iridoids and 7-deoxyloganic-acid

Nepeta deflersiana (Lamiaceae) is a perennial herb used in the Saudi and Yemeni folk medicine as an anti-inflammatory, carminative, and antirheumatic agent.. This study explores the phytochemistry of the plant and the cardioprotective effect of N. deflersiana ethanolic extract (NDEE) against isoproterenol (ISP)-induced myocardial injury in rats.. Cardiac function, serum cardiac enzymes, myocardial antioxidants, inflammatory, and apoptotic biomarkers, and histopathological parameters were studied in ISP-injured Wistar rat heart tissues.. To the best of our knowledge, this is the first study to report the isolation of nine secondary metabolites from this plant: 1α-hydroxy-7α,14α,18-triacetoxy-isopimara-8,15-diene (1), β-sitosterol (2), lupeol (3), ursolic acid (4), 2,3-dihydroxy ursolic acid (5), caffeic acid (6), methyl rosmarinate (7), rosmarinic acid (8), and an irridoid glucoside 8-epi-7-deoxyloganic acid (9). To explain the mechanisms underlying the cardioprotective effect of NDEE, we evaluated the redox-sensitivity of NDEE in ISP-induced cardiac injury. The oral administration of NDEE (50 and 100 mg/kg b.w) prevented the depletion of endogenous antioxidants (CAT, SOD, NP-SH, and NO) and myocyte injury marker enzymes and inhibited lipid peroxidation (MDA, MPO). Moreover, NDEE downregulated the expression of pro-inflammatory cytokines (TNFα, IL-6, and IL-10) and apoptotic markers (caspase-3 and Bax) and upregulated the anti-apoptotic protein Bcl2. Furthermore, NDEE pretreatment significantly downregulated cardiac NF-κB (p65) expression, NF-κB-DNA binding activity, and MPO activity. Histological data showed that NDEE pretreatment reduced myonecrosis, edema, and infiltration of inflammatory cells and restored the architecture of cardiomyocytes.. NDEE demonstrated strong antioxidant, cardioprotective, anti-inflammatory, and anti-apoptotic potential against myocardial damage. This further endorses the use of N. deflersiana in Yemeni folk medicine against cardiovascular diseases.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Caspase 3; Cytokines; Down-Regulation; Heart; Inflammation; Iridoids; Isoproterenol; Lipid Peroxidation; Male; Myocardium; Nepeta; NF-kappa B; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; Sitosterols

Iridoids are a major group of biologically active molecules that are present in thousands of plant species, and one versatile iridoid, secologanin, is a precursor for the assembly of thousands of monoterpenoid indole alkaloids (MIAs) as well as a number of quinoline alkaloids. This study uses bioinformatics to screen large databases of annotated transcripts from various MIA-producing plant species to select candidate genes that may be involved in iridoid biosynthesis. Virus-induced gene silencing of the selected genes combined with metabolite analyses of silenced plants was then used to identify the 7-deoxyloganic acid 7-hydroxylase (CrDL7H) that is involved in the 3rd to last step in secologanin biosynthesis. Silencing of CrDL7H reduced secologanin levels by at least 70%, and increased the levels of 7-deoxyloganic acid to over 4 mg g(-1) fresh leaf weight compared to control plants in which this iridoid is not detected. Functional expression of this CrDL7H in yeast confirmed its biochemical activity, and substrate specificity studies showed its preference for 7-deoxyloganic acid over other closely related substrates. Together, these results suggest that hydroxylation precedes carboxy-O-methylation in the secologanin pathway in Catharanthus roseus.

Topics: Catharanthus; Gene Expression Regulation, Plant; Gene Silencing; Iridoids; Metabolome; Mixed Function Oxygenases; Phylogeny; Plant Proteins; Secologanin Tryptamine Alkaloids; Substrate Specificity

To study the chemical constituents of Dipsacus asper.. Column chromatography on Silica gel and RP-C18 were applied for isolation and purification of the constituents. Their structures were identified by spectral and chemical methods.. From the crude MeOH fraction of Dipsacus asper, 12 compounds were isolated and identified as Sucrose (1), beta-sitosterol (2), Oleanic acid (3), Triplostoside A (4), Loganin (5), Loganin acid (6), Sweroside (7), Epi-vogeloside ( 8), Vogeloside (9), Akebiasaponin D(10), Cauloside A(11),7-Deoxyloganic acid (12).. Compounds 8, 9, 12 are isolated from this plant for the first time.

Topics: Chromatography, Thin Layer; Dipsacaceae; Iridoids; Plant Roots; Triterpenes

Iridoids are one of the most widely distributed secondary metabolites in higher plants. They are pharmacologically active principles in various medicinal plants and key intermediates in the biosynthesis of monoterpenoid indole alkaloids as well as quinoline alkaloids. Although most iridoids are present as 1-O-glucosides, the glucosylation step in the biosynthetic pathway has remained obscure. We isolated a cDNA coding for UDP-glucose:iridoid glucosyltransferase (UGT85A24) from Gardenia jasminoides. UGT85A24 preferentially glucosylated the 1-O-hydroxyl group of 7-deoxyloganetin and genipin but exhibited only weak activity toward loganetin and no activity toward 7-deoxyloganetic acid. This suggests that, in the biosynthetic pathway of geniposide, a major iridoid compound in G. jasminoides, glucosylation occurs after methylation of 7-deoxyloganetic acid. UGT85A24 showed negligible activity toward any acceptor substrates other than iridoid aglycones. Thus, UGT85A24 has a remarkable specificity for iridoid aglycones. The mRNA level of UGT85A24 overlaps with the marked increase in genipin glucosylation activity in the methyl jasmonate-treated cell cultures of G. jasminoides and is related to iridoid accumulation in G. jasminoides fruits.

Topics: Base Sequence; DNA, Complementary; Fruit; Gardenia; Glycosyltransferases; Iridoids; Methylation; Molecular Sequence Data; Plant Proteins; Substrate Specificity

Two rare olive cultivars, Dhokar and Gemri-Dhokar, growing in the south of Tunisia were investigated to identify their phenolic profile and evaluate their sugar content and antioxidant activity. The highest value of phenolic content was detected in Gemri-Dhokar cultivar extract (6.97 g gallic acid equivalents/kg of fresh olive). In addition, sugar content was quantified; glucose (45.17 g/kg of fresh olive) was the predominant sugar in Dhokar cultivar, followed by fructose (40.83 g/kg of fresh olive). The identification of phenolic compounds was based on separation by high-performance liquid chromatography equipped with a diode array detector followed by liquid chromatography-mass spectrometry analysis. In both cultivars, Oleuropein aglycon derivatives and elenolic acid were the main phenolic components. Oleuropeins were the major compounds quantified in the Gemri-Dhokar drupes olives (61.04 mg/100 g of fresh olive), while 0.25 mg/100 g were found in fresh Dhokar. A new iridoid compound, isolated as pure compound, was not previously reported in the literature. Its structure was established by spectroscopic analyses (NMR, UV, MS, and IR). DPPH, ABTS, and FRAP assays showed that the most important antioxidant capacity of olive extracts was found in with Gemri-Dhokar cultivar.

Topics: Antioxidants; Chromatography, High Pressure Liquid; Flavonoids; Fructose; Fruit; Glucose; Iridoids; Molecular Structure; Olea; Phenols; Species Specificity; Tunisia

One new secoiridoid glycoside with conjugated diene, named 3-epi-swertiajaposide C (1), was isolated from the whole plants of Gentiana apiata N.E. Br., together with 11 known compounds, 7-deoxyloganic acid (2), isoorientin (3), gentiopicroside (4), silybin B (5), swertiamarin (6), asystasioside A (7), 6'-O-beta-D-glucopyranosylgentiopicroside (8), umbelliferone (9), oleanolic acid (10), kaempferol (11), and beta-sitosterol (12). The structure of the new compound (1) was elucidated on the basis of spectroscopic evidence including UV, IR, MS, NMR, HMBC, HMQC, and NOESY. Compounds 1, 2, 5, 6, 8, 9, and 11 were found in this plant for the first time. Moreover, silybin B (5) was isolated from the other plants besides Silybum marianum (L.) Gaertn for the first time by the present study.

Topics: Drugs, Chinese Herbal; Gentiana; Iridoids; Medicine, Traditional; Molecular Structure

7-Deoxyloganic acid (1), citrusin C (2), 3,4-dihydroxyl benzoic acid (3) and (E)-caffeic acid (4) were isolated from the water-soluble fraction of ethanol extracts of Morina nepalensis var. alba Hand.-Mazz. and their structures were determined on the basis of spectroscopic evidence. The total assignments of 1H and 13C NMR spectra of 1 in solvents CD3OD, D2O and CDCl3 were reported, in addition to the single-crystal X-ray diffraction analysis of its tetraacetate 1a. All compounds were obtained from Morina genus for the first time.

Topics: Iridoids; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Conformation; X-Ray Diffraction

The C-8-(S) isomer of deoxyloganic acid (7-deoxyloganic acid), together with beta-sitosteryl glucoside, five known stereoisomeric pentacyclic oxindole alkaloids and the tetracyclic oxindole isorhyncophylline, were isolated from the inner bark of Uncaria tomentosa. Structures of the isolated compounds were based on 1H and 13C NMR data, mainly 2D NMR experiments, including 1H-13C HMBC and 1H-1H NOESY correlation. Furthermore, the hitherto unreported 15N chemical shifts of the isomeric oxindole alkaloids, using 1H-15N HMBC experiments, were utilized to facilitate their characterization. Uncarine D showed weak cytotoxic activity against SK-MEL, KB, BT-549 and SK-OV-3 cell lines with IC(50) values between 30 and 40 microg/ml, while uncarine C exhibited weak cytotoxicity only against ovarian carcinoma (IC(50) at 37 microg/ml).

Topics: Alkaloids; Humans; Indoles; Iridoids; Magnetic Resonance Spectroscopy; Nitrogen Isotopes; Rubiaceae; Tumor Cells, Cultured