Reptoside

In silico Molecular Docking Approach to Identify Potential Antihypertensive Compounds from Ajuga integrifolia Buch.-Ham. Ex D. Don (Armagusa).[Pubmed:38495362]

Adv Appl Bioinform Chem. 2024 Mar 11;17:47-59.

BACKGROUND: Ajuga integrifolia (Armagusa) is used as a decoction to treat high blood pressure and diabetes, widely in Ethiopia. Specific compounds for anti-hypertension activity were not identified so far. This study aims to provide a scientific basis for the therapeutic use of A. integrifolia as an antihypertension agent. METHODS: In silico studies were used to evaluate the antihypertensive components of A. integrifolia. Flavonoids identified using HPLC analysis and iridoid glycosides isolated from A. integrifolia in this study and those isolated from synonyms (A. remota and A. bractosa) were considered in the molecular docking study. Interactions were studied by using Autodock vina (1.2) on PyRx 0.8 and visualizing in 2D and 3D using ligPlot+ and Discovery studio software. Activities like vasoprotection and druglikeness properties were predicted using online servers. RESULTS: Flavonoids such as quercetin, myricetin, and rutin were identified and quantified by HPLC analysis from different extracts of A. integrifolia. Reptoside and 8-O-acetylharpgide isolated from the aerial part of A. integrifolia. The binding energies of all 17 candidates considered in this study range from -10.2 kcal/mol to -7.5 kcal/mol and are lower than enalapril (reference drug: -5.9 kcal/mol). The binding energies, in most case, constitute hydrogen bonding. Biological activity predicted using PASS test also showed that the flavonoids have more probability of activity than the iridoid glycosides. Druglikeness properties of the candidate molecules showed that most follow the Lipinski rule of five with few violations. CONCLUSION: Lower binding energies involving hydrogen bonding and predicted activities concerning hypertension confirm the traditional use of the aerial part of the medicinal plant concerned. Flavonoids: rutin, myricetin, quercetin, and kaempferol take the leading role in the antihypertensive activity of the aerial part of A. integrifolia. The iridoid glycosides studied are almost similar in their effect on their antihypertensive activity and still better than the reference drug.

Network pharmacology of iridoid glycosides from Eucommia ulmoides Oliver against osteoporosis.[Pubmed:35523810]

Sci Rep. 2022 May 6;12(1):7430.

Eucommia ulmoides Oliver is one of the commonly used traditional Chinese medicines for the treatment of osteoporosis, and iridoid glycosides are considered to be its active ingredients against osteoporosis. This study aims to clarify the chemical components and molecular mechanism of iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis by integrating network pharmacology and molecular simulations. The active iridoid glycosides and their potential targets were retrieved from text mining as well as Swiss Target Prediction, TargetNet database, and STITCH databases. At the same time, DisGeNET, GeneCards, and Therapeutic Target Database were used to search for the targets associated with osteoporosis. A protein-protein interaction network was built to analyze the interactions between targets. Then, DAVID bioinformatics resources and R 3.6.3 project were used to carry out Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Moreover, interactions between active compounds and potential targets were investigated through molecular docking, molecular dynamic simulation, and binding free energy analysis. The results showed that a total of 12 iridoid glycosides were identified as the active iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis. Among them, aucubin, Reptoside, geniposide and ajugoside were the core compounds. The enrichment analysis suggested iridoid glycosides of Eucommia ulmoides Oliver prevented osteoporosis mainly through PI3K-Akt signaling pathway, MAPK signaling pathway and Estrogen signaling pathway. Molecular docking results indicated that the 12 iridoid glycosides had good binding ability with 25 hub target proteins, which played a critical role in the treatment of osteoporosis. Molecular dynamic and molecular mechanics Poisson-Boltzmann surface area results revealed these compounds showed stable binding to the active sites of the target proteins during the simulations. In conclusion, our research demonstrated that iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis involved a multi-component, multi-target and multi-pathway mechanism, which provided new suggestions and theoretical support for treating osteoporosis.

Reassessment of the polar fraction of Stachys alopecuros (L.) Benth. subsp. divulsa (Ten.) Grande (Lamiaceae) from the Monti Sibillini National Park: A potential source of bioactive compounds.[Pubmed:28512595]

J Intercult Ethnopharmacol. 2017 Apr 12;6(2):144-153.

BACKGROUND: The phytochemical analysis of Stachys alopecuros subsp. divulsa, an endemic Italian species, has been recently reported and has showed the presence of 8-O-acetylharpagide (2), harpagide (3), allobetonicoside (4), and 4 cent-O-galactopyranosyl-teuhircoside (5). In this paper, an in deep study of its glycosidic fraction with the aim to widen the knowledge on its secondary metabolites content is reported. MATERIALS AND METHODS: Chromatographic techniques were used for the isolation of constituents while spectroscopic and spectrometric techniques were applied for the structures elucidation. RESULTS: Besides the known constituents, all of them reconfirmed, ajugoside (1), Reptoside (6) and 6-O-acetyl-ajugol (7) were also identified among the iridoids while the phenolic components resulted to be chlorogenic acid (8), b-arbutin (9), verbascoside (10), and stachysoside A (11), instead. CONCLUSION: The iridoid pattern of S. alopecuros subsp. divulsa has been expanded with the identification of not previously reported compounds as well as for the phenolic fraction. Except for the reconfirmed verbascoside (10), the other phenolic compounds were recognized for the first time in the studied species. The complete NMR assignment of compound (1) by means of bidimensional techniques is reported, and both the chemotaxonomic and pharmacological relevance of the isolated compounds is largely discussed.

Phytochemistry, micromorphology and bioactivities of Ajuga chamaepitys (L.) Schreb. (Lamiaceae, Ajugoideae): Two new harpagide derivatives and an unusual iridoid glycosides pattern.[Pubmed:27373875]

Fitoterapia. 2016 Sep;113:35-43.

Ajuga chamaepitys (L.) Schreb, well-known as Camaepitium or Ground Pine, is an annual herb typical of the Mediterranean area accounting several uses in the traditional medicine. In this work we have, analyzed the plant iridoid fraction together with the essential oil composition and study of the plant indumentum. Finally, we assayed the polar extracts and essential oil obtained from the aerial parts for antioxidant activity and cytotoxicity on tumor cells. The analysis of the monoterpene glycosides allowed us to isolate from roots and aerial parts and to structurally elucidate by NMR and MS the following compounds: ajugoside (1), Reptoside (2), 8-O-acetylharpagide (3), harpagide (4), 5-O-beta-d-glucopyranosyl-harpagide (5), asperulosidic acid (6), deacetyl asperulosidic acid (7) and 5-O-beta-d-glucopyranosyl-8-O-acetylharpagide (8), among which 5 and 8 were two new natural products. Chemotaxomic relevance of these constituents was discussed. The chemical analysis of A. chamaepitys essential oil by GC-FID and GC-MS showed ethyl linoleate (13.7%), germacrene D (13.4%), kaurene (8.4%), beta-pinene (6.8%), and (E)-phytol (5.3%) as the major volatile components. The micromorphological and histochemical study showed that iridoids and essential oil are mainly produced in the type III capitates and peltate trichomes of leaves and flowers. Biological evaluations of A. chamaepitys polar extracts and essential oil showed that the former were more potent as radical scavengers than the latter. MTT assay revealed that essential oil and ethanolic extracts were moderately cytotoxic on tumor cells with IC50 of 36.88 and 59.24mug/mL on MDA-MB 231 cell line, respectively, and IC50 of 60.48 and 64.12mug/mL on HCT116, respectively.

Anti-inflammatory effect of Ajuga bracteosa Wall Ex Benth. mediated through cyclooxygenase (COX) inhibition.[Pubmed:21073945]

J Ethnopharmacol. 2011 Jan 27;133(2):928-30.

ETHNOPHARMACOLOGICAL RELEVANCE: Ajuga bracteosa Wall Ex Benth. (Labiateae) is described in Ayurveda for the treatment of rheumatism, gout, palsy and amenorrhea. AIM OF THE STUDY: 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. MATERIALS AND METHODS: 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. RESULTS: 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 mug/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 muM concentration. CONCLUSIONS: 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.

A new phthalic acid ester from Ajuga bracteosa.[Pubmed:16835093]

Nat Prod Res. 2006 May 20;20(6):593-7.

A new phthalic acid ester 1,2-benzenedicarboxylic acid bis(2S-methyl heptyl) ester (1) was isolated from the hexane extract of the whole plant of Ajuga bracteosa. In addition, chloroform and methanol extracts yielded neo-clerodane diterpene ajugarin-I and two iridoid glycosides, Reptoside and 8-O-acetyl harpagide. The structures of all the compounds were confirmed by extensive spectroscopic analysis. From the two oily fractions nine and six volatile constituents respectively were identified by GCMS. Linalyl acetate was found to be common in both the oil fractions. This plant is a new source of linalyl acetate, a valuable perfumery compound.

DNA damaging activities of methanol extract of Ajuga postii and iridoid glucoside reptoside.[Pubmed:15938192]

Nat Prod Res. 2005 Jul;19(5):457-60.

An iridoid glucoside Reptoside (1) has been isolated as a DNA damaging active agent by bioassay-guided fractionation of the methanol extract of Ajuga postii. Furthermore, from the acetone extract of A. postii two known triterpenic compounds ursolic acid, alpha-amyrin and two steroidal compounds (24S)-24-ethylcholesta-5,25-dien-3beta-ol and beta-sitosterol were isolated. Their structures were elucidated based on 1D and 2D NMR techniques and mass data.