What is the role of phenolic compounds of yerba mate (Ilex paraguariensis) in gut microbiota?

Diet actively influences gut microbiota and body homeostasis. The predominance of beneficial species results in symbiosis, while dysbiosis is characterized by an imbalance between microbial communities. Food plays a key role in this dynamic and in promoting the health of individuals. Ilex paraguariensis, also known as yerba mate, is a traditional plant from Latin America that has a complex matrix of bioactive substances, including methylxanthines, triterpenes, saponins, and phenolics. The consumption of yerba mate is associated with antioxidant, cardioprotective, anti-inflammatory, and anti-obesity effects. However, to the best of our knowledge, there have been no studies on yerba mate as a modulating agent of intestinal microbiota. Phenolics are the major compounds in yerba mate and have been reported to act in modulating the microbiome. In this review, we explore the activity of yerba mate as a possible stimulant of gut microbiota and present its main phenolics and their biological effects. We also propose different mechanisms of action of these phenolics and possible doses for their effectiveness.

Ursane-type triterpene oligoglycosides with anti-hepatosteatosis and anti-hyperlipidemic activity from the leaves of Ilex paraguariensis A. St.-Hil.

The methanol extract from the leaves of Ilex paraguariensis A. St.-Hil. (Aquifoliaceae), popularly known as mate, maté, or yerba maté, inhibits the intracellular triglyceride accumulation in HepG2 cells and suppresses the plasma triglyceride elevation in olive oil-treated mice. Three new triterpene saponins, termed mateosides I (1), II (2), and III (3), were isolated from the extract along with 29 known compounds. The structures of 1-3 were elucidated based on chemical and spectroscopic evidence. Among the isolates, principal saponin constituents, 2 and matesaponins 1 (7) and 2 (9), potently inhibited the triglyceride accumulation in HepG2 cells simultaneously treated with oleic acid and high glucose. In vivo assay of the methanol extract of I. paraguariensis revealed that 7 and 9 showed anti-hyperlipidemic activities in olive oil-treated mice. These results suggested that the saponin constituents of I. paraguariensis could be valuable bioactive marker for the anti-obesogenic activity.

Comparative analysis of complete Ilex (Aquifoliaceae) chloroplast genomes: insights into evolutionary dynamics and phylogenetic relationships.

BACKGROUND: Ilex (Aquifoliaceae) are of great horticultural importance throughout the world for their foliage and decorative berries, yet a dearth of genetic information has hampered our understanding of phylogenetic relationships and evolutionary history. Here, we compare chloroplast genomes from across Ilex and estimate phylogenetic relationships. RESULTS: We sequenced the chloroplast genomes of seven Ilex species and compared them with 34 previously published Ilex plastomes. The length of the seven newly sequenced Ilex chloroplast genomes ranged from 157,182 bp to 158,009 bp, and contained a total of 118 genes, including 83 protein-coding, 31 rRNA, and four tRNA genes. GC content ranged from 37.6 to 37.69%. Comparative analysis showed shared genomic structures and gene rearrangements. Expansion and contraction of the inverted repeat regions at the LSC/IRa and IRa/SSC junctions were observed in 22 and 26 taxa, respectively; in contrast, the IRb boundary was largely invariant. A total of 2146 simple sequence repeats and 2843 large repeats were detected in the 41 Ilex plastomes. Additionally, six genes (psaC, rbcL, trnQ, trnR, trnT, and ycf1) and two intergenic spacer regions (ndhC-trnV and petN-psbM) were identified as hypervariable, and thus potentially useful for future phylogenetic studies and DNA barcoding. We recovered consistent phylogenetic relationships regardless of inference methodology or choice of loci. We recovered five distinct, major clades, which were inconsistent with traditional taxonomic systems. CONCLUSION: Our findings challenge traditional circumscriptions of the genus Ilex and provide new insights into the evolutionary history of this important clade. Furthermore, we detail hypervariable and repetitive regions that will be useful for future phylogenetic and population genetic studies.

New benzoic acid and caffeoyl derivatives with anti-inflammatory activities isolated from leaves of Ilex kaushue.

A new benzoic acid, 3-[2-(2-hydroxyphenyl)acetoxy]benzoic acid (1), and two new caffeoyl derivatives, methyl (3E,5Z)-di-O-caffeoylquinate (2) and dhurrin 6'-O-caffeate (3), along with 20 known compounds were isolated from the leaves of Ilex kaushue collected in Vietnam. Their structures were elucidated on the basis of 1 D and 2 D NMR spectroscopy, and high-resolution MS spectrometry. The absolute configuration of 2 and 3 was unambiguously established by comparison of experimental and calculated ECD spectra and/or chemical reactivity. In addition, new compounds were evaluated for inhibitory effects of their tumor necrosis factor-α (TNF-α) production and cell cytotoxicity on lipopolysaccharide-induced RAW264 macrophage cells. All of those moderately suppressed TNF-α production in ratios of approximately 50% or higher at 25-100 µM, without cell cytotoxicity.

[Triterpenoids from leaves of Ilex guayusa].

The chemical constituents from the leaves of Ilex guayusa were investigated. Sixteen triterpenoids were isolated from the 95% ethanol extract of dried leaves of I. guayusa by silica gel, Sephadex LH-20, and ODS column chromatographies and semi-prepa-rative HPLC. Those triterpenoids were identified by NMR, HR-MS, and literature analysis: 3ß-hydroxy-11α,12α-epoxy-24-nor-urs-4(23)-ene-28,13ß-olide(1), 3ß-hydroxy-24-nor-4(23),12-oleanadien-28-methyl ester(2), oleanolic acid(3), 3ß,28-dihydroxy-12-oleanene(4), 2α,3ß-dihydroxy-11α,12α-epoxy-24-'nor-olean-4(23)-ene-28,13ß-olide(5), ursolic acid(6), 3ß,23-dihydroxy ursolic acid(7), 3ß,28-dihydroxy-12-ursene(8), 3ß-28-nor-urs-12-ene-3,17-diol(9), 3ß-hydroxyurs-11-ene-28,13ß-olide(10), 13ß,28-epoxy-3ß-hydroxy-11-ursene(11), 3ß-hydroxy-28,28-dimethoxy-12-ursene(12), 3ß-hydroxy-24-nor-urs-4(23),12-dien-28-oic acid(13), 3ß-hydroxy-24-nor-urs-4(23),12-dien-28-methyl ester(14), 2α,3ß-dihydroxy-11α,12α-epoxy-24-nor-urs-4(23)-ene-28,13ß-olide(15) and 2α,3ß-dihydroxy-11α,12α-epoxy-24-nor-urs-4(23),20(30)-dien-28,13ß-olide(16). Compounds 1-2 were new compounds, and compounds 4-5, 7 and 9-16 were isolated from I. guayusa for the first time.

Characterization and phylogenetic analysis of the complete chloroplast genome of Ilex rotunda, traditional Chinese medicine plant.

Ilex rotunda is a traditional Chinese medicine plant. In this study, we characterized the complete chloroplast (cp) genome sequence of I. rotunda to investigate its phylogenetic relationship. The cp genome of I. rotunda was 157,743 bp in length with 37.62% overall GC content, including a large single-copy (LSC) region of 87,060bp, a small single-copy (SSC) region of 18,432 bp, which were separated by a pair of inverted repeats (IRS) of 26,121 bp. The cp genome contained 133 genes, including 88 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Phylogenetic analysis based on whole cp genome sequences showed that I. rotunda is closely related to I. pubescens and I. polyneura.

Characterization of the complete chloroplast genome of Ilex crenata Thunb. (Aquifoliaceae).

Ilex crenata Thunb. is a species of Aquifoliaceae with high ornamental and ecological values. In this study, the complete chloroplast (cp) genome of I. crenata was assembled and characterized through Illumina sequencing data. The entire cp genome of I. crenata was 157,988 bp in length with 37.64% overall GC content, containing a large single-copy (LSC) region of 87,414 bp and a small single-copy (SSC) region of 18,422 bp, which were separated by a pair of 26,076 bp inverted repeat (IR) regions. A total of 135 genes were annotated, including 88 protein-coding genes, 39 tRNA genes, and 8 rRNA genes. Phylogenetic analysis based on 78 conserved protein-coding genes demonstrated that I. crenata is closely related to I. viridis and I. szechwanensis.

Triterpenoids from leaves of Ilex guayusa / 中国中药杂志

The chemical constituents from the leaves of Ilex guayusa were investigated. Sixteen triterpenoids were isolated from the 95% ethanol extract of dried leaves of I. guayusa by silica gel, Sephadex LH-20, and ODS column chromatographies and semi-prepa-rative HPLC. Those triterpenoids were identified by NMR, HR-MS, and literature analysis: 3β-hydroxy-11α,12α-epoxy-24-nor-urs-4(23)-ene-28,13β-olide(1), 3β-hydroxy-24-nor-4(23),12-oleanadien-28-methyl ester(2), oleanolic acid(3), 3β,28-dihydroxy-12-oleanene(4), 2α,3β-dihydroxy-11α,12α-epoxy-24-'nor-olean-4(23)-ene-28,13β-olide(5), ursolic acid(6), 3β,23-dihydroxy ursolic acid(7), 3β,28-dihydroxy-12-ursene(8), 3β-28-nor-urs-12-ene-3,17-diol(9), 3β-hydroxyurs-11-ene-28,13β-olide(10), 13β,28-epoxy-3β-hydroxy-11-ursene(11), 3β-hydroxy-28,28-dimethoxy-12-ursene(12), 3β-hydroxy-24-nor-urs-4(23),12-dien-28-oic acid(13), 3β-hydroxy-24-nor-urs-4(23),12-dien-28-methyl ester(14), 2α,3β-dihydroxy-11α,12α-epoxy-24-nor-urs-4(23)-ene-28,13β-olide(15) and 2α,3β-dihydroxy-11α,12α-epoxy-24-nor-urs-4(23),20(30)-dien-28,13β-olide(16). Compounds 1-2 were new compounds, and compounds 4-5, 7 and 9-16 were isolated from I. guayusa for the first time.

Pubescenosides Q-R, two new phenolic glycosides from Ilex pubescens.

Two new phenolic glycosides (1-2), along with six existing compounds (3-8), were isolated from the ethanolic extract of Ilex pubescens roots, a traditional folk medicine. These structures were determined using HR-ESI-MS, IR, UV, and NMR (including 1 D, 2 D-NMR). The anti-inflammatory activities of three phenolic glycosides (1-3) were evaluated in the human HepG2 cell lines. The results showed that compound 3 could induce P-gp and BCRP expression through the Nrf2-mediated pathway.[Formula: see text].

Anti-adipogenic 18,19-seco-ursane stereoisomers and oleane-type saponins from Ilex cornuta leaves.

Three undescribed seco-ursane stereoisomers, ilexcornutosides A-C, two undescribed triterpenoid saponins, ilexcornutosides D-E, and 11 known triterpenoids were isolated from the leaves of Ilex cornuta Lindl. & Paxton. Ilexcornutosides A-C and F with the same planar structures are unique 13(18)-ene-18,19-seco-ursane skeleton triterpenoids, identified as (3S,12R)-3-O-[ß-d-glucopyranosyl-(1 â†’ 2)-α-l-arabinopyranosyl]-12-hydroxyl-19-oxo-18,19-secours-13(18)-en-28,21-lactone. Among them, ilexcornutosides A and F (or ilexcornutosides B and C) are a pair of diastereomers at the C-20 position; ilexcornutosides A and C (or ilexcornutosides B and F) are a pair of diastereomers with epimerization at the C-21. Their structures were established by extensive spectroscopic (IR, 1D and 2D NMR, and HR-ESI-MS) and chemical analyses. The absolute configurations of ilexcornutosides A, B, D and F were determined by a single crystal X-ray diffraction analysis with a Cu Kα radiation. The inhibitory effect of ilexcornutosides A-F on the PPARγ expression was assessed in the 3T3-L1-Lenti-PPARγ-Luc cells using a single luciferase reporter assay. Ilexcornutosides A and C showed a comparable activity in decrease of the PPARγ expression to the positive control (T0070907) at 5 µM.

Structural characterization and biological evaluation of chemical constituents from Ilex cornuta.

One new ursane-type triterpenoid (1), one new ursane-type triterpenoid glycoside (2), and one new oleanane-type triterpenoid glycoside (3), along with 20 known compounds, were isolated from the leaves of Ilex cornuta. The structures of these natural products were elucidated on the basis of detailed spectroscopic analyses and chemical derivation. Our biological evaluation established that selective compounds showed moderate to significant antioxidant activities in the 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) methods.

Terpenoid and phenolic constituents from the roots of Ilex pubescens.

Five new metabolites, including two monoterpene glycosides Pubescenosides L-M (1-2) and three phenolic glycosides, Pubescenosides N-P (3-5), along with nineteen known ones, including liganoids, hemiterpenoids and caffeoylquinic acid derivates, were isolated from the roots of Ilex pubescens. Their structures were elucidated from extensive spectroscopic analysis, including 1D and 2D NMR experiments. This study is the first to report monoterpene glycosides with ß-pinene aglycone in Aquifoliaceae. Nine of these compounds were evaluated in vitro for their anti-platelet aggregation activities. Among them, compounds 3 and 4 showed moderate inhibitory activities on ADP-induced blood platelet aggregation [inhibition (%): 32.3 and 33.6, respectively] as compared to aspirin.

Eleven New Triterpenoid Glycosides from the Roots of Ilex asprella.

Asprellosides A-K, nine new ursane-type triterpenoid glycosides (1-9), and two new oleanane-type triterpenoid glycosides (10 and 11), including six rare sulfated triterpenoid glycosides, were isolated from the roots of Ilex asprella. Their structures were determined on the basis of comprehensive spectroscopic analysis and chemical methods. Among these compounds, asprelloside B (2) and asprelloside C (3) are the first examples of triterpenoid glycosides bearing a rare 3,4-O-disulfo-xylopyranosyl residue. All the saponins isolated showed no significant effects against respiratory syncytial virus (RSV) and lipopolysaccharide-induced nitric oxide production in Raw264.7 macrophages.

A new para-quinone-type flavan from the leaves of Ilex centrochinensis and its anti-inflammatory activities.

A new para-quinone-type flavan, (2S)-7-methoxy-3',4'-dihydroxy-5,8-quinoflavan (1), together with three known compounds, were isolated from the leaves of Ilex centrochinensis. Their structures were elucidated by detailed spectroscopic analyses for new structure and in comparison with published data for known compounds. Moreover, the new compound was evaluated its cytotoxic and anti-inflammatory activities in vitro on LPS induced RAW 264.7 cells and the results showed that 1 has promising anti-inflammatory activities.

Complete plastome sequence of Ilex asprella (Hooker and Arnott) Champion ex Bentham (Aquifoliaceae), a Chinese folk herbal medicine.

The complete chloroplast genome of Ilex asprella, a species of Aquifoliaceae is reported for the first time in this study. The complete chloroplast genome of I. asprella is 157,856 bp in length with a typical quadripartite structure, consisting of a large single-copy region (LSC, 87,258 bp), a single-copy region (SSC, 18,441 bp) and a pair of inverted repeats (IRs, 26,082 bp). There are 114 genes annotated, including 85 unique protein-coding genes, four unique ribosomal RNA genes, and 30 transfer RNA genes. To investigate the evolution status of T. concolor, as well as Scrophulariaceae, we build a phylogenetic tree with I. asprella and other eight species based on their complete chloroplast genomes. According to the phylogenetic topologies, I. asprella was closely related to I. wilsonii.

Two New Ursane-type Triterpenoid Glycosides from Ilex Cornuta.

Ilex cornuta (I. cornuta) is a traditional Chinese medicine (TCM) that has been used in clinical practice for hundreds of years. In order to provide more information about the chemical basis of its pharmacological effects, phytochemical investigation on the roots of I. cornuta was conducted in this study. The roots of the plant were firstly extracted with 95% EtOH, and then the crude was partitioned with petroleum ether, EtOAc and n-butyl alcohol. Different chromatographies were employed to isolate the crude step by step and the crude was further purified by semipreparative high performance liquid chromatography (HPLC). As a result, two new triterpenoid saponins (1, 2), together with 12 known compounds (3-14), were isolated from the roots of I. cornuta. Their structures were determined based on nuclear magnetic resonance (NMR), mass spectrum (MS) technologies, chemical reactions as well as gas chromatography (GC). Compounds 4, 6, 8, 11, 12 and 13 were isolated from this genus for the first time. The structures of compounds 1 and 2 were determined as 3ß-O-α-D-xylopyranosyl-(1→3)-α-L-2-O-acetylarabinopyranosyl-(1→2)-ß-D glucopyranosyl-23-hydroxyl-20α(H)-urs-12-en-28-oic acid 28-O-ß-D-glucopyranosyl ester (1) and 3ß-O-α-D-xylopyranosly-(1→3)-α-L-2-O-acetylarabinopyranosyl-(1→2)-ß-Dglucopyranosyl- 19α,23-dihydroxyl-20α(H)-urs-12-en-28-oic acid 28-O-ß-D-glucopyranosyl ester (2).

[Phenolic constituents from stems of Ilex asprella].

Phytochemical investigation on Ilex asprella stems by using various chromatographic techniques led to the isolation of 18 phenolic constituents. Based on spectroscopic data analyses and/or comparison of the spectroscopic data with those in literature, these constituents were identified, including two lignans (1, 2), five phenylpropanes (3-7), six chlorogenic analogues (8-13), and five benzoic analogues (14-18). Among them, compounds 3-7, 9, 11, 13, 14, 17, and 18 were isolated from genus Ilex for the first time, and 2, 8, 10, 15, and 16 were isolated from this species for the first time. The in vitro anti-inflammatory assay results showed that compounds 8, 9, 11, 13, and 15 possessed moderate inhibition on the NO production in RAW264.7 cells with IC50 values of 51.1-85.8 µmol·L⁻¹. The present study brought preliminary reference for the clarification of therapeutic ingredients of I. asprella with anti-inflammatory efficacy and its quality evaluation.

New triterpenoid saponins from the leaves of Ilex chinensis.

Eight new triterpenoid saponins, including four ursane-type saponins, ilexchinenosides J-M (1-4), and four oleanane-type saponins, ilexchinenosides N-Q (5-8), along with three known triterpenoid saponins (9-11) were isolated from the leaves of Ilex chinensis Sims. Their structures were established by 1D, 2D NMR and MS spectroscopic analyses and through comparisons with known compounds. Moreover, compounds 1, 3, 5, 7-9 and 11 exhibited significant levels of hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage in in vitro assays while compound 10 had moderately inhibitory effects on the NO production of lipopolysaccharide (LPS)-induced murine macrophages.

Three new triterpenoid saponins from the stems of Ilex asprella.

Three new triterpenoid saponins, namely asprellinoids A-C (1-3), featuring a sulfate substitution in sugar moiety, were isolated from the stems of Ilex asprella (Hook. et Arn.) Champ. ex Benth. Their structures were elucidated by the spectroscopic data analyses including HR-ESI-MS, IR, and NMR spectra, and chemical method.