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In a search for new and effective analgesic substances from the Brazilian biodiversity, the present study evaluates the chemical composition and antinociceptive potential of the methanol extract and a pure compound obtained from the seeds of Garcinia achachairu Rusby (Clusiaceae). The methanolic seed extract was directly subjected to purification by column chromatography and the purification was monitored by thin-layer chromatography. The main isolated compound was identified as Guttiferone A by comparison of conventional spectroscopic data (IR, NMR-H and C) to the literature data which was isolated for the first time from this plant. When evaluated in the acetic acid-induced nociception model in mice, the methanolic seed extract had an ID (Inhibitory dose) of 13.1 (11.23-14.91) mg/kg and a maximal inhibition of 72 ± 4%. In the same model, Guttiferone A had an ID of 4.54 (3.29-6.24) mg/kg and a maximal inhibition of 73 ± 5%. The methanolic seed extract and Guttiferone A were also active in pain models induced by formalin, capsaicin, glutamate and carrageenan. These data suggest that the antinociceptive effect of Guttiferone A partly depends on its interference with the synthesis or activity of the cytokine TNF-α, the keratinocyte-derived chemokine KC, and/or PGE. These data support, at least in part, the use of G. achachairu in folk medicine and suggest that this plant is an important source of compounds with a suitable profile for development as new and effective medicinal agents to treat pain processes. [ABSTRACT FROM AUTHOR]

The hexane, chloroform, ethyl acetate and aqueous-soluble fractions from leaves of Maytenus robusta (Celastraceae) were evaluated for their protective actions against ethanol-induced gastric lesions in rats. The treatment with all fractions (150 mg/kg) and omeprazol (30 mg/kg) significantly reduced the lesion index, the total lesion area, and the percentage of lesion, in comparison with the control group (p<0.05). Since the ethyl acetate-soluble fraction was found to be most active in the pylorus ligated model, this fraction was further investigated and resulted in the isolation of triterpene 3,15-dioxo-21α-hydroxy friedelane. The triterpene was evaluated in the HCl/ethanol-induced ulcer model in mice. In this assay, both the groups treated with 3,15-dioxo-21α-hydroxy friedelane and omeprazol, at a dose of 30 mg/kg, presented a significant reduction in lesion index, total lesion area, and in the percentage of the lesion, when compared with the control group (p<0.05). The result suggests that the antiulcer effect observed in the extract and fractions may be attributed, at least in part, to this compound. Further experiments are underway to determine which antiulcer mechanisms involved in gastroprotection. [ABSTRACT FROM AUTHOR]

Epidendrum mosenii is a Brazilian medicinal plant, traditionally used to treat infective and dolorous processes. The present article reports a comparative study of the chemical and pharmacological aspects of different parts and seasons of this plant. The results demonstrate that 24-methylenecycloartanol (1), one of the main active principles present in this plant, is located practically in all the parts and during all seasons, but it is much more concentrated in the stems when collected in spring and summer. The pharmacological results indicate that dichloromethane extracts collected in spring and summer were the most active when evaluated against the writhing test in mice, being several times more potent than some reference drugs used as comparison. Together, the results strongly suggest that the antinociceptive effect of E. mosenii is related, at least in part, to the presence of compound 1, and this finding could be useful for quality control of phytopreparations based on this plant. [ABSTRACT FROM AUTHOR]

A new triterpene 3,15-dioxo-21α-hydroxy friedelane has been isolated from methanol extract of Maytenus robusta and its structure elucidated on the basis of spectral analysis. Stigmasterol, friedelin, friedelanol and 3,15-dioxo friedelane were also obtained. 3,15-dioxo-21α-hydroxy friedelane was analyzed against the writhing test in mice and exhibited potent dose-dependent effects with an ID50 value of 12.5 ± 2.1 µmol kg-1 and a maximal inhibition of 85.90%. It was about 10-fold more active than aspirin and paracetamol, used as reference drugs. [ABSTRACT FROM AUTHOR]

Benzophenones from natural sources and those of synthetic analogues present several reports of potent biological properties, and Guttiferone A represents a promising medicinal natural compound with analgesic and gastroprotective profiles. Considering that there are no reports that assess the genetic toxicity of Guttiferone A, the present study was undertaken to investigate the genotoxic potential of this benzophenone isolated from seeds of Garcinia achachairu in terms of DNA damage in different cells of Swiss albino mice using the comet assay, and its clastogenic/aneugenic effects in bone marrow cells in vivo by the micronucleus test. Cytotoxicity was assessed by scoring polychromatic (PCE) and normochromatic (NCE) erythrocytes ratio. Guttiferone A was administered by oral gavage at doses of 15, 30 and 60 mg/kg. The results showed that Guttiferone A produced genotoxic effects in leukocytes, liver, bone marrow, brain and testicle cells and clastogenic/aneugenic effects in bone marrow erythrocytes of mice. The PCE/NCE ratio indicated no cytotoxicity. Since guttiferone A is harmful to the genetic material we suggest caution in its use by humans. [ABSTRACT FROM AUTHOR]

• A rare glucoside flavonoid (1) was isolated from Citharexylum myrianthum leaves. • Both 1 and its aglycone (2) induce diuresis and natriuresis in rats. • Compound 1, but not 2 , revealed a potassium-sparing effect. • Atropine and indomethacin fully prevented compound 1 and 2 -induced diuresis. Citharexylum myrianthum Cham. belongs to the Verbenaceae family, which is widespread in traditional medicine and has promising therapeutic potential. However, studies about C. myrianthum are rare in the literature. Therefore, this study shows the isolation and identification of the main chemical constituents present in this plant species and its diuretic effect in rats. A glucoside flavonoid (1), 6- O -glycosyl-4′,5-dihydroxy-3′,7-dimethoxyflavone, was isolated from hexane fraction of leaves by precipitation, and its aglycone (2), 5,6,4′-trihydroxy-7,3′-dimethoxyflavone, was obtained by acid hydrolysis. Their structures were characterized by spectroscopic analysis, including 1D and 2D NMR, LC-ESI-MS/MS, and EIMS data in comparison with literature. Compound 1 is a rare example of natural products, featured as a flavonoid with an O -glucoside moiety on the C-6 position. Both compounds 1 and 2 showed a diuretic and natriuretic effect at a dose of 3 mg/kg. Besides, compound 1 revealed a potassium-sparing effect. Atropine (a non-selective muscarinic receptor antagonist) and indomethacin (a cyclooxygenase inhibitor) fully prevented compound 1 and 2 -induced diuresis. For the first time, our study demonstrates the diuretic effect of the flavonoid 1 and its aglycone 2 in rats. [ABSTRACT FROM AUTHOR]

The diuretic effect of 3-demethyl-2-geranyl-4-prenylbellidypholine xanthone (DGP) and 1,5,8-trihydroxy-4′,5′-dimethyl-2H-pyrano(2,3:3,2)-4-(3-methylbut-2-enyl) xanthone (TDP), two natural prenylated xanthones, was investigated in female normotensive (NTR) and spontaneously hypertensive rats (SHR). The rats received a single treatment with DGP, TDP, hydrochlorothiazide (HCTZ), or vehicle (VEH) after an oral load of physiological saline. The effects of DGP and TDP in combination with diuretics of clinical use, as well as with L-NAME, atropine and indomethacin were also explored. The urinary parameters were measured at the end of the 8-h experiment. When orally given to rats, DGP was able to increase the urine volume, at doses of 0.03–0.3 mg/kg, associated with a K+-sparing effect. TDP, in turn, at doses of 0.03–0.3 mg/kg, induced diuresis and saluresis (i.e. augmented urinary levels of Na+ and Cl−) in NTR, while decreased the urinary content of Ca2+ in both NTR and SHR. The combination with HCTZ, but not with furosemide or amiloride, significantly enhanced DGP and TDP induced diuresis, which was accompanied by an increase of the electrolytes content in the urine. Instead, amiloride in combination with DGP or TDP enhanced urinary Na+ and Cl− and decreased K+ elimination. Furthermore, the effect of DGP and TDP were heightened after pretreatment with L-NAME. While atropine was able to prevent DGP-induced diuresis, the pretreatment with indomethacin precluded TDP-induced diuresis. Besides, TDP exerted protective effects against urinary calcium oxalate crystals formation. Taken together, our data revealed the diuretic effect of two xanthones in rats and their possible underlying mode of action. Image 1 [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the diuretic effect of 1,3,5,6-tetrahydroxyxanthone (THX), isolated from preparations of Garcinia achachairu Rusby (Clusiaceae) branches, in rats. Wistar normotensive (NTR) and spontaneously hypertensive rats (SHR) received a single oral treatment with THX, hydrochlorothiazide (HCTZ) or just vehicle (VEH). The effects of THX in combination with diuretics of clinical use, as well as with l -NAME, atropine, and indomethacin were also explored. Cumulative urine volume and urinary parameters were measured at the end of the 8-h or 24-h experiment. THX was able to stimulate 8-h and 24-h diuresis in both NTR and SHR, as well as urinary Na+ and K+ excretion, at a dose of 0.1 mg/kg; while 8-h urinary Cl− levels were only significantly increased in the group of animals treated with THX at the dose of 0.3 mg/kg. In addition, Ca2+ content was reduced in the 24-h urine of THX-treated NTR and SHR, like that obtained in the HCTZ (10 mg/kg) group. The combination with HCTZ or furosemide, but not with amiloride, significantly enhanced THX-induced diuresis. The diuretic effect with HCTZ plus THX treatment was accompanied by an increase of the urinary Na+, K+, and Cl− excretion. On the other hand, when given THX in combination with amiloride, there was a significant increase in Na+ and a decrease in K+ excretion, an effect characteristic of this class of diuretics. Moreover, the diuretic effect of THX was heightened after pretreatment with l -NAME, and its ability to induce diuresis was prevented neither in the presence of indomethacin nor in the presence of atropine. However, the pretreatment with atropine completely avoided the saluretic effect stimulated by THX, suggesting, at least in part, the role of muscarinic receptors in the renal effects of THX disclosed in this study. Image 1 • 1,3,5,6-tetrahydroxyxanthone induces 8-h and 24-h diuresis and saluresis in rats. • 1,3,5,6-tetrahydroxyxanthone decreases urinary excretion of Ca2+. • HCTZ plus xanthone treatment heightened urinary Na+, K+ and Cl− excretion. • Amiloride plus xanthone treatment augmented the excretion of Na+ while spared of K+. • Atropine fully avoided the saluretic effect stimulated by 1,3,5,6-tetrahydroxyxanthone [ABSTRACT FROM AUTHOR]

Rubus imperialis (Rosaceae) is a Brazilian medicinal plant that already exhibited therapeutical perspectives. However, previous studies revealed cellular and/or genetic toxicity of extracts from aerial parts of this plant, as well as other species of the Rubus genus. Being 2β,3β-19α-trihydroxyursolic acid (2B) one of the major compounds of this plant, with proven pharmacological effect, it is important to investigate the biosafety of this isolated compound. Therefore, in the present study, (2B) was tested by several cytogenotoxic endpoints up to 20 μg/ml in human hepatoma HepG2/C3A cells. The test compound did not produce any decreased cell viability, DNA damage, chromosomal mutations, cell cycle changes, or apoptotic effects in the tested cells. Additionally, RT-qPCR analysis revealed the downregulation of CYP3A4 (metabolism), M-TOR (cell death), and CDKN1A (cell cycle) genes. Under the experimental conditions used, the 2B compound did not show cytogenotoxic activity after a single exposure to HepG2/C3A human cells., (© 2024 John Wiley & Sons, Ltd.)

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., (© 2024 John Wiley & Sons Ltd.)

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 Ca 2+ 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.

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 Ca 2+ -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.

Objectives: The diuretic and kidney protective effect of the 3-demethyl-2-geranyl-4-prenylbellidifoline (DGP) were evaluated in rats., Methods: The normotensive (NTR) and spontaneously hypertensive rats (SHR) received, once a day for 7 days, oral treatment with DGP (0.1 mg/kg), hydrochlorothiazide (10 mg/kg), or vehicle (10 ml/kg). Urine, blood, and kidney samples were collected for further analysis., Key Findings: The urine and Na+ elimination content were significantly higher in the groups that received DGP. Furthermore, a Ca2+-sparing action was detected in the urine of DGP-treated groups, which was consistent with the reduction in calcium oxalate crystal formation. Relevantly, the treatment did not change the parameters examined in the blood. Concerning the renal analyses, DGP treatment recovered the morphological damages of the kidney corpuscle area of SHR. In addition to the differences observed between the NTR and SHR vehicle groups, DGP augmented the amount of reduced glutathione and the activity of glutathione S-transferase GST while reducing the catalase and N-acetyl-β-D-glucosaminidase activity and nitrite levels., Conclusion: Together, this study displayed the prolonged diuretic action of DGP and its natriuretic, Ca2+-sparing, and antiurolytic effects. The antioxidative and anti-inflammatory effects of DGP were evidenced in SHR kidneys, opening perspectives for further studies regarding the benefits of this xanthone., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Plants with medicinal potential may also produce adverse effects in humans. This seems to be the case for the species Rubus rosifolius , where preliminary studies demonstrated genotoxic effects attributed to extracts obtained from leaves and stems of this plant using on HepG2/C3A human hepatoma cells as a model. Considering the beneficial properties of this plant as an antidiarrheal, analgesic, antimicrobial, and antihypertensive and its effects in the treatment of gastrointestinal diseases, the present study was developed with the aim of determining the cytotoxic and genotoxic potential of extracts of leaves and stems of R. rosifolius in primary without metabolic competence in human peripheral blood mononuclear cells (PBMC). Cell viability analyses at concentrations of between 0.01 and 100 µg/ml of both extracts did not markedly affect cell viability. In contrast, assessment of the genotoxic potential using the comet assay demonstrated significant damage to DNA within PBMC from a concentration of 10 µg/ml in the stem extract, and a clastogenic/aneugenic response without cytokinesis-block proliferation index (CBPI) alterations at concentrations of 10, 20, or 100 µg/ml for both extracts. Under our experimental conditions, the data obtained demonstrated genotoxic and mutagenic effects attributed to extracts from leaves and stems of R. rosifolius in cells in the absence of hepatic metabolism.

Rubus rosifolius, popularly known as "red mulberry", is a common medicinal plant in southern Brazil and is used as an antidiarrheal, analgesic, antimicrobial and antihypertensive, and to treat stomach diseases. The aim of this study was to analyze the R. rosifolius stem extract (RrSE) for possible in vitro cytotoxic and genotoxic effects, using the comet assay and the micronucleus test to assess genotoxicity, and flow cytometry to assess the impact on the cell cycle and apoptosis in HepG2/C3A cells, in addition to evaluating the expression of genes linked to the induction of DNA damage, cell cycle, apoptosis and metabolism of xenobiotics. The MTT assay observed no cytotoxic effects at concentrations between 0.01 and 100 μg/mL of the extract. However, genotoxic effects occurred in treatments with the extract from a 1 μg/mL concentration. Flow cytometry analysis revealed a significant increase in cells in the G2/M phase after treatment with 10 μg/mL, a decrease in cells in the G0/G1 phase in the treatment with 100 μg/mL, and a significant increase in total apoptotic cells. In the gene expression analysis, an increase in the CYP1A2 xenobiotics metabolizing gene expression was observed. Despite the promising pharmacological effects of R. rosifolius, the results revealed that the RrSE has genotoxic effect and induces apoptosis in HepG2/C3A cells, indicating danger in using this plant extract by humans., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. They also have read the manuscript and approved the submitted manuscript., (Copyright © 2022. Published by Elsevier Ltd.)

Garcinia humilis is popularly used to treat digestive, intestinal and inflammatory illness. We investigated the in vivo and in vitro effects of the methanol extract of G. humilis leaves (MEGh) on inflammatory cells behavior (migration and chemical mediators release) and hypersensitivity. Anti-inflammatory activity was investigated using carrageenan-induced inflammation in the subcutaneous tissue of male Swiss mice treated orally with MEGh (0.1-30 mg/kg). Leucocyte migration, chemical mediators secretion (TNF, IL-1β, IL-6 and CXCL1) and protein exudation were quantified in the exudate. The adhesion molecules expression (CD62L and CD18), chemical mediators and chemotaxis was evaluated using neutrophils or macrophages RAW.264.7 previously treated with the extract (1-100 µg/mL) and activated with LPS. The anti-inflammatory activity of the isolated compounds friedelin, canophyllol, amentoflavone and 3-desmethyl-2-geranyl-4-prenylbellidypholine xanthone (10 μM) was evaluated in macrophages nitric oxide (NO) and TNF release. MEGh, given orally (30 mg/kg), significantly reduced neutrophil migration and decreased TNF, IL-1β and CXCL1 levels, without interfering with protein exudation and IL-6. In vitro, the extract significantly reduced IL-1β and IL-6 levels but did not alter TNF and CXCL1. The MEGh also reduced the expression of CD62L and CD18 and consequently neutrophil chemotaxis. The compounds friedelin, amentoflavone and 3-demethyl-2-geranyl-4-prenylbellidypholine xanthone decreased the secretion of NO and TNF by RAW264.7. The MEGh effects were extended to the pain-like behaviour induced by carrageenan in the mice hindpaw. MEGh presented important anti-inflammatory effects probably due to its activity on neutrophil migration and on important chemical mediator release, scientifically reinforcing its use as medicinal plant.

The present work describes the evaluation of the antidepressant-like activity of the extract, fractions, and compounds obtained from the aerial parts of Solanum capsicoides. The methanolic extract (MESC) obtained by conventional maceration was partitioned with solvents of increasing polarities yielding the respective fractions of hexane (HE), dichloromethane (DCM), and ethyl acetate (EA). The dichloromethane and ethyl acetate fractions were submitted to chromatographic and spectroscopic techniques, leading to the isolation and identification of cilistadiol (1), astragalin (2), and cilistol A (3). In relation to the antidepressant activity, the extract was active against the forced swimming test (FST) at a concentration of 300 mg/kg an ED 50 (deffective dose that reduces 50% of immobility time) of 120.3 (117.3-123.4) mg/kg. Similar values were observed when evaluated in the tail suspension test (TST). In addition, the results showed no influence on motor behavior when evaluated in the open field test (OFT). Based on the observed profile of the MESC, dichloromethane fraction presenting the best profile, in both FST and TST test. Likewise, the fraction also did not present motor impairment when evaluated by the OFT test. Considering that the dichloromethane fraction was more effective, the isolated compounds cilistadiol and cilistol A were evaluated in the same experimental models. In FST, both compounds had a significant antidepressant-like effect, with ED 50 values of 0.22 (0.16-0.28) and 1.03 (0.89-1.18) μmol/kg, respectively. When evaluated in the TST, showed ED 50 values of 0.30 (0.18-0.52) and 1.49 (1.27-1.73) μmol/kg, respectively. The isolated compounds also did not present significant differences in the motor behavior when evaluated on OFT test in comparison with the control group. No toxicological parameters were observed until the highest dose of MESC (2000 mg/kg), demonstrating safety in the use of this plant.

Several studies have suggested that (-)-epicatechin-containing foods and plant extracts benefit conditions that affect the cardiovascular system, such as hypertension and endothelial dysfunction. However, no study was conducted so far to evaluate the potential of this flavonoid on diuretic activity assay. For that, female Wistar normotensive (NTR) and spontaneously hypertensive rats (SHR) received a single oral treatment with (-)-epicatechin (EPI), hydrochlorothiazide (HCTZ) or just vehicle (VEH). The effects of EPI in combination with diuretics for clinical use, as well as with L-NAME, atropine and indomethacin were also explored. Cumulative urine volume, plasma and urinary parameters were evaluated at the end of 8 h experiment. When given to NTR and SHR, at doses of 0.3, 1 and 3 mg/kg, EPI was able to stimulate both diuresis and saluresis (Na + , K + and Cl - ), without interfering with plasma electrolyte content or urinary pH and uric acid values, when compared with VEH-treated only rats. The combination with HCTZ, but not with furosemide or amiloride, successfully strengthened EPI-induced diuresis. This effect was not accompanied by a potentiation of the saluretic effects. On the other hand, when given EPI in combination with amiloride, a significant increase in Cl - excretion and maintenance of the potassium-sparing effects characteristic of this class of diuretics were detected. In addition, the diuretic effect of EPI was enhanced after pretreatment with L-NAME and its action was significantly precluded in the presence of indomethacin, a cyclooxygenase inhibitor. In conclusion, this study shows the diuretic and saluretic properties of EPI in rats, adding another biological activity whose effect may contribute to the different positive actions already described., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

We investigated the hepatoprotective effect of methanolic extract from Maytenus robusta leaves in mice and HepG2 cells. The administration of CCl 4 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% (p < 0.05), and 27.6% (p < 0.05), respectively, compared with the vehicle group. Moreover, the extract reduced hepatic inflammation by diminishing myeloperoxidase activity, TNF and interleukin-6 levels by 29.4% (p < 0.05), 46.1% (p < 0.01), and 59.5% (p < 0.0001), respectively, compared with the vehicle group. The viability of HepG2 cells after incubation with CCl 4 was 29.56± 3.07%, whereas the extract (300 μg/mL) restored the viability to 65.27± 8.75% and aspartate aminotransferase levels to 41.82 ± 4.41 U/L. The extract scavenged DPPH (IC 50  = 14.44 μg/mL) and ABTS (IC 50  = 3.00 μg/mL) radicals and did not produce acute toxicity in mice at 2000 mg/kg. In conclusion, was confirmed the hepatoprotective potential of M. robusta by its antioxidant effects., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Although diuretics have been widely used to treat hypertension along with others cardiovascular and renal disorders, no scientific data have been recorded to support the diuretic properties of Rubus rosaefolius Sm. (Rosaceae), a plant popularly used in Brazil to treat hypertension. Male Wistar rats were orally treated with: vehicle; hydrochlorothiazide; aqueous (AERR) and methanolic (MERR) extracts; dichloromethane (DCM), hexane (HEX) and ethyl acetate (EA) fractions; and the isolated compounds 2α,3β,19α-trihydroxy-urs-12-en-28-oic acid (TUA) and 5-hydroxy-3,6,7,8,4'-pentamethoxyflavone (PMF). At the end of the experiment (after 8 or 24 h), urine volume and other urine or plasma parameters were measured. AERR and MERR, at 100 and 30 mg/kg, respectively, induced diuretic, natriuretic and kaliuretic effect. Additionally, the DCM and HEX, but not EA, at 10 mg/kg, also increased urine volume and Na + and K + excretion. Both active constituents, TUA and PMF, at doses of 1 and 3 mg/kg, showed an augmented diuretic and natriuretic index. While TUA revealed a kaliuretic action, PMF did not interfere with potassium excretion. The compounds increased urinary creatinine, but not urea, levels. TUA was able to decrease calcium excretion, as well as HCTZ, while PMF effect was associated with increased urinary prostaglandin E 2 levels. The non-selective muscarinic receptor antagonist (atropine) prevented TUA-induced diuresis. In addition, indomethacin (a cyclooxygenase inhibitor) and atropine, exhibited the ability to block the diuretic effects prompted by PMF. Our study demonstrates the diuretic effect of extracts, fractions and two natural compounds obtained from R. rosaefolius leaves in rats.

The present study was designed to investigate the gastroprotective effect of xanthones 7-preniljacareubin (PJB), 1,3,5,6-tetrahydroxy xanthone (THX), 3-demethyl-2-geranyl-4-prenylbellidypholine (DGP) and 1,5,8-trihydroxy-4', 5'-dimethyl-2H-pyrane (2,3:3,2)-4-(3-methylbut-2-enyl) xanthone (TDP) isolated of branches from G. achachairu. Their structures were identified through the spectroscopic analysis in comparison with previously reported data. The xanthones were tested at dose of 10 mg/kg against ethanol 60%/HCl 0.3 N-induced gastric ulcer in female swiss mice. The xanthones PJB, THX, DGP and TDP exhibit gastroprotective effect after intraperitoneal treatment, but only the first two displayed anti-ulcer activity after oral administration. Both PJB and THX augmented the antioxidative capacity of tissue by an increase in glutathione levels, as well as were able to prevent an increase in myeloperoxidase activity and tumor necrosis factor level. On the other hand, only THX showed an in vitro free radical scavenger activity, and only PJB avoided mucus depletion on gastric mucosa, which was not associated with an increase in mucin production at glandular level. In addition, PJB and THX inhibited the in vitro H(+)K(+)-ATPase activity at similar range as omeprazole. Together, these results demonstrate the anti-ulcer efficacy of xanthones isolated from G. achachairu, which can contribute for future directions in the development of effective strategies to improve gastric diseases., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Maytenus robusta Reissek (Celastraceae) is traditionally used in Brazilian folk medicine to treat gastric ulcer, as a substitute for M. ilicifolia, which is almost extinct. The gastroprotective properties of M. robusta were demonstrated previously using only preventive approaches, such as acute gastric ulcer models. However, the healing effect of M. robusta in gastric ulcers remains unclear., Aim of the Study: The current study was carried out to investigate the healing effectiveness of M. robusta hydroalcoholic extract (HEMR) from aerial parts in the acetic acid-induced chronic ulcer model and to determine its effect on cell proliferation, scavenging free radicals, and inflammatory and oxidative damage., Material and Methods: To evaluate the healing properties of HEMR in vivo, chronic gastric ulcer was induced in rats by 80% acid acetic. Next, different groups of animals (n=6) were treated orally with vehicle (water plus 1% tween, 1 ml/kg), omeprazole (20mg/kg), or HEMR (1-10mg/kg), twice daily for 7 days. At the end of the treatment, the total ulcer area (mm(2)) was measured and a sample of gastric tissue was taken for histological and histochemical analysis. Evaluation of GSH and LOOH levels, GST, SOD, CAT and MPO activity was also performed at the site of the lesion. In parallel, radical scavenging activity, cytoprotective effect, and cell proliferation activity in fibroblasts (L929 cells) were determined by in vitro trials. The antisecretory properties were evaluated using the pylorus ligature model in rats, and the anti-Helicobacter pylori activity was determined in vitro. Acute toxicity was evaluated by relative organ weight and biochemical parameters in serum. The prokinetic properties were also evaluated in mice., Results: Oral administration of HEMR (10mg/kg) reduced the gastric ulcer area by 53%, compared to the vehicle group (120.0 ± 8.3mm(2)), the regeneration of gastric mucosa was evidenced in histological analysis. Moreover, HEMR treatment increased gastric mucin content and reduced oxidative stress and inflammatory parameters at the site of the ulcer. In vitro, HEMR (1-1000 µg/ml) was able to scavenge free radical DPPH and promote cytoprotection against H2O2 in fibroblasts at 0.1-100 µg/ml. Moreover, HEMR healing properties also were confirmed by enhancement of proliferation and coverage of scratched wounds in fibroblast monolayer. However, HEMR (10mg/kg) by the intraduodenal route did not promote changes in volume, pH, total acidity or pepsin activity in the pylorus ligature model, and HEMR up to 2000 µg/ml also did not present considerable activity against H. pylori. In relation to gastrointestinal motility, HEMR (10mg/kg, p.o) did not provoke alterations. It is also important to mention that oral administration of HEMR did not produce any sign of acute toxicity in animals., Conclusions: The data here obtained show that M. robusta has evident ulcer healing potential, mainly through the strengthening of protective factors of gastric mucosa, such as mucus layer, antioxidant defenses and cell proliferation. Taking into account the advantages of cultivation and harvesting of M. robusta compared to M. ilicifolia, and the evidence presented here, it is plausible to conclude that hydroalcoholic extract obtained from aerial parts of M. robusta is an interesting source for the development of a phytotherapeutic formulation to treat gastric ulcer., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

This study shows the evaluation the antiproliferative effect of the extract, fractions, and uncommon compounds isolated from R. rosaefolius leaves. The compounds were identified by conventional spectroscopic methods such as NMR-H(1) and C(13) and identified as 5,7-dihydroxy-6,8,4'-trimethoxyflavonol (1), 5-hydroxy-3,6,7,8,4'-pentamethoxyflavone (2), and tormentic acid (3). Both hexane and dichloromethane fractions showed selectivity for multidrug-resistant ovary cancer cell line (NCI-ADR/RES) with total growth inhibition values of 11.1 and 12.6 μg/ml, respectively. Compound 1 also showed selective activity against the same cell line (18.8 μg/ml); however, it was especially effective against glioma cells (2.8 μg/ml), suggesting that this compound may be involved with the in vitro antiproliferative action.

Achyrocline satureioides (Lam.) D.C. is a herb native to South America, and its inflorescences are popularly employed to treat inflammatory diseases. Here, the effects of the in vivo actions of the hydroalcoholic extract obtained from inflorescences of A. satureioides on neutrophil trafficking into inflamed tissue were investigated. Male Wistar rats were orally treated with A. satureioides extract, and inflammation was induced one hour later by lipopolysaccharide injection into the subcutaneous tissue. The number of leukocytes and the amount of chemotactic mediators were quantified in the inflammatory exudate, and adhesion molecule and toll-like receptor 4 (TLR-4) expressions and phorbol-myristate-acetate- (PMA-) stimulated oxidative burst were quantified in circulating neutrophils. Leukocyte-endothelial interactions were quantified in the mesentery tissue. Enzymes and tissue morphology of the liver and kidney were evaluated. Treatment with A. satureioides extract reduced neutrophil influx and secretion of leukotriene B4 and CINC-1 in the exudates, the number of rolling and adhered leukocytes in the mesentery postcapillary venules, neutrophil L-selectin, β 2-integrin and TLR-4 expression, and oxidative burst, but did not cause an alteration in the morphology and activities of liver and kidney. Together, the data show that A. satureioides extract inhibits neutrophil functions related to the innate response and does not cause systemic toxicity.

This study evaluates the effect of methanol extracts of three Brazilian medicinal plants on in vitro proliferation of human mononuclear cells. Lymphoproliferation assay was carried out by incubating human peripheral blood mononuclear cells from healthy donors (1 x 10(6) cells/mL) with extracts of Calophyllum brasiliense (roots), Ipomoea pes-caprae (whole plant) and Matayba elaeagnoides (bark), both at 10, 50, 100 and 200 microg/mL, alone or with phytohemagglutinin (PHA, 5 microg/mL), in 96-well microplates at 37 degrees C with 5% CO2, for 72 h. The quantification of cell proliferation assay was performed by blue tetrazolium (MTT) reduction with reading at 540 nm. Cells incubated with only the culture medium were used as negative control for cell proliferation, while the positive control consisted of cells and PHA. The results suggest that the extracts of all three studied plants induce T lymphocyte proliferation. I. pes-caprae showed immunostimulatory activity three times higher than the C. brasiliense extract, while that of the M. elaeagnoides extract was 1.5 times higher. The results demonstrate immunostimulatory effects of these three plants, therefore the continuity of these studies is recommended, in order to determine the active principles.

We developed reproducible protocols for micropropagation, callus culture, and root culture of the medicinal plant Phyllanthus urinaria, P. niruri, P. tenellus, P. corcovadensis, P. caroliniensis, P. stipulatus, and P. fraternus by using single node explants. Genotype-linked differences are visible among the Phyllanthus species concerning shoot culture, callus culture, and root culture growth. The protocols developed for phytochemical screening of callus and root extracts of P. urinaria, P. caroliniensis, P. stipulatus, and P. fraternus have shown the production of sterols and triterpenes. Both compounds are known to account for the antinociceptive activity of the methanolic extracts as glochidone and stigmasterol have strong activity against neurogenic and inflammatory pain. Similarly, methanolic callus extracts of P. tenellus, P. niruri and P. corcovadensis have potent analgesic properties, however phenolics are major compounds isolated from these species. The optimized micropropagation, callus culture, and root culture protocols offer the possibility to use cell/root culture techniques for vegetative propagation and secondary metabolite studies.

A mixture of triterpenes named lupeol (1), alpha-amyrin (2), beta-amyrin (3), and beta-sitosterol (4) has been isolated from the hexane fraction of Matayba elaeagnoides. In addition, scopoletin (5), umbelliferone (6), 3beta-O-D-glycopyranosyl-sitosterol (7) and betulin (8) were isolated from the chloroform fraction. All the structures were identified by spectroscopic techniques in accordance with literature data. The extracts (hydroalcoholic and methanolic) and some fractions (hexane, chloroform, ethyl acetate and butanol) exerted promising antinociceptive effects in mice. In addition, we have tested the pure compound betulin (8). When analyzed against induced pain using the writhing test (3-10 mg kg(-1), i.p.), betulin showed a dose-dependent effect with a calculated ID50 value of 7.74 (6.53-9.17) mg kg(-1) [17.5 (14.7-20.7) micromol kg(-1)] and a maximal inhibition (MI) of 58.3% in relation to the control group. When evaluated in the formalin test (3-10 mg kg(-1), i.p.), this compound inhibited both phases of pain (neurogenic and inflammatory pain), with calculated ID50 values of 18.3 (17.7-18.9) and 8.3 (7.7-8.9) mg kg(-1) [41.5 (38.4-42.7) and 18.8 (17.6-19.9) micromol kg(-1)] and maximal inhibition of 40.8 and 64.39% for the first and second phases, respectively. Using the same models, this compound was several times more active than two clinically used drugs, namely aspirin and paracetamol, suggesting that its main active principle is related to the antinociceptive effect found for the chloroform fraction of M. elaeagnoids barks.

Purpose: The present study aimed to evaluate the possible antispasmodic activity in vitro of methanolic extracts (ME) of six Brazilian medicinal plants., Methods: The extracts were evaluated on isolated guinea-pig ileum and rat duodenum preparations., Results: Rubus imperialis, Maytenus robusta, Ipomoea pes caprae and Epidendrum mosenii did not inhibit the contractile response elicited by acetylcholine on guinea-pig ileum. On the other hand, ME from Calophyllum brasiliense and Cynara scolymus exhibited significant inhibitory activity for the contractile response elicited by acetylcholine on guinea-pig ileum and on rat duodenum in a noncompetitive and concentration-dependent manner., Conclusions: The current study suggests that, of the six medicinal plants evaluated, only the ME of Calophyllum brasiliense and Cynara scolymus show probable antispasmodic activity, confirming and justifying their use in folk medicine for the treatment of intestinal disorders.