Chemodiversity of Arctic Plant Dryas oxyodonta: LC-MS Profile and Antioxidant Activity.

Dryas oxyodonta Yuz. is a perennial evergreen shrub from the Rosaceae family. D. oxyodonta thrives in subalpine and subarctic regions, as well as in highlands spanning from Central Asia to Siberia and Mongolia. Owing to a lack of information on its chemical composition, we conducted qualitative and quantitative chromatographic analyses on extracts from the leaves and flowers of D. oxyodonta sourced from various Siberian habitats. Employing high-performance liquid chromatography with photodiode-array detection and electrospray ionization triple-quadrupole mass spectrometric detection, we identified 40 compounds, encompassing gallotannins, hydroxycinnamates, procyanidins, catechins, flavonoids, and triterpenes. All Siberian populations of D. oxyodonta exhibited a notable abundance of phenolic compounds. Furthermore, we identified rare glycosides, such as sexangularetin and corniculatusin, as potential markers of the chemodiversity within the Dryas genus. Extracts from the flowers and leaves were effective scavengers of free radicals, including DPPH•, ABTS•+-, O2•-, and •OH radicals. Our findings unequivocally establish D. oxyodonta as a rich source of phenolic compounds with potent antioxidant activity, suggesting its potential utility in developing novel functional products.

Metabolites of Geum aleppicum and Sibbaldianthe bifurca: Diversity and α-Glucosidase Inhibitory Potential.

α-Glucosidase inhibitors are essential in the treatment of diabetes mellitus. Plant-derived drugs are promising sources of new compounds with glucosidase-inhibiting ability. The Geum aleppicum Jacq. and Sibbaldianthe bifurca (L.) Kurtto & T.Erikss. herbs are used in many traditional medical systems to treat diabetes. In this study, metabolites of the G. aleppicum and S. bifurca herbs in active growth, flowering, and fruiting stages were investigated using high-performance liquid chromatography with photodiode array and electrospray ionization triple quadrupole mass spectrometric detection (HPLC-PDA-ESI-tQ-MS/MS). In total, 29 compounds in G. aleppicum and 41 components in S. bifurca were identified including carbohydrates, organic acids, benzoic and ellagic acid derivatives, ellagitannins, flavonoids, and triterpenoids. Gemin A, miquelianin, niga-ichigoside F1, and 3,4-dihydroxybenzoic acid 4-O-glucoside were the dominant compounds in the G. aleppicum herb, while guaiaverin, miquelianin, tellimagrandin II2, casuarictin, and glucose were prevailing compounds in the S. bifurca herb. On the basis of HPLC activity-based profiling of the G. aleppicum herb extract, the most pronounced inhibition of α-glucosidase was observed for gemin A and quercetin-3-O-glucuronide. The latter compound and quercetin-3-O-arabinoside demonstrated maximal inhibition of α-glucosidase in the S. bifurca herb extract. The obtained results confirm the prospects of using these plant compounds as possible sources of hypoglycemic nutraceuticals.

Hogweed Seed Oil: Physico-Chemical Characterization, LC-MS Profile, and Neuroprotective Activity of Heracleum dissectum Nanosuspension.

The seeds of dissected hogweed (Heracleum dissectum Ledeb., Apiaceae) are the source of hogweed oil (HSO), which is still underexplored and requires careful chemical and biological studies. The performed physico-chemical analysis of HSO elucidated basic physical characteristics and revealed the presence of fatty acids, essential oil components, pigments, and coumarins. High-performance liquid chromatography with photodiode array detection and electrospray ionization triple quadrupole mass spectrometric detection (HPLC-PDA-ESI-tQ-MS/MS) identified 38 coumarins that were characterized and quantified. Various furanocoumarins were the major components of HSO polyphenolics, including imperatorin, phellopterin, and isoimperatorin, and the total coumarin content in HSO varied from 181.14 to 238.42 mg/mL. The analysis of storage stability of the selected compounds in HSO indicated their good preservation after 3-year storage at cold and freezing temperatures. The application of the CO2-assisted effervescence method allowed the production of an HSO nanosuspension, which was used in a brain ischemia model of rats. The HSO nanosuspension enhanced cerebral hemodynamics and decreased the frequency of necrotic processes in the brain tissue. Thus, H. dissectum seeds are a good source of coumarins, and HSO nanosuspension promotes neuroprotection of the brain after lesions, which supports earlier ethnopharmacological data.

Plant Pyranocoumarins: Description, Biosynthesis, Application.

This overview article contains information about pyranocoumarins over the last 55 years. The article is based on the authors' phytochemical and physiological studies in vivo and in vitro as well as search and analysis of data in literature available on Google Scholar, Web of Science, PubMed, and ScienceDirect before January 2022. Pyranocoumarins are synthesized in plants of the Apiaceae, Rutaceae families, and one species in each of the Cornaceae, Calophyllaceae, and Fabaceae families can synthesize this class of compounds. The physiological role of these compounds in plants is not clear. It has been proven that these substances have a wide range of biological activities: anti-cancer, anti-spasmatic, and anticoagulant, and they also inhibit erythrocyte lysis and accumulation of triacylglycerides. The overview generalizes the modern understanding of the classification, structure, and biological activity of natural pyranocoumarins, and summarizes dispersed data into a unified scheme of biosynthesis. The review analyzes data on the localization and productivity of these substances in individual organs and the whole plant. It discusses a link between the unique structure of these substances and their biological activity, as well as new opportunities for pyranocoumarins in pharmacology. The article evaluates the potential of different plant species as producers of pyranocoumarins and considers the possibilities of cell cultures to obtain the end product.

Polymeric Compounds of Lingonberry Waste: Characterization of Antioxidant and Hypolipidemic Polysaccharides and Polyphenol-Polysaccharide Conjugates from Vaccinium vitis-idaea Press Cake.

Lingonberry (Vaccinium vitis-idaea L.) fruits are important Ericaceous berries to include in a healthy diet of the Northern Hemisphere as a source of bioactive phenolics. The waste generated by the V. vitis-idaea processing industry is hard-skinned press cake that can be a potential source of dietary fiber and has not been studied thus far. In this study, water-soluble polysaccharides of V. vitis-idaea press cake were isolated, separated, and purified by ion-exchange and size-exclusion chromatography. The results of elemental composition, monosaccharide analysis, ultraviolet-visible and Fourier-transform infrared spectroscopy, molecular weight determination, linkage analysis, and alkaline destruction allowed us to characterize two polyphenol-polysaccharide conjugates (PPC) as neutral arabinogalactans cross-linked with monomeric and dimeric hydroxycinnamate residues with molecular weights of 108 and 157 kDa and two non-esterified galacturonans with molecular weights of 258 and 318 kDa. A combination of in vitro and in vivo assays confirmed that expressed antioxidant activity of PPC was due to phenolic-scavenged free radicals, nitrogen oxide, hydrogen peroxide, and chelate ferrous ions. Additionally, marked hypolipidemic potential of both PPC and acidic polymers bind bile acids, cholesterol, and fat, inhibit pancreatic lipase in the in vitro study, reduce body weight, serum level of cholesterol, triglycerides, low/high-density lipoprotein-cholesterol, and malondialdehyde, and increase the enzymatic activity of superoxide dismutase, glutathione peroxidase, and catalase in the livers of hamsters with a 1% cholesterol diet. Polysaccharides and PPC of V. vitis-idaea fruit press cake can be regarded as new antioxidants and hypolipidemic agents that can be potentially used to cure hyperlipidemic metabolic disorders.

Caucasian Dragonheads: Phenolic Compounds, Polysaccharides, and Bioactivity of Dracocephalum austriacum and Dracocephalum botryoides.

Dracocephalum botryoides Steven and Dracocephalum austriacum L. are unexplored species of the Dracocephalum genus (Lamiaceae family) with a distribution in the Caucasus, where they are used in folk medicine and local cuisine. There are no data on the chemical composition of these Dracocephalum species. In this study, the application of a liquid chromatography-mass spectrometry technique for the metabolite profiling of methanol extracts from herbs and roots of D. austriacum and D. botryoides resulted in the identification of 50 compounds, including benzoic acid derivatives, phenylpropanoids, flavonoids and lignans. Water-soluble polysaccharides of the herbs and roots of D. austriacum and D. botryoides were isolated and characterized as mostly pectins with additive arabinogalactan-protein complexes and starch-like compounds. The antioxidant potential of the studied extracts of Dracocephalum and selected phenolics and water-soluble polysaccharides were investigated via radical-scavenging and ferrous (II) ion chelating assays. This paper demonstrates that herbs and roots of D. austriacum and D. botryoides are rich sources of metabolites and could be valuable plants for new biologically active products. To the best of our knowledge, this is the first study of whole plant metabolites and their antioxidant activity in D. austriacum and D. botryoides.

Role of Lipids of the Evergreen Shrub Ephedra monosperma in Adaptation to Low Temperature in the Cryolithozone.

Lipids are the fundamental components of cell membranes and they play a significant role in their integrity and fluidity. The alteration in lipid composition of membranes has been reported to be a major response to abiotic environmental stresses. Seasonal dynamics of membrane lipids in the shoots of Ephedra monosperma J.G. Gmel. ex C.A. Mey. growing in natural conditions of permafrost ecosystems was studied using HPTLC, GC-MS and ESI-MS. An important role of lipid metabolism was established during the autumn-winter period when the shoots of the evergreen shrub were exposed to low positive (3.6 °C), negative (-8.3 °C) and extremely low temperatures (-38.4 °C). Maximum accumulation of phosphatidic acid (PA), the amount of which is times times greater than the sum of phosphatidylcholine and phosphatidylethanolamine (PC + PE) was noted in shoots of E. monosperma in the summer-autumn period. The autumn hardening period (3.6 °C) is accompanied by active biosynthesis and accumulation of membrane lipids, a decrease of saturated 34:1 PCs, 34:1 PEs and 34:1 PAs, and an increase in unsaturated long-chain 38:5 PEs, 38:6 PEs, indicating that the adaptation of E. monosperma occurs not at the level of lipid classes but at the level of molecular species. At a further decrease of average daily air temperature in October (-8.3 °C) a sharp decline of PA level was registered. At an extreme reduction of environmental temperature (-38.4 °C) the content of non-bilayer PE and PA increases, the level of unsaturated fatty acids (FA) rises due to the increase of C18:2(Δ9,12) and C18:3(Δ9,12,15) acids and the decrease of C16:0 acids. It is concluded that changes in lipid metabolism reflect structural and functional reorganization of cell membranes and are an integral component of the complex process of plant hardening to low temperatures, which contributes to the survival of E. monosperma monocotyledonous plants in the extreme conditions of the Yakutia cryolithozone.

Metabolites of Siberian Raspberries: LC-MS Profile, Seasonal Variation, Antioxidant Activity and, Thermal Stability of Rubus matsumuranus Phenolome.

Rubus matsumuranus H. Lev. & Vaniot, a famous Siberian shrub of the Rosaceae family, is used in the folk medicine of nomads (Buryats, Yakuts, Soyots, and Mongols) as a remedy for the treatment of diseases of the respiratory and hepatobiliary systems. The lack of scientific information on R. matsumuranus leaves contributed to the investigation of the metabolomic profile and biological activity of this plant. In this study, metabolites of R. matsumuranus leaves in three stages (active growth, flowering, and fruiting) were characterised using high-performance liquid chromatography with photodiode array and electrospray ionisation triple quadrupole mass spectrometric detection (HPLC-PDA-ESI-tQ-MS). In total, 63 compounds were identified, including gallic acid derivatives, hydroxycinnamates, catechins, procyanidins, flavonols, and ellagitannins. Lambertianin C (57.11 mg/g of dry weight, DW), miquelianin (39.63 mg/g DW), and kaempferol-3-O-glucuronide (31.18 mg/g DW) were the major compounds in R. matsumuranus leaves. As a result of the HPLC-PDA-based assay to determine the antioxidant activity, it was revealed that lambertianin A, sanguiin H6, lambertianin C, and sanguiin H11 were effective scavengers of free radicals (2,2-diphenyl-1-picrylhydrazyl, DPPH•) and possessed Fe2+-chelating activity. After an investigation of the phenolic content in infusions and decoctions obtained by extraction with water at different temperatures, it was revealed that a hot infusion (80 °C) is a phenolic-rich preparation of R. matsumuranus leaves. Our research suggests that R. matsumuranus leaves are a rich source of phenolic compounds with high antioxidant properties and that this could be a prospective plant for new functional products.

Metabolites of Prickly Rose: Chemodiversity and Digestive-Enzyme-Inhibiting Potential of Rosa acicularis and the Main Ellagitannin Rugosin D.

Prickly rose (Rosaacicularis Lindl.) is the most distributed rose species in the Northern Hemisphere, used by indigenous people for various food purposes. The lack of detailed information about the chemical composition of R. acicularis has led us to study the phytochemical composition and metabolic profile of prickly rose extracts using chromatographic techniques. Many groups of phenolic and non-phenolic compounds were quantified in the leaves, flowers, roots and fruits of R. acicularis. Phenolic compounds were the dominant phytochemicals in the aerial parts and roots of R. acicularis. A precise study by high-performance liquid chromatography with photodiode array detection and electrospray ionization triple quadrupole mass spectrometric detection showed the presence of 123 compounds, among which ellagic acid derivatives, ellagitannins, gallotannins, catechins, catechin oligomers, hydroxycinnamates and flavonoid glycosides of kaempferol, quercetin and dihydroquercetin were all identified for the first time. The most abundant phenolic compounds were ellagitannins and flavonoid glycosides, with a maximal content of 70.04 mg/g in leaves and 66.72 mg/g in flowers, respectively, indicating the great ability of R. acicularis organs to accumulate phenolic compounds. By applying a standardized static, simulated gastrointestinal digestion method, we found the inhibitory potential of the leaf extract against digestive α-amylases. A pancreatic α-amylase activity-inhibiting assay coupled with HPLC microfractionation demonstrated high inhibition of enzyme activity by ellagitannin rugosin D, which was later confirmed by a microplate reaction with mammalian α-amylases and the simulated digestion method. This study clearly demonstrates that R. acicularis leaf extract and its main component, ellagitannin rugosin D, strongly inhibit digestive α-amylase, and may be a prospective antidiabetic agent.

Water-Soluble Melanoidin Pigment as a New Antioxidant Component of Fermented Willowherb Leaves (Epilobium angustifolium).

Willowherb (Epilobium angustifolium L., family Onagraceae) is a well-known food and medicinal plant used after fermentation as a source of beverages with high antioxidant potential. Despite this long history of use, only a few papers have described the chemical profile and bioactivity of fermented willowherb tea in general. To understand the basic metabolic differences of non-fermented and fermented E. angustifolium leaves, we used general chemical analysis, high-performance liquid chromatography with photodiode array detection and electrospray ionization triple quadrupole mass spectrometric detection assay, and an isolation technique. As a result, the content of 14 chemical groups of compounds was compared in the two plant materials; 59 compounds were detected, including 36 new metabolites; and a new water-soluble phenolic polymer of melanoidin nature was isolated and characterized. The fundamental chemical shifts in fermented E. angustifolium leaves relate mainly to the decrease of ellagitannin content, while there is an increase of melanoidin percentage and saving of the antioxidant potential, despite the significant changes detected. The strong antioxidative properties of the new melanoidin were revealed in a series of in vitro bioassays, and a simulated gastrointestinal and colonic digestion model demonstrated the stability of melanoidin and its antioxidant activity. Finally, we concluded that the new melanoidin is a basic antioxidant of the fermented leaves of E. angustifolium, and it can be recommended for additional study as a promising food and medicinal antioxidant agent.

Sagan Dalya Tea, a New "Old" Probable Adaptogenic Drug: Metabolic Characterization and Bioactivity Potentials of Rhododendron adamsii Leaves.

Adams' rhododendron (Rhododendron adamsii Rehder) or Sagan Dalya tea is a famous Siberian evergreen medical plant of the Ericaceae family used in traditional medicines of Buryats, Yakuts, and Mongols as a tonic, stimulant, and adaptogenic drug. The high popularity of R. adamsii coupled with poor scientific knowledge prompted the addressing of gaps related to metabolic and biomedical data of Sagan Dalya tea. The application of solid-phase extraction and liquid chromatography-mass spectrometric techniques for the metabolomic study of R. adamsii leaf extracts resulted in the identification of more than 170 compounds, including carbohydrates, organic acids, simple phenol glycosides, triterpene glycosides, flavonoids, prenylated phenols, benzoic acid derivatives, hydroxycinnamates, dihydrochalcones, catechins, and procyanidins, most of which were identified for the first time in the plant. Extended surveys of the seasonal content of all detected compounds prove that specific metabolite variations reflect the bioactivity of R. adamsii extracts. Regarding in vitro methods, the expressed antioxidant potential of R. adamsii extracts was investigated via radical-scavenging, nitric oxide scavenging, and ferrous (II) ion chelating assays. The animal-based swimming to exhaustion test demonstrates the stimulating influence of R. adamsii extract on physical performance and endurance, concluding that the drug could act as an adaptogen. Thus, Sagan Dalya tea (R. adamsii) has confirmed its "old" application as a tonic remedy and requires further precise study as a novel adaptogenic plant.

Influence of Extremely Low Temperatures of the Pole of Cold on the Lipid and Fatty-Acid Composition of Aerial Parts of the Horsetail Family (Equisetaceae).

The lipid composition of two species of vascular plants, Equisetum variegatum Schleich. ex. Web. and E. scirpoides Michx., growing in the permafrost zone (Northeastern Yakutia, the Pole of Cold of the Northern Hemisphere), with average daily air temperatures in summer of +17.8 °C, in autumn of +0.6 °C, and in winter of -46.7 °C, was comparatively studied. The most significant seasonal trend of lipid composition was an accumulation of PA in both horsetail species in the autumn-winter period. Cold acclimation in autumn was accompanied by a decrease in the proportion of bilayer-forming lipids (phosphatidylcholine in the non-photosynthetic membranes and MGDG in photosynthetic membranes), an increase in the desaturation degree due to the accumulation of triene fatty acids (E. scirpoides), and an accumulation of betaine lipids O-(1,2-diacylglycero)-N,N,N-trimethylhomoserine (DGTS). The inverse changes in some parameters were registered in the winter period, including an increase in the proportion of "bilayer" lipids and decrease in the unsaturation degree. According to the data obtained, it can be concluded that high levels of accumulation of membrane lipids and polyunsaturated FAs (PUFAs), as well as the presence of Δ5 FAs in lipids, are apparently features of cold hardening of perennial herbaceous plants in the cryolithozone.

Fragaria viridis Fruit Metabolites: Variation of LC-MS Profile and Antioxidant Potential during Ripening and Storage.

Fragaria viridis Weston or creamy strawberry is one of the less-known species of the Fragaria genus (Rosaceae family) with a wide distribution in Eurasia and is still in the shadow of more popular relatives F. ananassa (garden strawberry) or F. vesca (wild strawberry). Importantly, there is a lack of scientific knowledge on F. viridis compounds, their stability in the postharvest period, and bioactivity. In this study, metabolites of F. viridis fruits in three ripening stages were characterized with high-performance liquid chromatography with photodiode array and electrospray ionization triple quadrupole mass spectrometric detection (HPLC-PAD-ESI-tQ-MS). In total, 95 compounds of various groups including carbohydrates, organic acids, phenolics, and triterpenes, were identified for the first time. The quantitative content of the compounds varied differently during the ripening progress; some of them increased (anthocyanins, organic acids, and carbohydrates), while others demonstrated a decrease (ellagitannins, flavonols, etc.). The most abundant secondary metabolites of F. viridis fruits were ellagitannins (5.97-7.54 mg/g of fresh weight), with agrimoniin (1.41-2.63 mg/g) and lambertianin C (1.20-1.86 mg/g) as major components. Antioxidant properties estimated by in vitro assays (2,2-diphenyl-1-picrylhydrazyl radical (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) cation radical (ABTS), ferric reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC)) showed good antioxidant potential in all ripening stages of F. viridis fruits. The pilot human experiment on the effect of F. viridis fruit consumption on the serum total antioxidant capacity confirmed the effectiveness of this kind of strawberry. Postharvest storage of ripe fruits at 4 °C and 20 °C lead to declining content in the majority of compounds particularly ascorbic acid, ellagitannins, and flavonols, with the most significant loss at room temperature storage. These results suggest that F. viridis fruits are a prospective source of numerous metabolites that have potential health benefits.

LC-MS Profile, Gastrointestinal and Gut Microbiota Stability and Antioxidant Activity of Rhodiola rosea Herb Metabolites: A Comparative Study with Subterranean Organs.

Golden root (Rhodiola rosea L., Crassulaceae) is a famous medical plant with a one-sided history of scientific interest in the roots and rhizomes as sources of bioactive compounds, unlike the herb, which has not been studied extensively. To address this deficiency, we used high-performance liquid chromatography with diode array and electrospray triple quadrupole mass detection for comparative qualitative and quantitative analysis of the metabolic profiles of Rhodiola rosea organs before and after gastrointestinal digestion in simulated conditions together with various biochemical assays to determine antioxidant properties of the extracts and selected compounds. R. rosea organs showed 146 compounds, including galloyl O-glucosides, catechins, procyanidins, simple phenolics, phenethyl alcohol derivatives, (hydroxy)cinnamates, hydroxynitrile glucosides, monoterpene O-glucosides, and flavonol O-glycosides, most of them for the first time in the species. The organ-specific distribution of compounds found for catechins, procyanidins, and cinnamyl alcohols and glucosides was typical for underground organs and flavonoids and galloylated glucoses concentrated in the herb. Extracts from rhizomes, leaves and flowers showed high phenolic content and were effective scavengers of free radicals (2,2-diphenyl-1-picrylhydrazyl (DPPH•), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+), O2•-, •OH) and protected ß-carotene in a bleaching assay. Digestion in the gastric and intestine phase influenced the composition of R. rosea extracts negatively, affecting the content of catechins, procyanidins, and galloyl glucoses, and therefore, the antioxidativity level. After gut microbiota treatment, the antioxidant capacity of rhizome extract was lower than leaves and flowers due to the aglycone composition found in the colonic phase of digestion. Our study demonstrated that the herb of R. rosea is a rich source of metabolites with high antioxidant properties and could be a valuable plant for new bioactive products.

Caucasian Gentiana Species: Untargeted LC-MS Metabolic Profiling, Antioxidant and Digestive Enzyme Inhibiting Activity of Six Plants.

The members of Gentiana genus are widely distributed in the Caucasus region where they are used as phytoremedies, but they still have not been studied for their chemical composition and bioactivity. High-performance liquid chromatography with diode array and electrospray triple quadrupole mass detection (HPLC-DAD-ESI-QQQ-MS) was used to investigate metabolites of herb and roots of six gentians (Gentiana asclepiadea, G. cruciata, G. gelida, G. paradoxa, G. pneumonanthe, G. septemfida) grown in the Caucasus. In total, 137 compounds were found including three carbohydrates, 71 iridoid glycosides (mostly loganic acid), loganin, swertiamarin, gentiopicroside and sweroside derivatives, 40 flavones C-, O-, C,O-glycosides (such as luteolin, apigenin, chrysoeriol, and acacetin derivatives), two phenolic O-glycosides, five hydroxycinnamates, eight xanthones, and seven triterpene glycosides. Most of these compounds were identified in gentian samples for the first time. Quantitative differences were found in levels of seven iridoid glycosides, nine glycosylflavones, and two xanthones obtained by HPLC-DAD assay. The gentian extracts were evaluated for their radical-scavenging properties against DPPH and superoxide anion radicals, lipid peroxidation inhibition, and α-amylase/α-glycosidase inhibition. The herb extracts showed higher activity than root extracts. Positive correlations were found between the content of quantified phenolics and antioxidant and digestive enzymes inhibiting activity. The findings presented in our work suggest that the Caucasian gentians are a good source of bioactive phytocompounds with antioxidant and antidiabetic potential.

Caffeoylquinic Acids and Flavonoids of Fringed Sagewort (Artemisia frigida Willd.): HPLC-DAD-ESI-QQQ-MS Profile, HPLC-DAD Quantification, in Vitro Digestion Stability, and Antioxidant Capacity.

Fringed sagewort (Artemisia frigida Willd., Compositae family) is a well-known medicinal plant in Asian medical systems. Fifty-nine hydroxycinnamates and flavonoids have been found in A. frigida herbs of Siberian origin by high-performance liquid chromatography with diode array and electrospray triple quadrupole mass detection (HPLC-DAD-ESI-QQQ-MS). Their structures were determined after mass fragmentation analysis as caffeoylquinic acids, flavone O-/C-glycosides, flavones, and flavonol aglycones. Most of the discovered components were described in A. frigida for the first time. It was shown that flavonoids with different types of substitution have chemotaxonomic significance for species of Artemisia subsection Frigidae (section Absinthium). After HPLC-DAD quantification of 16 major phenolics in 21 Siberian populations of A. frigida and subsequent principal component analysis, we found substantial variation in the selected compounds, suggesting the existence of two geographical groups of A. frigida. The antioxidant activity of A. frigida herbal tea was determined using 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH•) and hydrophilic/lipophilic oxygen radical absorbance capacity (ORAC) assays and DPPH•-HPLC profiling, revealing it to be high. The effect of digestive media on the phenolic profile and antioxidant capacity of A. frigida herbal tea was assessed under simulated gastrointestinal digestion. We found a minor reduction in caffeoylquinic acid content and ORAC values, but remaining levels were satisfactory for antioxidant protection. These results suggest that A. frigida and its food derivate herbal tea could be recommended as new plant antioxidants rich in phenolics.

Khellactone Derivatives and Other Phenolics of Phlojodicarpus sibiricus (Apiaceae): HPLC-DAD-ESI-QQQ-MS/MS and HPLC-UV Profile, and Antiobesity Potential of Dihydrosamidin.

With obesity, the consumption of phenolic-enriched food additives as a part of traditional nutrition avoids the negative implications of eating high-calorie products. This study investigated the new herbal food additive, Phlojodicarpus sibiricus roots and herb, ubiquitously used in Siberia as a spice. Chromatographic techniques such as HPLC-DAD-ESI-QQQ-MS/MS and microcolumn HPLC-UV were the basic instruments for component profiling and quantification, and antiobesity potential was investigated using a differentiated 3T3-L1 adipocytes assay. We found that the roots and herb of P. sibiricus were high-coumarin-containing additives inhibiting triacylglycerol accumulation in 3T3-L1 preadipocytes. Forty-one phenolics were detected in P. sibiricus extracts, and 35 were coumarins, including 27 khellactone derivatives present as esters and glucosides. Total coumarin content varied from 36.16 mg/g of herb to 98.24 mg/g of roots, and from 0.32 mg/mL to 52.91 mg/mL in P. sibiricus preparations. Moreover, Siberian populations of P. sibiricus were characterised by a different HPLC-based coumarin profile. The most pronounced inhibiting effect on triacylglycerol accumulation in 3T3-L1 preadipocytes was shown for dihydrosamidin (khellactone 3'-O-isovaleroyl-4'-O-acetyl ester), which was more active than other khellactone esters and glucosides. The results demonstrated that if used as a food additive Phlojodicarpus sibiricus could be a source of bioactive coumarins of the khellactone group with high antiobesity potential.

Angelica gigas Nakai and Decursin Downregulate Myc Expression to Promote Cell Death in B-cell Lymphoma.

Angelica gigas Nakai (AGN) is an oriental traditional medicine to treat anemia, dysmenorrhea, and migraine. However, its anti-lymphoma effect is yet to be tested. Here, we demonstrated that AGN and its major component decursin target Myc to suppress lymphomagenesis in vitro and in vivo. AGN inhibited cell viability in multiple B lymphoma cells, while sparing normal splenocytes and bone marrow cells. Increased cleaved PARP level and caspase 3/7 activity and the repression of survival-promoting AKT/mTOR and MAPK pathways downstream of BCR, were responsible for the pro-apoptotic effects of AGN. We found that Myc, a prominent downstream target of these signaling pathways, contributes to AGN-induced cell death. Moreover, co-treatment with AGN and a Myc inhibitor, JQ1 or 10058-F4 yielded synergistic cytotoxic activities against cancer cells with markedly reduced Myc expression. AGN downregulated Myc expression and suppressed tumorigenesis in Eµ-myc transgenic mice. The proapoptotic activities of AGN were recapitulated by decursin, indicating that the anti-tumor effect of AGN was mainly caused by decursin. These findings suggest that AGN and decursin possess potent anti-lymphoma activity, and combination therapies with AGN/decursin and a Myc inhibitor to target Myc more efficiently could be a valuable avenue to explore in the treatment of B-cell lymphoma.

Bioactive Phenolics of the Genus Artemisia (Asteraceae): HPLC-DAD-ESI-TQ-MS/MS Profile of the Siberian Species and Their Inhibitory Potential Against α-Amylase and α-Glucosidase.

Artemisia genus of Asteraceae family is a source of medicinal plants known worldwide and used as ethnopharmacological remedies for the treatment of diabetes in Northern Asia (Siberia). The aim of this study was to determine the phenolic profile of 12 Siberian Artemisia species (A. anethifolia, A. commutata, A. desertorum, A. integrifolia, A. latifolia, A. leucophylla, A. macrocephala, A. messerschmidtiana, A. palustris, A. sericea, A. tanacetifolia, A. umbrosa) and to test the efficacy of plant extracts and pure compounds for antidiabetic potential. Finally, by HPLC-DAD-ESI-TQ-MS/MS technique, 112 individual phenolic compounds were detected in Artemisia extracts in a wide range of concentrations. Some species accumulated rare plant phenolics, such as coumarin-hemiterpene ethers (lacarol derivatives) from A. latifolia and A. tanacetifolia; melilotoside from A. tanacetifolia; dihydrochalcones (davidigenin analogs) from A. palustris; chrysoeriol glucosides from A. anethifolia, A. sericea, and A. umbrosa; eriodictyol glycosides from A. messerschmidtiana; and some uncommon flavones and flavonols. The predominant phenolic group from Artemisia species herb was caffeoylquinic acid (CQAs), and in all species, the major CQAs were 5-O-CQA (20.28-127.99 µg/g) and 3,5-di-O-CQA (7.35-243.61 µg/g). In a series of in vitro bioassays, all studied Artemisia extracts showed inhibitory activity against principal enzymes of carbohydrate metabolism, such as α-amylase (IC50 = 150.24-384.14 µg/mL) and α-glucosidase (IC50 = 214.42-754.12 µg/mL). Although many phenolic compounds can be inhibitors, experimental evidence suggests that the CQAs were key to the biological response of Artemisia extracts. Mono-, di- and tri-substituted CQAs were assayed and showed inhibition of α-amylase and α-glucosidase, with IC50 values of 40.57-172.47 µM and 61.08-1240.35 µM, respectively, and they were more effective than acarbose, a well-known enzyme inhibitor. The results obtained in this study reveal that Siberian Artemisia species and CQAs possess a pronounced inhibitory activity against α-amylase and α-glucosidase and could become a complement to synthetic antidiabetic drugs for controlling blood glucose level.

Effect of Low Temperature Cultivation on the Phytochemical Profile and Bioactivity of Arctic Plants: A Case of Dracocephalum palmatum.

The influence of climatic factors, e.g., low temperature, on the phytochemical composition and bioactivity of the arctic plant Dracocephalum palmatum Steph. ax Willd. (palmate dragonhead), a traditional food and medical herb of Northern Siberia, was investigated. D. palmatum seedlings were grown in a greenhouse experiment at normal (20 °C, NT) and low (1 °C, LT) temperature levels and five groups of components that were lipophilic and hydrophilic in nature were characterized. The analyses indicated that D. palmatum under NT demonstrates high content of photosynthetic pigments, specific fatty acid (FA) profile with domination of saturated FA (53.3%) and the essential oil with trans-pinocamphone as a main component (37.9%). Phenolic compounds were identified using a combination of high performance liquid chromatography with diode array detection and electrospray ionization mass-spectrometric detection (HPLC-DAD-ESI-MS) techniques, as well as free carbohydrates and water soluble polysaccharides. For the first time, it was established that the cold acclimation of D. palmatum seedlings resulted in various changes in physiological and biochemical parameters such as membrane permeability, photosynthetic potential, membrane fluidity, leaf surface secretory function, reactive oxygen species-antioxidant balance, osmoregulator content and cell wall polymers. In brief, results showed that the adaptive strategy of D. palmatum under LT was realized on the accumulation of membrane or surface components with more fluid properties (unsaturated FA and essential oils), antioxidants (phenolic compounds and enzymes), osmoprotectants (free sugars) and cell wall components (polysaccharides). In addition, the occurrence of unusual flavonoids including two new isomeric malonyl esters of eriodictyol-7-O-glucoside was found in LT samples. Data thus obtained allow improving our understanding of ecophysiological mechanisms of cold adaptation of arctic plants.