Dracocephalum moldavica L. and Melissa officinalis L. : Chemistry and Bioactivities Relevant in Alzheimer’s Disease Therapy

Oksidatiivisen stressin eli liiallisen reaktiivisten happiyhdisteiden määrän soluissa on jo pitkään arveltu olevan tärkeä Alzheimerin taudin kehittymiseen ja etenemiseen vaikuttava tekijä. Tämän vuoksi kiinnostus erilaisten antioksidanttien (yhdisteitä, jotka neutraloivat näitä happiradikaaleja soluissa) mahdollisia terapeuttisia ominaisuuksia Alzheimerin taudin hoidossa on tutkittu laajalti. Tähän mennessä ei kuitenkaan ole vielä onnistuttu löytämään antioksidanttia, joka olisi hyödyksi Alzheimerin taudin hoidossa. Tämän vuoksi on tärkeää pyrkiä löytämään uusia antioksidanttien lähteitä sekä tutkia niistä löytyviä aktiivisia yhdisteitä. Kiinnostus luonnon antioksidantteja kohtaan on kasvanut voimakkaasti viime aikoina. Huomio on kiinnittynyt erityisesti aromaattisista sekä lääkekasveista löytyviin antioksidantteihin. Lamiaceae- perheeseen kuuluvia tuoksuampiaisyrttiä (Dracocephalum moldavica L.) ja sitruunamelissaa (Melissa officinalis L.) on käytetty Iranissa pitkään sekä ruoanlaitossa että lääkinnässä, minkä vuoksi näiden kasvien uutteiden antioksidanttisisältöä päätettiin analysoida käyttäen useaa erilaista in vitro- menetelmää. Näissä kokeissa ilmeni, että uutteilla oli useita antioksidanttisia vaikutuksia. Näistä antioksidanttisista vaikutuksista vastaavia yhdisteitä pyrittiin tunnistamaan käyttäen HPLC-PDA- tekniikkaa, minkä seurauksena niiden havaittiin sisältävän erilaisia polyfenoleita, kuten hydroksyloituneita bentsoeeni- ja cinnamamidihapon johdannaisia sekä flavonoideja. Kummankin kasvin uutteissa runsaimmin esiintynyt yhdiste oli rosmariinihappo. Sitruunamelissaa (M. officinalis) on käytetty antiikin ajoista alkaen kognitiivisten toimintojen häiriöiden hoidossa. Perustuen tietoon kasvin käytöstä perinteisessä lääkinnässä, sen tehoa Alzheimerin taudin hoidossa on tutkittu viime aikoina kliinisin kokein. Sitruunamelissan todettiinkin olevan hyödyksi lievää ja keskivaikeaa Alzheimeimerin tautia sairastavien potilaiden hoidossa. Väitöskirjan osanan olevasta kooste-artikkelista käy ilmi, että tutkimalla lääkekasvien ominaisuuksia voidaan saada arvokkaita suuntaa-antavia vihjeitä Alzheimerin taudin lääkehoidon kehittämiseen. Tämän perusteella päätettiinkin testatata myös sitruunamelissauutteen kykyä estää asetyylikoliiniesteraasin (AChE) toimintaa, koska tämän entsyymin toiminna estämisen tiedetään olevan hyödyksi Alzheimerin taudin hoidossa. Uute kykeni estämään AChE:n toimintaa, minkä vuoksi uutteen sisältämiä komponentteja päätettiin tutkia terkemmin. Uute jaettiin erilaisiin fraktioihin käyttäen HPLC-menetelmää, minkä jälkeen testattiin jokaisen fraktion kykyä inhiboida AchE. Suurin osa fraktioista kykeni inhiboimaan AChE:n toimintaa selkeästi tehokkaammin, kuin raakauute. Kaikista tehokkainta fraktiota analysoitiin tarkemmin sen aktiivisten yhdisteiden tunnistamiseksi, minkä seurauksena sen sisältämät yhdisteet tunnistettiin cis ja trans-rosmariinihapoiksi. Tässä tutkimuksessa tunnistettujen yhdisteiden hyödyllisyyttä Alzheimerin taudin hoidossa tulisi seuraavaksi tutkia erilaisissa in vivo-malleissa. Lisäksi jäljellä olevien fraktioiden kemiallinen koostumus tulisi selvittää sekä antioksidanttiaktiivisuuden ja AChE:n toiminnan inhiboinnin välistä mahdollista yhteyttä tulisi tutkia tarkemmin. Tämä tutkimus osoittaa tuoksuampiasyrtin (D. moldavica) sekä sitruunamelissan (M. officinalis) sisältävän monenlaisia aktiivisia antioksidantteja. Lisäksi sitruunamelissan sisältämät yhdisteet kykenivät estämään asetyylikoliiniesteraasin (AchE) toimintaa. Nämä tulokset tukevat osaltaan väitöskirjan osana olevan kooste-artikkelin johtopäätöksiä, joiden mukaan etnofarmakologinen kasvitutkimus voi osoittautua erittäin hyödylliseksi kehitettäessä uutta lääkehoitoa Alzheimerin tautiin. Lisäksi tässä väitöskirjassa kuvattu tutkimus osoittaakin, että perinteisesti lääkekasvina käytettyä sitruunamelissaa voidaan mahdollisesti hyödyntää uusien Alzheimerin taudin hoitoon käytettävien lääkkeiden kehityksessä.Oxidative stress has been proposed to play a cardinal role in the aetiology and pathogenesis of Alzheimer’s disease (AD). Therefore, antioxidants have been studied for their therapeutic potential in AD therapy. However, there is still a need for novel sources of antioxidants. Recently, there has been an increased interest in aromatic and medicinal plants as sources of natural antioxidants. The plants Dracocephalum moldavica L. and Melissa officinalis L., which belong to the family Lamiaceae, have been used in Iran for their culinary usefulness and medicinal properties. Therefore, extracts of the plants were screened for antioxidant properties in a battery of in vitro assays. The plant extracts demonstrated a wide range of antioxidant activities. Furthermore, because it was important to determine which constituents present within the extracts may contribute to the observed activity, compositional fingerprint analyses were carried out using HPLC-PDA techniques. The extracts were found to contain polyphenolic compounds such as hydroxylated benzoic and cinnamic acid derivatives and flavonoids. Rosmarinic acid was the most abundant constituent in both plants. The plant M. officinalis has been used since antiquity in the treatment of cognitive dysfunction. The plant was recently assessed for its clinical efficacy against AD and was found to be effective in the management of mild to moderate AD patients. According to a review carried out by the author, screening of medicinal plants for bioactivities relevant in the treatment AD can provide useful leads in the discovery of drugs against AD. Therefore, in addition to antioxidant evaluation, M. officinalis was screened for another bioactivity relevant to AD therapy, viz. acetylcholinesterase (AChE) inhibition. The plant extract showed AChE inhibitory activity, which formed the basis for activity guided fractionation. The extract was fractionated using semipreparative scale HPLC fractionation. Fractions were subsequently subjected to AChE inhibitory screening. Most of the fractions demonstrated inhibitory activity and were proved to be significantly (P < 0.05) more potent than the crude extract. This is an indication of the complex nature of potential interactions between various components within the extract. The contents of the most potent fraction were tentatively identified as a mixture of cis- and trans-rosmarinic acid using LC-DAD-MS and NMR techniques. There is a need to further investigate the efficacy of these chemical constituents in in vivo AD models. The remaining potent fractions should be analysed further to determine the identity of their chemical constituents and the possibility of a correlation existing between antioxidant activity and AChE inhibition should be investigated. The current study showed the multifaceted nature of antioxidant action of D. moldavica and M. officinalis. Furthermore, the latter demonstrated AChE inhibitory activity. A review of the potential benefits of ethnopharmacological screening of plants in AD therapy was made and the importance of bioactivity guided screening and fractionation of medicinal plants was highlighted. It can be concluded that M. officinalis is a potential source for discovery and development of drugs against AD

Solving the Jigsaw Puzzle of Wound-Healing Potato Cultivars: Metabolite Profiling and Antioxidant Activity of Polar Extracts

Potato (Solanum tuberosum L.) is a worldwide food staple, but substantial waste accompanies the cultivation of this crop due to wounding of the outer skin and subsequent unfavorable healing conditions. Motivated by both economic and nutritional considerations, this metabolite profiling study aims to improve understanding of closing layer and wound periderm formation and guide the development of new methods to ensure faster and more complete healing after skin breakage. The polar metabolites of wound-healing tissues from four potato cultivars with differing patterns of tuber skin russeting (Norkotah Russet, Atlantic, Chipeta, and Yukon Gold) were analyzed at three and seven days after wounding, during suberized closing layer formation and nascent wound periderm development, respectively. The polar extracts were assessed using LC-MS and NMR spectroscopic methods, including multivariate analysis and tentative identification of 22 of the 24 biomarkers that discriminate among the cultivars at a given wound-healing time point or between developmental stages. Differences among the metabolites that could be identified from NMR- and MS-derived biomarkers highlight the strengths and limitations of each method, also demonstrating the complementarity of these approaches in terms of assembling a complete molecular picture of the tissue extracts. Both methods revealed that differences among the cultivar metabolite profiles diminish as healing proceeds during the period following wounding. The biomarkers included polyphenolic amines, flavonoid glycosides, phenolic acids and glycoalkaloids. Because wound healing is associated with oxidative stress, the free radical scavenging activities of the extracts from different cultivars were measured at each wounding time point, revealing significantly higher scavenging activity of the Yukon Gold periderm especially after 7 days of wounding

Chemical composition and in vitro antioxidant evaluation of a water-soluble Moldavian balm (Dracocephalum moldavica L.) extract

WOS: 000241664300008The chemical composition and antioxidant properties of a water-soluble extract of Moldavian balm (Dracocephalum moldavica L., syn. Moldavian dragonhead) prepared by hydrodistillation are presented in this study. The total phenol content was estimated as gallic acid equivalents by the Folin-Ciocalteu reagent method, while the qualitative-quantitative composition of the extract was determined by high performance liquid chromatography coupled with photodiode array detection. The antioxidant properties assessed included iron(III) reduction and iron(II) chelation and 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) and superoxide anion free radical scavenging. In addition, the ability of the extract to protect 2-deoxy-D-ribose and bovine brain-derived phospholipids against hydroxyl radical-mediated degradation was assessed. The extract principally contained polar compounds including hydroxycinnamic acids and flavonoids, with caffeic and ferulic acids, lutcolin-7-O-glucoside, rosmarinic acid, luteolin and apigenin being identified from their chromatographic behavior and spectral characteristics. The Moldavian balm extract demonstrated activity in all the antioxidant assays; however, it was not as potent as the positive control except in the phospholipid-based assay where its hydroxyl radical scavenging activity was statistically indistinguishable from that demonstrated by Pycnogenol

Metabolite Profiling of Jaboticaba (Myrciaria cauliflora) and Other Dark-Colored Fruit Juices

Many dark-colored fruit juices, rich in anthocyanins, are thought to be important for human health. Joboticaba (Myrciaria cauliflora) fruits, native to Brazil, have phenolics including anthocyanins and are processed into juice and other products. The phenolic constituents in the fruits of jaboticaba were studied by high-performance liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry. Twenty-two compounds were identified or tentatively determined by detailed analysis of their mass spectral fragmentation patterns; 11 compounds including 7 gallotannins, 2 ellagic acid derivatives, syringin, and its glucoside were detected for the first time in the fruit. The compositional differences among the fruit extracts and their commercial products were also compared by principal component analysis; two anthocyanins, delphinidin 3-<i>O</i>-glucoside and cyanidin-3-<i>O</i>-glucoside, as well as two depsides, jaboticabin and 2-<i>O</i>-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxyphenylacetic acid, present in the fruit extracts were not detected unexpectedly in commercial jaboticaba juice or jam. Therefore, the stability of anthocyanins in jaboticaba fresh fruits and products has been compared directly with that of other dark-colored fruit products made from blueberry and Concord grape, and the same trend of decreasing amounts of anthocyanins was observed in all tested products. The antioxidant activities (DPPH^• and ABTS^•+) of jaboticaba fresh fruit extract and commercial samples were also compared. Principal component analysis proved to be a useful way to discern changes between fresh and processed fruits. Jaboticaba is a promising fruit with antioxidant capacity similar to those of other so-called superfruits; however, during processing the levels of some of anthocyanins and other polyphenols decrease significantly, and therefore the capacity of these products to affect human health may vary significantly from that of the fresh fruit