The Antioxidant, Antibacterial and Cell-Protective Properties of Bioactive Compounds Extracted from Rowanberry (Sorbus aucuparia L.) Fruits In Vitro.

Considering that Sorbus aucuparia fruits have been underutilized despite their tremendous potential, this study aimed to correlate the in vitro antioxidant, antibacterial and cell-protective abilities of fruit extracts derived from Sorbus aucuparia Romanian cultivars with their phytochemical composition. Therefore, following the preparation of ethanolic and carotenoid extracts, phytochemical screening was performed using UV-Vis and HPLC-DAD-ESI-MS methods. The antioxidant activity was analyzed using DPPH and FRAP tests. As the results revealed high contents of bioactive compounds (polyphenols 1.11 mg GAE/g DM, flavonoids 430.06 µg QE/g DM and carotenoids 95.68 µg/g DM) and an important antiradical action (DPPH 24.51 mg/mL and FRAP 0.016 µM TE/mL), we chose to further examine the fruits' biological properties. The antibacterial capacity was assessed employing agar well diffusion and broth microdilution techniques, with fruits displaying an intense activity against MSSA, MRSA and Enterococcus faecalis, but also E. coli and Pseudomonas aeruginosa. The cell-protective activity was analyzed on gentamicin-stressed renal cells, through MTT and Annexin V-FITC assays. Importantly, a significant increase in viability was registered on stressed cells following extract administration in low doses; nevertheless, viability was noticed to decline when exposed to elevated concentrations, potentially due to the cumulative actions of the extract and gentamicin. These findings offer novel light on the antibacterial activity of Sorbus aucuparia Romanian cultivars, as well as their cell-protective ability in renal cell injury.

The Nephroprotective Effect of Cornelian Cherry (Cornus mas L.) and Rowanberry (Sorbus aucuparia L.) in Gentamicin-Induced Nephrotoxicity on Wistar Rats with Emphasis on the Evaluation of Novel Renal Biomarkers and the Antioxidant Capacity in Correlation with Nitro-Oxidative Stress.

In spite of its well-known nephrotoxicity, gentamicin is nonetheless routinely used in humans and animals. However, no adjuvant treatments have been implemented to mitigate this harmful effect. Given this concern, medicinal plants represent a significant reservoir of natural antioxidants that could potentially reduce the renal oxidative stress induced by gentamicin. Therefore, the main objective of this research was to investigate the nephroprotective properties of Cornus mas and Sorbus aucuparia fruits in an experimental model of nephrotoxicity. The 3-week study was performed on male Wistar rats, which were randomly divided into six experimental groups, being subcutaneously treated with 50 mg/kg gentamicin and orally given Cornus mas and Sorbus aucuparia extracts, in doses of 40 mg/kg and 10 mg/kg, respectively. Antioxidant therapy significantly improved the nitro-oxidative stress parameters as well as the specific renal biomarkers KIM-1 and iNAG, demonstrating a considerable renal tubular protective impact. These outcomes were reinforced by biochemical and histopathological enhancements. Nevertheless, neither of the tested extracts succeeded in substantially diminishing BUN levels. Additionally, CysC did not significantly decline following extracts treatment, suggesting that the remedies did not effectively protect renal glomeruli against gentamicin stress. Future studies are required in order to determine the underlying mechanisms of these berries.

Phytochemical Profile, Antioxidant, Antimicrobial and Cytoprotective Effects of Cornelian Cherry (Cornus mas L.) Fruit Extracts.

Cornus mas L. is characterized by an increased quantity of bioactive compounds, namely polyphenols, monoterpenes, organic acids, vitamin C and lipophilic compounds such as carotenoids, being anciently used in the treatment of various diseases. This paper's objectives were to characterize the phytochemical profile of Cornus mas L. fruits and to evaluate the in vitro antioxidant, antimicrobial and cytoprotective effects on renal cells exposed to gentamicin. As such, two ethanolic extracts were obtained. The resulting extracts were used to assess the total polyphenols, flavonoids and carotenoids through spectral and chromatographic methods. The antioxidant capacity was assessed using DPPH and FRAP assays. Due to the high content of phenolic compounds analyzed in fruits and the results obtained regarding antioxidant capacity, we decided to further use the ethanolic extract to investigate the in vitro antimicrobial and cytoprotective effects on renal cells stressed with gentamicin. The antimicrobial activity was assessed using agar well diffusion and broth microdilution methods, with great results regarding Pseudomonas aeruginosa. The cytotoxic activity was assessed using MTT and Annexin-V assays. According to the findings, extract-treated cells had a higher cell viability. However, at high concentrations, viability was shown to decline, most likely due to the extract and gentamicin's additive effects.

Immunomodulatory Effect of Novel Electrospun Nanofibers Loaded with Doxycycline as an Adjuvant Treatment in Periodontitis.

The immunomodulatory effect of a novel biomaterial obtained through electrospinning, based on polylactic acid (PLA) and nano-hydroxyapatite (nano-HAP), loaded with doxycycline (doxy) was evaluated in an animal model. The treatment capabilities as a local non-surgical treatment of periodontitis was investigated on the lower incisors of Wistar rats, after the induction of localized periodontitis using the ligature technique. Following the induction of the disease, the non-surgical treatment of scaling and root planing was applied, in conjunction with the application of the new material. The results of the treatment were evaluated clinically, using the tooth mobility and gingival index scores, as well as histologically. The salivary concentrations of matrix metalloproteinase 8 (MMP-8) and plasmatic concentrations of interleukin 1 (IL-1), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) were also monitored. Two weeks after the ligature application, the periodontal disease was successfully induced in rats. The application of the novel biomaterial obtained through electrospinning was proven to be more effective in improving the clinical parameters, while decreasing the salivary MMP-8 and plasmatic IL-1 and TNF-α concentrations, compared to the simple scaling and root planing. Thus, the novel electrospun biomaterial could be a strong candidate as an adjuvant to the non-surgical periodontal therapy.

Inhibition of Tumor Growth and Modulation of Antioxidant Activity of Rhodoxanthin Isolated from Taxus baccata Aril against B16F10 Murine Malignant Melanoma.

Malignant melanoma is the most aggressive type of skin cancer, and due to the numerous limitations of current treatment methods, there is an urgent need to develop novel approaches for both the prevention and treatment of malignant melanoma, with research-oriented bioactive substances representing a notable first step. The current study decided to expand on previous rhodoxanthin research by investigating the possible anti-tumor effect as well as the effect on the antioxidant status in the case of murine melanoma in an experimental model. The 21-day study was carried out on female C57BL/6J mice. On the first day of the experiment, they were subcutaneously inoculated with 106 B16F10 cells and were given rhodoxanthin orally until the end of the study. Rhodoxanthin supplementation significantly reduced tumor growth (42.18%) and weight (15.74%). Furthermore, the epidermal growth factor (EGF) activity was reduced and the concentration of 8-OHdG dropped in the treated melanoma-bearing mice compared to the untreated ones, demonstrating the role of rhodoxanthin in slowing tumor growth, one of the mechanisms being the reduction of EGF level and the decrease of DNA oxidation. The administration of rhodoxanthin determined variations in antioxidant enzymes, both at the plasma level and at the tissue level.

Phytochemical Characterization of Taxus baccata L. Aril with Emphasis on Evaluation of the Antiproliferative and Pro-Apoptotic Activity of Rhodoxanthin.

Taxus baccata L., an evergreen tree, was known until recently due to its high concentration of toxic compounds. The purpose of the present study was to focus on the only non-poisonous part, the red arils, which have recently been described as an important source of various bioactive constituents. To establish total phenolic, flavonoid, and carotenoid content, antioxidant capacity, and cytotoxic properties, two types of extracts were obtained. The chemical profile of the ethanolic extract was evaluated using chromatographic (HPLC-DAD-ESI+) and spectral (UV-Vis) methods, and the antioxidant activity of the ethanolic extract was assessed using DPPH and FRAP assays, yielding moderate results. In the second type of extract (methanol: ethyl acetate: petroleum ether (1:1:1, v/v/v)) we identified three carotenoids using open column chromatography and RP-PAD-HPLC, with rhodoxanthin being the most abundant. Considering the above and mainly because of the lack of information in the literature about this pigment and its biological effects, we decided to further investigate the cytotoxic activity of rhodoxanthin, the main carotenoid presented in aril, and its protective effect against H2O2-induced oxidative stress using two cell lines: human HaCaT keratinocytes and B16F10 murine malignant melanoma. The MTT and Annexin-V Apoptosis assays showed a substantial cytotoxic potential expressed in a dose-dependent manner towards the melanoma cell line, however, no obvious cytotoxic effects on human keratinocytes were noticed.

Recent Advances in the Antiproliferative and Proapoptotic Activity of Various Plant Extracts and Constituents against Murine Malignant Melanoma.

Although conventional medicine, chemical drug synthesis and pharmaceutical research are advancing at a rapid pace, nature remains a major supplier of biological molecules. Natural bioactive compounds are studied closely especially as an alternative to the limitations of conventional therapy in many diseases, melanoma being one of them. Malignant melanoma is a highly aggressive type of cancer, and the current methods of treatment used are cryotherapy, external surgery, radiation therapy, chemotherapy, photodynamic therapy, biological therapy, and targeted drug therapy. Unfortunately, these treatment methods are often inefficient, extremely expensive and cause many side effects, which is why focusing on melanoma chemoprevention and adjuvant therapy with natural herbal phytoconstituents is an emerging strategy to prevent, cure or treat melanoma. This review aims to examine the latest discoveries in terms of potential natural bioactive compounds that possess important activity against the development and spread of murine melanoma cancer. In particular, the use of different phytochemicals such as phenolic acids, flavonoids, anthocyanins, terpenoids, essential oils and carotenoids in vitro and in vivo models will be discussed. These data are helpful in guiding researchers in the direction of studying phytonutrients with important effects in the prevention and treatment of melanoma.

Chemical Profile, Cytotoxic Activity and Oxidative Stress Reduction of Different Syringa vulgaris L. Extracts.

Syringa vulgaris L. (common lilac) is one of the most popular ornamental species, but also a promising not comprehensively studied source of bioactive compounds with important therapeutic potential. Our study was designed to characterize the chemical composition and to assess the antioxidant and cytotoxic properties of ethanolic extracts obtained from S. vulgaris L. flowers, leaves, bark, and fruit. The chemical profile of the ethanolic extracts was investigated using chromatographic (HPLC-DAD-ESI+, GC-MS) and spectral (UV-Vis, FT-IR) methods, while the protective effect against free radicals was evaluated in vitro by different chemical assays (DPPH, FRAP, CUPRAC). The cytotoxic activity was tested on two tumoral cell lines, HeLa, B16F10, using the MTT assay. Significant amounts of free or glycosylated chemical components belonging to various therapeutically important structural classes, such as phenyl-propanoids (syringin, acteoside, echinacoside), flavonoids (quercetin, kaempferol derivatives) and secoiridoids (secologanoside, oleuropein, 10-hydroxy oleuropein, demethyloleuropein, syringalactone A, nuzhenide, lingstroside) were obtained for the flowers, leaves and bark extracts, respectively. Furthermore, MTT tests pointed out a significant cytotoxic potential expressed in a non-dose-dependent manner toward the tumoral lines. The performed methods underlined that S. vulgaris extracts, in particular belonging to flowers and leaves, represent valuable sources of compounds with antioxidant and antitumoral potential.

Effects of astaxanthin supplementation on chemically induced tumorigenesis in Wistar rats.

BACKGROUND: Astaxanthin (ASTA) is a fat-soluble xanthophyll with powerful antioxidant functions. It is extracted from e.g. salmon, an important food source for certain human populations known to have a reduced risk of tumor development. It is possible that ASTA plays a role in cancer chemoprevention in such populations. The purpose of this study was to investigate the effects of dietary ASTA on chemically induced mammary tumorigenesis using N-methyl-N-nitroso-urea (MNU) in immature Wistar rats. METHODS: Thirty-six 37 days old juvenile female Wistar rats were at random allocated to 4 groups of which Groups 1 and 2 received a single dose of 55 mg MNU/kg body weight. The effects of ASTA was evaluated by giving rats of Groups 2 and 4 a dose of 50 mg ASTA/kg/day for the entire duration of the study. Group 3 rats received feed added alimentary oil.Necropsy and histopathological examinations were carried out on each rat 14 months after the administration of MNU. Haematological values and antioxidative status were determined. Oxidative stress was evaluated by monitoring superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in hepatic tissue. Lipid peroxidation and carbonylation of proteins was determined in protein extracts from the liver. RESULTS: Tumor development occurred only in rats of Groups 1 and 2, i.e. MNU exposed animals. Frequency of tumor development in general and average number of tumors per animal were insignificant between these two groups. Mammary gland tumors developed in equal frequencies in Group 1 and 2 rats, respectively. Although only rather few tumors were found in the mammary glands, a substantial number of other tumors were found in Group 1 and 2 rats, but at equal rates.Biochemical analyses showed significant higher levels of GPx, malondialdehyde and dinitrophenylhydrazine in Group 1 rats that for rats in all other groups thus indicating protective effects of ASTA on MNU induced hepatic oxidative stress. CONCLUSIONS: Supplementation with ASTA did not reduce tumorigenesis induced by MNU in Wistar rats. However, supplementation with ASTA seemed to have anti-inflammatory effects.