Review manuscripts: Before writing their manuscripts, potential authors of review articles should forward the title and a short abstract to molecules@mdpi.org, with a copy to the Guest Editors Prof. Dr. José Alberto Pereira (jpereira@ipb.pt),
Prof. Dr. Paula Andrade (pandrade@ff.up.pt), and Dr. Derek McPhee (mcphee@mdpi.org). We will then provide feedback on the suitability of the topic.

Molecules Manuscript ID: phenolics-20080606-Schempp-de
Type of the paper: Review
Title: Anti-carcinogenic Effects of luteolin and Other Flavonoids
Authors: Günter Seelinger,  Irmgard Merfort, Ute Wölfle and Christoph M. Schempp*
E-mail: christoph.schempp@uniklinik-freiburg.de
Affiliations:
Dr. Günter Seelinger, Medical and Pharmaceutical Services, Berlin, Germany.
Prof. Dr. Irmgard Merfort, Institute of Pharmaceutical Sciences, Department of Pharmaceutical Biology, University of Freiburg, Germany.
Prof. Dr. Christoph Schempp, Competence center skintegral, Department of Dermatology, University Medical Center Freiburg, Hauptstr. 7, D-79102 Freiburg, Germany
Tel.: +49 761 270 6701; Fax: +49 761 270 6829
Abstract: Luteolin is a flavonoid which is part of our daily nutrition in relatively low amounts (less than 1 mg/day). Nevertheless, some epidemiological studies suggest an inverse correlation between luteolin intake and risk of some cancer types. Luteolin displays specific anti-inflammatory and anti-carcinogenic effects, which can only partly be explained by its anti-oxidant and free radical scavenging capacities. Luteolin can delay or block the development of cancer cells in vitro and in vivo by protection from carcinogenic stimuli, by inhibition of tumor cell proliferation, by induction of cell cycle arrest and by induction of apoptosis via intrinsic and extrinsic signaling pathways. When compared to other flavonoids, luteolin was usually the most effective, or one the most effective ones with IC50 values between 3 and 50 µM in vitro and 0.1 to 30 mg/kg i.p. in vivo. Luteolin is orally bioavailable and can penetrate into human skin, making it a candidate for the prevention and treatment of skin cancer.

Molecules Manuscript ID: phenolics-20080606-Bruni-it
Type of the paper: Review
Title: Factors Affecting Polyphenol Biosynthesis in Wild and Field Grown St. John’s Wort (Hypericum perforatum L.)
Authors: Renato Bruni
E-mail: renato.bruni@.unipr.it
Abstract: The steadily increasing diffusion of herbal products is posing new questions: why are the consumer available products often different in their composition and efficacy? Which approach is more suitable and which steps are more relevant in order to increase biochemical productivity of medicinal plants with large-scale, low-cost solutions? Can the phytochemical profile of a medicinal plant be modulated in order to reduce some unwanted substances and increase the accumulation of the most valuable ones? Will medicinal crops ever be traded as commodities? Providing a proactive answer to such questions is an extremely hard task, due to the large number of variables involved: plant breeding, intraspecific chemodiversity, ontogenetic stage, agronomic conditions, climate and latitude, post-harvest handling and exposure to noxious agents, to name a few. An ideal path should include the definition of optimum pre-harvesting and post-harvesting conditions and the availability of specific Good Agricultural Practices centered on secondary metabolism enhancement. The first steps to be taken in this direction are undoubtedly the evaluation and the organization of scattered data regarding the diverse factors involved in the optimization of medicinal plant cultivation, both in terms of biomass and active principles, in order to provide an interdisciplinary overview of main possibilities, weaknesses and drawbacks. This review will provide an overview of the knowledge on this regard focused on Hypericum perforatum L. (Hypericaceae/Guttiferae), summarizing data treating topics directly and indirectly related with factors influencing the production of biomass and phenolic secondary metabolites of St. John’s Wort (dianthrones, flavonoids, cinnamic derivatives) with the aim to provide a reference on the state-of-the-art of its cultivation and to suggest its evolution towards the maximization of bioactive constituents. Factors considered emerge not only from in field agronomic results, but also from physiological, genetical, biotic, abiotic and phytochemical data that can be scaled up to the applicative level. To increase quality for final beneficiaries, growers profit and ultimately transform phenolic-rich medicinal crops into commodities, the emerging trend suggest an integrated and synergic approach. Agronomy and genetics will need to develop their breeding strategies taking account of the suggestions of phytochemistry, pharmacognosy and pharmacology, without lose sight of the economic balance of the production. Indications on possible future developments and needs have been outlined.
Keywords: Hypericum perforatum, hypericins, polyphenols, flavonoids secondary metabolism optimization.

Molecules Manuscript ID: phenolics-20080610-Duan-cn
Type of the paper: Review
Title: Biosynthesis and Genetic Regulation of Proanthocyanidins in Plants
Authors: Fei He, Qiu-Hong Pan, Ying Shi, Chang-Qing Duan*
Affiliations: Centre for Viticulture & Enology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China; Tel.: +86 10 62737136; Fax: +86 10 62737136; Email: chqduan@yahoo.com.cn
Abstract: Proanthocyanidins (PAs), also known as condensed tannins, are a group of polyphenolic secondary metabolites synthesized as oligomers or polymers of flavan-3-ol units via the flavonoid pathway in plants. Due to their structure complexity and composition variety, only in the recent years, has the study on the biosynthesis and regulation of proanthocyanidins in plants been broken through, but some synthetic mechanism remains unclear. The present paper aims to summarize the research status of the structures of proanthocyanidins in plants, the genes encoding key enzymes of biosynthetic pathway, the transport factors, the regulation of proanthocyanidins biosynthesis and genetic manipulation of proanthocyanidins. The problems of this field were also discussed, including the final “enzymes” which catalyze the polymerization reaction of proanthocyanidins and the possible mechanism how the elementary units of flavanols are assembled in vivo.
Keywords: Proanthocyanidins, Condensed Tannins, Structures, Flavonoid Biosynthesis, Regulatory Genes, Transport Factors.

Manuscript ID: phenolics-20080619-Duan-cn
Type of the paper: Review
Title: Chemical Synthesis of Proanthocyanidins in Vitro and Their Reactions in Aging Wines
Authors: Fei He, Qiu-Hong Pan, Ying Shi, Chang-Qing Duan*
Affiliations: Centre for Viticulture & Enology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China; Tel.: +86 10 62737136; Fax: +86 10 62737136; Email: chqduan@yahoo.com.cn
Abstract: Proanthocyanidins are present in many fruits and plant products like wine, and contribute to their taste and health benefits. In the past decades of years, a series of substantial progresses have been achieved in the identification of composition and structure of proanthocyanidins, but the debate concerning the existence of an enzymatic or nonenzymatic mechanism for proanthocyanidin condensation still goes on. Enough attention has been paid to elucidating the potential forming mechanism by means of biomimetic and chemical synthesis in vitro. The present paper aims to summarize the research status on chemical synthesis of proanthocyanidins, including non-enzymatic synthesis of proanthocyanidin precursors, chemical synthesis of proanthocyanidins with direct condensation of flavanols and stereoselective synthesis of proanthocyanidins. Proanthocyanidin-involved reactions in aging wines are also reviewed such as direct and indirect reactions among proanthocyanidins, flavanols and anthocyanins. The future research objects in this field are put forward.
Keywords: Proanthocyanidins, Condensed Tannins, Chemical Synthesis, Stereoselective Synthesis, Flavanols, Anthocyanins, Wine.

Molecules Manuscript ID: phenolics-20080710-Santana Rodríguez-es
Type of the paper: Review
Title: Micellar Media in the Extraction and Determination of Phenolic Compounds in Environmental Samples: New Approaches
Authors: Cristina Mahugo Santana, Zoraida Sosa Ferrera, M. Esther Torres Padrón, José Juan Santana Rodríguez*
Affiliations: Department of Chemistry, Faculty of Marine Sciences, University of Las Palmas de Gran Canaria, 35017, Las Palmas de Gran Canaria, Spain; Tel.: +34 928452915; Fax: +34 928452922; Email: jsantana@dqui.ulpgc.es
Abstract: Phenolic derivatives are some of the most important contaminants present in the environment. These compounds are used in several industrial processes to manufacture chemicals such as pesticides, explosives, drugs and dyes. They also are used in the bleaching process of paper manufacturing. Apart from these sources, phenolic compounds have substantial applications in agriculture as herbicides, insecticides and fungicides. However, phenolic compounds are not only generated by human activity, but they are also formed naturally, e.g., during the decomposition of leaves or wood. As a result of these applications, they are found in soils and sediments and this often leads to wastewater and ground water contamination. Owing to their high toxicity and persistence in the environment, both, the US Environmental Protection Agency (EPA) and the European Union have included some of them in their lists of priority pollutants. Current standard methods of phenolic compounds analysis in water samples are based on liquid¨Cliquid extraction (LLE) while Soxhlet extraction is the most used technique for isolating phenols from solid matrices. However, these techniques require extensive cleanup procedures that are time-intensive and involve expensive and hazardous organic solvents, which are undesirable for health and disposal reasons. In the last years, the use of news methodologies such as solid-phase extraction (SPE) and solid-phase microextraction (SPME) have increased for the extraction of phenolic compounds from liquid samples. In the case of solid samples, microwave assisted extraction (MAE) is demonstrated to be an efficient technique for the determination of these compounds. In this work we review the developed methods in the extraction and determination of phenolic derivatives in different types of environmental matrices such as water, sediments and soils using micellar media. Moreover, we present the new approach in the use of micellar media coupled with SPME process for the extraction of phenolic compounds. The advantages of micellar media over conventional extractants are reduction of organic solvent, low cost, easy handling and shorter time procedures.

Molecules Manuscript ID: phenolics-20080712-Katula-us
Type of the paper: Review
Title: Phytochemical Modulation of NF-kB Activity: the Good and the Bad of it
Author: Karen S. Katula
Affiliations: Dept. of Biology, UNCG. P.O. Box 26174. Greensboro, NC 27402-6174; Tel.: 336-334-4951; Fax: 336-334-5839; Email: kskatula@uncg.edu
Abstract: NF-kB includes a family of related proteins that in dimeric form function as transcription factors to regulate over 200 different genes. In most cells, NF-kB is maintained in an inactive form in the cytoplasm complexed with IkB. Diverse stimuli due to inflammation, viral and bacterial infection, and other cellular stresses, lead to degradation of IkB and release of NF-kB, which then translocates into the nucleus. The role of NF-kB and inflammation in cancer and other human diseases is well documented. Numerous studies have been published documenting the effects of individual, dietary phytochemicals on NF-kB activity, thus providing in some cases a possible explanation for the anti cancer and other health benefits of these dietary compounds. However, there is contrary data suggesting that certain compounds can negatively impact NF-kB activity. In this review, the results of these studies will be summarized and compared with a particular focus on structural features, concentrations, and assay system. The goal of this review is to provide a summary and generalities regarding phytochemical effects on NF-kB activity.

Molecules Manuscript ID: phenolics-20080720-Meulenberg-nl
Type of the paper: Review
Title: Phenolics: Occurrence and Immunochemical Detection in Environment and Food
Author: Eline P. Meulenberg
Affiliations: ELTI Support VOF, Drieskensacker 12-10, 6546 MH Nijmegen, The Netherlands. E-mail: E.Meulenberg@eltisupport.nl
Abstract: Phenolic compounds may be of natural or anthropogenic origin and be present in the environment as well as in food. They comprise a large and diverse group of compounds that may be either beneficial or harmful for consumers. In this review first a non-exhausting overview of interesting phenolics is given, in particular with regard to their presence in environment and food. For some of these compounds, beneficial, toxicological and/or optionally endocrine disrupting activities will be presented. Further, immunochemical detection and/or isolation methods developed will be discussed, including advantages and disadvantages thereof in comparison with conventional analytical methods such as HPLC, GC, MS. A short overview of new sensor-like methods will also be included for present and future application.