iridoids and harpagide

Asthma is a chronic airway disorder with a hallmark feature of airflow obstruction that associated with the remodeling and inflammation in the airway wall. Effective therapy for controlling both remodeling and inflammation is still urgently needed. Leonuride is the main pharmacological component identified from Bu-Shen-Yi-Qi-Tang (BSYQT) which has been traditionally used in treatment of lung diseases. However, no pharmacological effects of leonuride in asthma were reported.. Here we aimed to investigated whether leonuride provided a therapeutic efficacy in reversing asthma airway remodeling and inflammation and uncover the underlying mechanisms.. Mouse models of chronic asthma were developed with ovalbumin (OVA) exposure for 8 weeks. Respiratory mechanics, lung histopathology and asthma-related cytokines were examined. Lung tissues were analyzed using RNA sequencing to reveal the transcriptional profiling changes.. After oral administration with leonuride (15 mg/kg or 30 mg/kg), mice exhibited a lower airway hyperresponsiveness in comparison to asthmatic mice. Leonuride suppressed airway inflammation evidenced by the significant reductions in accumulation of inflammatory cells around bronchi and vessels, leukocyte population counts and the abundance of type 2 inflammatory mediators (OVA specific IgE, IL-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF). On the other hand, leonuride slowed down the process of active remodeling as demonstrated by weaker goblet cell metaplasia and subepithelial fibrosis in lung histopathology and lower transforming growth factor (TGF)-β1 levels in serum and BALF in comparison to mice treated with OVA only. Furthermore, we uncovered transcriptional profiling alternations in lung tissue of mice after OVA exposure and leonuride treatment. Gene sets belonging to type-2 cytokine/chemokine activity stood out in leonuride target transcripts. Those upregulated (Bmp10, Ccl12, Ccl22, Ccl8, Ccl9, Cxcl15, Il13, Il33, Tnfrsf9, Il31ra, Il5ra, Il13ra2 and Ccl24) or downregulated (Acvr1c and Il18) genes in asthmatic mice, were all reversely regulated by leonuride treatment.. Our results revealed the therapeutic efficacy of leonuride in experimental chronic asthma for the first time, and implied that its anti-inflammatory and antifibrotic properties might be mediated by regulation of type-2 high cytokine/chemokines responses.

Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Chemokines; Cytokines; Disease Models, Animal; Inflammation; Iridoid Glycosides; Iridoids; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; Pyrans

The present study was undertaken to evaluate the in vivo analgesic activities of the extracts prepared from the aerial parts and roots of Scrophularia kotscyhana and to isolate the bioactive metabolites from the most active extract. Analgesic activities of all extracts and subextracts at the doses of 5, 10 and 30 mg/kg (i.p.) were examined using hot plate test in mice. Among the tested extracts, MeOH extract prepared from the aerial parts and the n-butanol subextract prepared thereof displayed the best analgesic activity at all doses. Phytochemical studies on n-butanol subextract led to the isolation of two new iridoid glycosides as an inseparable mixture, 8-O-acetyl-4'-O-(E)-(p-coumaroyl)-harpagide (1) and 8-O-acetyl-4'-O-(Z)-(p-coumaroyl)-harpagide (2) along with five known secondary metabolites, β-sitosterol 3-O-β-glucopyranoside (3), apigenin 7-O-β-glucopyranoside (4), apigenin 7-O-rutinoside (5), luteolin 7-O-β-glucopyranoside (6) and luteolin 7-O-rutinoside (7). The iridoid mixture (1 and 2), 3 and 4 elicited significant inhibition of pain at 5 mg/kg dose.

Topics: Analgesics; Animals; Apigenin; Chemical Fractionation; Glucosides; Glycosides; Iridoid Glycosides; Iridoids; Luteolin; Mice; Pain; Plant Components, Aerial; Plant Extracts; Pyrans; Scrophularia; Sitosterols

Harpagide and its derivatives have valuable medicinal properties, such as anti-inflammatory, analgesic and potential antirheumatic effects. There is the demand for searching plant species containing these iridoids or developing biotechnological methods to obtain the compounds. The present study investigated the effects of methyl jasmonate (MeJa, 50 μM), ethephon (Eth, 50 μM) and L-phenylalanine (L-Phe, 2.4 g/L of medium), added to previously selected variant of Murashige and Skoog medium (supplemented with plant growth regulators: 6-benzylaminopurine 1.0 mg/L, α-naphthaleneacetic acid 0.5 mg/L, gibberellic acid 0.25 mg/L) on the accumulation of harpagide and 8-O-acetyl-harpagide in Melittis melissophyllum L. agitated shoot cultures. Plant material was harvested 2 and 8 days after the supplementation. Iridoids were quantitatively analyzed by the UPLC-MS/MS method in extracts from the biomass and the culture medium. It was found that all of the variants caused an increase in the accumulation of harpagide. In the biomass harvested after 2 days, the highest harpagide content of 247.3 mg/100 g DW was found for variant F (L-Phe and Eth), and the highest 8-O-acetyl-harpagide content of 138 mg/100 g DW for variant E (L-Phe and MeJa). After 8 days, in some variants, a portion of the metabolites was released into the culture medium. Considering the total amount of the compounds (in the biomass and medium), the highest accumulation of harpagide, amounting to 619 mg/100 g DW, was found in variant F, and the highest amount of 8-O-acetyl-harpagide, of 255.4 mg/100 g DW, was found in variant H (L-Phe, MeJa, Eth) when harvested on the 8th day. These amounts were, respectively, 24.7 and 4.8 times higher than in the control culture, and were, respectively, 15 and 6.7 times higher than in the leaves of the soil-grown plant. The total amount of the two iridoids was highest for variant F (0.78% DW) and variant H (0.68% DW) when harvested on the 8th day. The results indicate that the agitated shoot cultures of M. melissophyllum can be a rich source of harpagide and 8-O-acetyl-harpagide, having a potential practical application. To the best of our knowledge we present for the first time the results of the quantitative UPLC-MS/MS analysis of harpagide and 8-O-acetyl-harpagide in M. melissophyllum shoot cultures and the enhancement of their accumulation by means of medium supplementation with elicitors and precursor.

Topics: Acetates; Chromatography, High Pressure Liquid; Culture Media; Cyclopentanes; Iridoid Glycosides; Iridoids; Lamiaceae; Mass Spectrometry; Organophosphorus Compounds; Oxylipins; Phenylalanine; Plant Leaves; Plant Shoots; Pyrans

We report the first analysis in absolute, and in particular, concerning the phytochemical pattern, about an endemic Italian species, Ajuga tenorei C. Presl. The analysis, performed by means of techniques such as Column Chromatography and NMR spectroscopy and Mass spectrometry, led to the isolation and the identification of five compounds namely verbascoside (1), echinacoside (2), ajugoside (3), harpagide (4) and 8-O-acetylharpagide (5). The presence of these compounds is important from both chemotaxonomic and ethno-pharmacological point of view. For what concerns the first point is confirmed the correct botanical classification of the species. The isolated compounds are also known to exert peculiar pharmacological activities and their presence may give a rationale to the historical medicinal properties associated to the Ajuga genus in general, since these plants have a long traditional use in many parts of the world. Such fact might suggest the use of also this species in this sense.

Topics: Ajuga; Glucosides; Glycosides; Iridoid Glycosides; Iridoids; Italy; Mass Spectrometry; Phenols; Plant Components, Aerial; Plant Extracts; Plants, Medicinal; Pyrans

The analysis of the polar fraction of Melittis melissophyllum L. subsp. melissophyllum led to the identification of several iridoid glycosides: monomelittoside (1), melittoside (2), harpagide (3), acetyl-harpagide (4) and ajugoside (5). Compounds 3 and 4 are considered marker compounds for the genus and, as well as compounds 1, 2 and 5, were already evidenced in a previous study on the nominal species. It was noteworthy of the presence of allobetonicoside (6) which was never reported for this genus. The isolation of 6 is very relevant because of its allose residue on the structure. Allose has been often found in the species of the subfamily Lamioideae even if it mostly regarded flavonoids considered of chemotaxonomical relevance for some correlated genera of Lamiaceae. Same as allosyl-glycosidic flavonoids, the presence of allosyl-glycosidic iridoids may also be an additional chemosystematic evidence of botanical relationships among Lamiaceae species and genera.

Topics: Glucosides; Iridoid Glycosides; Iridoids; Lamiaceae; Molecular Structure; Plants, Medicinal; Pyrans

Ajuga bracteosa Wall Ex Benth. (Labiateae) is described in Ayurveda for the treatment of rheumatism, gout, palsy and amenorrhea.. The aim of present investigation is to study anti-inflammatory activity of Ajuga bracteosa, to understand possible mechanism of action and to identify the constituents responsible for its activity.. The anti-inflammatory activity of 70% ethanolic extract was evaluated in TPA-induced mouse ear edema assay and in vitro cyclooxygenase (COX)-1 and COX-2 inhibitory activity was determined using EIA kits employing appropriate reference standards. Aajugarin I, lupulin A, withaferin A, reptoside and 6-deoxyharpagide were isolated from the 70% ethanolic extract by silica gel column chromatography.. The 70% ethanol extract of whole plants of Ajuga bracteosa showed a significant (p<0.05) and dose-dependent anti-inflammatory activity in an acute inflammation model at the dose of 0.5 and 1.0 mg/ear. The extract also exhibited a strong in vitro COX-1 and COX-2 inhibitory activity at 25 and 50 μg/mL concentration. Among the isolated compounds 6-deoxyharpagide exhibited highest COX-2 inhibition while rest of the compounds exhibited weak to moderate COX-1 and COX-2 inhibition at 30 μM concentration.. The results suggest that the 70% ethanol extract of Ajuga bracteosa possesses promising anti-inflammatory activity, which is possibly mediated through inhibition of COX-1 and COX-2 enzymes. The isolated constituents could be responsible in part for its anti-inflammatory and COX inhibitory activity. The study supports traditional use of Ajuga bracteosa for inflammatory diseases.

Topics: Ajuga; Animals; Anti-Inflammatory Agents; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Diterpenes; Edema; Ethnopharmacology; Female; Humans; In Vitro Techniques; India; Iridoid Glycosides; Iridoids; Medicine, Ayurvedic; Mice; Phytotherapy; Plant Extracts; Plants, Medicinal; Pyrans; Withanolides

The antioxidant principles isolated from the various parts of the plant are verminoside (leaf, stem bark and flowers; EC(50) = 2.04 µg/ml), Specioside (flowers; EC(50) = 17.44 µg/ml), Kampeferol diglucoside (leaf; EC(50) = 8.87 µg/ml) and Caffeic acid (leaf and fruits). The non anti-oxidant components isolated in the study include ajugol (stem bark and fruits) and phytol (leaf).

Topics: Antioxidants; Bignoniaceae; Caffeic Acids; Flowers; Fruit; Glycosides; Iridoid Glucosides; Iridoid Glycosides; Iridoids; Kaempferols; Phytol; Plant Extracts; Plant Leaves; Plant Stems; Pyrans

Two saponins: scrokoelziside A (1), scrokoelziside B (2), one iridoid glycoside, eurostoside (3), and two flavonoids: nepitrin (4) and homoplantaginin (5), were isolated from the leaves of Scrophularia ningpoensis for the first time. Moreover, eight known compounds: cane sugar (6), harpagide (7), aucubin (8), 6-O-methylcatalpol (9), harpagoside (10), angoroside C (11), beta-sitosterol (12) and beta-sitosterol glucoside (13) were isolated from the roots of S. ningpoensis. Furthermore, the antimicrobial activity of the extracts of the leaves of S. ningpoensis and the 10 compounds (1, 2, 3, 4, 5, 7, 8, 9, 10, 11) was studied in vitro against eight reference strains of bacteria by using the disc-diffusion method and micro-well dilution assay. The extracts of leaves and scrokoelziside A are effective against beta-haemolytic streptococci but had no effect against other strains. The extract of roots and other compounds showed no activity against all bacterial strains at the test concentration.

Topics: Anti-Infective Agents; Bacteria; Flavonoids; Glucosides; Glycosides; Iridoid Glucosides; Iridoid Glycosides; Iridoids; Luteolin; Microbial Sensitivity Tests; Molecular Structure; Plant Extracts; Plant Leaves; Plant Roots; Pyrans; Scrophularia; Sitosterols; Triterpenes

The cytotoxic activity of Stachys plants and of aucubin and harpagide against MCF7-breast adenocarcinoma, HeLa-cervix adenocarcinoma, A431-skin carcinoma of epithelial origin is reported in this study. Cisplatin and doxorubicin were use as reference compound.

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Proliferation; Cytotoxins; Female; Glucosides; Humans; Iridoid Glucosides; Iridoid Glycosides; Iridoids; Neoplasms; Phytotherapy; Plant Components, Aerial; Plant Extracts; Pyrans; Stachys

LC-DAD-MS monitored fractionation of a Harpagophytum procumbens DC. (Pedaliaceae) root extract was combined with a hyphenated LC-DAD-MS/SPE-NMR technique, thus providing the spectral data needed for structure elucidation. This approach allowed the characterization of isobaric iridoid glycoside regioisomers present only as minor constituents. The analytes were identified as the (E/Z) pairs of 6'-O-(p-coumaroyl)harpagide (6'-PCHG) and 8-O-(p-coumaroyl)-harpagide (8-PCHG). The fact that 8-(Z)-PCHG constitutes a new natural product underlines the analytical power of this combined approach. Furthermore, derivatives 6'-(Z)- and 6'-(E)-PCHG are new constituents for H. procumbens.

Topics: Glycosides; Harpagophytum; Iridoid Glycosides; Iridoids; Isomerism; Magnetic Resonance Spectroscopy; Plant Extracts; Plant Roots; Plants, Medicinal; Pyrans

Growth inhibitory activities and nutritional indices of catalpol (1), 8-O-acetylharpagide (2), and harpagide (3) were determinated in larvae and adults of Tribolium castaneum, respectively. Compound 1 produced a series of allelochemical effects probably related with the DNA synthesis. This iridoid possessed the highest inhibitory activity against DNA polymerase. Molecular orbital calculations suggest that a pi-pi charge transfer recognition model could explain the action of iridioids toward nucleic acid synthesis.

Topics: Animals; Enzyme Inhibitors; Glucosides; Insect Control; Iridoid Glucosides; Iridoid Glycosides; Iridoids; Larva; Models, Molecular; Molecular Structure; Nucleic Acid Synthesis Inhibitors; Pyrans; Tribolium

The new flavonoid glycoside stachyspinoside (1), and the three iridoids, 7-O-acetyl-8-epi-loganic acid (2), ajugol (3) and harpagide (4) were isolated from Stachys spinosa. The structures of these compounds were established on the basis of mass spectrometry (ESMS and tandem MS), one- and two-dimensional nuclear magnetic resonance experiments (COSY, COSY LR, HMQC, TOCSY and HMBC) as well as simple chemical derivatization.

Topics: Antioxidants; Chromatography, Liquid; Flavonoids; Glucosides; Glycosides; Greece; Hydrolysis; Inhibitory Concentration 50; Iridoid Glycosides; Iridoids; Lamiaceae; Mass Spectrometry; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Plants, Medicinal; Pyrans; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Ultraviolet