Therapeutic Potential of 1,8-Dihydroanthraquinone Derivatives for Breast Cancer.

Breast cancer (BC) is the most common malignancy among women worldwide. In recent years, significant progress has been made in BC therapy. However, serious side effects resulting from the use of standard chemotherapeutic drugs, as well as the phenomenon of multidrug resistance (MDR), limit the effectiveness of approved therapies. Advanced research in the BC area is necessary to create more effective and safer forms of therapy to improve the outlook for individuals diagnosed with this aggressive neoplasm. For decades, plants and natural products with anticancer properties have been successfully utilized in treating various medical conditions. Anthraquinone derivatives are tricyclic secondary metabolites of natural origin that have been identified in plants, lichens, and fungi. They represent a few botanical families, e.g., Rhamnaceae, Rubiaceae, Fabaceae, Polygonaceae, and others. The review comprehensively covers and analyzes the most recent advances in the anticancer activity of 1,8-dihydroanthraquinone derivatives (emodin, aloe-emodin, hypericin, chrysophanol, rhein, and physcion) applied both individually, or in combination with other chemotherapeutic agents, in in vitro and in vivo BC models. The application of nanoparticles for in vitro and in vivo evidence in the context of 1,8-dihydroanthraquinone derivatives was also described.

Zingiber officinale Rosc. in the Treatment of Metabolic Syndrome Disorders-A Review of In Vivo Studies.

Inflammation is a protective reaction of the innate immune system as a response to imbalances caused by a specific stimulus, a disease or a pathogen. A prolonged inflammatory condition may lead to the development of metabolic syndrome, which affects more than one-fourth of the world's population. This condition leads to the development of multi-organ disorders based on disrupted blood lipid and sugar levels, hypertension and oxidative stress. The review aims to present Zingiber officinale Rosc. as a plant that exhibits a variety of healing properties and restores the organism's equilibrium. Ginger (GI) rhizomes have been commonly used in traditional medicine to treat arthritis, stomach ache, nonalcoholic fatty liver disease, rheumatism, nervous system syndromes, asthma, diabetes and nausea caused by pregnancy or chemotherapy. This review gathers together data from in vivo experiments related to the application of ginger for the treatment of inflammatory conditions, obesity, diabetes and other related disorders as a consequence of metabolic syndrome, including the confirmed molecular mechanisms of action.

Magnoflorine-Isolation and the Anticancer Potential against NCI-H1299 Lung, MDA-MB-468 Breast, T98G Glioma, and TE671 Rhabdomyosarcoma Cancer Cells.

Magnoflorine (MGN) is a quaternary aporphine alkaloid that exhibits numerous therapeutic properties, including neuropsychopharmacological, anti-anxiety, immunomodulatory, anti-inflammatory, antioxidant, or antifungal activities. The aim of the present study was an investigation of the influence of MGN on viability, proliferation, induction of apoptosis, and cell cycle arrest in NCI-H1299 lung, MDA-MB-468 breast, T98G glioma, and TE671 rhabdomyosarcoma cancer cells. MGN was isolated from the roots of Berberis cretica L. by counter-current partition chromatography (CPC). Cell viability and proliferation assessments were performed by means of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and 5-bromo-2'-deoxyuridine (BrDU) assays, respectively. The induction of apoptosis and cell cycle progression was measured using fluorescence-activated cell sorting analysis. MGN in high doses inhibits proliferation, induces apoptosis, and inhibits cell cycle in S/G2 phases in a dose-dependent manner. MGN seems to be a promising anti-cancer compound in therapy of some types of lung, breast, glioma, and rhabdomyosarcoma cancers, for which current standard therapies are limited or have severe strong side effects.

Synergistic or Additive Pharmacological Interactions between Magnoflorine and Cisplatin in Human Cancer Cells of Different Histological Origin.

Magnoflorine is an aporphine alkaloid present in plant species belonging to the Berberidaceae, Magnoliaceae, Menispermaceae, or Papaveraceae botanical families. The interest of magnoflorine has increased recently due to its multiplicity of pharmacological properties. The aim of this study was the analysis of combined anti-proliferative effect of magnoflorine and cisplatin and the assessment of drug-drug pharmacological interaction between these agents using isobolographic method in MDA-MB-468 human breast, NCIH1299 lung, TE671 rhabdomyosarcoma, or T98G glioblastoma cancer cell lines. Magnoflorine in combination with cisplatin at a fixed ratio of 1:1 augmented their anticancer action and yielded synergistic or additive pharmacological interactions by means of isobolographic method, therefore combined therapy using these two active agents can be a promising chemotherapy regimen in the treatment of some types of breast, lung, rhabdomyosarcoma, and glioblastoma cancers.

Acetylcholinesterase Inhibitors among Zingiber officinale Terpenes-Extraction Conditions and Thin Layer Chromatography-Based Bioautography Studies.

Although numerous studies have been conducted on ginger extracts and fractions, the data on the pharmacological activity of single constituents of Zingiber officinale are still insufficient. To assess the antidementia properties of the plant, a thin layer chromatography (TLC)-based bioautography acetylcholinesterase inhibitory assay was performed on the Zingiber officinale diethyl ether extract. It led to the recognition of three active inhibitors among volatile constituents of the plant: ar-curcumene (A), α-sesquiphellandrene (B) and a-zingiberene (C). The identification of the components was possible thanks to the application of a TLC-HPLC-MS interface analysis of active zones and the GC-MS qualitative analysis of the tested samples. Based on the obtained results, the influence of several extraction techniques (hydrodistillation-HD, pressurized liquid extraction or accelerated solvent extraction-ASE, shaking maceration-SM, supercritical fluid extraction-SFE, and ultrasound-assisted extraction-UAE) on the recovery of the active metabolites from plant material was assessed to deliver enriched extracts. As a result, HD and SFE, were found to be the most efficient methods to recover the volatile components and the concentrations of A, B, and C reached 0.51 ± 0.025, 0.77 ± 0.045, and 1.67 ± 0.11 percent, respectively. Only HD and SFE were found to recover monoterpene hydrocarbons from the plant matrix. The remaining techniques provided extracts rich in more complex constituents, like sesquiterpenes.

Advances in Chemistry and Bioactivity of Magnoflorine and Magnoflorine-Containing Extracts.

The review collects together some recent information on the identity and pharmacological properties of magnoflorine, a quaternary aporphine alkaloid, that is widely distributed within the representatives of several botanical families like Berberidaceae, Magnoliaceae, Papaveraceae, or Menispermaceae. Several findings published in the scientific publications mention its application in the treatment of a wide spectrum of diseases including inflammatory ones, allergies, hypertension, osteoporosis, bacterial, viral and fungal infections, and some civilization diseases like cancer, obesity, diabetes, dementia, or depression. The pharmacokinetics and perspectives on its introduction to therapeutic strategies will also be discussed.

Superior anticancer activity is demonstrated by total extract of Curcuma longa L. as opposed to individual curcuminoids separated by centrifugal partition chromatography.

Three curcuminoids: bisdemethoxycurcumin, demethoxycurcumin, and curcumin from turmeric were successfully separated by a high capacity solvent system composed of heptane: chloroform: methanol: water mixture (5: 6: 3: 2 v/v/v/v) tailored for centrifugal partition chromatographs at K-values of 0.504, 1.057, 1.644, respectively. These three ferulic acid derivatives obtained at a purity rate exceeding 95% were analysed by an HPLC-MS spectrometer. Turmeric extract inhibited the proliferation/viability of A549 human lung cancer, HT29 colon cancer, and T98G glioblastoma cell lines in (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay (MTT). Single curcuminoids significantly decreased the viability/proliferation of lung cancer cells in a dose-dependent manner. However, total extract displayed the superior anticancer activity in the investigated cell lines. Crude extract in combination with cisplatin augmented the decrease in the viability of cancer cells compared with single compound treatment in A549 lung cancer cells. Total extract of Curcuma longa could be regarded as being more effective against lung cancer cells in vitro than its separated compounds.

Recent Advances in Obesity: The Role of Turmeric Tuber and Its Metabolites in the Prophylaxis and Therapeutical Strategies.

BACKGROUND: Obesity in the 21st century society became an important health problem, alarming both the scientists and medicine doctors around the world. That is why, the search for new drug candidates capable to reduce the body weight is of high concern. OBJECTIVE: This contribution tends to collect current findings on the biochemistry of obesity and on the application of plants and in particular turmeric tuber - a commonly used spice - as an anti-obesity agent. METHODS: Following an introduction on the biochemical characteristics of obesity, the description of Curcuma secondary metabolites, their pharmacological applications and a study on the plants' regulatory properties in obesity was summarized. Particular attention was paid to curcumin - the major metabolite present in the extracts of Curcuma spp., which is known to exhibit a variety of pharmacological actions. Also, the characteristics of some semisynthetic analogues of this ferulic acid derivative, characterized by a higher polarity and better bioavailability will be discussed. RESULTS: Numerous scientific papers treat on the influence of turmeric on weight loss. Additionally, some of them describe its anti-inflammatory properties. CONCLUSIONS: This important spice tends to fight the 21st century plague, which is an excessive weight gain, related to the development of metabolic syndrome, to the occurrence of cardiovascular problems and diabetes, and, in consequence, leading to a significant shortening of life span. As herein proven, the extracts of turmeric play an important role in the regulation of inflammatory reactions which are evoked in the overweight patients, helping them reduce the excess body weight.

Combination of Osthole and Cisplatin Against Rhabdomyosarcoma TE671 Cells Yielded Additive Pharmacologic Interaction by Means of Isobolographic Analysis.

BACKGROUND/AIM: Osthole is a simple coumarin that has been found to have anticancer, anti-inflammatory, antiviral, anticoagulant, anticonvulsant and antiallergic activities. The aim of this study was to analyze the combined anti-proliferative effect of cisplatin (CDDP) and osthole on a rhabdomyosarcoma cell line, and assess the pharmacology of drug-drug interaction between these drugs using isobolographic analysis. MATERIALS AND METHODS: The anticancer actions of osthole in combination with CDDP were evaluated using the tetrazolium dye-based MTT cell proliferation assay. RESULTS: Osthole and CDDP applied together augmented their anti-cancer activities and yielded an additive type of pharmacologic interaction by means of isobolographic analysis. CONCLUSION: Combined therapy using osthole and cisplatin could be suggested as a potential chemotherapy regimen against rhabdomyosarcoma.

Pharmacological features of osthole.

Coumarins are a group of naturally occurring compounds common in the plant world. These substances and their derivatives exhibit a broad range of biological activities. One of the naturally occurring coumarins is osthole, which can most frequently be found in plants of the Apiaceae family. Cnidium monnieri (L.) Cusson ex Juss. Angelica pubescens Maxim. and Peucedanum ostruthium (L.). It has anti-proliferative, anti-inflammatory, anti-convulsant, and antiallergic properties; apart from that, inhibition of platelet aggregation has also been proved. The impact of osthole on bone metabolism has been demonstrated; also its hepatoprotective and neuroprotective properties have been confirmed. The inhibitory effect of this metokcompound on the development of neurodegenerative diseases has been proved in experimental models. Anticancer features of osthole have been also demonstrated both in vitro on different cell lines, and in vivo using animals xenografts. Osthole inhibited proliferation, motility and invasiveness of tumor cells, which may be associated with the induction of apoptosis and cell cycle slowdown. The exact molecular mechanism of osthole anti-cancer mode of action has not been fully elucidated. A synergistic effect of osthole with other anti-tumor substances has been also reported. Modification of its chemical structure led to the synthesis of many derivatives with significant anticancer effects. To sum up, osthole is an interesting therapeutic option, due to both its direct effect on tumor cells, as well as its neuroprotective or anti-inflammatory properties. Thus, there is a chance to use osthole or its synthetic derivatives in the treatment of cancer.

Additive Interaction of Cisplatin and Histone Deacetylase Inhibitors Combined Treatment in Rhabdomyosarcoma Cells - An Isobolographic Analysis.

BACKGROUND/AIM: The aim of this study was to assess the anticancer effect and the type of pharmacologic drug-drug interaction of cisplatin (CDDP) and histone deacetylase inhibitors (HDIs) combined treatment on the rhabdomyosarcoma cell line. MATERIALS AND METHODS: The antiproliferative actions of cisplatin and suberoylanilide hydroxamic acid (SAHA, vorinostat), as well as valproic acid (VPA) alone and in combination, were evaluated using the tetrazolium dye-based MTT cell proliferation assay and isobolographic analysis. RESULTS: All tested compounds inhibited proliferation of rhabdomyosarcoma cancer cells in a dose-dependent manner. The combinations of CDDP with SAHA and CDDP with VPA produced additive interaction with type-I isobolographic analysis. CONCLUSION: When adding SAHA or VPA to CDDP therapy, one can expect additive anticancer effects in the rhabdomyosarcoma cell line.

Isobolographic analysis demonstrates additive effect of cisplatin and HDIs combined treatment augmenting their anti-cancer activity in lung cancer cell lines.

Histone deacetylase inhibitors (HDIs) are a new class of drugs which affect the activity of HDACs resulting in changed of acetylation in many proteins. HDIs can induce differentiation, cell growth arrest, apoptosis, inhibit proliferation and angiogenesis in cancer, whereas normal cells are comparatively resistant to the action of HDIs. The aim of this study was to investigate the combined effect of a well-known cytostatic agent-cisplatin (CDDP) and a histone deacetylase inhibitors-either suberoylanilide hydroxamic acid (SAHA, vorinostat) or valproic acid (VPA), on the proliferation of lung cancer cells, as well as induction of apoptosis and inhibition of the cell cycle progression. The anti-proliferative activity of VPA or SAHA used alone, or in combination with CDDP were determined by means of MTT test. The type of pharmacologic interactions between HDAC inhibitors and CDDP was assessed using isobolographic analysis. We observed additive interactions for the CCDP with SAHA, as well as for the CDDP with VPA combinations with respect to their anti-proliferative effects on three different lung cancer cell lines (A549, NCI-H1563 and NCI-H2170). Such additive effects were observed regardless of the histologic type (adenocarcinoma or squamous cell carcinoma) and sensitivity for the drugs applied. Combination treatment also augmented the induction of apoptosis and cell cycle perturbation mediated by CDDP alone, thereby enhancing anti-cancer effect of tested drugs. In conclusion, the combined therapy of HDIs and CDDP may be a promising therapeutic tool in the treatment of lung cancer.

Osthole induces apoptosis, suppresses cell-cycle progression and proliferation of cancer cells.

BACKGROUND: The aim of the present study was to determine the effects of osthole on cell proliferation and viability, cell-cycle progression and induction of apoptosis in human laryngeal cancer RK33 and human medulloblastoma TE671 cell lines. MATERIALS AND METHODS: Cell viability was measured by means of the MTT method and cell proliferation by the 5-bromo-2-deoxyuridine (BrdU) incorporation assay. Cell-cycle progression was determined by flow cytometry, and induction of apoptosis by release of oligonucleosomes to the cytosol. The gene expression was estimated by a quantitative polymerase chain reaction (qPCR) method. High-performance counter-current chromatography (HPCCC) was applied for isolation of osthole from fruits of Mutellina purpurea. RESULTS: Osthole decreased proliferation and cell viability of cancer cells in a dose-dependent manner. The tested compound induced apoptosis, increased the cell numbers in G1 and decreased cell number in S/G2 phases of the cell cycle, differentially regulating CDKN1A and TP53 gene expression depending on cancer cell type. CONCLUSION: Osthole could be considered as a potential compound for cancer therapy and chemoprevention.

[Stress oxidative in schizophrenia]. / Stres oksydacyjny w schizofrenii.

Etiopathogenesis of schizophrenia development is unknown yet in 1% of human population. There is damaged metabolism of biological membranes, abused production of free radicals and altered activity of antioxidant enzymes in patients with schizophrenia. Recently, a study showed that many of the genes and proteins whose expression is modified in the schizophrenic brain are related to glutathione and oxidative stress pathways. According to the researchers changes in permeability of biological membranes in brain could involve the pathophisiology of all--subtypes of schizophrenia as a result of oxidative stress. Brain is particularly sensitive to oxidative damage. There is a lot of phospholipids and polyunsaturated fatty acids in brain tissue under physiological conditions. The changes in polyunsaturated fatty acids metabolism, increased lipid peroxidation and the presence of oxidative stress are found in schizophrenia. They can course to appear instabilities of neuron membranes or even cell death owing to oxidative stress. Mainly to getting to know the molecular disease mechanism is associated with a disorder of the brain. The results suggest that at least some of the schizophrenia disease process can be traced in peripheral tissue like plasma, blood cells or liver. In various types of schizophrenia antipsychotic treatment affects oxidative state of erythrocyte membranes in a different way. Research into changes of antioxidant enzymes level during the treatment of typical and atypical neuroleptic drugs could contribute to widening the knowledge on the reasons of undesirable effects during pharmacotherapy with typical neuroleptic drugs.