Ellagic Acid: A Review on Its Natural Sources, Chemical Stability, and Therapeutic Potential

Ellagic acid (EA) is a bioactive polyphenolic compound naturally occurring as secondary metabolite in many plant taxa. EA content is considerable in pomegranate (Punica granatum L.) and in wood and bark of some tree species. Structurally, EA is a dilactone of hexahydroxydiphenic acid (HHDP), a dimeric gallic acid derivative, produced mainly by hydrolysis of ellagitannins, a widely distributed group of secondary metabolites. EA is attracting attention due to its antioxidant, anti-inflammatory, antimutagenic, and antiproliferative properties. EA displayed pharmacological effects in various in vitro and in vivo model systems. Furthermore, EA has also been well documented for its antiallergic, antiatherosclerotic, cardioprotective, hepatoprotective, nephroprotective, and neuroprotective properties. This review reports on the health-promoting effects of EA, along with possible mechanisms of its action in maintaining the health status, by summarizing the literature related to the therapeutic potential of this polyphenolic in the treatment of several human diseases

Notch Signaling and MicroRNA: The Dynamic Duo Steering Between Neurogenesis and Glioblastomas.

Notch signaling is an evolutionary conserved pathway that plays a central role in development and differentiation of eukaryotic cells. It has been well documented that Notch signaling is inevitable for neuronal cell growth and homeostasis. It regulates process of differentiation from early embryonic stages to fully developed brain. To achieve this streamlined development of neuronal cells, a number of cellular processes are being orchestrated by the Notch signaling. Abrogated Notch signaling is related to several brain tumors, including glioblastomas. On the other hand, microRNAs are small molecules that play decisive role in mediating and modulating Notch signaling. This review discusses the crucial role of Notch signaling in development of nervous system and how this versatile pathway interplay with microRNAs in glioblastoma. This review sheds light on interplay between abrogated Notch signaling and miRNAs in the regulation of neuronal differentiation with special focus on miRNAs mediated regulation of tumorigenesis in glioblastoma. Furthermore, it discusses different aspects of neurogenesis modulated by the Notch signaling that could be exploited for the identification of new diagnostic tools and therapies for the treatment of glioblastoma

Paclitaxel: Application in Modern Oncology and Nanomedicine-Based Cancer Therapy

Paclitaxel is a broad-spectrum anticancer compound, which was derived mainly from a medicinal plant, in particular, from the bark of the yew tree Taxus brevifolia Nutt. It is a representative of a class of diterpene taxanes, which are nowadays used as the most common chemotherapeutic agent against many forms of cancer. It possesses scientifically proven anticancer activity against, e.g., ovarian, lung, and breast cancers. The application of this compound is difficult because of limited solubility, recrystalization upon dilution, and cosolvent-induced toxicity. In these cases, nanotechnology and nanoparticles provide certain advantages such as increased drug half-life, lowered toxicity, and specific and selective delivery over free drugs. Nanodrugs possess the capability to buildup in the tissue which might be linked to enhanced permeability and retention as well as enhanced antitumour influence possessing minimal toxicity in normal tissues. This article presents information about paclitaxel, its chemical structure, formulations, mechanism of action, and toxicity. Attention is drawn on nanotechnology, the usefulness of nanoparticles containing paclitaxel, its opportunities, and also future perspective. This review article is aimed at summarizing the current state of continuous pharmaceutical development and employment of nanotechnology in the enhancement of the pharmacokinetic and pharmacodynamic features of paclitaxel as a chemotherapeutic agent

The determination of different effective concentration of ethanolic extract of bee pollen on biochemical analysis in liver, spleen and heart tissues of rainbow trout, Oncorhynchus mykiss (Walbaum, 1792)

The aim of this study was to investigate the effective concentration of ethanolic extract of bee pollen on liver, spleen and heart tissues of fish. Bee pollen extract in various concentrations (0.5, 2.5, 5, 10, 20 and 30 ppm) was administered to fish for 96 h under aquarium conditions. The malondialdehyde (MDA) levels, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) and levels of total free sulfhydryl groups were investigated in liver, spleen and heart in fish samples. MDA levels in liver, spleen and heart tissues of various concentration groups (2.5, 5, 10, 20 and 30 ppm) decreased (p<0.05) compared to the control group. The highest value of TAS (P<0.05) and the lowest value of TOS (p<0.05) occured in liver and heart tissues of 10 and 20 ppm concentration groups. The lowest levels of OSI were recorded in liver and heart tissues of 10, 20 and 30 ppm concentration groups compared to control group (p<0.05). The highest values of total sulfhydryl groups were recorded (p<0.05) in all tissues of 10 and 20 ppm groups compared with that in the control group. Finally it was observed that in liver, spleen and heart tissues of fish, the antioxidant effects of ethanolic extract of bee pollen depended on concentrations

Role of propolis on oxidative stress in various tissues of fish

The aim of this study was to investigate the therapeutic effects of propolis on biochemical parameters in tissues of rainbow trout (Oncorhynchus mykiss) exposed to Cypermethrin. Cypermethrin is a potential toxic pollutant that directly threats the aquatic ecosystems and environment. Sublethal Cypermethrin concentration of 0.0082 ppm was applied to the fish for 96 h. Propolis is a natural product collected from plants by honey bees. Its polyphenolic components, caffeic acid derivatives and flavonoids in particular, are matter of interest because of their strong antioxidant properties. Therapeutic concentration of propolis has been determined as 10 ppm in a previous study. Herein, malondialdehyde (MDA) levels and catalase (CAT) activities were determined in spleen and heart tissues of rainbow trouts. Results showed that CAT activities and MDA levels increased (P?0.001) in tissues of fish exposed to Cypermethrin compared to control group. CAT activities and MDA levels in the tissues of fish decreased in cyperme-thrin+propolis group (P?0.001) compared to Cypermethrin group. Propolis (10 ppm) on the tissues of the rainbow trout showed significant therapeutic effects. Propolis may serve as an antitoxic agent against pesticide toxicity to aquatic animals

Investigation of biological effects of some Mannich Bases containing Bis-1,2,4- Triazole

In this study, the effects of Mannich bases containing bis-1,2,4-triazole on the levels of in vivo malondialdehyde (MDA) and antioxidant vitamins (A, E, C) were examined in serum, livers and kidneys of rats. DA and vitamin (A, E, C) levels were determined by high performance liquid chromatography (HPLC). Antioxidant effect was investigated by determining the MDA levels in Saccharomyces cerevisiae cells as in vitro. Furthermore, the antitumor effects of compounds were investigated against MCF-7 human breast cancer cells. Interrelations of results among control and compound groups were evaluated using SPSS statistical software package. As a result, some of the compounds showed effective biological activity when compared to control conditions. The test compounds used in this study may be effective for utilization in the selection and design of model compounds for further studies

Thymoquinone improves testicular damage and sperm quality in experimentally varicocele-induced adolescent rats

The aim of this study was to investigate the protective and therapeutic effects of thymoquinone against the negative effects of varicocele on testicular tissue and sperm morphology. Five groups were formed by random selection from a total of 40 adult male Wistar rats (n = 8). Thymoquinone (5 mg/kg/day) was administered intraperitoneally to the varicocele-dimethyl sulfoxide-olive oil-thymoquinone (VT) group and the sham-thymoquinone group. At the end of the 60th day, all groups were anaesthetised and the left testis was removed from the body quickly. One half of the testis tissue, which was divided into two, was separated for biochemical and Western blot analysis, while the other half were fixed in Bouin's fixative. As a result of biochemical, molecular and histopathological analyses, a statistically significant increase was found in the varicocele group testicular tissues in the malondialdehyde level, apoptotic index, Bax expression, cytochrome c expression and Bax/Bcl-2 ratio compared with the sham group. In addition, histopathological changes characterised by partial or complete degeneration of the germinal epithelium were observed in the seminiferous tubules in the same group. Total oxidant status level and sperm count with abnormal morphology increased in varicocele group, whereas total antioxidant status level decreased. In the VT group, all of the biochemical, molecular and histopathological changes detected in the varicocele group were statistically significantly reduced. When the findings obtained in this study are evaluated, it can be said that thymoquinone has the potential to be used as a preventive and therapeutic pharmacological agent in the medical treatment of varicocele. Although the exact mechanism of action of thymoquinone has not been fully elucidated, the findings obtained in this study support the view that thymoquinone showed a cytoprotective effect by reducing apoptosis, oxidative stress and lipid peroxidation

Cellular targets and molecular activity mechanisms of bee venom in cancer: recent trends and developments

Bee venom therapy is known as a traditional approach to curing many medical conditions such as arthritis, pain and rheumatism. Bee venom also provides promising potential for treating many cancers such as breast, lung, ovary, stomach, kidney, prostate, cervical, colon and esophageal cancers, osteosarcoma, leukemia, melanoma and hepatocellular carcinoma. We therefore focused not only on the molecular activity mechanisms and cellular targets of bee venom and its components, but also on modern solutions as cutting-edge nanotechnological advances to overcome existing bottlenecks, and the latest advances in the anticancer application of bee venom in clinical settings