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Rosemary (Rosmarinus officinalis) originated in the Mediterranean region, but, due to its adaptive nature, can be readily grown across the world. It contains many bioactive phytochemical moieties, especially polyphenols. Rosemary is used as a flavoring agent, spice condiment, and preservative. Recent studies have shown that rosemary natural extracts have bioactive properties such as antifungal, antibacterial, antioxidant, and anti-inflammatory. Rosemary can withstand dry spells, warm conditions and thrive across many soil textures. Carnosic acid is now a well-known compound that is the main component of rosemary. The key components that were extracted from rosemary consisted of cirsimaritin, diosmin, and genkwanin. Rosmarinic acid in the form of carnosol and carnosic acid possesses significant antioxidant properties. Oil analysis revealed the presence of six monodominant and six intermediate chemotypes. Monoterpenes were dominant in rosemary oil composition across all seasons. Bioclimatic factors, including the temperature of the habitat, were found to be a biogenetic factors leading to differentiation in populations. The phenolic contents are reported to vary depending upon processing and agronomical properties. The major active ingredients are lipophilic compounds (carnosic acid and carnosol). Rosemary extracts are also reported to have volatile compounds that confer a unique flavor, color and aroma. Oleanolic acid is endowed with antiviral, antioxidative, and antiproliferative properties vis-a-vis protection against oxidative apoptosis. Ursolic acid helps to prevent cancer. This review provides a comprehensive overview of rosemary species cultivation, bioactive compounds, health benefits, and applications in the food industry. Rosemary was reported to enhance the levels of antioxidant enzymes. Although the current demand in the food industry is to reduce or eliminate the use of synthetic food additives, rosemary oil and extracts can help to meet that demand. This review provides a comprehensive overview of rosemary species cultivation, bioactive compounds, health benefits, and applications in the food industry.

Plant polyphenols have always attracted the attention of researchers with their excellent biological activity potentials. In this study, roots, leaves and seeds of Draba cemileae (Karaer) were evaluated for their chemical compositions and biological activities. Spectrophotometric analysis showed that phenolics and flavonoids were present in high quantities in leaf and seed extracts (22.84 mg GAEs/g and 23.32 mg REs/g, respectively). Chromatographic analysis showed that the p-hydroxybenzoic acid and chlorogenic acid contents of the extracts were significantly high. The seed extract also contained 550 mg/g of rosmarinic acid. While the leaf extract showed high activity in phosphomolybdenum, CUPRAC, FRAP and ferrous ion chelating activity tests (0.88, 2.23, 1.73 and 3.68 mg/ml, respectively), DPPH and ABTS scavenging activity tests resulted in the superiority of the seed extract (3.75 and 2.53 mg/ml, respectively). The leaf extract also showed the highest activity in α-amylase and tyrosinase inhibitory activity tests (1.78 and 4.99 mg/ml, respectively). On the other hand, the seed extract exhibited higher activity than the others in α-glucosidase, AChE and BChE inhibitory activity tests (7.14, 1.13 and 5.11 mg/ml, respectively). Correlation coefficients between the composition and the biological activities were over 0.9. It was concluded that D. cemileae could be a new and effective source of antioxidant and enzyme inhibitory phytochemicals in medicine, food and cosmetics industries.

This study aimed to investigate the phytochemical compositions and biological activities of the Thymus cariensis and T. cilicicus. The phytochemical compositions were identified by HPLC-DAD. Luteolin, rosmarinic acid, and coumarin were the major compounds in the extracts of T. cariensis while rosmarinic and vanillic acids were the dominant compounds in the extracts of T. cilicicus. The methanol extract of T. cilicicus exhibited the highest antioxidant activity in β-carotene-linoleic acid (IC50: 9.65 ± 0.81 µg/mL), and CUPRAC (A0.50: 24.79 ± 0.02 µg/mL) assays while the methanol extract of T. cariensis were found to be active in DPPH• (IC50: 17.90 ± 0.15 µg/mL) and ABTS•+ (IC50: 12.71 ± 0.40 µg/mL) assays. The methanol extracts of T. cariensis and T. cilicicus showed the best cytotoxicity against MCF-7 with IC50 values of 27.65 ± 0.96, 83.57 ± 1.20 µg/mL, respectively. The methanol extract of T. cariensis was the most efficient extract against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), urease and tyrosinase enzymes whereas the hexane extract of T. cariensis was active against α-amylase and α-glucosidase enzymes. Moreover, a significant correlation was found between phenolic compounds and biological activities. These results show that Thymus species could be considered as a valuable resource for the food pharmaceutic and cosmetic industries due to their significant biological effects.

In this study, it was aimed to determine the in vitro antioxidant and enzyme inhibitory activities of methanol (MeOH) extracts isolated from Onosma gracilis (Trautv.) and O. oreodoxa (Boiss. & Heldr.). O. oreodoxa was found to be richer in both phenolics and flavonoids than O. gracilis. The amounts of total phenolics and flavonoids in O. oreodoxa were 53.76 mg GAEs/g and 25.29 mg QEs/g, respectively. In addition to spectrophometric analysis, in chromatographic analyzes, twenty-four and twenty-six compounds were identified in O. gracilis and O. oreodoxa, respectively. High amounts of hesperidin (6647.2 and 5260.75 µg/g extract, respectively), hyperoside (7153.26 and 10216.74 µg/g extract, respectively) and rosmarinic acid (21824.33 and 87493.19 µg/g extract, respectively) were found in O. gracilis and O. oreodoxa. While O. oreodoxa showed higher activity in cupric reducing antioxidant power (CUPRAC), ferric reducing antioxidant power (FRAP), phosphomolybdenum, 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging, and ferrous ion chelating assays (324.22, 175.41, 719.50, 125.60 mg TEs/g extract and 25.11 mg EDTAEs/g extract, respectively), ABTS radical scavenging activity of O. gracilis (164.55 mg TEs/g extract) was higher than that of O. oreodoxa. O. gracilis also exhibited higher inhibitory activity on acetylcholinesterase (AChE), butyrylcholinesterase (BChE) (2.57 mg GALAEs/g extract) and α-glucosidase (1674.24 mg ACEs/g extract). On the other hand, the sample showing the most effective inhibition on α-amylase and tyrosinase was O. oreodoxa (417.34 mg ACEs/g extract and 136.18 mg KAEs/g extract, respectively). As a result of the molecular docking analysis performed to determine the contribution of hesperidin, hyperoside and rosmarinic acid to the enzyme inhibitory activity, the binding affinity and inhibition constant of hyperoside to all enzymes were quite high and therefore it was concluded that it may be the compound that contribute to the activity.

Background Pancreatic cancer is one of the most notorious cancers and is known for its highly invasive characteristics, drug resistance, and metastatic progression. Unfortunately, resistance towards gemcitabine develops in many with advanced pancreatic cancer. Orthosiphon stamineus (O.s) is used widely as a traditional medicine for the treatment of multiple ailments, including cancer in South East Asia. The present in vitro study was designed to investigate complementary effects of an ethanolic extract of O.s (Et. O.s) compared to rosmarinic acid in combination with gemcitabine on Panc-1 (pancreatic cancer) cells. Method Cell viability and colony formation assays were used to determine the IC50 of Et. O.s, rosmarinic acid, and gemcitabine. Different doses of gemcitabine in combination with Et. O.s or rosmarinic acid were tested against Panc-1 to select the best concentrations which possessed synergistic effects. Elucidation of molecular mechanisms responsible for mediating chemo-sensitivity in Panc-1 was performed using qPCR, flow cytometry and staining techniques. Results Et. O.s was found to significantly sensitise Panc-1 towards gemcitabine by reducing expression of multidrug-resistant (MDR-1, MRP-4, and MRP-5) and epithelial-mesenchymal transition (ZEB-1 and Snail-1) genes through human equilibrate nucleoside transporter-1 (hENT-1) induction. Et. O.s-gemcitabine combination induced cellular senescence and cell death through cell cycle regulation and Notch pathway inhibition. In contrast, rosmarinic acid-gemcitabine combination showed no additional effects on cellular senescence, apoptosis, EMT markers, the MRP-4 and MRP-5 multi-drug resistance protein family, hENT-1, and the Notch pathway through Notch 1 intracellular domain. Conclusion This study provides valuable information on the use of Et. O.s to complement gemcitabine in targeting pancreatic cancer in vitro and demonstrates its potential use as a novel complementary treatment in pancreatic cancer patients.

The genus Salvia is regarded as an important medicinal plant and also as spice worldwide. Current report might be counted as one of the first investigations to reveal the enzyme inhibitory and antiglycation activities, together with phenolic and antioxidant profiles of 80% methanolic extract prepared from the aerial parts of S.virgata (SVM). Furthermore, the bioavailability parameters of major phenolic compounds in SVM were evaluated. An in vitro human digestion simulation model composed of both gastric and intestinal phases was used for this purpose. Total phenolic, phenolic acid and flavonoid components of each of these phases were calculated in order to assess the phenolic profile of the samples. In addition, quantitative analysis of major bioactive compounds (rutin and rosmarinic acid), before and after the simulation, was practiced by employing High Performance Thin Layer Chromatography (HPTLC) system. Moreover, the potential of non-digested (ND) and bioavailable (IN) phases on the inhibition of diabetes-related enzymes (α-amylase and α-glucosidase) was determined. Also, the inhibitory effect of the samples on the advanced glycation end products (AGEs), formed due to hyperglycemia, was detected. In addition, cholinesterase enzyme inhibition activity of both ND and IN samples was determined. Since, the role of oxidative stress on diabetes and neurodegenerative diseases is well-known, the antioxidant potential of the samples was also estimated by different methods: DPPH and DMPD tests for free radical scavenging activity, FRAP and CUPRAC tests for metal reducing activity and total antioxidant capacity test, as well. The results showed that total phenolic contents, antioxidant potential and diabetes-related and cholinesterase enzymes inhibition of the bioavailable phase were lower than non-digested sample. Besides, in vitro human digestion simulation system had a declining influence on the concentrations of the major bioactive metabolites (rutin and rosmarinic acid).

The use of Salvia species among the public and their importance in the scientific world increase due to theirnumerous pharmacological and biological activities on a daily basis. In this study, the phytochemical contents ofdifferent parts (root, branch, leaf, flower, whole) of different specimens of Salvia siirtica (SS) (in vivo and in vitro)extracts prepared with various solvents (petroleumether, chloroformand ethanol) were determined using differenttechniques (GC-MS and LC-MS/MS) and the results were compared. In addition, biological activities (antioxidant,cytotoxic, anticholinesterase antiurease, antityrosinase, antielastase and anticollagenase) of all sampleswere determined and compared. The antioxidant potential of the analysed samples was found to be high, andtheir enzyme activity potential was low. Besides, in vitro SS-TIS (Temporary Immersion System) sample showedhigh cytotoxic activity (viability% 2.12 § 0.06) against MCF-7 (breast cancer) cell line. The results of GC-MS andLC-MS/MS analyses indicated that ferruginol and sugiol could be isolated from the ethanol extract of S. siirticaroots, salvigenin and b-sitosterol from the chloroform extract of the aerial parts, and phenolic compounds fromthe ethanol extract of the aerial parts. In addition, the amount of rosmarinic acid, caffeic acid and 12-demethylmulticaulineof in vitro samples were found to be higher than those of in vivo samples. Furthermore, all samples,both in vivo and in vitro, contained high levels of rosmarinic acid and b-sitosterol. The whole chloroform extract(SSWC) could be the source extract for salvigenin (33952.13 mg/g) and b-sitosterol (16369.71 mg/g), and the rootethanol extract (SSRE) for ferruginol (17721.99 mg/g). As a result, it is understood that the nature of the plantmaterial, the choice of an appropriate solvent and the parts of the material used are quite effective in chemicalcontent. S. siirtica promise potential natural antioxidant agent in food and/or pharmaceutical industry due to itsphytochemical content (rosmarinic and caffeic acids, ferruginol, salvigenin) and antioxidant activity.

Phenolic acids are one of the most valuable groups of bioactive compounds in Salvia species. In this work, the effect of MeJA (50 μM) and AgNO3 (15 μM) on the phenolic acids accumulation and the expression of some crucial genes involved in the synthesis of these compounds were evaluated in two Salvia species of Iran, S. officinalis and S. verticillata, as the two rich sources of phenolic acids. Twelve-leaf plantlets of the each examined Salvia species were foliar sprayed with 50 µM MeJA and 15 µM AgNO3 until they were entirely soaked. The leaf samples were then harvested after 0, 4, 8, 24, 48, and 72 hours of treatment for analyses. Results demonstrated that the application of MeJA and Ag+ considerably enhanced the accumulation of four predominant phenolic acids of rosmarinic acid (RA), caffeic acid (CA), salvianolic acid B (Sal-B), and salvianolic acid A (Sal-A) in both of the assessed species. Furthermore, Ag+ was more effective than MeJA to induce the phenolic acids accumulation in the studied Salvia plants. The expression of the principal genes (PAL, TAT, HPPR, RAS, and CYP98A14) in both of the phenylpropanoid and tyrosine pathways were affected by MeJA and Ag+ in the examined Salvia species. Our findings showed that expression levels of TAT and CYP98A14 were significantly correlated with phenolic acids production in both of the studied species after elicitation with MeJA. The results provided new information on the putative genes for the production of phenolic acids in the tested Salvia species under the elicitation of MeJA and Ag+.

Basil (Ocimum basilicum L) extracts showed significant antioxidant activity and represent a rich source of antioxidants that could contribute to its disease-fighting potential. Basil contains functional ingredients due to its rich content of phenolic compounds, characterized as main carriers of its antioxidant activity. The objective of this study was to determine the influence of the conditions and methods of extraction on chemical composition of basil extracts and also to find similarities or dissimilarities of the extraction procedures in the scope of determined content of functional ingredients. The determination of phenolic compounds (phenolic acids and flavonoids) of 100 basil extracts was performed using HPLC. The concentration of phenolic acids (chlorogenic, p-hydroxybenzoic, caffeic, ferulic, vanillic, cinnamic and rosmarinic) varied from 0.01 to 79.88 mg/kg of dried extract (DE). Concentration of flavonoid components (quercetin, naringenin, rutin) ranged from 0.06 to 72.24 mg/kg of DE. Extraction with dichloromethane (10 min), chloroform (10 min), n-hexane (30 min) and infusion provided high content of rosmarinic acid and quercetin, but also a significant content of chlorogenic acid, vanillic acid, naringenin, cinnamic and ferulic acid. Chemometric analysis indicated the most effective experimental procedure and provided an overview of their grouping in the space of the extracted ingredients.

Salvia palaestina aqueous and methanol extracts were prepared from the aerial parts, which were evaluated for the in vitro anti-inflammatory properties using the lipoxygenase (LO) enzyme inhibition assay. While the aqueous extract showed no activity at test concentrations, a significant (p

This work reports the synthesis and application of uniform and spherical molecularly imprinted polymeric (MIP) nanobeads for selective and efficient preconcentration of Rosmarinic acid (RA). The as-prepared RA MIP nanobeads were characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and Brunauer–Emmett–Teller (BET) techniques. As analyzed, nano-sized particles of MIP with spherical and uniform shape and the average size of 88 nm were synthesized. The prepared MIP nanobeads were used in an ultrasonic-assisted dispersive solid phase extraction approach (UA-DSPE) for extraction of RA as a natural antioxidant specie from the extract of Salvia Officinalis leaves. In UA-DSPE process, the RA content of the samples was determined using high-performance liquid chromatography (HPLC). The highest recovery percentage (>90%) was observed after loading of RA solution (pH 5.7) and after elution with 3 mL of acetic acid aqueous solution, followed by 6 min sonication. The selectivity studies demonstrated a selective and high affinity binding of the template molecule (i.e. RA) toward MIP sorbent compared to other compounds such as gallic acid, caffeic acid, and pyrocatechol.

This research was performed to evaluate the efficiency of ultrasound in obtaining the total extract, caffeic acid and rosmarinic acid from Perilla frutescens using supercritical CO2 (USCCO2) extraction. Compared with traditional heat-reflux, ultrasonic-assisted and SCCO2 extractions, the USCCO2 technique decreased the extraction duration (1.12–1.92 times) and the consumption of solvent (1.90–285.71 times) at lower extraction temperatures and obtained a higher yield from the plant matrix. Furthermore, a second-order kinetic model and Fick’s second diffusion model were implemented to ascertain the extraction rate constant, equilibrium concentration, initial extraction rate, effective diffusion coefficient, mass transfer coefficient, Biot number, equilibrium constant and thermodynamic parameters of the USCCO2 and SCCO2 dynamic extractions of rosmarinic acid from P. frutescens. These results provide valuable insights into the kinetic and mass transfer behaviors that occur during the USCCO2 and SCCO2 procedures and explain the reasons for the better extraction efficiency of the former procedure.

Candida infections and related mortality have become a challenge to global health. Nontoxic and natural bioactive compounds from plants are regarded as promising candidates to inhibit these multidrug resistant strains. In the present study, in vitro assays and in silico molecular docking approach was combined to evaluate the inhibitory effect of crude extracts from Allium ampeloprasum and its variety A. porrum on Candida pathogens. Phytochemical screening revealed the presence of phenolic acids and flavonoids in higher quantity. Spectral studies of the extracts support the presence of phenols, flavonoids and organosulfur compounds. Aqueous extract of A. ampeloprasum showed a total antioxidant capacity of 68 ± 1.7 mg AAE/ g and an IC50 value of 0.88 ± 2.1 mg/ml was obtained for DPPH radicals scavenging assay. C. albicans were highly susceptible (19.9 ± 1.1 mm) when treated with aqueous A. ampeloprasum extract. Minimum inhibitory concentrations were within the range of 19–40 μg/ml and the results were significant (p ≤ 0.05). In silico molecular docking studies demonstrated that bioactive phytocompounds of A. ampeloprasum and A. porrum efficiently interacted with the active site of Secreted aspartyl proteinase 2 enzyme that is responsible for the virulence of pathogenic yeasts. Rosmarinic acid and Myricetin exhibited low binding energies and higher number of hydrogen bond interactions with the protein target. Thus the study concludes that A. ampeloprasum and A. porrum that remain as underutilized vegetables in the Allium genus are potential anti-candida agents and their pharmacologically active compounds must be considered as competent candidates for drug discovery.

Shirazi thyme (Zataria multiflora Boiss.) belongs to the Lamiaceae family, an aromatic perennial shrub native to Iran, Afghanistan, and Pakistan. In the present study, diversity of thirty-one Zataria multiflora populations (ZMPs), collected from different geographical regions of Iran was studied based on total phenolic content (TPC), total flavonoid content (TFC), rosmarinic acid (RA) content, antioxidant and antibacterial activity for further consideration in domestication, breeding and cultivation programs. RA content of studied ZMPs ranged between 1.4–8.0 mg/g dry weight (DW). The minimum (9.6 ± 0.6 mg GAE/g DW) and maximum (43.8 ± 2.9 mg GAE/g DW) TPC was observed in ZMP27 (Sirjan1) and ZMP22 (Konar Siah) populations, respectively. TFC varied from 54.6 ± 2.2 to 137.0 ± 2.9 mg rutin/g DW. Antioxidant activity (IC50) of ZMPs extracts ranged from 0.03 to 32 µg/mL. Broth microdilution procedure was utilized to determine minimum inhibitory concentration (MIC) against ten pathogenic bacteria. The plant extracts were found to be effective against both Gram-positive and Gram-negative bacteria. Our findings revealed that some Iranian ZMPs are potential sources of beneficial compounds with health-preventing effects, which can be exploited agricultural systems for further uses in food and pharmaceutical industries. Consequently, habitat suitability of Z. multiflora was depicted by frequency ratio (FR) model based on altitude, averages of annual rainfall and annual temperature. This information can be considered for further habitat modeling to find suitable cultivation areas for this economic medicinal and aromatic plant.

Natural antioxidants, like phenolic acids, possess a unique chemical space that can protect cellular components from oxidative stress. However, their polar carboxylic acid chemotype reduces full intracellular antioxidant potential due to limited diffusion through biological membranes. Here, we have designed and developed a new generation of hydrophobic turn-on fluorescent antioxidant precursors that upon penetration of the cell membrane, reveal a more polar and more potent antioxidant core and simultaneously become fluorescent allowing their intracellular tracking. Their activation is stimulated by polarity alteration by sensing intracellular signals and specifically biothiols. In our design, the carboxylic group of phenolic acids that originally restricts cell entrance is derivatized and conjugated through Copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) to a coumarin derivative that its fluorescence properties are quenched with a biothiol activatable element. This more hydrophobic precursor readily penetrates cell membrane and once inside the cell the antioxidant core is revealed upon sensing glutathione, its fluorescence is restored in a turn-on manner and the generation of a more polar character traps the molecule inside the cell. This turn-on fluorescent antioxidant precursor that can be applied to phenolic acids, was developed for rosmarinic acid and the conjugate was named as RCG. The selectivity and responsiveness of RCG towards the most abundant biothiols was monitored through a variety of biophysical techniques including UV-Vis, fluorescence and NMR spectroscopy. The electrochemical behavior and free radical scavenging capacity of the precursor RCG and the active compound (RC) was evaluated and compared with the parent compound (rosmarinic acid) through cyclic voltammetry and EPR spectroscopy, respectively. The stability of the newly synthesized bioactive conjugate RC was found significantly higher than the parent rosmarinic acid when exposed to oxygen. Cell uptake experiments were conducted and revealed the internalization of RCG. The degree of intracellular DNA protection offered by RCG and its active drug (RC) on exposure to H2O2 was also evaluated in Jurkat cells.

A novel feruloyl esterase (BpFae12) with rosmarinic acid (RA) hydrolysis activity was isolated from Bacillus pumilus W3 and expressed in Escherichia coli BL21 (DE3). With RA as a substrate, the optimal pH and temperature of BpFae12 were pH 8.0 and 50 °C, respectively. The specific enzyme activity was 12.8 U·mg−1. BpFae12 showed the highest activity and substrate affinity toward RA (Vmax of 13.13 U·mg−1, Km of 0.41 mM). Moreover, it also presented strong hydrolysis performance against chlorogenic acid (190.17 U·mg−1). RA was effectively Hydrolyzed into more bioactive caffeic acid and 3,4-dihydroxyphenyllactic acid by BpFae12, which have potential applications in the food industry.

A kinetic study of the phenolic compounds extraction from the solid residue remaining after the hydro-distillation of oregano (Origanum vulgare ssp. hirtum) was performed. Ethanol-in-water mixtures were used for the extraction and the effect of ethanol concentration, solid particle size, solid-to-liquid ratio, and temperature was examined. The experimental data were adequately fitted by both Peleg’s model and Fick’s law considering two stages of extraction, a high-rate initial one (up to 30 min), followed by a slower stage. The higher rate of phenolic compounds extraction was obtained with 60%, v/v ethanol. Increase in temperature from 22 °C to 60 °C, decrease in particle size (from >1000 μm to The HPLC analysis indicated mainly the presence of rosmarinic acid, lithospermic acid, flavonoid glycosides and carvacrol. The 60% ethanol as solvent exhibited the highest phenolics recovery and the strongest antiradical capacity. Increase in temperature from 22 °C to 60 °C led to improvement of both time and efficiency of the extraction performed with pure ethanol.

Dracocephalum kotschyi Boiss. and D. polychaetum Bornm. (Lamiaceae family) are wild medicinal herbs native to Iran and a source of potential bioactive compounds for pharmaceutical and food industries. For their bulk production, the present work aimed to investigate the effects of explants, different plant growth regulators (PGRs), and photoperiod conditions on the callus induction and cell suspension of two Dracocephalum species. A factorial experiment method based on a completely randomized design with three replications was chosen. The best conditions for callus growth obtained on the 45th day from hypocotyl, stem, and leaf explants in Murashige and Skoog (MS) medium supplemented by 1.0 mg. L−1 1-naphthalene acetic acid (NAA) and 4.5 mg. L−1 6-benzylaminopurine (BAP) in both D. polychaetum and D. kotschyi, while the best condition for callus growth from root explant was MS medium supplemented by 1.0 mg. L−1 NAA and 6.0 mg. L−1 BAP in both species. The cell suspension cultures of two species showed the highest growth rate in B5 media supplemented by 1.0 mg L−1 NAA and 2.5 mg L−1 BAP, with friable callus. The methanolic extracts of D. kotschyi and D. polychaetum cells were then determined by high performance liquid chromatography and recognized as a valuable source of such phenolics as rosmarinic acid, naringin, epicatechin, thymol, carvacrol, rutin, p-coumaric acid, gallic acid, benzoic acid, cinnamic acid, apigenin, quercetin, chlorogenic acid, and 4-hydroxybenzoic acid.

Owing to the growing applications of the multi-walled carbon nanotubes (MWCNTs) in the communications and energy industries, they have attracted increasing attention for their effects on the environment and plants. Therefore, we investigated the impact of foliar exposure to MWCNTs on the oxidative stress responses in the Salvia verticillata as a medicinal plant. Furthermore, we evaluated the possible correlations between gene expression and activity of the key enzymes in the phenolic acids biosynthesis pathways and their accumulation in the treated leaves. The leaves of two-month-old plants were sprayed with different concentrations (0–1000 mg L−1) of MWCNTs. Raman's data and Transmission Electron Microscopy images have confirmed the absorption of MWCNTs via epidermal cells layer into the parenchymal cells of the exposed leaves. The results showed that exposure to MWCNTs led to a decrease in the photosynthetic pigments and increases in the oxidative stress indices (enzymatic and non-enzymatic antioxidants) in the leaves with a dose-dependent manner. The content of rosmarinic acid as a main phenolic acid was increased in the MWCNTs-exposed leaves to 50 and 1000 mg L−1, nearly four times relative to the control. Unlike with other examined enzymes, a positive correlation was deduced between the activity and gene expression patterns of the rosmarinic acid synthase with the rosmarinic acid accumulation in the treatments. Overall, MWCNTs at the low concentrations could promote the production of the pharmaceutical metabolites by the changes in the ROS generation. However, at the higher concentrations, MWCNTs were toxic and induced the oxidative damages in S. verticillata.

Microwave-assisted hydro-distillation (MAHD) at different power levels has been applied for the extraction of essential oil from O. vulgare L. ssp. hirtum. Hydrolats and residual extracts, which present by-products, were also collected. A comparison was done with conventional hydro-distillation (HD) in terms of extraction time, extraction yield, the chemical composition of essential oils and environmental impact. MAHD proved to be a technique with many advantages compared to conventional HD. MAHD had shorter extraction time (24–45 min) compared to HD (136 min), better yields of essential oil (2.55–7.10 % for MAHD compared to 5.81 % for HD), higher content of oxygenated compounds (78.89–85.15 % for MAHD compared to 76.82 for HD), and a more environmentally friendly approach (electrical consumption was from 0.135–0.240 kW h for MAHD compared to 1.360 kW h for HD). The main component in all essential oils, as well as in hydrolats, was carvacrol. MAHD at the power level of 600 W may be considered as the most promising among the tested power levels with respect to all investigated parameters. Residual extracts after HD and MAHD showed to be valuable by-products rich in phenolic compounds, with rosmarinic acid as dominant.

Rosmarinic acid (RA) is a phenolic compound with remarkable antioxidant activity; however it presents low bioavailability. Cyclodextrin (CD) derivatives, such as hydroxypropyl-β-CD (HPβCD) and methyl-β-CD (MβCD), have been used to solve the low bioavailability of drugs, increasing their solubility or permeability. The aim of the present study was to investigate the complexation of RA with two derivative CDs, HPβCD and MβCD, and the resulting antioxidant activity. A phase-solubility study was performed to determine the stoichiometric ratio and apparent stability constant, and electrospray ionization coupled to mass spectroscopy (ESI–MS) was used to confirm the stoichiometric ratio. The freeze-dried (FD) complexes were characterized by liquid chromatography (LC), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and nuclear magnetic resonance (NMR). The antioxidant activity of RA and the FD complexes was evaluated by the DPPH method. A 2:1 (RA:CD) stoichiometric ratio and strong apparent constant stability were found for both complexes using a phase-solubility study, and ESI-MS spectra confirmed a signal corresponding to the 2:1 complex. The FD complexes showed high yield and RA content. The results of DSC, FTIR and SEM demonstrate changes in the physical-chemical characteristics of RA, suggesting its interaction with CDs. These interactions were confirmed by NMR, which revealed the formation of inclusion and non-inclusion complexes. The antioxidant activity of the RA:HPβCD and RA:MβCD FD complexes were higher than that of RA. The results suggest that FD complexes can be a technological approach to the development of formulations containing high content of RA with a view to increasing antioxidant potential.

The Verbascum L. genus (Scrophulariaceae) is rich in phenols, flavonoids, and iridoid glycosides, which have been used extensively in traditional medicine. This study aimed to examine the association between genetics and metabolomics of V. songaricum populations (VSPs), collected from different geographical regions of Iran for further breeding and exploitation programs. Inter-simple sequence repeat (ISSR) analysis showed a significant difference among the twelve studied VSPs, which were classified into five main groups based on an unweighted pair-group method with arithmetic and principal coordinate analysis. Ninety-six bands were produced by fourteen ISSR primers, among which 92.7% of them were polymorphic at the species level. The essential oils were analyzed by means GC–FID and GC–MS and five main chemotypes, including docosane (I), methyl chavicol (II), methyl eugenol (III), β-damascenone (IV), and α-bisabolol (V) were characterized. HPLC–PDA–MS was further used to detect and to measure the phenolic compounds and harpagoside content in methanolic extract of VSPs. The main compounds identified in the VSPs extracts were rutin, quercetin, rosmarinic acid, salicylic acid, ferulic acid, p-coumaric acid, 2, 5-dihydroxybenzoic acid, 3, 4-dihydroxybenzoic acid, and harpagoside. Cluster analysis based on phytochemical data divided VSPs into nine groups. Subsequently, data were analyzed by multiple regression analysis to identify the correlation between genetic and metabolic diversity. The phytochemical data as the dependent variable showed significant association with bands obtained from molecular data. The high variation observed in essential oils, phenolics, and harpagoside among the VSPs establish a good potential to select the best genotype in breeding projects.

Bardakci, Hilal/0000-0001-8799-6565 WOS:000488195200010 The purpose of the present work is to screen phenolic composition and evaluate the antioxidant and antimicrobial activities of the main extract and subextracts of Salvia heldreichiana, an endemic plant from Turkey. The aerial parts have been powdered and extracted with MeOH initially and then partitioned with chloroform (CHCl3), ethyl acetate (EtOAc) for the generation of subextracts along with the remaining water (R-H2O). Total phenolic, phenolic acid, flavonoid and proanthocyanidin contents present in the MeOH, CHCl3, EtOAc and R-H2O extracts were measured. Presence of 22 phenolic metabolites were confirmed by utilizing LC-MS/MS in MRM scan mode and then Rosmarinic acid (RA) contents of each extract were quantified by HPTLC-densitometry, since the biological effects of many medicinal plants, including Salvia sp. is attributed to RA content. Antioxidant capacities of the aforementioned extracts were estimated using several procedures including free radical scavenging and metal-associated activity and then disc diffusion method was employed to designate their antibacterial and antifungal activities. The results obtained from the current study has revealed a positive correlation between the phenolic composition and the antioxidant profile as well as the antimicrobial activities of the extracts. Among the tested extracts, EtOAc subextract showed the highest antioxidant and antimicrobial activities consistent with the highest phenolic and RA content. (C) 2019 SAAB. Published by Elsevier B.V. All rights reserved.

Natural products in drug discovery are in high demand. Thus, researchers are driven to investigate existing and new technologies for effective separation and fractionation of bioactive compounds for industrial applications. Rosmarinus officinalis L. is a medicinal and aromatic herb whose compounds hold global interest for their diverse ethno-pharmacological properties in the medicinal field. This study includes the brief history, chemical composition and an extensive in-depth analysis of R. officinalis L. into various extraction technologies (traditional, current and those with promising future prospects). According to the reviewed studies, carnosic acid, carnosol and rosmarinic acid are the most investigated compounds because they are the primary contributors of the bioassays with the highest potential in natural drugs. For the production of fractions enriched with these compounds, pressurized liquid and supercritical (SC) fluid extraction followed by SC antisolvent fractionation are amongst the most extensively investigated technologies. Moreover, this study highlights the exploitation of deep eutectic solvent-based aqueous two-phase system for the production of enriched fraction from R. officinalis L.

This study was undertaken to estimate the concentrations of the formed polycyclic aromatic hydrocarbons (PAHs) in heat-treated (boiled, pan-fried and grilled) meats collected from Egypt. Dietary intakes and cancer risks of PAHs among Egyptian adults were calculated. Benzo[a]pyrene (B[a]P)-induced mutagenicity and oxidative stress in human colon (CaCo-2) cell line and mechanisms behind such effects were also investigated. Finally, protection trials using rosmarinic (RMA) and ascorbic acids (ASA) were carried out. The results indicated formation of PAHs at high levels in the heat-treated meats. Calculated incremental life time cancer risk among Egyptian adults were 7.05179E−07, 7.00604 E−06 and 1.86069 E−05 due to ingestion of boiled, pan-fried and grilled meats, respectively. B[a]P-exposed CaCo-2 cells had high abilities for mutagenicity (490.05 ± 21.37 His + revertants) and production of reactive oxygen species. RMA and ASA protected CaCo-2 cells via reduction of B[a]P-induced mutagenicity and oxidative stress and upregulation of phase II detoxification enzymes and xenobiotic transporters.

Remarkable quantitative variability of rosmarinic acid (RA) among and within wild populations of Satureja rechingeri has previously been investigated. In the following domestication process of the plant and in order to identify the superior varieties for the mass cultivation, the agro-morphological characteristics, total phenols, total flavonoids, RA content and antioxidant activity of the 82 cultivated clones of the plant were presently evaluated. The highest content of RA was observed in clones of G99 (7.22%), K22 (6.47%) and G92 (5.13%), respectively. The highest drug (leaves and flowers) yield was recorded in the clones of E77, E96 and E104 with 200, 182.9 and 178 g/plant, respectively. Multivariate statistics were used to categorize and interpret the data of antioxidant parameters and agro-morphological specifications of the clones. Superior varieties in the studied traits can be extensively cultivated in the agricultural systems and used in food and pharmaceutical industries.

Salvia miltiorrhiza Bunge is a traditional Chinese medicine, and its water-soluble phenolic acid active compounds have very important medicinal value; however, the synthesis pathways of the main active ingredients remain unknown. Here, we employed nuclear magnetic resonance (NMR)-based metabolomics and transcriptomics techniques to study the biosynthesis mechanism of salvianolic acids. High-performance liquid chromatography (HPLC) combined with NMR showed an improvement over traditional techniques, and 54 metabolites were detected. The results of the multivariate statistical analysis showed that salvianolic acid B (SAB), rosmarinic acid (RA), caffeic acid, succinate, and citrate were among the multiple compounds that were increased in the methyl jasmonate (MeJA)-elicited group; the levels of sucrose, fructose, glutamine, and tyrosine were decreased. Combined with the differentially expressed genes (DEGs) found by transcriptome sequencing, we speculate that the synthesis of RA after MeJA treatment mostly occurred through caffeic acid and bypassed 4-hydroxyphenyllactic acid. This provides useful information for the study of salvianolic acids synthesis.

Phenolic acids are one of the main active components in Salvia miltiorrhiza root, which have been proved to have extensive pharmacological activities. In this study, quantitative trait loci (QTL) for phenolic acids contents were identified by a new genetic map constructed based on genomic simple sequence repeat (SSR) markers. The results demonstrated that the map comprised eight linkage groups which were in accord with the haploid chromosome number of S. miltiorrhiza (2n = 2x = 16). The map spanned 397.5 cM with average inter-marker distance as 3.6 cM. A total of six QTL were identified through interval mapping, including three salvianolic acid B (SAB) content-related QTL on linkage group (LG) 7, two lithospermic acid (LA) content markers on LG2 and LG4, as well as one rosmarinic acid (RA) content-linked QTL on LG7. These QTL could be used in marker-assisted breeding for the phenolic acids contents of S. miltiorrhiza.

The current work was the first to conduct tyrosinase inhibition and antioxidant properties as well as phenolic phytochemicals in the seeds of Korean perilla species such as cultivated and wild types. The 80% methanol extract (80 μg/mL) of this source showed potent biological activities, especially, P. frutescens var. frutescens had the highest antityrosinase and antioxidant effects with 86 and 87%. To investigate the phenolics on their capacities, the above extract was chromatographed, which yielded six compounds, including caffeic acid (1), rosmarinic acid-3-O-glucoside (2), rosmarinic acid (3), luteolin (4), apigenin (5), and chrysoeriol (6) using UHPLC-ESI-Q-TOF-MS/MS and NMR. Highly absolute tyrosinase inhibitory activities were found in phenolics 3–6 with IC50s of 24.6, 20.8, 17.3, and 15.8 μM compared to positive control (kojic acid; 45.7 μM). Moreover, phenolics 1, 3, and 4 exhibited significant scavenging abilities with IC50 values of 4.6, 5.5, and 8.7 μM (ABTS) as well as 11.7, 15.5, and 14.3 μM (DPPH), respectively. Six phenolics 1–6 also differed considerably with the range of 2273.0–4773.9 μg/g in five species, especially, P. frutescens var. frutescens showed the highest contents and rosmarinic acid (3) was the predominant constituent (703.9–2965.0 μg/g), representing approximately 19–74% of the total phenolics. Our results suggest that perilla seeds may be utilized as a potent natural source of antityrosinase and antioxidant for the development of breeding lines and functional foods.

Dracocephalum kotschyi Boiss. is one of the important threatened traditional species of medicinal herbs; last pharmaceutical research has shown that rosmarinic acid (RA) and methoxylated flavonoids, particularly, xanthomicrol and cirsimaritin of this plant have anti-cancer, anti-spasm and anti-platelet properties. In this study, Hairy roots were derived from four-week-old leaves inoculated with Agrobacterium rhizogenes strain ATCC15834. The influence of various silicon dioxide nanoparticles (SiO2 NPs) concentrations at two exposure time (24 and 48 h) on growth, antioxidant enzyme capacity, total phenols and flavonoids content (TPC and TFC) and some biochemical traits were investigated. The expression of phenylalanine ammonia-lyase (pal) and rosmarinic acid synthase (ras) genes expression in RA biosynthetic pathway were quantified. The biomass of cultures has substantially by elicitation raised in comparison with control. The activity of antioxidant enzymes, TPC and TFC were impressed by the concentration and duration of treatment. The high RA content (1016.6 μg/g FW) with 8.26-fold increase compared to control, was observed in hairy roots culture elicited with SiO2 NPs (100 mg/L) after 48 h exposure time. The pal and ras genes expression rate in this elicitor concentration and exposure time enhanced notably. Anticancer flavonoids including xanthomicrol, cirsimaritin and isokaempferide showed 13, 13.42 and 10-fold increases compared to the control respectively. Stimulation of D. kotschyi hairy roots by SiO2 NPs caused huge increase in induction and production of important pharmaceutical compounds such as rosmarinic acid and xantomicrol.

Agastache rugosa (Fischer & C.A.Meyer) O.Kuntze (Lamiaceae) is an East Asian medicinal and aromatic plant. It is rich in polyphenolic compounds such as rosmarinic, chlorogenic, ferulic acids and apigenin glycosides. in vitro shoot cultures were used to study influence of various factors on polyphenol profile using Ultra Performance Liquid Chromatography coupled to high resolution mass spectrometry (UPLC-ESI-qTOF-MS). Large differences in the morphology and polyphenol profile were observed in experiments with various illumination (white fluorescent lamps or white and photosynthetically active radiation LEDs) and supplementation with plant growth regulators and amino acids. Shoots were cultured on the MS basal agar medium with or without plant growth regulators (6-benzylaminopurine - BA, indole-3-acetic acid – IAA), or supplemented with different concentrations of phenylpropanoid biosynthesis precursor - l -phenylalanine or an amino acid mixture (casein hydrolysate). The composition of polyphenols in methanolic extracts was analyzed using UPLC-DAD-qTOF-MS. Three phenolic acids: cryptochlorogenic acid, feruloyl-quinic acid, rosmarinic acid, a rosmarinic acid methyl ester and two isomeric ferulic acid glucosides, as well as one flavonoid – an apigenin derivative were detected. Rosmarinic acid (RA) was the most abundant compound found in the analyzed plant material. Supplementation with amino acids resulted in highest content of RA in shoots cultured for 196 days on media containing either low concentration (1 mg/L) of l -phenylalanine or two of the highest - 20, 50 mg/L. The effect of casein hydrolysate supplementation was noticed from the beginning of shoot culture and reached maximum of 23.3 mg/g on 140 day. On the other hand, shoots that were growing under different illumination produced over 20 mg/g dw of RA after 70 days of culture. In conclusion, the production of phenolic compounds in A. rugosa in vitro shoots was influenced by the age of the shoot cultures, illumination regime and amino acids supplementation.

The co-pigmentation of black chokeberry (Aronia melanocarpa) anthocyanins with ten phenolic co-pigments was studied. Tested compounds provoked different co-pigmentation effect, manifested by hyperchromic and batochromic shifts. The co-pigmentation was accompanied by a magnification of color intensity and decrease of color hue, both related to a more pleasant color. The hyperchromic effect was the most significant for rosmarinic acid (51.02%), syringic acid (43.24%) and catechin (39.73%). However, it was observed at the highest pigment/co-pigment ratio (1:50), not achievable in plant matter. Targeting the potential practical application of co-pigmentation, we tested eight herbal extracts for their co-pigmentation ability with aronia anthocyanins. The use of herbal extracts led to a significant hyperchromic effect at much lower pigment/co-pigment ratios, compared to pure compounds. The use of selected herbal extracts as co-pigments opens realistic prospects for development of aronia functional foods with improved sensory properties and biological effects, due to enhanced color and anthocyanin stability.

Dragonhead (Dracocephalum moldavica L.) has valuable secondary metabolites including rosmarinic acid, anthocyanin, carotenoid and flavonoid which may vary in composition and amount under the effects of environmental factors (e.g. temperature) within a species. Abscisic acid (ABA) has been used to elicit secondary metabolites production. The objective of this study was to evaluate the effect of temperature (at 15, 25 and 35 °C) and exogenous ABA (at the concentrations of 0, 5, 10, 20 and 40 μM) on rosmarinic acid, total phenolic, anthocyanin, carotenoid and flavonoid content of dragonhead. Both growing temperature and ABA application induced a significant change in rosmarinic acid, total phenol and total flavonoid content. Without ABA application, the highest carotenoid, anthocyanin, and flavonoid content were observed in plants grown under the temperature of 15, 35, and 15 °C, respectively, while rosmarinic acid and total phenolic content were not affected by temperature. Treatment of plants with 20 μM of ABA showed 53.56%, 48.87%, and 36.59% increase in rosmarinic acid, total phenolic, and total flavonoid content, respectively, as compared to the control. The increase in rosmarinic acid content was completely correlated with phenylalanine ammonia-lyase (PAL) activity so that PAL activity was enhanced by increasing ABA concentration. Both low (15 °C) and high (35 °C) temperatures significantly decreased leaf area and total dry weight. The results showed that application of 20 μM ABA is the most effective treatment to elicit rosmarinic acid, and phenolics content. We conclude that ABA (especially at the concentration of 20 μM) may induce the accumulation of secondary metabolites including rosmarinic acid, total phenolic, anthocyanin, carotenoid and flavonoid in dragonhead leaves when growth temperature is decreased to 15 °C.

Soy phosphatidylcholine liposomes encapsulating increasing concentrations of two sea fennel extracts (aqueous and ethanolic) prepared by ultrasonication were freeze-dried, using glycerol as lyoprotectant. Particle properties, water dispersibility, colour, thermal properties and antioxidant capacity (radical scavenging capacity, ferric ion reducing power, Folin-reactive substances) of the liposomal preparations were determined. The freeze-drying process caused an overall increase in particle size and polydispersity index, while the zeta-potential became more electronegative. Both sea fennel extracts were rich in chlorogenic acid (42.61 and 58.48 mg/g for the aqueous and ethanolic extracts, respectively) and showed great antioxidant activity. Vitamin C was identified in the aqueous extract, whereas rutin and rosmarinic acid in the ethanolic one. The entrapment efficiency, determined in the liposomes prepared at the highest extract concentration, was 65.6% and 49.1% for the aqueous extract and the ethanolic extract, respectively. The liposomal antioxidant activity and total phenolic content followed a linear increasing tendency as a result of increasing the extract concentration, irrespective of the type of extract. Higher antioxidant activity was found in the liposomes loaded with the ethanolic extract, in a clear relationship to the greater amount of highly antioxidant phenolic compounds extracted, and also to their lower entrapment efficiency, which caused a greater amount of extract to remain outside the liposome. Both extracts were suitable for producing liposomes with antioxidant properties which could be dried and used to design functional foods., The authors wish to thank the Spanish Ministry of Economy and Competitiveness (MINECO) for financial support (projects AGL2014-52825 and AGL2017-84161-C2-1-R).

Dracocephalum forrestii is known as a medicinal plant in China. The present work evaluates the potential of its shoots to biosynthesise phenolic compounds during bioreactor cultivation. Qualitative UPLC-PDA-ESI-MS analysis revealed the presence of nine caffeic acid derivatives in the hydromethanolic extract. Quantitative UPLC-PDA analysis then found the predominant compounds to be rosmarinic acid (17.90 mg/g DW) and salvianolic acid B (6.5 mg/g DW). Regarding antioxidant activity, the extract demonstrated strong potential to scavenge both DPPH and O2∙− radicals (NBT) (IC50 values 30.67 μg/ml and 69.06 μg/ml, respectively) and reduce Fe3+ ions (1319 μM Fe(II)/g DW of extract – FRAP test). The extract also showed moderate growth-limiting activity against 13 selected pathogenic bacteria and fungi strains, with the MIC and MBC values ranging from 2.5 to 5.0 mg/ml in most cases.

Different in vitro cultures of the Turkish origin medicinal plant species, Salvia viridis, were estimated in order to investigate their potential for the accumulation of phenolic compounds. Among the seventeen detected compounds, thirteen phenolic acid derivatives and four phenylethanoids were identified in extracts from shoot and/or callus cultures using the UPLC-DAD/ESI-MS method. The accumulation of the compound depended on the type of culture (callus, shoot), the medium composition and age of culture (6, 12, 18 and 24 months in in vitro conditions). Six of the seventeen detected compounds were estimated in all the analyzed samples, however, sometimes only in trace amounts. The predominant metabolite was rosmarinic acid (RA). Its content ranged between 2.4 and 11.5 mg/g dry weight (DW). The highest levels of rosmarinic acid and total phenolic compounds were found in a half-year-old shoot culture. The content of the RA was nine times higher than that in the shoots of plant grown in field conditions. The antioxidant activity of S. viridis cultures was examined by the O2− and 1-1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging test and FRAP (ferric reducing antioxidant power) assay. In addition, the antifungal and the antibacterial activities were examined against a wide spectrum of micro-organisms. All the samples showed promising antioxidant potential; however, the shoot extract had the highest antioxidant activity in all the assays. Preliminary results demonstrated that all the analyzed extracts inhibited the growth of Gram-positive and Gram-negative bacteria. The extracts also showed strong activity against Candida and Aspergillus species.

Background Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) are two key protein-bound uremic toxins that accumulate in patients with end-stage renal disease. IS and pCS cannot be efficiently removed by conventional hemodialysis because they are highly bound to proteins. One promising means to optimize the removal of protein-bound uremic toxins involves using binding competitors to liberate uremic toxins from protein-binding partners. Purpose In this study, we try to identify potential binding competitors that can enhance the dialysis removal of IS and pCS in natural compounds of phytomedicine. Methods We employed microdialysis to evaluate whether Danhong injection (DHI) and its salvianolic acids can increase the free fractions of IS and pCS and thus improve their dialysis efficiency in vitro. Furthermore, we confirmed the positive effects of DHI and salvianolic acids in vivo on chronic kidney disease model rats in which IS and pCS had heavily accumulated. Results DHI significantly increased the dialysis efficiency of IS and pCS by 99.13% and 142.00% in vitro (10-fold dilution), respectively, and by 135.61% and 272.13% in vivo (4.16 ml/kg). Salvianolic acids including lithospermic acid (LA), salvianolic acid A (SaA), tanshinol (DSS), caffeic acid (CA), salvianolic acid B (SaB), protocatechuic aldehyde (PA) and rosmarinic acid (RA) significantly enhanced the dialysis removal of IS and pCS in a concentration-dependent manner. LA, the best competitor of the tested salvianolic acids, increased dialysis efficiency levels of IS and pCS by 197.23% and 198.31% in vitro (400 μM), respectively, and by 119.55% and 127.56% in vivo (24.69 mg/kg). Conclusion The removal of protein-bound uremic toxins IS and pCS using DHI or salvianolic acids as protein-bound competitors is superior to previously reported strategies and drugs and may contribute to clinical hemodialysis therapeutic practice.

In the present research, the chemical composition of aerial parts of cultivated citral chemotype of Thymus pannonicus All. (Lamiaceae), growing at different soil conditions was studied. Two plant lineages were unfertilized or treated using either nitrogen or phosphorus fertilizers at different concentration levels. Essential oil (EO) content, EO composition, and composition of hydromethanol extracts (MEs) were compared to the results obtained for wild growing plants in order to evaluate the potential of T. pannonicus for its industrial production. EO content (%, V/m) in cultivated samples varied between 0.32-0.75% and 0.62–1.05% within two examined lineages, whereas the herbs from the natural habitat contained 0.49–1.29% of EO. GC-FID/MS analysis showed that citral, i.e. mixture of isomers geranial and neral, was the most abundant constituent in all EOs (51.90–81.96%). HPLC analysis revealed that total caffeic acid derivatives, with rosmarinic acid (RA) as the most abundant compound in all extracts, as well as total apigenin glycosides contents were significantly higher in the extracts originating from the cultivated herbs (112.15–184.94 mg/g and 5.08–15.29 mg/g, respectively), in comparison to the extracts of the herbs from the natural habitats (67.61–98.75 mg/g and 1.17–1.32 mg/g). In general, the composition of cultivated herbs varied less than that of samples originating from natural habitats, indicating that controlled cultivation of citral chemotype of T. pannonicus can provide herbal drug with favourable characteristics. Only minor differences were observed between cultivated samples treated with different fertilizers.

Fishy odor was always generated in hairtail fish balls, decreasing the quality and reducing commercial acceptance. Improving the flavor of hairtail fish balls is a challenge in recent seafood industry. Extracts from sage leaves, oregano leaves and grape seeds (SOG) were proved to be effective in reducing the fishy odor in hairtail fish balls. The primary antioxidants were catechin, epicatechin and rosmarinic acid in SOG with the antioxidant capacity of 0.09 ± 0.01 mg gallic acid equivalents (GAE)/mL. Gas chromatography mass spectrometry (GC-MS) showed that about 50% volatility off-flavor compounds including aldehydes, ketones, alcohols and hydrocarbons, were reduced by the application of SOG. Inhibition of fishy odor by SOG was directly related with the reduced thiobarbituric acid reactive substances value (TBARs value) and total volatile basic nitrogen (TVB-N), which was likely due to the decreased lipid oxidation and bacteria growth, respectively. These results suggested the beneficial potential for SOG in inhibiting fishy odor formation and improving flavor of hairtail fish balls during storage.

Microwave-assisted extraction (MAE) was used for the recovery of bioactive compounds of two Lamiaceae species: Origanum glandulosum and Thymus fontanesii. MAE was combined with response surface methodology (RSM) to optimize the effect of concentration of ethanol (%EtOH), temperature and extraction time on the total phenolic content (TPC), the extraction yield and the antioxidant capacity from the aerial parts of O. glandulosum and T. fontanesii. The total phenolic content was determined using the Folin-Ciocalteu reagent, while the antioxidant capacity was evaluated using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radicals. Optimum conditions obtained for O. glandulosum MAE extracts were 0% ethanol, 42 °C and 2 min of extraction time, which give individual response values of 23.29 ± 0.38%, 311.36 ± 6.09 mg GAE/g extract, 5.54 ± 0.42 μg/mL and 3.61 ± 0.14 mmol Trolox/g extract for yield, TPC, DPPH (EC50) and trolox equivalent antioxidant activity (TEAC) assay, respectively. Whereas, the optimum conditions obtained for T. fontanesii MAE extracts were 50% ethanol, 150 °C, and 9.5 min. These latter give individual response values of 26.81 ± 0.30%, 227.63 ± 31.87 mg GAE/g extract, 8.58 ± 1.75 μg/mL, 3.92 ± 0.61 mmol Trolox/g extract for yield, TPC, DPPH (EC50) and TEAC assay, respectively. The main phenolic compounds identified in O. glandulosum and T. fontanesii optimized MAE extracts, using the HPLC-DAD-ESI-MS/MS method were gallocatechin and rosmarinic acid, respectively., This work was supported by the projects AGL2017-89417-R (Ministerio de Economía y Competitividad, Spain) and PNE-2015 (Ministry of High Education and Scientific Research, Algeria). The pre-doctoral fellowship of N. NABET was financed by the Ministry of High Education and Scientific Research of Algeria.

A sensitive and efficient method was established and validated for qualitative and quantitative analysis on the chemical constituents in Orthosiphon stamineus Benth. (O. stamineus) using ultra high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. Based on the retention time and MS spectra, 61 compounds were detected by using ultra high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. 52 chemical structures in the O. stamineus extracts including 26 phenolic acids, 11 flavonoids, 6 diterpenoids, 4 fatty acids and 5 tanshinones were tentatively identified without the time-consuming process of isolation. Moreover, five chemical constituents (Danshensu, Caffeic acid, Rosmarinic acid, Sinensetin and Eupatorin) were quantified in three different batches of O. stamineus samples by the developed ultra high-performance liquid chromatography coupled with electrospray ionization triple-quadrupole mass spectrometry method in 10 min. The method validation of the five compounds was performed with acceptable linearity (R2, 0.9930–0.9997), precision (RSD, 1.87–10.36%), repeatability (RSD, 0.59–4.87%) and recovery (105.30–110.53%, RSD ≤ 13.90%).

This work has analysed the influence of CdCl2, NiCl2 and CuCl2 on simple phenolic acids, such as the 3PPP (phenylpyruvic, phenylacetic, and 4-hydroxyphenylpyruvic) and 2DR (3,4-dihydroxyphenylacetic and rosmarinic) phenolic acids for the first time and studied their interactions with antioxidant systems and the glutathione-ascorbate cycle in the freshwater green microalga Scenedesmus quadricauda. The compounds investigated are related to both the catabolic and anabolic pathways of l -phenylalanine and l -tyrosine, the main molecules in the biosynthesis of polyphenols. The concentrations of the simple phenolic acids responded significantly to NiCl2, CdCl2 and CuCl2 at 5, 20 and 40 μM concentrations. The 3PPP phenolic acid concentrations after 24 h were always higher in metal-treated cells than in controls, while the 2DR concentrations were significantly lower in the metal-treated cells than the controls. The GSH/GSSG ratio was lower in all experimental groups treated with the selected metals (especially so at 40 μM). Pearson correlation analysis indicated a strong negative correlation between ascorbate and rosmarinic acid content (−0.670; p

International audience; Ocimum basilicum is a medicinal plant with multiple health benefits including cardiovascular, cancer and diabetics. In the present study, the influences of light emitting diodes (LEDs) were investigated on the accumulation of biologically active ingredients in callus cultures of Ocimum basilicum. Among the various tested treatments optimum levels of Total phenolic content (TPC) was noted in callus culture grown under blue lights as compared to control, while maximum accumulation of Total flavonoid content (TFC) was noted in callus culture grown under red light as compared to control. HPLC analyses showed that highest concentrations of Rosmarinic acid (96.0 mg/g DW) and Eugenol (0.273 mg/g DW) were accumulated in blue light which was 2.46 and 2.25 times greater than control (39.0 mg/g DW, 0.171 mg/g DW), respectively. Chicoric acid (81.40 mg/g DW) optimum accumulation was noted in callus grown under the continuous white light, which was almost 4.52 times greater than control. Anthocyanins content were also analyzed, the highest amount of Peonidin (0.127 mg/g DW) and cyanidin (0.1216 mg/g DW) were found in callus culture grown under red light. These findings suggest that application of LED's is a promising strategy for enhancing production of biologically active ingredients in callus cultures Ocimum basilicum.

Alkanna sfikasiana Tan, Vold and Strid is an endemic Greek species of Boraginaceae family. From the roots, the new natural product disodium rabdosiin (1) along with rosmarinic acid (2) were isolated from the methanolic extract and lanosta-7,24-dien-3β-ol (3) and linoleic acid (4) from the cyclohexane extract. From the methanolic extract of the aerial parts two flavonoids quercetin 3-Ο-β-D-glucoside (5) and quercetin 3-Ο-β-D-rutinoside (6) were isolated. The antioxidant properties exhibited good radical scavenging activity (96.00 mgTE/g for DPPH; 441.97 mgTE/g for ABTS) and reducing power ability (720.81 mgTE/g for CUPRAC and 413.94 mgTE/g for FRAP) for the new compound 1. Enzyme inhibitory activity has been also evaluated, showing inhibitory effects on AChE (4.32 mgGALAE/g), BChE (3.63 mgGALAE/g) and α-amylase (3.83 mmolACAE/g). Consequently, our study could provide a potential candidate for developing novel phyto-pharmaceutics and it could be considered a new starting point on the studied species.

Decreasing availability and rising costs of high quality water for irrigation, results in more frequent use of saline water sources in many crop production systems. The effect of salinity on biomass yield has been the focus of most salinity studies with basil, and a few studies have reported how salinity influences basil polyphenolic composition. Two basil cultivars [Ocimum basilicum L. ‘Sweet Broadleaf’ (SB) and ‘Siam Queen’ (SQ)] were grown hydroponically for 71 d with four different concentrations of NaCl (no NaCl, Low, Moderate, and High) to determine whether the phenolic and elemental composition of leaves is altered by salinity. Salinity in the hydroponic solution reached as high as 20 dS m-1 at the highest NaCl level. Salinity had no influence on leaf color or plant mortality and minimal leaf necrosis occurred during the experiment. Compared with controls, NaCl decreased leaf biomass only at the highest salinity level. Salinity increased K concentrations in leaves, and plants generally excluded Na from leaves except at the highest NaCl level. Levels of salinity that altered basil leaf polyphenolic and nutrient composition were lower than those that influenced yield (leaf biomass). In both cultivars, salinity increased leaf concentrations of certain caffeic acid derivatives, caftaric acid, cinnamyl malic acid, and feruloyl tartaric acid and decreased concentrations of chicoric acid. In SB, salinity increased leaf concentrations of the two of the major polyphenolics in basil leaves, quercetin-rutinoside and rosmarinic acid. In contrast, salinity decreased concentrations of rosmarinic acid in SQ leaves. Effects of salinity on leaf concentrations of elements other than Na, Cl, K, and Mg, were not directly related to effects of salinity on polyphenolics. Salinity levels that do not influence biomass yield in basil may negatively impact yield of certain polyphenolics important to quality.

Rosmarinic acid (RA) is a naturally occurring polyphenolic compound. In this study, we demonstrated that RA could protect against the degeneration of the nigrostriatal dopaminergic system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease (PD). In addition, RA could inhibit MPTP-induced decrease of superoxide dismutase (SOD) and tyrosine hydroxylase (TH) and increase in nigral iron content. Further studies elucidated the effects of RA on iron-induced neurotoxicity and the possible underlying mechanisms in the SK-N-SH cells. Results showed that iron could induce a decrease in the mitochondrial transmembrane potential and result in α-synuclein aggregation in the SK-N-SH cells, which could be restored by RA pretreatment. Further results showed RA pretreatment could inhibit iron-induced α-synuclein aggregation by up-regulating hemeoxygenase-1 (HO-1). In addition, iron could increase the mRNA levels of α-synuclein via iron responsive element/iron regulatory protein (IRE/IRP) system. RA pretreatment could decrease the mRNA levels of α-synuclein by decreasing the protein levels of IRP1. These results indicated that RA protected against iron-induced α-synuclein aggregation by up-regulating HO-1 and inhibiting α-synuclein expression.

Glechoma longituba is a widespread crop in China. With high concentrations of many bioactive compounds, it has long been treated as a health beneficial ingredient for human diet and even some medicine. In order to gain comprehensive understandings of current resources of Glechoma longituba, samples from seventeen geographical origins in fifteen Chinese provinces were collected to reveal the connections between different influence factors and certain bioactive compounds. Firstly, high variations in the contents of ethanol-soluble extracts, total flavonoid, chlorogenic acid, caffeic acid, rosmarinic acid, oleanolic acid and ursolic acid were proved among different Glechoma longituba populations. Totally four parameters of soil physical properties, twelve parameters of soil chemical properties, thirty years’ climate records and genetic diversity among different Glechoma longituba populations were thoroughly investigated. As a result, soil chemical property and climate condition with significant correlation between each other were both indicated to have the strongest positive correlations with bioactive compounds of Glechoma longituba, among which soil phosphorus, soil iron, temperature and moisture were showed to act as key factors. Neither the genetic variation nor the soil physical property was significantly related to the concentrations of bioactive compounds. These results laid the first theoretical foundation for further study of how to improve the quality of Glechoma longituba resources, as well as provided guidance for breeders to focus more on choosing planting areas with ideal climate conditions and modulating the optimum soil chemical properties for better Glechoma longituba cultivation.

Ocimum sanctum Linn., widely used in food preparation, has been reported for several biological beneficial activities and thus potential for treatment of various health conditions. However, the biological activities related to skin anti-ageing, including anti-collagenase, anti-elastase, and anti-hyaluronidase activities, have not been reported so far. Therefore, this study aimed to investigate the skin anti-ageing activity of O. sanctum extracts. The aerial part of O. sanctum was extracted by fractionated extraction using n-hexane, ethyl acetate, and ethanol, respectively. Rosmarinic acid and total phenolic content was investigated. Antioxidant activity was determined by in vitro methods. Anti-inflammatory activity was investigated according to the inhibition of nuclear factor kappa B (NF-κB) expression and interleukin-6 (IL-6) secretion. The anti-ageing activity was investigated by in vitro inhibition of collagenase, elastase, and hyaluronidase activities. The ethanolic extract of O. sanctum, which had the highest yield (6.5%), contained the highest rosmarinic acid (19.3% w/w) and the highest total phenolic content (50.2 ± 0.6 mg gallic acid/g sample). Additionally, it possessed the most potent antioxidant activity with the Trolox equivalent antioxidant capacity of 270.1 ± 15.1 μM/mg, equivalent concentration of 459.3 ± 91.4 μM/mg, and inhibition against 2, 2-diphenyl-1-picrylhydrazyl radical of 34.0 ± 0.7%. The ethanolic extract also showed the highest anti-inflammatory activity with the inhibition against IL-6 secretion and NF-κB expression of 54.7 ± 3.1% and 79.3 ± 9.6%, respectively. Moreover, it also exerted the highest inhibition against matrix metallopeptidase-1 and hyaluronidase with the inhibition of 77.7 ± 9.0% and 98.1 ± 0.1%, respectively. Rosmarinic acid was found as the major compound responsible for those anti-ageing activities. Therefore, the ethanolic extract of O. sanctum is an attractive natural source of anti-skin ageing ingredient for further applications in cosmetic and/or cosmeceutical industry.

Variations in polyphenolic contents and antioxidant capacities depending on the collection sites of Salvia aegyptiaca, were examined. Total polyphenolics assessed by the Folin-Ciocalteu procedure reached the values of 79.67 and 77.91 mg GAE/g DW in post-distilled Salvia aegyptiaca from Enfida and Chott Meriem. HPLC analysis permitted the identification of 14 phenolic components. Methyl carnosate (416.29–4052.24 µg/g DW), rosmarinic acid (562.46–1172.24 µg/g DW) and apigenin-7-glucoside (512.96–774.02 µg/g DW) were detected as the main phenolics. Samples of Chott Meriem were characterized by the best antioxidant performance as evaluated by DPPH (IC50, 29.62 µg/mL), ABTS (198.48 µM TE/mg) and FRAP (155.34 mM Fe(II)/mg) assays. Also, significant (p

Graphical abstract, Pancreatic cancer has the highest mortality rate among cancers due to its aggressive biology and lack of effective treatment. Gemcitabine, the first line anticancer drug has reduced efficacy due to acquired resistance. The current study evaluates the toxicological effects of Orthosiphon stamineus (O.s) and its marker compound (rosmarinic acid) in combination with gemcitabine. O.s (200 or 400 mg/kg/day) and rosmarinic acid (32 mg/kg/day) were administered orally and gemcitabine (10 mg/kg/3 days) intraperitoneally either alone or in combination treatment for fourteen days. Parameters including blood serum biochemistry, hematology, myeloid-erythroid ratio, incident of lethality, and histopathological analysis of liver, kidney, and spleen tissues were studied. Neither, individual drugs/extract nor chemo-herbal combinations at tested doses induced any toxicity and damage to organs in nude mice when compared to control group. Toxicological data obtained from this study will help to select the best doses of chemo-herbal combination for future pancreatic xenograft tumor studies.