Nanocomposite based on bacterial cellulose and silver nanoparticles improve wound healing without exhibiting toxic effect.

Wound healing is an important and complex process, containing a multifaceted process governed by sequential yet overlapping phases. Certain treatments can optimize local physiological conditions and improve wound healing. Silver nanoparticles (AgNP) are widely known for their antimicrobial activity. On the other hand, bacterial cellulose (BC) films have been used as a dressing that temporarily substitutes the skin, offering many advantages in optimizing wound healing, in addition to being highly biocompatible. Considering the promising activities of AgNP and BC films, the present study aimed to evaluate the wound healing activity in Wistar Hannover rats using a nanocomposite based on bacterial cellulose containing AgNP (AgBC). In a period of 21 days, its influence on the wound area, microbial growth, histopathological parameters, and collagen content were analyzed. In addition, toxicity indicators were assessed, such as weight gain, water consumption, and creatinine and alanine transaminase levels. After 14 days of injury, the animals treated with AgBC showed a significant increase in wound contraction. The treatment with AgBC significantly reduced the number of microbial colonies compared to other treatments in the first 48 h after the injury. At the end of the 21 experimental days, an average wound contraction rate greater than 97% in relation to the initial area was observed, in addition to a significant increase in the amount of collagen fibers at the edge of the wounds, lower scores of necrosis, angiogenesis and inflammation, associated with with no systemic toxicity. Therefore, it is concluded that the combination of preexisting products to form a new nanocomposite based on BC and AgNP amplified the biological activity of these products, increasing the effectiveness of wound healing and minimizing possible toxic effects of silver.

Ruthenium(II) complex with 2-mercaptothiazoline ligand induces selective cytotoxicity involving DNA damage and apoptosis in melanoma cells.

Melanoma is the most aggressive and lethal type of skin cancer due to its characteristics such as high metastatic potential and low response rate to existing treatment modalities. In this way, new drug prototypes are being studied to solve the problem of treating patients with melanoma. Among these, ruthenium-based metallopharmaceuticals may be promising alternatives due to their antitumor characteristics and low systemic toxicity. In this context, the present study evaluated the antineoplastic effect of the ruthenium complex [Ru(mtz)(dppe)2]PF6-2-mercaptothiazoline-di-1,2-bis(diphenylphosphine) ethaneruthenium(II), namely RuMTZ, on human melanoma (A-375) and murine (B16-F10) cells, considering different approaches. Through XTT colorimetric and clonogenic efficiency assays, the complex revealed the selective cytotoxic activity, with the lowest IC50 (0.4 µM) observed for A375 cells. RuMTZ also induced changes in cell morphology, increased cell population in the sub-G0 phase and inhibiting cell migration. The levels of γH2AX and cleaved caspase 3 proteins were increased in both cell lines treated with RuMTZ. These findings indicated that the cytotoxic activity of RuMTZ on melanoma cells is related, at least in part, to the induction of DNA damage and apoptosis. Therefore, RuMTZ exhibited promising antineoplastic activity against melanoma cells.

Efficacy and safety of guttiferone E in melanoma-bearing mice.

Melanoma, an aggressive and potentially fatal skin cancer, is constrained by immunosuppression, resistance, and high toxicity in its treatment. Consequently, there is an urgent need for innovative antineoplastic agents. Therefore, this study investigated the antimelanoma potential of guttiferone E (GE). In an allogeneic murine B16 melanoma model, GE was administered subcutaneously and intraperitoneally. Antitumor evaluation included tumor volume/weight measurements and histopathological and immunohistochemical analysis. Furthermore, the toxicity of the treatments was evaluated through body/organ weights, biochemical parameters, and genotoxicity. Subcutaneous administration of 20 mg/kg of GE resulted in a significant reduction in both tumor volume and weight, effectively suppressing melanoma cell proliferation as evidenced by a decrease in mitotic figures. The tumor growth inhibition rate was equivalent to 54%. This treatment upregulated cleaved caspase-3, indicating apoptosis induction. On the other hand, intraperitoneal administration of GE showed no antimelanoma effect. Remarkably, GE treatments exhibited no toxicity, evidenced by non-significant differences in body weight gain, as well as organ weight, biochemical parameters of nephrotoxicity and hepatotoxicity, and genotoxic damage. This study revealed, for the first time, the efficacy of subcutaneous administration of GE in reducing melanoma, in the absence of toxicity. Furthermore, it was observed that the apoptotic signaling pathway is involved in the antimelanoma property of GE. These findings offer valuable insights for further exploring GE's therapeutic applications in melanoma treatment.

HPLC method for quantifying verbascoside in Stizophyllum perforatum and assessment of verbascoside acute toxicity and antileishmanial activity.

We report the chemical composition of the crude leaf extracts obtained from Stizophyllum perforatum (Cham.) Miers (Bignoniaceae), a simple high-performance liquid chromatography-diode array detection (HPLC-DAD) method based on mangiferin as an internal standard to quantify verbascoside, and the verbascoside acute oral toxicity and antileishmanial activity. HPLC-high-resolution mass spectrometry-DAD (HPLC-HRMS-DAD) analyses of the crude ethanol S. perforatum leaf extracts (CE-1 and CE-2) revealed that verbascoside was the major constituent in both extracts. CE-1 was purified, and verbascoside and casticin, among other compounds, were isolated. The developed HPLC-DAD method was validated and met the required standards. Investigation of the CE-2 acute toxicity indicated a lethal dose (LD50) greater than 2,000 mg/kg of body weight. Both CE-1 and CE-2 exhibited antileishmanial activity. The isolated compounds, verbascoside and casticin, also displayed antileishmanial activity with effective concentrations (IC50) of 6.23 and 24.20 µM against promastigote forms and 3.71 and 18.97 µM against amastigote forms of Leishmania amazonensis, respectively, but they were not cytotoxic to J774A.1 macrophages. Scanning electron microscopy of the L. amazonensis promastigotes showed that the parasites became more rounded and that their plasma membrane was altered in the presence of verbascoside. Additionally, transmission electron microscopy demonstrated that vacuoles emerged, lipids accumulated, kinetoplast size increased, and interstitial extravasation occurred in L. amazonensis promastigotes exposed to verbascoside. These findings suggest that S. perforatum is a promising candidate for further in vivo investigations against L. amazonensis.

Guttiferone E Displays Antineoplastic Activity Against Melanoma Cells.

Guttiferone E (GE) is a benzophenone found in Brazilian red propolis. In the present study, the effect of GE on human (A-375) and murine (B16-F10) melanoma cells was investigated. GE significantly reduced the cellular viability of melanoma cells in a time-dependent manner. In addition, GE demonstrated antiproliferative effect, with IC50 values equivalent to 9.0 and 6.6 µM for A-375 and B16-F10 cells, respectively. The treatment of A-375 cells with GE significantly increased cell populations in G0/G1 phase and decreased those in G2/M phase. Conversely, on B16-F10 cells, GE led to a significant decrease in the populations of cells in G0/G1 phase and concomitantly an increase in the population of cells in phase S. A significantly higher percentage of apoptotic cells was observed in A-375 (43.5%) and B16-F10 (49.9%) cultures after treatment with GE. Treatments with GE caused morphological changes and significant decrease to the melanoma cells' density. GE (10 µM) inhibited the migration of melanoma cells, with a higher rate of inhibition in B16-F10 cells (73.4%) observed. In addition, GE significantly reduced the adhesion of A375 cells, but showed no effect on B16-F10. Treatment with GE did not induce changes in P53 levels in A375 cultures. Molecular docking calculations showed that GE is stable in the active sites of the tubulin dimer with a similar energy to taxol chemotherapy. Taken together, the data suggest that GE has promising antineoplastic potential against melanoma.

Antimelanoma effect of manool in 2D cell cultures and reconstructed human skin models.

Melanoma is the most aggressive and lethal type of skin cancer, characterized by therapeutic resistance. In this context, the present study aimed to investigate the cytotoxic potential of manool, a diterpene from Salvia officinalis L., in human (A375) and murine (B16F10) melanoma cell lines. The analysis of cytotoxicity using the XTT assay showed the lowest IC50 after 48 h of treatment with the manool, being 17.6 and 18.2 µg/ml for A375 and B16F10, respectively. A selective antiproliferative effect of manool was observed on the A375 cells based on the colony formation assay, showing an IC50 equivalent to 5.6 µg/ml. The manool treatments led to 43.5% inhibition of the A375 cell migration at a concentration of 5.0 µg/ml. However, it did not affect cell migration in the B16F10 cells. Cell cycle analysis revealed that the manool interfered in the cell cycle of the A375 cells, blocking the G2/M phase. No changes in the cell cycle were observed in the B16F10 cells. Interestingly, manool did not induce apoptosis in the A375 cells, but apoptosis was observed after treatment of the B16F10 cells. Additionally, manool showed an antimelanoma effect in a reconstructed human skin model. Furthermore, in silico studies, showed that manool is stabilized in the active sites of the tubulin dimer with comparable energy concerning taxol, indicating that both structures can inhibit the proliferation of cancer cells. Altogether, it is concluded that manool, through the modulation of the cell cycle, presents a selective antiproliferative activity and a potential antimelanoma effect.

Genotoxicity and toxicological evaluations of Brazilian red propolis oral ingestion in a preclinical rodent model.

ETHNOPHARMACOLOGICAL RELEVANCE: Brazilian red propolis is a natural product known due to its medicinal properties. The efficacy of this natural resin has been proved; however, few studies report the safety of its oral use. Some toxic effects of natural products may not be expressed in traditional use, and preclinical studies are necessary to guarantee their safety. Health regulatory agency currently requires these non-clinical studies to develop drugs and herbal medicines, including genotoxic and oral toxicity tests. AIM OF THE STUDY: Accomplish the preclinical toxicity studies of Brazilian red propolis extract (BRP) in rodents, including genotoxicity, acute and sub-chronic toxicities. MATERIAL AND METHODS: Genotoxicity assays followed the erythrocyte micronucleus test protocol in a range of 500-2000 mg/kg BRP oral treatment on male Swiss mice. After an up-and-down procedure, acute oral toxicity (single dose) was performed on female Wistar Hannover rats, reaching a 2000 mg/kg BRP oral gavage concentration. Animals were monitored periodically until 14 days and euthanized for a macroscopic necropsy analysis. The sub-chronic oral toxicity test (90 days) was achieved with 1000 mg/kg of BRP on Wistar Hannover rats (males/females). Animals were monitored to evaluated behavioral and biometrical changes, then were euthanized to perfomed hematological, biochemical, and histopathological analyses. RESULTS: No genotoxic effect of the BRP was detected. The acute toxicity indicated no toxicity of a single oral dose of 2000 mg/kg of BRP. The long-term oral toxicity performed with 1000 mg/kg of BRP altered water and food intake and the biometrics, hematological and biochemical parameters. Biochemical alterations in hepatic and renal parameters were detected only in the males. Despite the detection of biochemical alterations, no histopathological changes were detected in the organs of any group. CONCLUSIONS: BRP, at a higher dose, showed no signs of immediate toxicity. However, the obtained results suggest that the chemical composition and the intake of higher doses deserve special attention regarding possible toxicity.

Red propolis exhibits chemopreventive effect associated with antiproliferative and anti-inflammatory activities.

INTRODUCTION: Red propolis is synthetized from exudates of Dalbergia ecastophyllum (L) Taub. and Symphonia globulifera L.f., presents isoflavones, guttiferone E, xanthochymol, and oblongifolin B and has anti-inflammatory, antioxidant, and antiproliferative activities. OBJECTIVES: This study aimed to evaluate the antigenotoxic and anticarcinogenic potential of red propolis hydroalcoholic extract (RPHE) in rodents. METHODS: The influence of RPHE in doxorubicin (DXR)-induced genotoxicity was investigated through the micronucleus test in Swiss mice. Blood samples were also collected to investigate oxidative stress, hepatotoxicity, and nephrotoxicity. Was investigated the influence of RPHE in 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci, as well as its influence in proliferating cell nuclear antigen (PCNA) and the cyclooxygenase-2 (COX-2) expression in colon of rats, by immunohistochemistry. RESULTS: The results showed that RPHE (48 mg/kg) reduced DXR-induced genotoxicity. Animals treated with DXR showed significantly lower GSH serum levels in comparison to the negative control. RPHE treatments did not attenuated significantly the DXR-induced GSH depletion. No difference was observed in cytotoxicity parameters of mice hematopoietic tissues between the treatment groups, as well as the biochemical parameters of hepatotoxicity and nephrotoxicity. RPHE (12 mg/kg) reduced the DMH-induced carcinogenicity and toxicity, as well as DMH-induced PCNA and COX-2 expression in colon tissue. CONCLUSION: Therefore, was observed that the RPHE has chemopreventive effect, associated to antiproliferative and anti-inflammatory activities.

In vitro evaluation of the antibacterial and cytotoxic activities of the Euclea natalensis crude extract and fractions against oral infection agents.

OBJECTIVE: This study aimed (i) to evaluate the antibacterial and cytotoxic activities of the crude extract and fractions obtained from Euclea natalensis A.D.C. roots against bacteria that cause periodontal disease and caries and (ii) to identify the isolated compounds. DESIGN: The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of the extract and fractions were determined by the microplate dilution assay. The cytotoxicity of the extract and fractions was evaluated by using the XTT colorimetric assay and normal human fibroblast cells (GM07492A, lung fibroblasts). The compounds present in the most promising fraction were determined by qualitative analysis through liquid chromatography coupled to mass spectrometry (HPLC-MS-ESI). RESULTS: The MIC results ranged from 25 to > 400 µg/mL for the extract and from 1.56 to > 400 µg/mL for the fractions. To evaluate cytotoxicity, the tested concentrations of the extract and fractions ranged from 19.5 to 2500 µg/mL; IC50 values between 625 and 1250 µg/mL were obtained. Analysis of the main bioactive fraction by HPLC-MS-ESI identified phenolic acids, coumarins, naphthoquinones, lignans, and fatty acids. CONCLUSIONS: The E. natalensis root extract and fractions displayed good antibacterial activity against periodontal pathogenic and cariogenic bacteria. The antibacterial activity may be due to compounds present in the extract and fractions, which also showed low cytotoxicity to normal human cells. These data are relevant and encourage further research into this plant species, which may contribute to the discovery of new herbal medicines that will help to mitigate the problems caused by oral pathogenic bacteria.

Ozonated oil is effective at killing Candida species and Streptococcus mutans biofilm-derived cells under aerobic and microaerobic conditions.

This study explores the growth of bacterial, fungal, and interkingdom biofilms under aerobiosis or microaerobic conditions and the effect of ozonated sunflower oil on these biofilms. Candida species and Streptococcus mutans were used to study this interaction due to their importance in oral health and disease as these microorganisms display a synergistic relationship that manifests in the onset of caries and tooth decay. Biofilms were developed in a 96-well microtiter plate at 37ºC for 24 h, under aerobiosis or microaerobic conditions, and treated with ozonated oil for 5 to 120 min. All the microorganisms formed biofilms in both oxygenation conditions. Scanning electron microscopy was used to visualize biofilm morphology. Rodent experiments were performed to verify the oil-related toxicity and its efficacy in oral candidiasis. The growth of all Candida species was increased when co-cultured with S. mutans, whilst the growth of bacterium was greater only when co-cultured with C. krusei and C. orthopsilosis under aerobiosis and microaerobic conditions, respectively. Regardless of the oxygenation condition, ozonated oil significantly reduced the viability of all the tested biofilms and infected mice, showing remarkable microbicidal activity as corroborated with confocal microscopy and minimal toxicity. Thus, ozonated oil therapy can be explored as a strategy to control diseases associated with these biofilms especially in the oral cavity. LAY SUMMARY: We demonstrated that ozonated sunflower oil is effective at killing the biofilms formed by Candida species, by the bacterium Streptococcus mutans, or by both micoorganisms that can interact in the oral cavity, making it a potential therapeutic option for the treatment of these infections.

Pharmacokinetic study of AmB-NP-GR: A new granule form with amphotericin B to treat leishmaniasis and fungal infections.

Amphotericin B (AmB) has been the gold standard to treat systemic fungal infections. The use of AmB is restricted to hospitals because it poses several risks, mainly risks related to its high nephrotoxicity. Given the importance of this drug in medicine, new therapeutics and AmB formulations with nanotechnological improvements are required and could bring many benefits to patients. A new drug formulation with gastro-resistant coated granules has been proposed. The lipid-based system containing AmB was produced and used as raw material in the granulation/coated process. The new developed formulation (AmB-NP-GR) was characterized by optical microscopy, granulometry, and atomic force microscopy (AFM) after disintegration test. AmB-NP-GR showed granular shape, with most granules measured between 250 and 500 µm (37 ± 7% w/w). The AFM images indicated that the granule formulation should disintegrate in the intestine, to release the lipid-based carriers, making them available for absorption and allowing them to reach the blood circulation. The developed formulation was administered to rats in a single dose of 4.0 or 8.0 mg kg-1 and the pharmacokinetics was studied. The samples were analyzed by liquid chromatography coupled to mass spectrometry. Before the pharmacokinetic studies were conducted, the bioanalytical method was validated according to the EMA guideline and all evaluated parameters agreed with this guideline. The pharmacokinetic results showed that Cmax was similar for both doses and that tmax was reached at 4-12 h for dose of 4.0 mg kg-1 and 4 h for dose of 8.0 mg kg-1. The half-life related to the dose of 8.0 mg kg-1 increased significantly compared to the dose of 4.0 mg kg-1 (an increase of more than 3 times). In addition, the mean residence time related to the dose of 8.0 mg kg-1 was 4 times higher than for the lower dose. The clearance value showed to be higher for the lower dose. Together, these results provide important conclusions for experimental design of other in vivo safety and efficacy studies of AmB-NP-GR.

Toxicological and chemoprevention studies of Dalbergia ecastaphyllum (L.) Taub. stem, the botanical source of Brazilian red propolis.

OBJECTIVES: Dalbergia ecastaphyllum (L.) Taub. is a semi-prostrate species associated with estuaries, mangroves and dunes. This plant species has great ecological and economic importance, especially concerning apiculture pasture and Brazilian red propolis production. In this study, non-clinical toxicological evaluations of the hydroalcoholic extract of D. ecastaphyllum stems (DEHE), the resin production source, were conducted. In addition, the action of DEHE on genomic instability and colon carcinogenesis was investigated. METHODS AND RESULTS: The extract's chemical profile was analysed by HPLC, and medicarpin, vestitol and neovestitol were found as major compounds. DEHE showed an IC50 equivalent to 373.2 µg/ml and LC50 equal 24.4 mg/L, when evaluated using the XTT colorimetric test and the zebrafish acute toxicity assay, respectively. DEHE was neither genotoxic nor cytotoxic at the highest dose, 2000 mg/kg, by peripheral blood micronucleus test. The treatments DEHE (6 and 24 mg/kg) led to the reduction of micronuclei induced by doxorubicin (DXR) in mice. Furthermore, significantly higher serum levels of reduced glutathione were observed in animals treated with DEHE plus DXR, revealing an antioxidant effect. Treatments with DEHE (48 mg/kg) led to a significant reduction in pre-neoplastic lesions induced by the 1,2-dimethylhydrazine (DMH) carcinogen in the rat colon. Immunohistochemical analysis revealed significantly lower levels of expression of COX-2 (86%) and PCNA (83%) in the colon of rats treated with DEHE plus DMH, concerning those treated with the carcinogen. CONCLUSIONS: These results indicate the involvement of anti-inflammatory and antiproliferative pathways in the protective effect of DEHE.

Antitumor activity of solamargine in mouse melanoma model: relevance to clinical safety.

Melanoma is the most aggressive type of skin cancer, and thus it is important to develop new drugs for its treatment. The present study aimed to examine the antitumor effects of solamargine a major alkaloid heteroside present in Solanum lycocarpum fruit. In addition solamargine was incorporated into nanoparticles (NP) of yttrium vanadate functionalized with 3-chloropropyltrimethoxysilane (YVO4:Eu3+:CPTES:SM) to determine antitumor activity. The anti-melanoma assessment was performed using a syngeneic mouse melanoma model B16F10 cell line. In addition, systemic toxicity, nephrotoxic, and genotoxic parameters were assessed. Solamargine, at doses of 5 or 10 mg/kg/day administered subcutaneously to male C57BL/6 mice for 5 days, decreased tumor size and frequency of mitoses in tumor tissue, indicative of a decrease in cell proliferation. Treatments with YVO4:Eu3+:CPTES:SM significantly reduced the number of mitoses in tumor tissue, associated with no change in tumor size. There were no apparent signs of systemic toxicity, nephrotoxicity, and genotoxicity initiated by treatments either with solamargine alone or plant alkaloid incorporated into NP. The animals treated with YVO4:Eu3+:CPTES:SM exhibited significant increase in spleen weight accompanied by no apparent histological changes in all tissues examined. In addition, animals treated with solamargine (10 mg/kg/day) and YVO4:Eu3+:CPTES:SM demonstrated significant reduction in hepatic DNA damage which was induced by tumor growth. Therefore, data suggest that solamargine may be considered a promising candidate in cancer therapy with no apparent toxic effects.

Phenothiazinium dyes for photodynamic treatment present lower environmental risk compared to a formulation of trifloxystrobin and tebuconazole.

The widespread use of conventional chemical antifungal agents has led to worldwide concern regarding the selection of resistant isolates. In this scenario, antimicrobial photodynamic treatment (APDT) has emerged as a promising alternative to overcome this issue. The technique is based on the use of a photosensitizer (PS) and light in the presence of molecular oxygen. Under these conditions, the PS generates reactive oxygen species which damage the biomolecules of the target organism leading to cell death. The great potential of APDT against plant-pathogenic fungi has already been reported both in vitro and in planta, indicating this control measure has the potential to be widely used in crop plants. However, there is a lack of studies on environmental risk with ecotoxicological assessment of PSs used in APDT. Therefore, this study aimed to evaluate the environmental toxicity of four phenothiazinium PSs: i) methylene blue (MB), ii) new methylene blue N (NMBN), iii) toluidine blue O (TBO), and iv) dimethylmethylene blue (DMMB) and also of the commercial antifungal NATIVO®, a mixture of trifloxystrobin and tebuconazole. The experiments were performed with Daphnia similis neonates and zebrafish embryos. Our results showed that the PSs tested had different levels of toxicity, with MB being the less toxic and DMMB being the most. Nonetheless, the environmental toxicity of these PSs were lower when compared to that of NATIVO®. Furthermore, estimates of bioconcentration and of biotransformation half-life indicated that the PSs are environmentally safer than NATIVO®. Taken together, our results show that the toxicity associated with phenothiazinium PSs would not constitute an impediment to their use in APDT. Therefore, APDT is a promising approach to control plant-pathogenic fungi with reduced risk for selecting resistant isolates and lower environmental impacts when compared to commonly used antifungal agents.

Hypericin, a medicinal compound from St. John's Wort, inhibits genotoxicity induced by mutagenic agents in V79 cells.

This study evaluated the cytotoxic, genotoxic, and the modulatory effects on DNA damage of hypericin in Chinese hamster lung fibroblasts (V79 cells). The hypericin is a natural polycyclic quinone, mainly extracted from St. John's Wort (Hypericum perforatum L.). Along with hyperforin, the hypericins are responsible for the antidepressant activity of St. John's Wort. Cytotoxicity was assessed by the XTT colorimetric assay and the nuclear division index (NDI). The genotoxic activity was studied by the micronucleus test at concentrations of 30, 60, 120, and 240 µg/mL. Mutagenic agents, methyl methanesulfonate (MMS, 44 µg/mL), doxorubicin (DXR, 0.5 µg/mL), and etoposide (VP16, 1 µg/mL) were used in combination with different concentrations of hypericin in order to evaluate the modulatory effect on DNA damage. Results showed that the hypericin was cytotoxic at concentrations above 156.2 µg/mL and genotoxic above 120 µg/mL. The hypericin significantly reduced DNA damage frequency induced by DXR, at concentrations of 30 and 60 µg/mL, and MMS at a concentration of 30 µg/mL, but was unable to reduce damage when combined with VP-16. These results demonstrate the non-photoactivated hypericin toxicological safety limits, its protective effect on DNA damage and provide a basis for future studies that may characterize better its chemopreventive mechanism.

Watermelon Reduces the Toxicity of Cisplatin Treatment in C57BL/6 Mice with Induced Melanoma.

An alternative to reduce the undesirable effects of antineoplastic agents has been the combination of classical treatments with nutritional strategies aimed at reducing systemic toxicity without decreasing the antitumor activity of already used drugs. Within this context, this study evaluated the possible reduction of toxicity when cisplatin treatment is combined with watermelon pulp juice supplementation in C57BL/6 mice with melanoma. Watermelon is a fruit rich in vitamins, minerals, proteins, lycopene, carotene, and xanthophylls, which has shown effectiveness in the treatment of cardiovascular diseases, weight loss, urinary infections, gout, hypertension, and mutagenicity. The following parameters were analyzed: animal survival, bone marrow genotoxicity, serum creatinine and urea, histopathological features of the tumor tissue, tumor weight and volume, and weight of non-tumor tissues (kidney, liver, spleen, heart, and lung). The results showed that watermelon had no antitumor effect but reduced the toxicity of cisplatin, as demonstrated by an increase in the number of bone marrow cells and a decrease in serum creatinine and urea levels. The data suggest that watermelon pulp juice can be an alternative for reducing the side effects of antineoplastic agents.

Chemical study of Adenocalymma axillarum crude leaf extract and isolated compounds

Abstract Adenocalymma axillarum (K.Schum.) L.G. Lohmann is a liana belonging to the family Bignoniaceae. In traditional medicine, the genus Adenocalymma is used to treat fever, skin ailments, and body, joint, and facial muscle pains, and it is also applied as cosmetic. Biological assays conducted with the A. axillarum crude leaf ethanol extract have indicated leishmanicidal activity and absence of cytotoxicity. This study aimed to analyze the A. axillarum leaf ethanol crude extract by high-performance liquid chromatography-high-resolution mass spectrometry- diode array detector (HPLC-HRMS-DAD) and to evaluate the leishmanicidal and cytotoxic activities of this crude extract, its fractions, and isolated compounds. HPLC-HRMS-DAD analysis of this extract revealed that it consisted mainly of flavonoids, with nine major compounds. Extract purification yielded 4-hydroxy-N-methylproline, 6-β-hydroxyipolamiide, quercetin-3-O-robinobioside, hyperin, isorhamnetin-3-O-robinobioside, and 3'-O-methylhyperin, which were identified by Nuclear Magnetic Resonance. The isolated compounds were inactive against Leishmania amazonensis promastigotes and human lung fibroblast cells.

Hexane Extract from Tradescantia pallida (Rose) D.R. Hunt (Commelinaceae): Its Volatile Constituents and in vitro Antifungal and Cytotoxic Activities

Abstract: Tradescantia pallida (Commelinaceae) has shown promising antibacterial, antioxidant and anticancer activities. This study aimed at extracting hexane from T. pallida (HE-TP) aerial parts to identify and quantify its volatile compounds by GC-MS and GC-FID and at evaluating its antifungal and antiproliferative activities. (E)-4-Methoxycynnamic acid (50.2%), 2,5-di-tert-butyl-1,4-benzoquinone (13.7%) and epijuvabione (10.4%) were the major components identified in HE-TP. HE-TP was incorporated into PDA medium, poured into Petri dishes and transferred to mycelial discs of pathogens. Percentages of inhibition of fungal growth were determined. HE-TP showed remarkable antifungal potential at the dose of 400 µL since it inhibited 100% of Penicillium digitatum and Sclerotinia sclerotiorum growth and 92.6% of Rhizopus stolonifer growth. Besides, HE-TP demonstrated cytotoxic activity against different human tumor cell lines with IC50 values between 231.43 and 428.76 µg/mL. Therefore, results showed that HE-TP has potential against fungi of agronomic interest and tumor cells.

Anti-melanoma effect of ruthenium(II)-diphosphine complexes containing naphthoquinone ligand.

The use of natural products as potential ligands has been explored as a strategy in the development of metal-based chemotherapy. Since ruthenium complexes are promising alternatives to traditional antitumor agents, this study evaluated the anti-melanoma potential of two ruthenium(II) complexes containing the naphthoquinone ligands lapachol (lap), [Ru(lap)(dppm)2]PF6, and lawsone (law), [Ru(law)(dppm)2]PF6, in addition to the bis(diphenylphosphino)methane (dppm) ligand, referred to as complexes (1) and (2), respectively, using a syngeneic murine melanoma model. Activation of the apoptotic pathway by the treatments was assessed by immunohistochemistry in tumor tissue. Additionally, toxicity of the treatments was evaluated by variation in body and organ weight, quantification of biochemical indicators of renal damage, and genotoxicity in bone marrow and hepatocytes. First, the antiproliferative activity of (1) and (2) was observed in B16F10 cells, with IC50 values of 2.78 and 1.68 µM, respectively. The results obtained in mice showed that, unlike complex (1), (2) possesses significant anti-melanoma activity demonstrated by a reduction in tumor volume and mass (88.42%), as well as in mitosis frequency (83.86%). Additionally, complex (2) increased the levels of cleaved caspase-3, inducing tumor cell apoptosis. When compared to the metallodrug cisplatin, complex (2) exhibited similar anti-melanoma activity and lower toxicity considering all parameters evaluated. In silico studies demonstrated no difference in the binding energy of the naphthoquinone complex between complexes (1) and (2). However, the complex containing the lawsone ligand has a lower molar volume, which may be important for interactions with minor DNA grooves. The present results demonstrate the antitumor efficiency of complex (2) and a significantly lower systemic toxicity compared to cisplatin.

Styrax camporum, a typical species of the Brazilian cerrado, attenuates DNA damage, preneoplastic lesions and oxidative stress in experimental rat colon carcinogenesis.

Styrax camporum Pohl, a typical species from the Brazilian cerrado, commonly known as "benjoeiro", is used to treat gastroduodenal diseases. In previous studies carried out by our research group, hydroalcoholic extract of S. camporum stems (SCHE) exhibited antigenotoxic and antiproliferative effects. For a comparative analysis of the chemopreventive effect of SCHE, the aim of this study was to investigate the influence of SCHE against carcinogen 1,2-dimethylhydrazine (DMH)-induced DNA damage and pre-neoplastic lesions in Wistar rat colon. Animals were treated orally with SCHE at 250, 500 or 1000 mg/kg body weight in conjunction with a subcutaneous injection of DMH. DNA damage was assessed using the comet assay while tpre-neoplastic lesions by aberrant crypt foci (ACF) assay. The following hepatic oxidative stress markers were determined including activities of catalase (CAT) and glutathione S-transferase (GST) as well as levels of reduced glutathione (GSH) and malondialdehyde (MDA). Treatment with SCHE was not genotoxic or carcinogenic at the highest dose tested (1000 mg/kg b.w.). The extract effectively inhibited DNA damage and pre-neoplastic lesions induced by DMH administration at all concentrations tested. Measurement of CAT, and GST activities and levels of GSH showed that SCHE did not reduce oxidative processes. In contrast, treatment with SCHE (1000 mg/kg b.w.) decreased liver MDA levels. Taken together, these findings suggested the chemopreventive effect attributed to SCHE in colon carcinogenesis, may be related to its capacity to inhibit DNA damage as well as an antioxidant action associated with its chemical constituents egonol and homoegonol.