Overview of the Anticancer Profile of Avenanthramides from Oat.

Cancer represents one of the leading causes of death worldwide. Progresses in treatment of cancer have continued at a rapid pace. However, undesirable side effects and drug resistance remain major challenges for therapeutic success. Natural products represent a valuable starting point to develop new anticancer strategies. Polyphenols, well-known as antioxidant, exert anticancer effects through the modulation of multiple pathways and mechanisms. Oat (Avena sativa L., Poaceae) is a unique source of avenanthramides (AVAs), a group of polyphenolic alkaloids, considered as its signature compounds. The present review aims to offer a comprehensive and critical perspective on the chemopreventive and chemotherapeutic potential of AVAs. AVAs prevent cancer mainly by blocking reactive species. Moreover, they exhibit potential therapeutic activity through the modulation of different pathways including the activation of apoptosis and senescence, the block of cell proliferation, and the inhibition of epithelial mesenchymal transition and metastatization. AVAs are promising chemopreventive and anticancer phytochemicals, which need further clinical trials and toxicological studies to define their efficacy in preventing and reducing the burden of cancer diseases.

Phytochemical composition, antioxidant and antiproliferative activities and effects on nuclear DNA of ethanolic extract from an Italian mycelial isolate of Ganoderma lucidum.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (Curtis) P. Karst. (also known as Linghzhi and Reishi) is the most appreciated and revered medicinal mushroom across many Asian countries, but its properties have also attracted interest in Western countries. Indeed, in the West, it is now commercially available as a dietary supplement in preparations mainly made from spores, fruiting bodies and mycelia. It is employed in both nutraceutical and pharmacological formulations either for its immuno-modulating anti-inflammatory properties or as an effective adjuvant therapy in the treatment of several chronic diseases as well as in cancer treatment. AIM OF THE STUDY: The aim of this investigation was to show the phytochemical composition and antioxidant and antiproliferative activities of an ethanolic extract from an Italian mycelial isolate of Ganoderma lucidum and to assess its effects on nuclear DNA. MATERIALS AND METHODS: LC/ESI-MS and tandem mass spectrometry MSMS were used to obtain structural identification of ethanolic G. lucidum extract constituents. Antioxidant activities were determined by the DPPH method, chelating effect on Fe2+ and lipoxygenase inhibition while cytotoxic activities using the MTT assay. Effects on nuclear DNA were evaluated using the DNA nicking assay in a cell-free system and the fast halo assay performed on oxidatively injured human U937 cells; apoptosis induction was investigated using the non-denaturing fast halo assay and DNA laddering detection. RESULTS: This extract was rich in several bioactive compounds, mainly phenolic and triterpenic acids. It showed antioxidant activity and protective effects in oxidatively injured DNA in cell-free analyses and antiproliferative, genotoxic, and proapoptotic effects in the cell model. CONCLUSIONS: Italian G. lucidum mycelium isolate appears to be a source of various natural compounds that may have applications as chemopreventive agents or functional foods.

The potential effects of Ocimum basilicum on health: a review of pharmacological and toxicological studies.

INTRODUCTION: Basil (Ocimum basilicum L., OB) is a plant world widely used as a spice and a typical ingredient of the healthy Mediterranean diet. In traditional medicine, OB is indicated for many maladies and conditions; OB-containing nutritional supplements are increasingly sold. Conversely, safety concerns have been raised about the promutagens and procarcinogens alkenylbenzenes contained in OB. Areas covered: A critical review of the current status of OB as a nutraceutical, the pharmacology of its bioactive components, the rationale for its indications, and its safety. Expert opinion: Due to the polyphenolic and flavonoidic content, OB can be considered as an important ingredient in healthy diets; OB preparations may be effective as chemopreventive agents or adjunctive therapy in the treatment of different clinical conditions. From a toxicological perspective, since the tumorigenic potential of alkenylbenzenes is counteracted by other OB constituents such as nevadensin, it can be concluded that OB consumption in food and preparations is safe. The only concern relates to OB essential oils: in this case, a concentration limit for alkenylbenzenes should be precautionary defined, and the use of plant chemotypes with no or low levels of these alkylbenzenes for the preparation of essential oils should be made compulsory.

In Vitro Study of the Cytotoxic, Cytostatic, and Antigenotoxic Profile of Hemidesmus indicus (L.) R.Br. (Apocynaceae) Crude Drug Extract on T Lymphoblastic Cells.

In traditional Indian medicine, the crude drug Hemidesmus indicus root-commonly known as Indian sarsaparilla-is used alone or in poly-herbal preparations for the treatment of a wide range of diseases. The present study focuses on the cancer chemopreventive and therapeutic potential of H. indicus extracts on an acute lymphoblastic leukemia cell line (CCRF-CEM). With this aim in mind, we subjected H. indicus roots to two subsequent extractions (hydro-alcoholic extraction and soxhlet extraction). As DNA damage is an important prerequisite for the induction of mutations/cancer by genotoxic carcinogens, cancer chemoprevention may be achieved by preventing genotoxicity. Through an integrated experimental approach, we explored the genoprotective potential of the soxhlet H. indicus extract against different mutagenic compounds and its cytotoxic, proapoptotic, and cytostatic properties. In our experimental conditions, H. indicus induced a cytotoxic effect involving the activation of both intrinsic and extrinsic apoptotic pathways and blocked the cell cycle in the S phase. Moreover, the antigenotoxicity results showed that the extract was able to mitigate DNA damage, an essential mechanism for its applicability as a chemopreventive agent, via either the modulation of extracellular and intracellular events involved in DNA damage. These data add to the growing body of evidence that H. indicus can represent a noteworthy strategy to target early and late stages of cancer.

The effect of topical thiocolchicoside in preventing and reducing the increase of muscle tone, stiffness, and soreness: A real-life study on top-level road cyclists during stage competition.

In professional road cyclists, the majority of overuse injuries affect the lower limbs and are mostly represented by contractures or muscle shortening, characterized by an increase of tone and stiffness and a variation of elasticity. Treatment and prevention of these specific conditions may include physical, supplementary, and pharmacologic support. The aim of this real-life study was to determine: first, the alterations of tone, stiffness, elasticity, and soreness of rectus femoris (RF) and biceps femoris (BF) in top class cyclists engaged in 3 multistage races, and second, whether any variable in the management of the athletes may affect the prevention and/or reduction of such alterations.Twenty-three professional cyclists competing in 3 international, cycling stage races were assessed. Athletes could receive, upon the approval of the medical staff, physical, dietary, and/or pharmacological management which could include treatments with topical over-the-counter myorelaxants to prevent and/or reduce muscle contractures. MyotonPro was used to daily measure tone, stiffness, and elasticity in RF and BF in relaxed and contracted state after every stage. In parallel, BF and RF soreness was also assessed with a Likert scale.All athletes received the same general massage management; none of them received dietary supplements; some of the athletes were treated with a topical myorelaxant thiocolchicoside (TCC 0.25%) foam 3 times daily. TCC was identified as the only variable able to affect these muscle parameters in the cyclists. Tone, stiffness (regardless of the state), and soreness significantly increased over time either in BF or RF in all athletes. In the group of athletes that used TCC (n = 11; TCC+) the increase in tone, stiffness, and soreness was significantly lower than in the group not receiving TCC (n = 12; No-TCC). Elasticity varied coherently with tone and stiffness.A very intense and protracted sport activity increases muscular tone, stiffness, and soreness over time. Topical TCC foam significantly attenuates these alterations and might represent an efficient strategy both to prevent and manage contractures and their consequences in professional cyclists as well in athletes from other disciplines involving similar workloads.

Protective Effect of Juglans regia L. Walnut Extract Against Oxidative DNA Damage.

Walnuts (Juglans regia L.) are relevant components of the Mediterranean diet providing important macronutrients, micronutrients and other bioactive constituents including unsaturated fatty acids, proteins, fiber, vitamins, minerals, phytosterols and polyphenols. Although the walnut beneficial effects in human health are widely recognized by a lot of epidemiologic studies very little is known regarding its effect on damaged DNA. The aim of the present study was to investigate the effect of Juglans regia L. ethanolic extract from kernel on the induction of DNA strand breaks by thiol/Fe3+/O2 mixed function oxidase, tert-butyl hydroperoxide or UVC radiations in acellular and cellular models. Plasmid DNA cleavage and fast Halo assay were used to monitor oxidative damage to DNA. Both approaches showed protection of oxidatively injured DNA. These results agree with a lot of scientific proofs which recommend walnut as dietary adjunct in health promotion and prevention as well as in treatment of lifestyle-related oxidative diseases.

Protective Role of Italian Juglans regia L. nut Ethanolic Extract in Human Keratinocytes under Oxidative and Inflammatory Stress.

OBJECTIVE: In this research, fatty acid profile and polyphenolic content of an ethanolic extract of walnut from Juglans regia L. collected in Central Italy, were characterized. The potential antioxidant and anti-inflammatory effects of the extract were investigated in the human keratinocytes cell line. METHODS: Fatty acid profile was determined by gas chromatography/mass spectrometry analysis, total phenolic content by Folin-Ciocalteu method and aluminum chloride colorimetric method was used for determination of total flavonoids. Kertatinocytes were exposed to t-butyl hydroperoxide or Tumor Necrosis Factor alfa in the absence or presence of extract. Reduced glutathione was determined by Sedlak method; lipid peroxidation was assessed by measuring thiobarbituric acid reactive substances. t-butyl hydroperoxide and Tumor Necrosis Factor alfa-induced intracellular reactive oxygen species were monitored by fluorescent probes. The expression of some genes related to the inflammatory process (IL-6, IL-8, ikB, and ICAM) were analysed by Real-time PCR. RESULTS: JRE contains a favourable fatty acid profile with low saturated fats (19%) and high-unsaturated fats (81%) with a prevalence of the omega-6 linoleic acid (48%). Also a significant amount of polyphenols was found (5,0052 mg gallic acid equivalent/gdw). Antioxidant and anti-inflammatory properties of JRE were observed on analysed cellular model. JRE antioxidants counteracted ROS production, GSH depletion and lipid peroxidation as well downregulated the expression of some genes related to the inflammatory process. Moreover, polyunsaturated fatty acids exhibited anti-inflammatory properties. CONCLUSION: The obtained results uphold walnut as dietary adjunct in health promotion and drive towards its development in drug therapy against chronic inflammatory disorders, including inflammatory skin diseases.

Withania somnifera Induces Cytotoxic and Cytostatic Effects on Human T Leukemia Cells.

Cancer chemotherapy is characterized by an elevated intrinsic toxicity and the development of drug resistance. Thus, there is a compelling need for new intervention strategies with an improved therapeutic profile. Immunogenic cell death (ICD) represents an innovative anticancer strategy where dying cancer cells release damage-associated molecular patterns promoting tumor-specific immune responses. The roots of Withania somnifera (W. somnifera) are used in the Indian traditional medicine for their anti-inflammatory, immunomodulating, neuroprotective, and anticancer activities. The present study is designed to explore the antileukemic activity of the dimethyl sulfoxide extract obtained from the roots of W. somnifera (WE). We studied its cytostatic and cytotoxic activity, its ability to induce ICD, and its genotoxic potential on a human T-lymphoblastoid cell line by using different flow cytometric assays. Our results show that WE has a significant cytotoxic and cytostatic potential, and induces ICD. Its proapoptotic mechanism involves intracellular Ca(2+) accumulation and the generation of reactive oxygen species. In our experimental conditions, the extract possesses a genotoxic potential. Since the use of Withania is suggested in different contexts including anti-infertility and osteoarthritis care, its genotoxicity should be carefully considered for an accurate assessment of its risk-benefit profile.

Cytotoxic activity of essential oils of aerial parts and ripe fruits of Echinophora spinosa (Apiaceae).

The cytotoxic effects of the essential oils obtained from the flowering aerial parts (APO) and ripe fruits (RFO) of Echinophora spinosa L. (Apiaceae) from central Italy toward human U937 promonocytoid cells were studied; the contribution of each of the major constituents to the whole cytotoxic activity of either APO or RFO was also characterized. The major components of APO were beta-phellandrene (34.7%), myristicin (16.5%), p-cymene (16.3%), delta3-carene (12.6%), alpha-pinene (6.7%) and alpha-phellandrene (6.2%); those of RFO p-cymene (50.2%), myristicin (15.3%), alpha-pinene (15.1%) and alpha-phellandrene (8.1%). Both oils tested were toxic to U937 cells, but RFO was much more cytotoxic: indeed, the IC50 values calculated from the linear regression curves of RFO and APO were 14.5 +/- 0.85 and 43.4 +/- 2.81 microg/mL, respectively. alpha-Pinene and alpha-phellandrene were identified as the most toxically relevant constituents: however, they did not completely account for the toxic effects of genuine APO and RFO. Interestingly, we found that p-cymene, although per se devoid of toxicity within the tested range of concentrations, was capable of significantly sensitizing U937 cells to the cytotoxic activity of alpha-pinene and alpha-phellandrene, and that specific mixtures of these three terpenes were as toxic as genuine APO and RFO.

Aqueous extract from Vitis vinifera tendrils is able to enrich keratinocyte antioxidant defences.

An aqueous extract of V. vinifera L. tendrils was evaluated for its ability to enrich the antioxidant capacity of cultured cells. The long-time antioxidant capability of the extract was measured by in vitro chemical methods, and its influence on reduced glutathione levels and plasma membrane oxido reductase activity was determined in cultured human keratinocytes (NCTC 2544). Keratinocytes are cells normally exposed to oxidative stress, and for this reason adequately equipped with antioxidant defences. However, it has long been suggested that exogenous antioxidants may play an important role in minimizing the adverse effects of oxidative stress on skin.We demonstrated that V. vinifera tendril aqueous extract was able to increase, in a time- and dose-dependent manner, the reduced glutathione concentration and activity of trans plasma membrane oxido reductase as an indirect evaluation of the intracellular redox status of the cells demonstrating a relevant antioxidant activity of this phytocomplex.

Rhodiola rosea ability to enrich cellular antioxidant defences of cultured human keratinocytes.

Keratinocytes are cells strongly exposed to oxidative stress, but normally good equipped for antioxidant responses. However, it has long been suggested that exogenous antioxidants could play a useful role in minimizing the adverse skin responses associated with such oxidant species. In this work it was paid attention to the extract of Rhodiola rosea L. roots by using the phytocomplex as a whole because of the important activity of its composition and mutual distribution of its components. We have measured the protection afforded by the extract to reduced glutathione levels, glyceraldehyde-3-phosphate dehydrogenase activity, and thiobarbituric acid reactive substances levels in cultured human keratinocytes (NCTC 2544) exposed to different oxidative insults: Fe(II)/ascorbate, Fe(II)/H(2)O(2), and tert-butyl-hydroperoxide. We also have investigated the influence of the R. rosea extract on the production of intracellular reactive oxygen species and on the activity of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase). Furthermore, we have demonstrated that R. rosea extract was able to increase in a time- and dose-dependent manner the activity of the trans plasma membrane oxido reductase activity as an indirect evaluation of the intracellular redox status and this effect was already evident with small concentration of the extract and in a long time. As a result, NCTC 2544 are able to better counteract to several oxidative insults if incubated with R. rosea extract demonstrating a very good antioxidant activity of this phytocomplex.