar spontaneously hypertensive rats (SHR) were used to test the effect of HSP on renal function. The rats were divided into different groups, treated orally, and placed in metabolic cages for urine collection for 8 h. HSP, at doses of 0.3-3 mg/kg, led to an increase in urine volume in both female and male SHR. This effect was associated with increased Na+ elimination (3 mg/kg) without causing any change in K+ excretion or pH and conductivity values. When given HSP in combination with hydrochlorothiazide (HCTZ) or amiloride (AMLR), urine volume and Na+ elimination were significantly increased compared to the group that received only HSP. In relation to K+ excretion, the depleting effect of HCTZ and the sparing of AMLR prevailed in both groups. Pre-treatment with a non-selective cholinergic receptor antagonist, atropine, partially prevented HSP-induced diuresis and natriuresis in male SHR, but this effect was not demonstrated with the non-selective inhibitor of the enzyme cyclooxygenase, indomethacin. This study shows the diuretic action of HSP in hypertensive rats, an activity probably associated with the cholinergic pathway. Although various biological actions have already been defined for HSP, this pioneering research reveals its potential as a diuretic medicine.

Preparations from Campomanesia reitziana reduce the gastrointestinal motility and castor oil-induced diarrhea in a non-opioid and non-dopaminergic pathway in mice and display antimicrobial activity in vitro.

BACKGROUND: This study investigated the antidiarrheal potential of the aqueous extract (AECR) and hydroalcoholic extract of Campomanesia reitziana leaves (HECR), its ethyl acetate (EAF) and dichloromethane fractions (DCMF), and myricitrin isolated from EAF. METHODS: The total phenols and flavonoids were measured, followed by chromatography and myricitrin isolation. The 2,2-diphenyl-1-picryl-hydrazyl scavenger activity, the cytotoxicity, and the effects on LPS-induced nitrite production in intestinal epithelial cells (IEC-6) were quantified. The effect of HECR, EAF, DCMF, and AECR on intestinal motility (IT), gastric emptying (GE), and castor oil-induced diarrhea in mice was determined, as well as its antimicrobial activity. KEY RESULTS: The administration of AECR 10% (10 ml/kg, p.o), but not HECR (300 mg/kg), reduced the GE and IT by 52 and 51%. The EAF and DCMF at 300 mg/kg also reduced IT but did not change GE. Moreover, AECR and EAF, but not DCMF, inhibited the castor oil-induced diarrhea and naloxone or metoclopramide pretreatment did not change these effects. Myricitrin did not change IT and the evacuation index of mice. Finally, the dry residue of AECR inhibited bacterial growth and EAF showed bacteriostatic activity against S. aureus, E. coli, and S. typhimurium and antifungal for C. albicans. However, none of the preparations alter the viability of Giardia spp. trophozoites. CONCLUSIONS: The AECR and EAF can be effective to treat diarrhea acting through opioid- or dopaminergic type 2 receptor-independent mechanisms and by its antimicrobial actions.

Ethyl Acetate Fraction from Leandra dasytricha (A. Gray) Cong. Leaves Promotes Vasodilatation and Reduces Blood Pressure in Normotensive and Hypertensive Rats.

Leandra dasytricha (A. Gray) Cong. is widely distributed in the south of Brazil and is commonly used for cardiovascular and kidney ailments. For this study, we used male Wistar normotensive rats (NTRs) and spontaneously hypertensive rats (SHRs) to verify the effects of the ethyl acetate fraction (EAF) obtained from L. dasytricha leaves on isolated aorta relaxation and in the arterial blood pressure. The EAF was analyzed by LC-DAD-MS, and several components were annotated, including hydrolysable tannins, triterpenes, and O- and C-glycosylated dihydrochalcones, such as the most intense ion peak relative to C-hexosyl phloretin (nothofagin; compound number 13). The EAF caused a concentration and endothelium-dependent relaxation of the aorta in both NTRs and SHRs. This effect was abolished in the endothelium-denuded aorta. L-NAME, a nonselective nitric oxide synthase inhibitor, and ODQ, a soluble guanylate cyclase inhibitor, entirely blocked the EAF-induced relaxation. The presence of a muscarinic receptor antagonist or a cyclooxygenase inhibitor did not alter the EAF's effectiveness in relaxing the aorta. The preincubation with tetraethylammonium, a Ca2+-activated K+ channel blocker, and with 4-aminopyridine, a voltage-dependent K+ channel blocker, significantly interfered with the EAF's relaxation. However, the incubation with glibenclamide, an ATP-sensitive K+ channel blocker, and barium chloride, an inward-rectifier K+ channel blocker, did not interfere with the EAF-induced relaxation. The EAF treatment also caused a dose-dependent decrease in the mean arterial pressure, systolic arterial pressure, and diastolic arterial pressure of both NTRs and SHRs, without significantly interfering with heart rate values. In conclusion, this study demonstrated the EAF-induced vasorelaxant and hypotensive actions, primarily dependent on the endothelium function and mainly with the participation of the nitric oxide and Ca2+-activated and voltage-dependent K+ channels.

Prolonged Diuretic and Renoprotective Effects of a Xanthone Obtained from Garcinia achachairu Rusby in Normotensive and Hypertensive Rats.

The previous study showed that 1,5,8-trihydroxy-4',5'-dimethyl-2H-pyrano(2,3 : 3,2)-4-(3-methylbut-2-enyl) xanthone (TDP) obtained from Garcinia achachairu Rusby (Clusiaceae) branches induces acute diuresis in normotensive (NTR) and spontaneously hypertensive rats (SHR) after 8 h of the experiment. In complementarity, the present study evaluated the prolonged diuretic and renoprotective effects of TDP in both NTR and SHR. The animals received, once a day, oral treatment with TDP (0.1 mg/kg), hydrochlorothiazide (10 mg/kg), or vehicle (VEH; 10 mL/kg). At the end of 7 days, the urine, blood, and kidney samples were collected for biochemical and histological analyzes. The urinary volume of both NTR and SHR after 7 days of treatment with the TDP was significantly increased, associated with augmented urinary electrolyte excretion levels. The treatments did not modify the urinary pH values nor the parameters analyzed in plasma (Na+, K+, Cl-, and Ca2+). Concerning the renal analyzes, when compared with the VEH-treated NTR group, while the activity of the enzymes catalase (CAT) and N-acetyl-ß-D-glucosaminidase (NAG), as well as nitrite levels, were increased, the generation of lipid hydroperoxides and the activity of the enzyme myeloperoxidase (MPO) were unaltered. On the other hand, the activities of superoxide dismutase (SOD) and glutathione S-transferase (GST) and the levels of reduced glutathione (GSH) in kidney homogenates of the SHR group were decreased. However, TDP augmented the levels of GSH and GST activities and reduced the levels of nitrite and the activities of CAT and MPO, when compared with VEH-treated only SHR. Besides, the treatment with TDP alleviated the morphological changes of the renal corpuscle region of SHR. Together, these results revealed the prolonged diuretic effect of TDP and their renal protective effect by improving the antioxidative capacity.

Phytochemical Analysis and Antinociceptive Properties of Hydroalcoholic Extracts of Aleurites moluccanus Bark.

Aleurites moluccanus is used in folk medicine to treat many diseases including pain and inflammatory processes in general. Considering the potential of the leaf extract, evidenced in a previous study, the present study investigates the antinociceptive and anti-inflammatory properties of the hydroethanolic extract of A. moluccanus bark and isolated compounds in animal models of pain. The antinociceptive and anti-inflammatory activities of A. moluccanus bark were evaluated through hyperalgesia induced by carrageenan, PGE2, cytokines, bradykinin, epinephrine, Freund's complete adjuvant, and lipopolysaccharide. Five compounds were isolated from the dichloromethane bark extract: acetyl aleuritolic acid, atraric acid, spruceanol, (5ß,10α)-12-hydroxy-13-methoxy-8,11,13-podocarpatrien-3-one and sonderianol. To optimize the extraction conditions, ethanol 50, 70, and 90°GL were used as extracting solvent, in a 1 : 20 (w/v) drug : solvent ratio, under stirring at room temperature for 4 h. The extracts were named AMC50, AMC70, and AMC90, respectively. These extracts were administered to mice (250 mg/kg, p. o.) with reduced mechanical hyperalgesia activity in the carrageenan test. Of these, AMC90 showed the best results. Pure (5ß,10α)-12-hydroxy-13-methoxy-8,11,13-podocarpatrien-3-one showed a beneficial effect for up to 48 hours after the administration of carrageenan, while acetyl aleuritolic acid was effective only in the first hour. AMC90 was able to reverse the analgesia induced only by prostaglandin E2 and tumor necrosis factor. We also induced hyperalgesia using the lipopolysaccharide and Freund's complete adjuvant models, with positive results. These results support the antinociceptive and anti-inflammatory activity of A. moluccanus bark extract. The observed effects are partly due to the presence of acetyl aleuritolic acid, atraric acid, and (5ß,10α)-12-hydroxy-13-methoxy-8,11,13-podocarpatrien-3-one.

Taxifolin stability: In silico prediction and in vitro degradation with HPLC-UV/UPLC-ESI-MS monitoring.

Taxifolin has a plethora of therapeutic activities and is currently isolated from the stem bark of the tree Larix gmelinni (Dahurian larch). It is a flavonoid of high commercial interest for its use in supplements or in antioxidant-rich functional foods. However, its poor stability and low bioavailability hinder the use of flavonoid in nutritional or pharmaceutical formulations. In this work, taxifolin isolated from the seeds of Mimusops balata, was evaluated by in silico stability prediction studies and in vitro forced degradation studies (acid and alkaline hydrolysis, oxidation, visible/UV radiation, dry/humid heating) monitored by high performance liquid chromatography with ultraviolet detection (HPLC-UV) and ultrahigh performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS). The in silico stability prediction studies indicated the most susceptible regions in the molecule to nucleophilic and electrophilic attacks, as well as the sites susceptible to oxidation. The in vitro forced degradation tests were in agreement with the in silico stability prediction, indicating that taxifolin is extremely unstable (class 1) under alkaline hydrolysis. In addition, taxifolin thermal degradation was increased by humidity. On the other hand, with respect to photosensitivity, taxifolin can be classified as class 4 (stable). Moreover, the alkaline degradation products were characterized by UPLC-ESI-MS/MS as dimers of taxifolin. These results enabled an understanding of the intrinsic lability of taxifolin, contributing to the development of stability-indicating methods, and of appropriate drug release systems, with the aims of preserving its stability and improving its bioavailability.

Taxifolin and gastro-adhesive microparticles containing taxifolin promotes gastric healing in vivo, inhibits Helicobacter pylori in vitro and proton pump reversibly in silico.

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.

1,3,5,6-tetrahydroxyxanthone promotes diuresis, renal protection and antiurolithic properties in normotensive and hypertensive rats.

OBJECTIVES: This study investigated the prolonged diuretic and renal effects of 1,3,5,6- tetrahydroxyxanthone (THX) in rats. METHODS: Normotensive (NTR) and hypertensive rats (SHR) received orally the treatment with THX, hydrochlorothiazide or vehicle (VEH). Urine volume, urinary, plasma and kidney parameters were evaluated daily or at the end of 7 days of the experiment. KEY FINDINGS: The urinary volume of both NTR and SHR were significantly augmented with the THX treatment, an effect associated with increased levels of urinary Na+ and K+, besides a Ca2+-sparing effect. As well, THX decreased the quantity of monohydrate crystals in urines from NTR and SHR when compared with VEH-group. Regarding the renal analyses, the glutathione levels and the activities of superoxide dismutase, glutathione S-transferase and myeloperoxidase in kidney homogenates of the SHR group were decreased. In contrast, the generation of lipid hydroperoxides (LOOH) and catalase activity was significantly increased. THX reduced the content of LOOH and increased nitrite levels in kidney homogenates obtained from SHR. Additionally, THX also augmented the levels of nitrite in the plasma from the SHR group. CONCLUSIONS: Therefore, THX can be highlighted as a natural diuretic agent with renal protective properties and antiurolithic action.

Phenolic profile by HPLC-ESI-MS/MS of six Brazilian Eugenia species and their potential as cholinesterase inhibitors.

Eugenia genus is known for its phenolic metabolites, which may influence the progression of the Alzheimer Disease. This study aimed to evaluate the anticholinesterase effects of six Eugenia species from Brazil. Leaves and stems were submitted to maceration (methanol) and partitioned with dichloromethane and ethyl acetate (EtOAc). Samples were screened (200 µg mL-1) for the inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). HPLC-ESI-MS/MS analysis allowed the identification of twenty-eight phenolic compounds. Regarding the enzymatic activity, EtOAc fraction of E. mattosii exhibited the best results. Chemical and pharmacological aspects of seasonal E. mattosii extracts were evaluated. The extract from leaves collected in the winter was the most effective for AChE, and the extract from leaves collected in the spring was the most effective for BuChE. Correlating the enzymatic results with the chemical data, it was possible to associate these effects to isoquercitrin, quercetin, catechin, epicatechin, procatecuic acid and myricitrin content.

Antiparasitic activity of two Brazilian plants: Eugenia mattosii and Marlierea eugeniopsoides.

Parasitoses are very common throughout the world, generating serious consequences for public health. Leishmaniosis and giardiasis are examples of fairly recurrent, but neglected diseases. Several higher plants have demonstrated promising activity against the parasites. The aim of this study was to evaluate the biological activity of extracts, fractions and isolated compounds from the leaves and stems of two Brazilian plants: Eugenia mattosii and Marlierea eugeniopsoides (Myrtaceae) against Leishmania and Giardia. XTT and the fluorimetric method were used to for this evaluation, respectively. Cytotoxicity was evaluated against HeLa cells. The results demonstrated that chloroform fractions of E. matosii and pinostrobin presented the most pronounced antiparasitic activity, with the CLF-stems being the most effective against Leishmania amazonensis and Leishmania braziliensis. Pinostrobin also presented activity against G. lamblia. Therefore, E. mattosii stems and pinostrobin may be considered possible targets for the continuity of studies against other parasites.