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    Insights on the Use of ?-Lipoic Acid for Therapeutic Purposes
    (Mdpi, 2019) Salehi, Bahare; Yilmaz, Yakup Berkay; Antika, Gizem; Tumer, Tugba Boyunegmez; Mahomoodally, Mohamad Fawzi; Lobine, Devina; Akram, Muhammad
    alpha-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 alpha-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.
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    Phytochemical constituents, biological activities, and health-promoting effects of the genus Origanum
    (John Wiley and Sons Ltd, 2021) Sharifi-Rad, Mehdi; Yılmaz, Yakup Berkay; Antika, Gizem; Salehi, Bahare; Boyuneğmez Tümer, Tuğba
    Origanum species are mostly distributed around the Mediterranean, Euro-Siberian, and Iran-Siberian regions. Since time immemorial, the genus has popularly been used in Southern Europe, as well as on the American continent as a spice now known all over the world under the name “oregano” or “pizza-spice.” Origanum plants are also employed to prepare bitter tinctures, wines, vermouths, beer, and kvass. The major components of Origanum essential oil are various terpenes, phenols, phenolic acids, and flavonoids with predominant occurrence of carvacrol and thymol (with reasonable amounts of p-cymen and -terpinene) or of terpinene-4-ol, linalool, and sabinene hydrate. Many species of Origanum genus are used to treat kidney, digestive, nervous, and respiratory disorders, spasms, sore throat, diabetes, lean menstruation, hypertension, cold, insomnia, toothache, headache, epilepsy, urinary tract infections, etc. Origanum essential oil showed potent bioactivities owing to its major constituents' carvacrol, thymol, and monoterpenes. Several preclinical studies evidenced its pharmacological potential as antiproliferative or anticancer, antidiabetic, antihyperlipidemic, anti-obesity, renoprotective, antiinflammatory, vasoprotective, cardioprotective, antinociceptive, insecticidal, and hepatoprotective properties. Its nanotechnological applications as a promising pharmaceutical in order to enhance the solubility, physicochemical stability, and the accumulation rate of its essential oils have been investigated. However, Origanum has been reported causing angioedema, perioral dermatitis, allergic reaction, inhibition of platelet aggregation, hypoglycemia, and abortion. Conclusive evidences are still required for its clinical applications against human medical conditions. Toxicity analyses and risk assessment will aid to its safe and efficacious application. In addition, elaborate structure–activity studies are needed to explore the potential use of Origanum-derived phytochemicals as promising drug candidates.
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    Piper Species: A Comprehensive Review on Their Phytochemistry, Biological Activities and Applications
    (Mdpi, 2019) Salehi, Bahare; Zakaria, Zainul Amiruddin; Gyawali, Rabin; Ibrahim, Salam A.; Rajkovic, Jovana; Shinwari, Zabta Khan; Khan, Tariq
    Piper species are aromatic plants used as spices in the kitchen, but their secondary metabolites have also shown biological effects on human health. These plants are rich in essential oils, which can be found in their fruits, seeds, leaves, branches, roots and stems. Some Piper species have simple chemical profiles, while others, such as Piper nigrum, Piper betle, and Piper auritum, contain very diverse suites of secondary metabolites. In traditional medicine, Piper species have been used worldwide to treat several diseases such as urological problems, skin, liver and stomach ailments, for wound healing, and as antipyretic and anti-inflammatory agents. In addition, Piper species could be used as natural antioxidants and antimicrobial agents in food preservation. The phytochemicals and essential oils of Piper species have shown strong antioxidant activity, in comparison with synthetic antioxidants, and demonstrated antibacterial and antifungal activities against human pathogens. Moreover, Piper species possess therapeutic and preventive potential against several chronic disorders. Among the functional properties of Piper plants/extracts/active components the antiproliferative, anti-inflammatory, and neuropharmacological activities of the extracts and extract-derived bioactive constituents are thought to be key effects for the protection against chronic conditions, based on preclinical in vitro and in vivo studies, besides clinical studies. Habitats and cultivation of Piper species are also covered in this review. In this current work, available literature of chemical constituents of the essential oils Piper plants, their use in traditional medicine, their applications as a food preservative, their antiparasitic activities and other important biological activities are reviewed.
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    Plants of the genus Spinacia: From bioactive molecules to food and phytopharmacological applications
    (Elsevier Science London, 2019) Salehi, Bahare; Tumer, Tugba Boyunegmez; Ozleyen, Adem; Peron, Gregorio; Dall'Acqua, Stefano; Rajkovic, Jovana; Naz, Rabia
    Background: Spinacia plants, including the most recognized species of the genus Spinacia oleacea L. (spinach), have high nutritional value and high content in phytochemicals, such as flavonoids, polyphenols, carotenoids, and ascorbic acid. However, the amount of these phytochemicals depends on several factors, such as genotype, climatic conditions, and agronomic practices, harvesting, storage temperature and time. Scope and approach: This review focus on the therapeutic role of Spinacia genus as well as its contribution as food in industry. A special emphasis is also given to its biological activities including antioxidant and antimicrobial effects. Finally, the clinical efficacy of Spinacia plants, the respective roles, and mechanisms of bioactive compounds on human health are covered. Key findings and conclusions: Spinacia plants are rich in nitrate, thylakoids, glycoglycerolipids and their natural antioxidant mixture (NAO) shows renowned antioxidant, antiproliferative, anti-inflammatory, antimicrobial, anticancer and cardioprotective effects. Thus, the nutritional value and phytochemical composition of Spinacia plants make them an excellent matrix to be used in traditional medicine as also as a natural preservative ingredient in food.
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    Symphytum Species: A Comprehensive Review on Chemical Composition, Food Applications and Phytopharmacology
    (Mdpi, 2019) Salehi, Bahare; Sharopov, Farukh; Tumer, Tugba Boyunegmez; Ozleyen, Adem; Rodriguez-Perez, Celia; Ezzat, Shahira M.; Azzini, Elena
    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 efficacy and adverse effects. 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 effects 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 effects, 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.