Therapeutic potential of allicin-rich garlic preparations: Emphasis on clinical evidence toward upcoming drugs formulation

Garlic has been used for a long time in human history. Allicin, the main active compound present in freshly injured garlic, is enzymatically formed from alliin. Allicin has shown doubtless beneficial effects and even be conceived as medicine. The present review highlights allicin-associated studies. Indeed, clinical studies on healthy subjects have evidenced that standardized garlic treatment (900 mg/day) significantly reduces total cholesterol (TC) and low-density lipoprotein cholesterol (c-LDL). Besides, allicin also led to a marked improvement in mouth opening, burning sensation, and oral health-related quality of life on stage II oral submucous fibrosis patients. Interestingly, in children, allicin also has been proposed for thrush prevention and as an alternative antibiotic therapy. Nonetheless, there is particular attention to allicin bioavailability, given its high instability. Although clinical evidence has promoted allicin release from garlic powder tablets under simulated gastrointestinal conditions, garlic tablets are those that have provided less alliinase protection due to its fast disintegration, releasing low allicin amounts.Natália Martins would like to thank the Portuguese Foundation for Science and Technology (FCT-Portugal) for the Strategic project ref. UID/BIM/04293/2013 and "NORTE2020-Programa Operacional Regional do Norte" (NORTE-01-0145-FEDER-000012)

Melatonin in Medicinal and Food Plants : Occurrence, Bioavailability, and Health Potential for Humans

Melatonin is a widespread molecule among living organisms involved in multiple biological, hormonal, and physiological processes at cellular, tissue, and organic levels. It is well-known for its ability to cross the blood-brain barrier, and renowned antioxidant effects, acting as a free radical scavenger, up-regulating antioxidant enzymes, reducing mitochondrial electron leakage, and interfering with proinflammatory signaling pathways. Detected in various medicinal and food plants, its concentration is widely variable. Plant generative organs (e.g., flowers, fruits), and especially seeds, have been proposed as having the highest melatonin concentrations, markedly higher than those found in vertebrate tissues. In addition, seeds are also rich in other substances (lipids, sugars, and proteins), constituting the energetic reserve for a potentially growing seedling and beneficial for the human diet. Thus, given that dietary melatonin is absorbed in the gastrointestinal tract and transported into the bloodstream, the ingestion of medicinal and plant foods by mammals as a source of melatonin may be conceived as a key step in serum melatonin modulation and, consequently, health promotion

Insights on the use of a-lipoic acid for therapeutic purposes

a-lipoic acid (ALA, thioctic acid) is an organosulfur component produced from plants, animals, and humans. It has various properties, among them great antioxidant potential and is widely used as a racemic drug for diabetic polyneuropathy-associated pain and paresthesia. Naturally, ALA is located in mitochondria, where it is used as a cofactor for pyruvate dehydrogenase (PDH) and a-ketoglutarate dehydrogenase complexes. Despite its various potentials, ALA therapeutic efficacy is relatively low due to its pharmacokinetic profile. Data suggests that ALA has a short half-life and bioavailability (about 30%) triggered by its hepatic degradation, reduced solubility as well as instability in the stomach. However, the use of various innovative formulations has greatly improved ALA bioavailability. The R enantiomer of ALA shows better pharmacokinetic parameters, including increased bioavailability as compared to its S enantiomer. Indeed, the use of amphiphilic matrices has capability to improve ALA bioavailability and intestinal absorption. Also, ALA’s liquid formulations are associated with greater plasma concentration and bioavailability as compared to its solidified dosage form. Thus, improved formulations can increase both ALA absorption and bioavailability, leading to a raise in therapeutic efficacy. Interestingly, ALA bioavailability will be dependent on age, while no difference has been found for gender. The present review aims to provide an updated on studies from preclinical to clinical trials assessing ALA’s usages in diabetic patients with neuropathy, obesity, central nervous system-related diseases and abnormalities in pregnancy.N. Martins would like to thank the Portuguese Foundation for Science and Technology (FCT-Portugal) for the Strategic project ref. UID/BIM/04293/2013 and “NORTE2020 - Northern Regional Operational Program” (NORTE-01-0145-FEDER-000012)

Natural Coumarins: Exploring the Pharmacological Complexity and Underlying Molecular Mechanisms

Coumarins belong to the benzopyrone family commonly found in many medicinal plants. Natural coumarins demonstrated a wide spectrum of pharmacological activities, including anti-inflammatory, anticoagulant, anticancer, antibacterial, antimalarial, casein kinase-2 (CK2) inhibitory, antifungal, antiviral, Alzheimer's disease inhibition, neuroprotective, anticonvulsant, phytoalexins, ulcerogenic, and antihypertensive. There are very few studies on the bioavailability of coumarins; therefore, further investigations are necessitated to study the bioavailability of different coumarins which already showed good biological activities in previous studies. On the evidence of varied pharmacological properties, the present work presents an overall review of the derivation, availability, and biological capacities of coumarins with further consideration of the essential mode of their therapeutic actions. In conclusion, a wide variety of coumarins are available, and their pharmacological activities are of current interest thanks to their synthetic accessibility and riches in medicinal plants. Coumarins perform the valuable function as therapeutic agents in a range of medical fields

Paving Plant-Food-Derived Bioactives as Effective Therapeutic Agents in Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, where social and communication deficits and repetitive behaviors are present. Plant-derived bioactives have shown promising results in the treatment of autism. In this sense, this review is aimed at providing a careful view on the use of plant-derived bioactive molecules for the treatment of autism. Among the plethora of bioactives, curcumin, luteolin, and resveratrol have revealed excellent neuroprotective effects and can be effectively used in the treatment of neuropsychological disorders. However, the number of clinical trials is limited, and none of them have been approved for the treatment of autism or autism-related disorder. Further clinical studies are needed to effectively assess the real potential of such bioactive molecules.N.C.-M. acknowledges the Portuguese Foundation for Science and Technology under the Horizon 2020 Program (PTDC/PSI-GER/28076/2017)

Phytosterols: From Preclinical Evidence to Potential Clinical Applications

Phytosterols (PSs) are plant-originated steroids. Over 250 PSs have been isolated, and each plant species contains a characteristic phytosterol composition. A wide number of studies have reported remarkable pharmacological effects of PSs, acting as chemopreventive, anti-inflammatory, antioxidant, antidiabetic, and antiatherosclerotic agents. However, PS bioavailability is a key issue, as it can be influenced by several factors (type, source, processing, preparation, delivery method, food matrix, dose, time of administration into the body, and genetic factors), and the existence of a close relationship between their chemical structures (e.g., saturation degree and side-chain length) and low absorption rates has been stated. In this sense, the present review intends to provide in-depth data on PS therapeutic potential for human health, also emphasizing their preclinical effects and bioavailability-related issues.NCM acknowledges the Portuguese Foundation for Science and Technology under the Horizon 2020 Program (PTDC/PSI-GER/ 28076/2017)

Veronica plants-drifting from farm to traditional healing, food application, and phytopharmacology

The Veronica genus, with more than 200 species, belongs to the Plantaginaceae family and is distributed over most of the Northern Hemisphere and in many parts of Southern Hemisphere. These plants are traditionally used in medicine for wound healing, in the treatment of rheumatism, and in different human diseases. This paper reviews the chemical composition of some valuable Veronica species, the possibilities Veronica extracts have in food preservation and as food ingredients, and their functional properties. Veronica species represent a valuable source of biological active secondary metabolites, including iridoid glycosides and phenolic compounds. In particular, due to presence of these phytochemicals, Veronica species exhibit a wide spectrum of biological activities, including antimicrobial and antioxidant. In fact, some studies suggest that some Veronica extracts can inhibit foodborne pathogens, such as Listeria monocytogenes, but only a few of them were performed in food systems. Moreover, anticancer, anti-inflammatory, and other bioactivities were reported in vitro and in vivo. The bioactivity of Veronica plants was demonstrated, but further studies in food systems and in humans are required.M.d.M.C. is grateful for funding from the “Acción 6 del Plan de Apoyo a la Investigación de la Universidad de Jaén, 2017–2019”. N. Martins would like to thank the Portuguese Foundation for Science and Technology (FCT-Portugal) for the Strategic project ref. UID/BIM/04293/2013 and “NORTE2020 – Northern Regional Operational Program” (NORTE-01-0145-FEDER-000012)

Symphytum Species: A Comprehensive Review on Chemical Composition, Food Applications and Phytopharmacology

Symphytum species belongs to the Boraginaceae family and have been used for centuries for bone breakages, sprains and rheumatism, liver problems, gastritis, ulcers, skin problems, joint pain and contusions, wounds, gout, hematomas and thrombophlebitis. Considering the innumerable potentialities of the Symphytum species and their widespread use in the world, it is extremely important to provide data compiling the available literature to identify the areas of intense research and the main gaps in order to design future studies. The present review aims at summarizing the main data on the therapeutic indications of the Symphytum species based on the current evidence, also emphasizing data on both the e cacy and adverse e ects. The present review was carried out by consulting PubMed (Medline), Web of Science, Embase, Scopus, Cochrane Database, Science Direct and Google Scholar (as a search engine) databases to retrieve the most updated articles on this topic. All articles were carefully analyzed by the authors to assess their strengths and weaknesses, and to select the most useful ones for the purpose of review, prioritizing articles published from 1956 to 2018. The pharmacological e ects of the Symphytum species are attributed to several chemical compounds, among them allantoin, phenolic compounds, glycopeptides, polysaccharides and some toxic pyrrolizidine alkaloids. Not less important to highlight are the risks associated with its use. In fact, there is increasing consumption of over-the-counter drugs, which when associated with conventional drugs can cause serious and even fatal adverse events. Although clinical trials sustain the folk topical application of Symphytum species in musculoskeletal and blunt injuries, with minor adverse e ects, its antimicrobial potency was still poorly investigated. Further studies are needed to assess the antimicrobial spectrum of Symphytum species and to characterize the active molecules both in vitro and in vivo

Cucurbita plants: From farm to industry

The Cucurbita genus, a member of Cucurbitaceae family, also known as cucurbits, is native to the Americas. Genus members, like Cucurbita pepo and Cucurbita maxima, have been used for centuries in folk medicine for treating gastrointestinal diseases and intestinal parasites. These pharmacological effects are mainly attributed to their phytochemical composition. Indeed, Cucurbita species are a natural source of carotenoids, tocopherols, phenols, terpenoids, saponins, sterols, fatty acids, functional carbohydrates, and polysaccharides, that beyond exerting remarkable biological effects, have also been increasingly exploited for biotechnological applications. In this article, we specifically cover the habitat, cultivation, phytochemical composition, and food preservative abilities of Cucurbita plants.This work was supported by CONICYT PIA/APOYO CCTE AFB170007. N. Martins would like to thank the Portuguese Foundation for Science and Technology (FCT-Portugal) for the Strategic project ref. UID/BIM/04293/2013 and “NORTE2020-Northern Regional Operational Program” (NORTE-01-0145-FEDER-000012)