Xanthones are a class of heterocyclic natural products that have been widely studied for their pharmacological potential. In fact, they have been serving as scaffolds for the design of derivatives ...focusing on drug development. One of the main study targets of xanthones is their anticancer activity. Several compounds belonging to this class have already demonstrated cytotoxic and antitumor effects, making it a promising group for further exploration. This review therefore focuses on recently published studies, emphasizing their natural and synthetic sources and describing the main mechanisms of action responsible for the anticancer effect of promising xanthones.
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.
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.
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, 1ml/kg), omeprazole (20mg/kg), or HEMR (1–10mg/kg), twice daily for 7 days. At the end of the treatment, the total ulcer area (mm2) 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.
Oral administration of HEMR (10mg/kg) reduced the gastric ulcer area by 53%, compared to the vehicle group (120.0±8.3mm2), 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 (1–1000µg/ml) was able to scavenge free radical DPPH and promote cytoprotection against H2O2 in fibroblasts at 0.1–100µg/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 2000µg/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.
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.
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Plants belonging to the genus Maytenus (Celastraceae) are routinely used in folk medicine in Brazil and other countries to treat a variety of illnesses, the most common of which are gastric ...disorders. Several studies have reported on the importance of these biological effects, and the chemical substances, mostly terpenoids and flavonoid glycosides, responsible for them. This review summarizes the ethnopharmacological, chemical and pharmacological knowledge of plants of the Maytenus genus, with particular emphasis on those growing in Brazil.
3-demethyl-2-geranyl-4-prenylbellidifoline (DGP), a natural xanthone isolated from
, 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
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
-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.
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.
<!?tlsb=.005w>Caffeic acid and some of its derivatives such as caffeic acid phenetyl ester (CAPE) and octyl caffeate are potent antioxidants which present important anti-inflammatory actions. The ...present study assessed the in vitro and in vivo effects of five caffeic acid derivatives (caffeic acid methyl, ethyl, butyl, octyl and benzyl esters) and compared their actions to those of CAPE. In the model of LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages, the pre-incubation of all derivatives inhibited nitrite accumulation on the supernatant of stimulated cells, with mean IC50 ( M) values of 21.0, 12.0, 8.4, 2.4, 10.7 and 4.80 for methyl, ethyl, butyl, octyl, benzyl and CAPE, respectively. The effects of caffeic acid derivatives seem to be related to the scavenging of NO, as the compounds prevented SNAP-derived nitrite accumulation and decreased iNOS expression. In addition, butyl, octyl and CAPE derivatives significantly inhibited LPS-induced iNOS expression in RAW 264.7 macrophages. Extending the in vitro results, we showed that the pre-treatment of mice with butyl, octyl and CAPE derivatives inhibited carrageenan-induced paw edema and prevented the increase in IL-1 levels in the mouse paw by 30, 24 and 36%, respectively. Butyl, octyl and CAPE derivatives also prevented carrageenan-induced neutrophil influx in the mouse paw by 28, 49 and 31%, respectively. Present results confirm and extend literature data, showing that caffeic acid derivatives exert in vitro and in vivo anti-inflammatory actions, being their actions mediated, at least in part by the scavenging of NO and their ability to modulate iNOS expression and probably that of other inflammatory mediators.
This paper describes the seasonal phytochemical variation and the antimicrobial potential of V. zizanioides roots collected in Brazil. Considering the high levels of chemical constituents and their ...biological activity in dichloromethane fraction, the plants were grown in different seasons and the respective dichloromethane fractions were analyzed by gas chromatography-mass spectrometry. The antimicrobial activity was evaluated against several pathogenic microorganisms by determining the minimum inhibitory concentration (MIC) using the agar dilution method. Yields of dichloromethane fractions from plants collected in the autumn and spring occurred in a higher proportion than in other seasons. Khusimol (2) was isolated by column chromatography and identified by NMR and CG-MS, along with other sesquiterpenes, including β-vetivenene (1), vetiselinenol (3), isovalencenol (4), vetivenic acid (5), α-vetivone (6) and β-vetivone (7). Some extracts showed promising antimicrobial effects, with MICs ranging from 31.25 to 500 μg mL-1. Kushimol was slightly active against the tested microorganisms.
For over a century, ulcer has been a major cause of morbidity and mortality. Its treatment has progressed from vagotomy to proton pump inhibitors. However, the drugs used produce many adverse effects ...and are less effective than they ought to be. Therefore, there is a growing interest in alternative therapies and the use of natural products. This review emphasizes recent studies involving naturally occurring antiulcer metabolites, categorized according to their chemical structure. Both terrestrial and marine sources are included. More than a hundred and fifty different compounds are presented, and where possible, their main mechanisms of action are summarized. Considering that Helicobacter pylori is an important causal factor in the pathogenesis of ulcer disease, an overview of some natural compounds with anti-H. pylori activity is presented.
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-
1
H and
13
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
50
(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
50
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
2
. 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.
The Rubus species has been used in folk medicine to treat several ailments, including infectious and dolorous diseases. In this work we evaluate the phytochemical and analgesic activity of ...hydroalcoholic extract (HE), some fractions (hexane, dichloromethane, ethyl acetate and butanolic), as well as a pure compound denoted as 28-methoxytormentic acid (1) obtained from aerial parts of R. rosaefolius. The compounds were isolated and identified by chromatographic and spectroscopic analysis. The antinociceptive action was evaluated by two well know models of pain in mice: writhing and formalin induced-pain. The results showed that the HE, fractions and compound (1), exhibits potent and dose-related analgesic activity when evaluated in both models of pain. Compound (1), which seems to be the main active principle, showed promising analgesic effects, being several times more potent than aspirin and paracetamol, two well-known analgesic and antiinflammatory drugs used as reference. In the writhing test, it showed an ID50 of 5.10 (3.64—7.14) mg kg−1 and maximum inhibition (MI) of 64.22%. When analyzed by formalin induced-pain test, this compound showed ID50 values of 9.98 (8.08—12.31) and 6.31 (5.07—7.98) mg kg−1 and MI of 59.37 and 90.37% for the first and second phases, respectively. The results justify, at least partially the popular use of this plant for the treatment of dolorous processes, suggesting that 1 is one of the active principles of this plant.
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