Caucasian Gentiana Species: Untargeted LC-MS Metabolic Profiling, Antioxidant and Digestive Enzyme Inhibiting Activity of Six Plants
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H OH metabolites OH Article Caucasian Gentiana Species: Untargeted LC-MS Metabolic Profiling, Antioxidant and Digestive Enzyme Inhibiting Activity of Six Plants Daniil N. Olennikov 1,* , Aydan I. Gadimli 2, Javanshir I. Isaev 2, Nina I. Kashchenko 1 , Alexey S. Prokopyev 3, Tatyana N. Kataeva 3, Nadezhda K. Chirikova 4 and Cecile Vennos 5 1 Laboratory of Medical and Biological Research, Institute of General and Experimental Biology, Siberian Division, Russian Academy of Science, 6 Sakh’yanovoy Street, 670047 Ulan-Ude, Russia; [email protected] 2 Department of Pharmacognosy, Azerbaijan Medical University, Anvar Gasimzade Street 14, Baku AZ1022, Azerbaijan; [email protected] (A.I.G.); [email protected] (J.I.I.) 3 Siberian Botanic Garden, Tomsk State University, Lenin Avenue 34/1, 634050 Tomsk, Russia; [email protected] (A.S.P.); [email protected] (T.N.K.) 4 Department of Biochemistry and Biotechnology, North-Eastern Federal University, 58 Belinsky Street, 677027 Yakutsk, Russia; [email protected] 5 Regulatory and Medical Scientific Affairs, Padma AG, 30 Haldenstrasse, CH-8620 Wetzikon, Switzerland; [email protected] * Correspondence: [email protected]; Tel.: +7-9021-600-627 Received: 3 October 2019; Accepted: 5 November 2019; Published: 7 November 2019 Abstract: 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. Keywords: Gentiana; LC-MS profile; iridoid glycosides; flavone glycosides; xanthones; antioxidant activity; amylase/glycosidase inhibition 1. Introduction Gentiana L. is a cosmopolitan gentianaceous genus involving about 360 species with a wide distribution in both hemispheres [1]. The diversity of forms and the broad range of ecological tolerance has allowed the gentians to adapt to the various natural conditions. As a rich phytogeographic region, Metabolites 2019, 9, 271; doi:10.3390/metabo9110271 www.mdpi.com/journal/metabolites Metabolites 2019, 9, 271 2 of 30 Metabolites 2019, 9, x 2 of 29 the Caucasus was no exception and this region demonstrated the presence of about 20 species [2]. Manyphytogeographic gentians were usedregion, in the the Caucasus traditional was medical no except systemsion andof this the region Caucasus demonstrated native peoples. the presence However, the latestof about published 20 species paper [2]. Many about gentians medical were plants used of in Caucasus the traditional often medical overlooked systems aspects of the of Caucasus the gentians’ applicationnative peoples. in traditional However, medical the practicelatest published despite theirpaper wideabout use medi bycal native plants peoples of Caucasus [3–6]. Theoften known ethnopharmacologicaloverlooked aspects of data the ongentians’ uses of application the gentians in traditional as medical medical plants practice are various, despite and their the wide plants use have demonstratedby native peoples a wide spectrum[3–6]. The ofknown pathology ethnopharmacolog treatments (Supplementaryical data on uses of Materials, the gentians Table asS1). medical The most plants are various, and the plants have demonstrated a wide spectrum of pathology treatments frequently used Gentiana species in the Caucasus region are G. asclepiadea (willow gentian), G. cruciata (Supplementary Materials, Table S1). The most frequently used Gentiana species in the Caucasus (star gentian), G. gelida (cold gentian), G. paradoxa (peculiar gentian), G. pneumonanthe (marsh gentian), region are G. asclepiadea (willow gentian), G. cruciata (star gentian), G. gelida (cold gentian), G. and G.paradoxa septemfida (peculiar(crested gentian), gentian) G. pneumonanthe (Figure1). There (marsh are gentian), usual therapeutic and G. septemfida recommendations (crested gentian) for these species(Figure such 1). as There for appetizers, are usual therapeutic antipyretics, recommendat and antidiabetics.ions for these [7, 8species]. The such various as for native appetizers, peoples of Caucasusantipyretics, region and also antidiabetics. used mentioned [7,8]. speciesThe various as remedies native peoples against of hepatitis, Caucasus anaemia, region also stomach used pain, malaria,mentioned haemorrhoid, species as tuberculosis, remedies against bronchitis, hepatitis, and anaemia, pneumonia stomach [9–11 pain,]. malaria, haemorrhoid, tuberculosis, bronchitis, and pneumonia [9–11]. a b c d e f FigureFigure 1. Caucasian 1. Caucasian gentians gentians studied studied in in presentpresent work: GentianaGentiana asclepiadea asclepiadea (a), (G.a), cruciataG. cruciata (b), G.(b gelida), G. gelida (c), G.(c), paradoxa G. paradoxa(d), (dG.), pneumonantheG. pneumonanthe( e(e),),G. G. septemfidaseptemfida ((ff).). SomeSome chemical chemical aspects aspects of of fivefive species (G. (G. asclepiadea asclepiadea, G., cruciataG. cruciata, G. gelida, G., gelidaG. pneumonanthe, G. pneumonanthe, G. , G. septemfidaseptemfida)) werewere shown shown previously, previously, but but G. paradoxaG. paradoxa is stillis an still unstudied an unstudied species. species.The known The data known datainclude include information information about about flavonoids flavonoids (flavones (flavones only) in four only) species in [11–25], four species xanthones [11 (mangiferin,–25], xanthones gentisin and its glycosides) in three species [15–18,20,26,27], iridoid glycosides in five species (mangiferin, gentisin and its glycosides) in three species [15–18,20,26,27], iridoid glycosides [18,19,22,27–32], monoterpenes in G. pneumonanthe [32], and triterpenes and naphthodipyranodione in five species [18,19,22,27–32], monoterpenes in G. pneumonanthe [32], and triterpenes and in G. asclepiadea [32,33]. In total, thirty-nine compounds were found in five gentians with most naphthodipyranodionediverse classes of flavonoids in G. asclepiadeaand iridoid [glycosides32,33]. In (Table total, S2). thirty-nine We also establish compounds some facts were about found in fivepharmacological gentians with mostuses of diverse G. asclepiadea classes and of flavonoidsG. cruciate, and the iridoid spectrum glycosides of gentians’ (Table bioactivity S2). We also establishincludes some cytotoxic facts about [34], pharmacologicalantimicrobial [35], usesantige ofnotoxicG. asclepiadea [36], antioxidantand G. cruciate, [37], anticholinesteraseand the spectrum of gentians’[19], hepatoprotective bioactivity includes [38], and cytotoxic antibiofilm [34], potentia antimicrobiall [39]. Based [35], on antigenotoxic this short review, [36], it antioxidant is obvious [37], anticholinesterase [19], hepatoprotective [38], and antibiofilm potential [39]. Based on this short review, Metabolites 2019, 9, 271 3 of 30 it is obvious that Caucasian gentians should receive more attention as sources of phytocompounds and bioactive plant remedies. It is particularly significant that high-performance liquid chromatography (HPLC) profiling with diode array detection and/or mass detection was performed only for two species, (G. asclepiadea [37], G. cruciata [22]), although in limited manner. Therefore, a comprehensive and comparative study is needed for a clear understanding of the chemo-diversity of Caucasian gentians. The antioxidant studies of gentians are for the same reason and also essential to identify antioxidant principles of plants. The information about antidiabetic activity of selected gentians is still unknown; so, it would be useful to know their potential against key enzymes of carbohydrate metabolism such as α-amylase and α-glycosidase [40]. The aim of present paper was to profile soluble metabolites of six gentian herbs and roots using high-performance liquid chromatography with diode array and electrospray triple quadrupole mass detection (HPLC-DAD-ESI-QQQ-MS) techniques and to quantify selected flavonoids, xanthones and iridoid glycosides in gentian plants. In this paper, we also make a comparative study of antioxidant activity and the digestive enzyme inhibition potential of gentian extracts, and we found active compounds which were the bioactive principles of the gentians.