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.
Objectives
This study aimed to investigate the diuretic efficacy of myricetin‐3‐O‐α‐rhamnoside (myricitrin), a common naturally occurring plant‐derived flavonoid, obtained from Marlierea ...eugeniopsoides (D.Legrand & Kausel) D.Legrand leaves in rats.
Methods
For that, female Wistar rats were treated by oral route with the different treatments and kept in metaboloic cages for 8‐h or 24‐h experiment. The volume and urinary parameters were measured at the end of the period and compared between groups.
Key findings
When orally given to rats and compared to the vehicle‐treated group, myricitrin (0.3 and 1 mg/kg) was able to stimulate rat diuresis, natriuresis and kaliuresis. The combination myricitrin plus hydrochlorothiazide, but not plus furosemide or amiloride, potentiated the urinary volume when compared to the effects of drugs alone. Besides, the 8‐h renal effects of myricitrin were prevented in the presence of a cyclooxygenase inhibitor and a muscarinic receptor antagonist. However, all groups treated with myricitrin showed a significant reduction in Cl− excretion. In addition, a reduction in the urinary excretion of Cl− and HCO3- was detected on 24‐h analysis, a result that showed to be associated with an increase of these anions in the blood samples from the myricitrin‐treated group. Despite these alterations, no changes in urinary or blood pH were detected.
Conclusions
Taking together, although the results of this study point to the diuretic potential of myricitrin, the reduction in urinary Cl− and HCO3- excretion should be considered in future approaches, as well as for therapeutic applicability.
Cancer is a multi-factorial disease and is a major cause of morbidity and mortality worldwide. Dietary phytochemicals have been used for the treatment of cancer throughout history due to their ...safety, low toxicity, and general availability. Several studies have been performed to elucidate the effects of dietary phytochemicals on cancer metabolism, and many molecular targets of phytochemicals have been discovered. In spite of remarkable progress, their effects on cancer metabolism have not yet been fully clarified. Recent developments in metabolomics allowed to probe much further the metabolism of cancer, highlighting altered metabolic pathways and offering a new powerful tool to investigate cancer disease. In this review, we discuss the main metabolic alterations of cancer cells and the potentiality of phytochemicals as promising modulators of cancer metabolism. We will focus on the application of nuclear magnetic resonance-based metabolomics on breast and hepatocellular cancer cell lines to evaluate the impact of curcumin and resveratrol on cancer metabolome with the aim to demonstrate the premise of this approach to provide useful information for a better understanding of impact of diet components on cancer disease.
The diuretic and kidney protective effect of the 3-demethyl-2-geranyl-4-prenylbellidifoline (DGP) were evaluated in rats.
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.
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.
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.
This study evaluated the effects of flavonoid‐rich fraction from Bauhinia forficata leaves (FRF‐BF), against intestinal toxicity induced by irinotecan. The leaves of this plant are used like tea in ...Brazilian folk medicine, and it is rich in flavonoids, mainly kaempferitrin. First, the chemopreventive effects of FRF‐BF and kaempferitrin were evaluated in intestinal cells (IEC‐6 cells) exposed to irinotecan. Next, the effects were evaluated against irinotecan‐induced mucositis in mice. Lastly, melanoma was induced in C57BL/6 mice to evaluate FRF‐BF interference on irinotecan antitumor activity. The results showed that FRF‐BF and kaempferitrin exert no cytotoxic effects in IEC‐6 cells and confirmed that pretreatment with FRF‐BF and kaempferitrin displays chemoprotective effects against cytotoxicity induced by irinotecan. Interestingly, the FRF‐BF (100 mg/kg, p.o) reduced the intestinal motility in mice and attenuated parameters linked to irinotecan‐induced intestinal mucositis, including diarrhea, histological damage, depletion of duodenal GSH, amount of TNF‐α, and MPO activity in the small intestine. Also, FRF‐BF does not interfere in the antitumor activity of irinotecan and exerted antitumoral activity in murine melanoma. In conclusion, FRF‐BF (100 mg/kg, p.o) presents promising pharmacological potential to prevent and attenuate the severity of intestinal mucositis during chemotherapy treatment, related to the presence of kaempferitrin.
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.
Simaba ferruginea A. St.-Hil., Simaroubaceae, popularly known as “calunga” is a typical subtropical shrub used in Central Brazil mainly for infection, anti-inflammatory, analgesic and gastric ...duodenal-ulcers. It presents in its composition the alkaloid canthin-6-one, an alkaloid indole β-carboxylic.
This study aims to investigate the toxicity, antimicrobial activities of methanol extract of Simaba ferruginea (MESf) and canthin-6-one by using different experimental models.
The present study evaluated the phytochemical analysis by high performance liquid chromatography (HPLC), toxicological potential of MESf and canthin-6-one, using the cytotoxicity, genotoxicity assays with CHO-K1 cells and in vivo acute test in mice. Antimicrobial activity was evaluated by the broth microdilution assays, while the antimicrobial mechanism of action was also assessed using different in vitro bacterial and fungal models.
The HPLC analysis of MESf revealed the presence of canthin-6-one, kaempferol and morin. Differential in vitro toxicities were observed between MESf and canthin-6-one. In the cytotoxicity assay, MESf presented toxicity against CHO-K1, while canthin-6-one did not. In the case of in vitro genotoxicity, both showed to be potentially genotoxic. In the in vivo toxicity study, both MESf (up to 1000 mg/kg) and cantin-6-one (up to 100 mg/kg) caused no toxicologically relevant alterations and are thus considered not to be toxic. MESf was shown to be relatively safe with NOAEL (100 mg/kg) when administrate in mice. Both MESf and canthin-6-one also showed differential antimicrobial activities. On one hand, MESf demonstrated good spectrum of antibacterial action against Staphylococcus aureus (MIC 12.5 μg/mL) and Escherichia coli (MIC 25 μg/mL) and moderate activity against Enterococcus faecalis and Shigella flexneri (MIC 200 μg/mL) but no antifungal effect. On the hand, canthin-6-one showed no antibacterial activity, except against Staphylococcus aureus (100 μg/mL), but potent in vitro fungicidal activity against clinically important Aspergillus niger and Candida species at MFC intervals ranging from 3.12 to 25 μg/mL. Both MESf and canthin-6-one were bacteriostatic in action. MESf antimicrobial mechanism of actions are associated with changes in the permeability of bacterial membranes, evidenced by the increased entry of hydrophobic antibiotic in Shigella flexneri, intense K+ efflux (Shigella flexneri, Staphylococcus aureus) and nucleotides leakage (Staphylococcus aureus). In the antifungal mode of action, canthin-6-one inhibited Saccharomyces cerevisiae growth and including alteration in the cell membrane of Neurospora crassa.
The results of this work demonstrated the differential antimicrobial activities of MESf and its alkaloid isolate, canthin-6-one with antibacterial and antifungal activities, respectively. The present study support the popular use of Simaba ferruginea in combatting afflictions related to bacterial infections, and demonstrate that canthin-6-one as a promising antifungal agent. Both MESf and canthin-6-one are considered non-toxic based on the in vitro toxicological study.
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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.
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