A Focused Review on Cognitive Improvement by the Genus Salvia L. (Sage)-From Ethnopharmacology to Clinical Evidence.

Ethnopharmacology has been an important starting point in medical and pharmaceutical sciences for discovering drug candidates from natural sources. In this regard, the genus Salvia L., commonly known as sage, is one of the best-known medicinal and aromatic plants of the Lamiaceae family; it has been recorded as being used for memory enhancement in European folk medicine. Despite the various uses of sage in folk medicines, the records that have pointed out sage's memory-enhancing properties have paved the way for the aforementioned effect to be proven on scientific grounds. There are many preclinical studies and excellent reviews referring to the favorable effect of different species of sage against the cognitive dysfunction that is related to Alzheimer's disease (AD). Hence, the current review discusses clinical studies that provide evidence for the effect of Salvia species on cognitive dysfunction. Clinical studies have shown that some Salvia species, i.e., hydroalcoholic extracts and essential oils of S. officinalis L. and S. lavandulaefolia leaves in particular, have been the most prominently effective species in patients with mild to moderate AD, and these species have shown positive effects on the memory of young and healthy people. However, the numbers of subjects in the studies were small, and standardized extracts were not used for the most part. Our review points out to the need for longer-term clinical studies with higher numbers of subjects being administered standardized sage preparations.

Investigation of cytotoxic and apoptotic effects of 63 compounds obtained from Salvia species: Promising anticancer agents.

Since ancient time, Salvia L. species have been commonly used to treat colds, bronchitis, tuberculosis, heart diseases, and menstrual and digestive disorders in traditional medicine all around the world. They have been also used as tea and spice. Studies indicated that diterpenes and triterpenes isolated from Salvia species possess various pharmacological and biological effects such as anti-inflammatory, antiviral, cytotoxic, antioxidant, and hepatotoxic activities. Flavones were also shown to have antimicrobial, antioxidant, and cytotoxic potentials. Salvia extracts also exhibit anti-Alzheimer, antiseptic, cardiovascular, antihypertensive, and antituberculous effects. To investigate the effects of 63 secondary metabolites from Salvia species on cell viability and apoptosis, Salvia secondary metabolites including 25 phenolics, 4 fatty acids, 19 abietane diterpenoids, 12 triterpenoids, and three steroids were examined on healthy cell line (PDF), breast cancer (MCF-7), and colon cancer (HT-29) cell lines using MTT method. In addition, the effects of rosmarinic acid, 6,7-dehydroroyleanone, acetyl royleanone, ferruginol, carnosic acid, carnosol, cryptotanshinone, ß-sitosterol, and ursolic acid on pro-apoptotic Bax and antiapoptotic Bcl-2 protein expression levels were investigated by Western Blot method. PRACTICAL APPLICATIONS: Phenolic compounds (apigenin, chrysin, and luteolin) and diterpenes (especially dihydrotanshinone I, carnosic acid, and carnosol), and almost all of the triterpenes exhibited high toxic effects on healthy cell line. Cytotoxic effects of cryptotanshinone, 12-hydroxy abieta-1,3,5(10),8,11,13-hexaene, 12-demethylmulticauline, 6,7-dehydroroyleanone, acetyl royleanone, ferruginol, ursolic acid, and 3-acetyl lupeol were relatively higher than their toxic effects. Acetyl royleanone, 6,7-dehydroroyleanone, carnosic acid, and cryptotanshinone were found to have anticancer potential based on their modulating effects on the expression levels of Bax and Bcl-2 proteins which play important roles in the regulation of apoptosis. The results of the present study showed that acetyl royleanone, cryptotanshinone, 6,7-dehydroroyleanone, carnosic acid, and cryptotanshinone have potential to be used in the pharmaceutical industry.

Insight into isolation and elucidation of cytotoxic ergostanoids from the mushroom Sarcosphaera crassa (Santi) Pouzar: An edible mushroom.

Sarcosphaera crassa is a mushroom consumed in Europe and Anatolia after being cooked well. The cytotoxic activity of the extracts of unbaked S. crassa against MCF7, HT29, HeLa cancer cell lines and toxicity against PDF fibroblast healthy cell lines were studied using MTT assay. Acetone and methanol extracts of the mushroom exhibited significant cytotoxic activity. Further investigation of cytotoxic extracts afforded two new fatty acid sterols (1-2), a new ergosterol glycoside (4), and seven known compounds, including a fatty acid sterol (3), a steroid glycoside (5), two ergostanoids (6-7) and three sugars (8-10). These compounds were identified as brassicasteryl heptadecanoate (1), brassicasteryl palmitoleate (2), brassicasteryl linoleate (3), brassicasterol ß-ᴅ-xylofuranoside (4), brassicasterol ß-ᴅ-glucoside (5), brassicasterol (6), ergosterol-endoperoxide (7), mannitol (8), erythritol (9) and turanose (10). Among them, 7 exhibited a moderate cytotoxic activity against HeLa (IC50: 70.1 ± 2.0 µg/mL) and high activity against HT29 (IC50: 38.8 ± 0.9 µg/mL), and MCF7 (IC50: 62.9 ± 1.3 µg/mL) cancer cell lines. Compounds 4, 5, and 6 also exhibited significant cytotoxic activity against HT29 and MCF7. Moreover, all compounds exhibited weak toxicity against PDF healthy cell lines. This study indicates the potential use of Sarcosphaera crassa as a natural source of cytotoxic ergostanoids, which can be considered a dietary supplement for cancer prevention.

Phytochemical Contents of Different Parts of the Seeded Raisins from the South-East Anatolia: Enzyme Inhibitory Potential of Pulp Extracts.

In this study, some phytochemical properties of six seeded raisin species that are mainly cultivated in Southeastern Anatolia were investigated. Additionally, some physical and quality characteristics, phenolic contents (by LC-MS/MS; Liquid Chromatography Tandem Mass/Mass Spectrometer System), anticholinesterase, and antioxidant capacities (DPPH; 2,2-diphenyl-1-picrylhydrazyl free-radical scavenging, ABTS; 2,2-azinobis(3-ethylbenzothiazoline-6-sulphonic acid cation-radical scavenging activity and CUPRAC; cupric reducing antioxidant capacity) of the cultivars were investigated on ground raisins. In all three methods, the antioxidant activity values of seed extracts were determined to be higher than those of leaf and pulp extracts. Remarkably, the seed extract of Banazi Siyahi showed the highest antioxidant activity in ABTS (IC50 : 4.35±0.02 µg/mL), DPPH (IC50 : 10.78±0.78 µg/mL), and CUPRAC (A0.5: 9.33±0.45 µg/mL) methods. Additionally, the ethanol extracts of all pulp samples showed higher anticholinesterase activity against acetyl-(AChE) and butyrylcholinesterase (BChE) enzymes than galantamine. According to the LC-MS/MS results, catechin (21.362 mg analyte/g extract) and epicatechin (44.667 mg analyte/g extract) found to be quite rich in Kerküs seed extract and isoquercitrin (116.873 mg analyte/g extract) and astragalin (31.915 mg analyte/g extract) detected to be quite rich in Banazi Siyahi leaf extract. Considering the mineral content of the varieties and the soil samples they grow in, all of the grape varieties analyzed in the study was found to be rich. Based on these findings, it might be suggested that Banazi Siyahi and Kerküs varieties have potential to be utilized in pharmaceutical and food industries, due to their contents of catechins, isoquercitrin and astragalin.

Determination of essential oil and biological activities of Hypericum ternatum Poulter and H. scabrum L. species collected from different localities: is H. scabrum an alternative to multifunctional species ST JOHN'S WORT (H. perforatum)?

The importance of Hypericum L. species, being used in traditional medicine, in the scientific world is increasing day by day. Hypericum species are plants that have been used in the treatment of many diseases for a long time and have healing properties. In the current study, the essential oil compositions of Hypericum scabrum L. and H. ternatum Poulter collected from different localities in Turkey were determined by GC-MS/FID. In addition, their antioxidant, cytotoxic, and antimicrobial activities with their enzyme inhibitory potentials (cholinesterase, urease, tyrosinase, elastase, and collagenase) were investigated. Also, in vitro and in silico studies of the major components of the species have been carried out on the studied enzymes. It was determined that four H. scabrum samples mainly contained α-pinene (55.99%-62.80%) while three H. ternatum samples contained 2-methyloctane (9.45%-22.39%) and α-pinene (12.75%-33.08%). While H. scabrum essential oils possessed significant biological activity potential except for the antimicrobial activity, H. ternatum samples did not. All essential oil samples of H. scabrum exhibited a high cytotoxic effect (IC50 21.67 ± 0.34 to 34.67 ± 0.45 µg/mL) against colon cancer cell line (HT-29) and indicated higher acetyl-(Inhibiton% 83.30 ± 1.90 to 93.08 ± 1.04) and butyryl-cholinesterase (Inhibiton% 80.58 ± 1.19 to 93.28 ± 1.99) inhibitory activity than the standard compound, galantamine. Furthermore, all samples of H. scabrum showed high tyrosinase (Inhibiton% 69.00 ± 1.64 to 95.25 ± 1.42) and elastase (Inhibiton% 27.58 ± 0.34 to 36.69 ± 0.18) inhibitory effects. These biological activity results indicated that H. scabrum essential oil could be used in the cosmetic and pharmaceutical industries.

Determination of fingerprints contents of different extracts and parts of six endemic Salvia taxa by GC-MS: Source species for valuable compounds with drug or drug potential.

Public use of Salvia species and their importance in the scientific world is continually increasing. It is known that this use and the importance of Salvia species are mostly due to the terpenoid compounds that they contain. In this context, the terpenoid-steroid-flavonoid contents of extracts of six endemic Salvia (S. kurdica, S. pseudeuphratica, S. rosifolia, S. siirtica, S. cerino-pruinosa var. cerino-pruinosa and S. cerino-pruinosa var. elazigensis) species prepared with different solvents were determined by gas chromatography-mass spectrometry. Within the framework of the ingredient analysis, content analysis of the ethanol extracts of the root, branch, leaf and flower parts of the species collected in the same period between 2015 and 2017 years was performed. In general, extracts prepared with chloroform and ethanol were found to contain a wide variety of compounds while petroleum ether extracts were found to contain much less varied compounds. In addition, in general, root extracts are richer in terpenoid compounds than aerial part extracts. Some species can be used as source species in terms of ferruginol, cryptanol, 6,7-dehydroroyleanone, lup-(20)29-ene-2α-hydroxy-3ß-acetate, salvigenin and ß-sitosterol contents (52,114.28, 75,979.08, 101,247.41, 40,071.29, 33,952.13 and 34,010.90 µg analyte/g extract, respectively).

Development and Validation of a Novel LC-MS/MS Method for the Quantitation of 19 Fingerprint Phytochemicals in Salvia Species: A Chemometric Approach.

Being traditionally utilized mainly as appetizers and herbal teas as well as used to ease abdominal pains, colds and gastrointestinal issues, the genus Salvia L. has gained significant consideration owing to its remarkable phytochemicals and industrial importance. The present study aimed to develop and validate an LC-MS/MS method for the qualitative and quantitative investigation of 19 fingerprint phytochemicals in six endemic Salvia species. The validation parameters of the developed LC-MS/MS method were repeatability (intermediate precision), recovery (accuracy), limits of detection and quantification, linearity and uncertainty (U% at 95% confidence level (k = 2)). Reversed-phase HPLC separation and mass spectrometry parameters were optimized for each analyte. Ethanol extracts of the studied Salvia species collected in three consecutive years were screened for their fingerprint phytochemicals by using the developed and validated LC-MS/MS method. Moreover, studied Salvia species were subjected to multivariate analysis such as principal component analysis techniques to demonstrate the variabilities in phytochemical contents by years and parts of the samples. Roots, flowers, leaves, branches and whole plant of the Salvia species collected in 2015, 2016 and 2017 were used for the analyses. It was observed that the roots and branches of Salvia species were similar in terms of their salvianolic acid A, caffeic acid, and 6,7-dehydroroyleanone components. Accordingly, apigenin, rosmarinic acid, luteolin 7-O-glucoside, caffeic acid, salvianolic acid B, and 6,7-dehydroroyleanone were notable phytochemicals that were present in the studied Salvia species.

Cannabinoids for SARS-CoV-2 and is there evidence of their therapeutic efficacy?

To combat the coronaviruses and their novel variants, therapeutic drugs and the development of vaccines that are to be effective throughout human life are urgently needed. The endocannabinoid system (ECS) acts as a modulator in the activation of the microcirculation, immune system, and autonomic nervous system, along with controlling pharmacological functions such as emotional responses, homeostasis, motor functions, cognition, and motivation. The ECS contains endogenous cannabinoids, cannabinoid receptor (CBRs), and enzymes that regulate their biosynthesis, transport, and degradation. Moreover, phytocannabinoids and synthetic cannabinoids that mimic the action of endocannabinoids also play an essential role in the modulation of the ECS. Cannabinoids, the main constituents of cannabis (Cannabis sativa L.), are therapeutic compounds that have received international attention in the health field due to their therapeutic properties. Recently, they have been tested for the treatment of COVID-19 due to their antiviral properties. Indeed, cannabinoid-type compounds, and in particular cannabidiol (CBD), isolated from glandular trichomes found in the calyx of cannabis flowers with reported antiviral properties is hypothesized to be a therapeutic option in the ministration of SARS-CoV-2 consorted with COVID-19 disease. The relevant articles were determined from the database search published mainly in Web of Science, Google scholar, PubMed, Crossref, and ClinicalTrials.gov database during the pandemic period. The articles were evaluated for the therapeutic potentials, mechanisms of action of cannabinoids, the roles of the ECS in the immune system, impact of cannabinoids in SARS-CoV-2 septic, especially if they address the application of cannabinoids as drugs for the curability and management of SARS-CoV-2 and its novel variants. Although the evidence needed to be considered using cannabinoids in the control and treatment of viral diseases is currently in its infancy, they already offer an opportunity for clinicians due to their effects in relieving pain, improving appetite, and improving childhood epilepsy, especially in cancer and human immunodeficiency virus (HIV/AIDS) patients. In addition to these, the most recent scientific evidence emphasizes their use in the treatment of the coronavirus infected patients. In brief, all preclinic and clinic studies that have been reported show that, through the cannabinoid system, cannabinoids, particularly CBD, have many mechanisms that are effective in the treatment of patients infected by SARS-CoV-2. Thus, more extensive studies are necessary in this area to fully identify the effects of cannabinoids on SARS-CoV-2.

Identification of Phenolic Compounds by LC-MS/MS and Evaluation of Bioactive Properties of Two Edible Halophytes: Limonium effusum and L. sinuatum.

This work aimed to evaluate the phenolic content and in vitro antioxidant, antimicrobial and enzyme inhibitory activities of the methanol extracts and their fractions of two edible halophytic Limonium species, L. effusum (LE) and L. sinuatum (LS). The total phenolic content resulted about two-fold higher in the ethyl acetate fraction of LE (522.82 ± 5.67 mg GAE/g extract) than in that of LS (274.87 ± 1.87 mg GAE/g extract). LC-MS/MS analysis indicated that tannic acid was the most abundant phenolic acid in both species (71,439.56 ± 3643.3 µg/g extract in LE and 105,453.5 ± 5328.1 µg/g extract in LS), whereas hyperoside was the most abundant flavonoid (14,006.90 ± 686.1 µg/g extract in LE and 1708.51 ± 83.6 µg/g extract in LS). The antioxidant capacity was evaluated by DPPH and TAC assays, and the stronger antioxidant activity in ethyl acetate fractions was highlighted. Both species were more active against Gram-positive bacteria than Gram negatives and showed considerable growth inhibitions against tested fungi. Interestingly, selective acetylcholinesterase (AChE) activity was observed with LE and LS. Particularly, the water fraction of LS strongly inhibited AChE (IC50 = 0.199 ± 0.009 µg/mL). The ethyl acetate fractions of LE and LS, as well as the n-hexane fraction of LE, exhibited significant antityrosinase activity (IC50 = 245.56 ± 3.6, 295.18 ± 10.57 and 148.27 ± 3.33 µg/mL, respectively). The ethyl acetate fraction and methanol extract of LS also significantly inhibited pancreatic lipase (IC50 = 83.76 ± 4.19 and 162.2 ± 7.29 µg/mL, respectively). Taken together, these findings warrant further investigations to assess the potential of LE and LS as a bioactive source that can be exploited in pharmaceutical, cosmetics and food industries.

Phytochemical Fingerprints and Bioactivities of Ripe Disseminules (Fruit-Seeds) of Seventeen Gundelia (Kenger-Kereng Dikeni) Species from Anatolia with Chemometric Approach.

Gundelia species are known as "Kenger-kereng dikeni" in Anatolia, and their aerial parts are consumed as food. Also, roots and seeds (disseminules) of the Gundelia species are used to prepare gum and coffee. The chemical contents of ethanol and hexane extracts of disseminules of 17 Gundelia species, 13 of them are endemic, were studied using LC/MS/MS and GC/MS. Additionally, their antioxidant potential and enzyme inhibitory capacity against acetyl- and butyryl-cholinesterase, urease, and tyrosinase were determined. The unsaturated fatty acid ratios of Gundelia species were higher than their saturated fatty acid ratio. The highest sum of oleic and linoleic acid was detected in G. tournefortii var. tenuisecta (70.42 %). ß-Sitosterol, α-amyrin, 3-acetyllupeol were identified in 17 Gundelia species by GC/MS, while chlorogenic acid and luteolin by LC/MS/MS as major compounds. The ethanol and hexane extracts of G. siirtica, G. rosea, and G. mesopotamica indicated good cholinesterase inhibitory activity. Among all species, ethanol extract of G. colemerikensis exhibited the best activity in ABTS (IC50 : 32.30±0.98 µg/mL), DPPH (IC50 : 59.91±0.89 µg/mL), and CUPRAC (A0.5 : 57.41±1.03 µg/mL) assays. Ethanol extract of G. colemerikensis also displayed the highest inhibitory activity against butyrylcholinesterase (51.14±0.25 % at 200 µg/mL), urease (51.71±1.75 % at 200 µg/mL), and tyrosinase (39.50±0.85 % at 200 µg/mL) enzymes. According to the chemometric analysis of fatty acids, four groups were observed. Therefore, it is suggested that G. colemerikensis can be used in the pharmaceutical, food, and cosmetic industries due to its antioxidant and enzyme inhibition properties.

A Detailed Chemical and Biological Investigation of Twelve Allium Species from Eastern Anatolia with Chemometric Studies.

Allium species are widely consumed as food all over the world. The phenolic profile of ethanol extracts of aerial parts and roots of 12 Allium species, collected from five different Eastern Anatolia regions, were studied using LC-MS/MS. In vitro antioxidant, anticholinesterase, cytotoxic and antimicrobial activities were also tested. The multivariate analyses were performed using principal component and hierarchical cluster analyses. Seventeen of 27 standard compounds were detected in all Allium species. The major components were mainly identified as quinic acid, malic acid, vanillin, and p-coumaric acid. The aerial parts possessed better antioxidant activity than roots. Aerial parts of A. atroviolaceum, A. chrysantherum, A. kharputense, and A. shirnakiense exhibited high cytotoxic activity against DLD-1 colon cancer cell lines (IC50 12.5 µg/mL). A. shatakiense and A. vineale demonstrated good antimicrobial activity against S. aureus and E. coli (MIC 75 µg/mL). According to chemometric analysis, differences were detected between aerial parts and the roots. The aerial parts of A. atroviolaceum, A. chrysantherum, A. kharputense, and A. shirnakiense could be potent in the pharmaceutical industry while A. shatakiense and A. vineale in the food industry after further investigations.

A GC-MS method validation for quantitative investigation of some chemical markers in Salvia hypargeia Fisch. & C.A. Mey. of Turkey: Enzyme inhibitory potential of ferruginol.

In the present study, a GC-MS method used for quantitative screening of 26 compounds (sclareolide, sclareol, ferruginol, cryptanol, 6,7-dehydroroyleanone, suginal, 9,10-dihydro-7,8-dimethyl-2-(1-methylethyl) phenanthren-3-ol, sugiol, inuroyleanone, 12-demethylmulticauline, 7α-hydroxy-ß-sitosterol, stigmasterol, sitosterol, salvigenin, sinensetin, α-amyrin, lupeol, lupenone, 3-acetyl lupeol, 1α,21α-dihydroxy-2,3-(1'1'-dimethyl-dioxymethylene) urs-9(11),12-dien, uvaol, betulin, pyxinol, lup-(20),29-ene-2α-hydroxy-3ß-acetate, betulin 3ß, 28ß-diacetate, 21α-hydroxy,2α,3ß-diacetoxy urs-9(11),12-dien) specific to Turkish Salvia species was developed and validated. According to the GC-MS analysis results, Salvia hypargeia Fisch. & C.A. Mey. roots were found to be rich in ferruginol (30787.97 µg/g extract) and lupenone (23276.21 µg/g extract), and leaves in lupeol (20625.92 µg/g extract). Additionally, the essential oil and aroma contents of this species were identified by GC-MS technique. According to the LC-MS/MS results, especially S. hypargeia leaf extract was rich in rosmarinic acid (38035.7 µg/g extract) and isoquercitrin (4136.91 µg/g extract). Furthermore, anticholinesterase, antiurease, antityrosinase and antielastase inhibitory, antioxidant, cytotoxic activities of the ethanol extracts, essential oil, and major components of the species were evaluated. Antioxidant potentials of all extracts of this species were quite high in all studied antioxidant methods. Moreover, butyrylcholinesterase and elastase inhibitory capacities of ferruginol, the major component of S. hypargeia roots, were notable. For these reasons, this species has a high potential for food and pharmaceutical industries. PRACTICAL APPLICATIONS: This new GC-MS method was applied to S. hypargeia Fisch. & C.A. Mey. and it indicated that this species possessed high amount of ferruginol and lupeol, and that this species could be used for their natural sources. According to the results of the activity studies (antioxidant, anticholinesterase, tyrosinase, elastase, and cytotoxic), this method was used to exhibit which compound may be responsible for the activities. This developed and validated method could be easily applied to determine major/active/toxic secondary metabolites of Salvia species which are used and/or could be used in pharmaceutical, cosmetic, and food industries.

Selective in vitro and in silico enzymes inhibitory activities of phenolic acids and flavonoids of food plants: Relations with oxidative stress.

In this study, the inhibitory potentials of food originated 34 phenolic acids, and flavonoid compounds were screened against acetylcholinesterase, butyrylcholinesterase, urease, and tyrosinase enzymes. All compounds included in this study exhibited high antioxidant activity with an ignorable cytotoxic activity. In general, they also showed poor anti-urease and anti-tyrosinase activities. Compounds in aglycone form (quercetin, myricetin, chrysin, and luteolin) showed strong anticholinesterase activities. No relation was observed between the tested bioactivities except from the case that aglycone compounds exhibited a strong positive relationship between antioxidant activities and anticholinesterase activity. Interestingly, there was a relation between the molecular weights of aglycone compounds and their anticholinesterase activities. The study showed that flavonoids with molecular mass of 250-320 g/mol have high potential of anticholinesterase activities and are valuable for future experiments on animals and humans. Potential inhibitory effects of these molecules on target proteins were investigated using docking and molecular dynamics calculations.

A Detailed Biological and Chemical Investigation of Sixteen Achillea Species' Essential Oils via Chemometric Approach.

Representatives of the Achillea genus are widely used as foods or nutraceuticals. Considering the increasing demand for herbal dietary supplements with health promoting effects, the objective of this research was to evaluate the chemical composition and biological activities of the essential oils obtained from sixteen Achillea species (A. biebersteinii, A. wilhelmsii subsp. wilhelmsii, A. aleppica subsp. zederbaueri, A. vermicularis, A. monocephala, A. nobilis, A. goniocephala, A. sintenisii, A. coarctata, A. kotschyi subsp. kotschyi, A. millefolium subsp. millefolium, A. lycaonica, A. spinulifolia, A. teretifolia, A. setacea, and A. schischkinii). Anticholinesterase, antiurease, antityrosinase enzymes inhibition, antioxidant, antimicrobial, toxic and cytotoxic activities of obtained essential oils were investigated. DPPH activities were found to be very low in all studied samples, while ABTS and CUPRAC antioxidant activities were found to be moderate. In addition, all samples were found to have moderate anticholinesterase and antimicrobial effects. It has been determined that the studied species have low cytotoxicity and high toxicity. Besides, chemical composition of the essential oils were determined by GC/MS and the results were chemometrically analyzed. The chemometric analyses of Achillea species collected from nine different regions were accomplished by principal component analysis (PCA) and hierarchical cluster analysis (HCA) techniques. According to the PCA analysis, A. nobilis subsp. neilreichii was found to be different from all studied species in terms of essential oil composition. The major components found in these species were piperitone, camphor, α-terpinene, eucalyptol, artemisia ketone, endo-borneol, ß-eudesmol and verbenol. The fact that camphor was toxic and found in majority of the studied species stands out as a remarkable result.

Inhibition of Amyloid ß Aggregation Using Optimized Nano-Encapsulated Formulations of Plant Extracts with High Metal Chelator Activities.

BACKGROUND: The role of Fe+2, Cu+2 and Zn+2 in facilitating aggregation of Amyloid ß (Aß) and consequently, the progression of Alzheimer's disease (AD) is well established. OBJECTIVE: Development of non-toxic metal chelators is an emerging era in the treatment of AD, in which complete success has not been fully achieved. The purpose of this study was to determine plant extracts with high metal chelator and to encapsulate them in nano-micellar systems with the ability to pass through the Blood Brain Barrier (BBB). METHODS: Extracts of 36 different Anatolian plants were prepared, total phenolic and flavonoid contents were determined, and the extracts with high content were examined for their Fe+2, Cu+2 and Zn+2 chelating activities. Apolipoprotein E4 (Apo E) decorated nano-formulations of active extracts were prepared using Poly (Lactide-co-Glycolide) (PLGA) (final product ApoEPLGA) to provide BBB penetrating property. RESULTS: Verbascum flavidum aqueous extract was found as the most active sample, incubation of which, with Aß before and after metal-induced aggregation, resulted in successful inhibition of aggregate formation, while re-solubilization of pre-formed aggregates was not effectively achieved. The same results were obtained using ApoEPLGA. CONCLUSION: An optimized metal chelator nano-formulation with BBB penetrating ability was prepared and presented for further in-vivo studies.

A comprehensive LC-MS/MS method validation for the quantitative investigation of 37 fingerprint phytochemicals in Achillea species: A detailed examination of A. coarctata and A. monocephala.

The current study aims to optimize and validate a comprehensive LC-MS/MS method for the quantification of 37 phytochemicals (15 phenolic acids, 17 flavonoids, 3 non-phenolic organic acids, 1 phenolic aldehyde and 1 benzopyrene) in Achillea species. Though Achillea species were chosen as real life samples, the current method is applicable to a wide range of plant species. The developed method was fully validated in terms of linearity, accuracy (recovery), inter-day and intra-day precision (repeatability), limits of detection and quantification (LOD/LOQ) and relative standard uncertainty (U% at 95% confidence level (k = 2)). Reversed-phase ultrahigh performance liquid chromatography was optimized to achive optimum separation for 37 phytochemical compounds and to overcome the suppression effects. MS detection was performed using a triple quadrupole mass spectrometer and negative or positive ionization modes were optimized for each analyte. Multiple reaction monitoring (MRM) was used to quantify the analytes, related molecular ions and transition ions were optimized. Phytochemical screening of ethanol and methanol-chloroform extracts of root and aerial parts of A. coarctata and A. monocephala were performed by using the developed and validated LC-MS/MS method. Root and aerial parts of both species have considerable amounts of certain phenolic-nonphenolic acids (quinic, malic, fumaric, chlorogenic and vanillic acids) and flavonoids (rutin, hesperidin, isoquercitrin, apigetrin, luteolin, apigenin). Additionally, total phenolic and flavonoid amounts, antioxidant (DPPH free radical scavenging assay, ABTS radical cation decolorization assay, ß-carotene lipid peroxidation test system and CUPRAC cupper reduction capacity methods), anticholinesterase, tyrosinase, urease inhibition and cytotoxic activities (on HeLa (Human Cervical Carcinoma Cell Line) of A. coarctata and A. monocephala were also investigated. It has been determined that the studied Achillea species, that are rich in total phenolic-flavonoid and chlorogenic acid contents, have high antioxidant and cytotoxic potential at the same time. According to the results of LC-MS/MS, antioxidant and cytotoxic activity studies, after detailed chemical investigation and toxicity studies on these species, A. coarctata and A. monocephala may be promoted as promising sources of natural agents and used for the development of nutraceuticals or functional food ingredients in future.

Chemical profile by LC-MS/MS, GC/MS and antioxidant activities of the essential oils and crude extracts of two Euphorbia species.

In this study, it was aimed to investigate the chemical composition and antioxidant activities of two Euphorbia species. The major component of the fatty acid compositions obtained from the petroleum ether extracts was identified as palmitic acid for Euphorbia gaillardotii and Euphorbia macroclada. The main constituents of the essential oils were identified as arachidic acid for E. gaillardotii and tetratetracontane for E. macroclada. Among the 27 studied compounds, hesperidin, rutin, hyperoside and quinic, malic, gallic and tannic acids were found to be the most abundant compounds in the two Euphorbia species. The methanol extracts of E. gaillardotii and E. macroclada showed strong antioxidant activity in all tested methods. Particularly, IC50 values of E. macroclada methanol extract that was the richest in terms of total phenolic-flavonoid contents were found to be lower than α-tocopherol and butylated hydroxytoluene in ß-carotene bleaching, 2,2-diphenyl-1-picrylhydrazyl free and ABTS cation radical scavenging methods.

Chemical profile and biological activities of Veronica thymoides subsp. pseudocinerea.

CONTEXT: In Turkey, Veronica species (Plantaginaceae) have been used as a diuretic and for wound healing in traditional medicine. OBJECTIVE: To examine the fatty acid and essential oil profiles, the antioxidant, anticholinesterase, antimicrobial, and DNA damage effects of Veronica thymoides P.H. Davis subsp. pseudocinerea M.A. Fischer as a potential source of natural active compounds. MATERIALS AND METHODS: GC/MS was used to analyze essential oil and fatty acid obtained from whole plant. The antioxidant activity was evaluated by the ß-carotene-linoleic acid test system, DPPH-free and ABTS cation radicals scavenging, and cupric reducing antioxidant capacity assays. The anticholinesterase and antimicrobial activities were determined by Ellman and broth macrodillution methods, respectively. The effect of the methanol extract on DNA cleavage was investigated. RESULTS: Hexatriacontene (21.0%) was found to be the main constituent in essential oil, and linoleic acid (25.2%) and palmitic acid (20.6%) in fatty acid. Methanol extract demonstrated the best IC50 values in lipid peroxidation (49.81 ± 0.31 µg/ml) and DPPH-free radical scavenging activity (15.32 ± 0.17 µg/ml). Methanol and water extracts possessed strong ABTS cation radical scavenging activity with IC50 values 9.15 ± 0.28 and 8.90 ± 0.1 µg/ml, respectively. The acetone extract exhibited moderate butyrylcholinesterase inhibitory activity. The highest antimicrobial activity was determined in methanol extract against Escherichia coli with 31.25 µg/ml MIC value. Inhibition of methanol extract on plasmid DNA cleavage by OH radicals was found to be 93.32% at 500 µg/ml. CONCLUSION: The methanol extract having strong antioxidant and DNA damage effects could be investigated phytochemically to find natural active compounds.

Essential oil compositions and anticholinesterase activities of two edible plants Tragopogon latifolius var. angustifolius and Lycopsis orientalis.

This is the first report in the literature on essential oil compositions of Tragopogon latifolius var. angustifolius and Lycopsis orientalis which were analysed by using GC-FID and GC-MS techniques. The main constituents of T. latifolius var. angustifolius were identified as α-selinene (10.5%), 2,5-di-tert octyl-p-benzoquinone (9.5%) and valencene (7.0%); however, the main components of L. orientalis were identified as heptacosane (10.5%), τ-muurolene (9.6%) and tetratetracontane (9.4%). The essential oils of T. latifolius var. angustifolius and L. orientalis species exhibited moderate inhibitory activity against acetyl- and butyryl-cholinesterase enzymes at 200 µg/mL.

Chemical compositions by using LC-MS/MS and GC-MS and biological activities of Sedum sediforme (Jacq.) Pau.

In this research, the chemical composition and biological activities of various extracts obtained from whole parts of Sedum sediforme (Jacq.) Pau were compared. The amounts of total phenolic and flavonoid components in crude extracts were determined by expression as pyrocatechol and quercetin equivalents, respectively. All of the extracts (petroleum ether, acetone, methanol, and water) obtained from S. sediforme showed strong antioxidant activity in four tested methods. Particularly, the IC50 values of the methanol extract, which was the richest in terms of total phenolic and flavonoid contents, were found to be lower than those of α-tocopherol and BHT in ß-carotene bleaching (9.78 ± 0.06 µg/mL), DPPH free radical scavenging (9.07 ± 0.07 µg/mL), and ABTS cation radical scavenging (5.87 ± 0.03 µg/mL) methods. Furthermore, the methanol extract of S. sediforme showed higher inhibition activity than galanthamine against acetyl- and butyryl-cholinesterase enzymes. Also, acetone and methanol extracts exhibited moderate antimicrobial activity against Candida albicans. The main constituents of fatty acid and essential oil were identified as palmitic acid (C16:0) (28.8%) and α-selinene (20.4%), respectively, by GC-MS. In the methanol extract of S. sediforme, quercetin, rutin, naringenin, and protocatechuic, p-coumaric, caffeic, and chlorogenic acids were detected and quantified by LC-MS/MS. Results of the current study showed that the methanol extract of S. sediforme may also be used as a food supplement.