The tremendous therapeutic potential of voltage-gated sodium channels (Na(v)s) has been the subject of many studies in the past and is of intense interest today. Na(v)1.7 channels in particular have received much attention recently because of strong genetic validation of their involvement in nociception. Here we summarize the current status of research in the Na(v) field and present the most relevant recent developments with respect to the molecular structure, general physiology, and pharmacology of distinct Na(v) channel subtypes. We discuss Na(v) channel ligands such as small molecules, toxins isolated from animal venoms, and the recently identified Na(v)1.7-selective antibody. Furthermore, we review eight characterized ligand binding sites on the Na(v) channel α subunit. Finally, we examine possible therapeutic applications of Na(v) ligands and provide an update on current clinical studies.

http://pubs.acs.org/doi/pdf/10.1021/jm501981g

Voltage-Gated Sodium Channels: Structure, Function, Pharmacology, and Clinical Indications

Melissa officinalis L. - A review of its traditional uses, phytochemistry and pharmacology

Naturally occurring food-derived active ingredients have received huge attention for their chemopreventive and chemotherapy capabilities in several diseases. Rosmarinic acid (RA) is a caffeic acid ester and a naturally-occurring phenolic compound in a number of plants belonging to the Lamiaceae family, such as Rosmarinus officinalis (rosemary) from which it was formerly isolated. RA intervenes in carcinogenesis through different ways, including in tumor cell proliferation, apoptosis, metastasis, and inflammation. On the other hand, it also exerts powerful antimicrobial, anti-inflammatory, antioxidant and even antidepressant, anti-aging effects. The present review aims to provide an overview on anticancer activities of RA and to deliberate its therapeutic potential against a wide variety of diseases. Given the current evidence, RA may be considered as part of the daily diet in the treatment of several diseases, with pre-determined doses avoiding cytotoxicity.

https://www.mdpi.com/2076-3417/9/15/3139/pdf

Therapeutic Potential of Rosmarinic Acid: A Comprehensive Review

The biosynthesis and biotechnological production of Rosmarinic acid, a phenolic ester that is widespread in the plant kingdom, has been widely investigated. This compound has shown many remarkable biological and pharmacological activities, which have led to its pharmaceutical and analytical development, as well as clinical studies, which are summarized and analyzed here for the first time. This review compiles data from the Pubmed, Scopus, Scifinder, Web Of Science, and Science Direct databases published between 1990 and 2015, restricting the search to works with the keywords “Rosmarinic acid” in the title. The initial search identified more than 800 articles; after an initial screening and removal of duplicate works, the search was further refined, resulting in approximately 300 articles that were scrutinized and comprise this review. The articles were organized to describe extraction and isolation, analytical methods, pharmaceutical development, and biological and pharmacological activities [divided into nonclinical (in vitro, in vivo) and clinical studies], pharmacokinetic studies, and stability studies.

/pdf/rosmarinic-acid-pharmaceutical-and-clinical-aspects-1ug5smps9j.pdf

Rosmarinic Acid--Pharmaceutical and Clinical Aspects.

Nature has generously offered a wide range of herbs (e.g., thyme, oregano, rosemary, sage, mint, basil) rich in many polyphenols and other phenolic compounds with strong antioxidant and biochemical properties. This paper focuses on several natural occurring phenolic acids (caffeic, carnosic, ferulic, gallic, p-coumaric, rosmarinic, vanillic) and first gives an overview of their most common natural plant sources. A summary of the recently reported antioxidant activities of the phenolic acids in o/w emulsions is also provided as an in vitro lipid-based model system. Exploring the interfacial activity of phenolic acids could help to further elucidate their potential health properties against oxidative stress conditions of biological membranes (such as lipoproteins). Finally, this review reports on the latest literature evidence concerning specific biochemical properties of the examined phenolic acids.

Phenolic Acids of Plant Origin—A Review on Their Antioxidant Activity In Vitro (O/W Emulsion Systems) Along with Their in Vivo Health Biochemical Properties

Ciguatoxin (CTX), is a toxic compound produced by microalgae (dinoflagellate) Gambierdiscus spp., and is bio-accumulated and bio-transformed through the marine food chain causing neurological deficits. To determine the mechanism of CTX-mediated cytotoxicity in human neurons, we measured extracellular lactate dehydrogenase (LDH) activity, intracellular levels of nicotinamide adenine dinucleotide (NAD+) and H2AX phosphorylation at serine 139 as a measure for DNA damage in primary cultures of human neurons treated with Pacific (P)-CTX-1B and P-CTX-3C. We found these marine toxins can induce a time and dose-dependent increase in extracellular LDH activity, with a concomitant decline in intracellular NAD+ levels and increased DNA damage at the concentration range of 5–200 nM. We also showed that pre- and post-treatment with rosmarinic acid (RA), the active constituent of the Heliotropium foertherianum (Boraginaceae) can attenuate CTX-mediated neurotoxicity. These results further highlight the potential of RA in the treatment of CTX-induced neurological deficits.

Neuroprotective Effects of Rosmarinic Acid on Ciguatoxin in Primary Human Neurons

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Neuroprotective Effects of Rosmarinic Acid on Ciguatoxin in Primary Human Neurons