Dihydromelilotoside

Anti-tyrosinase and antimelanogenic effect of cinnamic acid derivatives from Prunus mahaleb L.: Phenolic composition, isolation, identification and inhibitory activity.[Pubmed:36924865]

J Ethnopharmacol. 2023 Jun 28;310:116378.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional use of Prunus species against skin diseases and especially for skin lightning cosmeceutical purposes is widespread in many cultures. Prunus mahaleb L. is a well known food plant and used in the baking industry for flavoring. The fruit kernels (endocarp) are used in India for hyperpigmentation. AIM OF THE STUDY: To investigate the chemical composition with the antimelanogenesis effect of P. mahaleb seed and kernel extracts and isolated compounds. MATERIALS AND METHODS: Isolation studies performed from the methanol extracts obtained from kernels and structures were determined using NMR and MS analysis. Antimelanogenesis effect was determined by mushroom tyrosinase assay, cellular tyrosinase assay and melanin content assay using B16F10 murine melanoma cells. RESULTS: Five cinnamic acid derivatives were isolated and their structures (2-O-beta-glucopyranosyloxy-4-methoxy-hydrocinnamic acid (1), cis-melilotoside (2), Dihydromelilotoside (3), trans-melilotoside (4), 2-O-beta-glucosyloxy-4-methoxy trans-cinnamic acid (5)) were elucidated using advanced spectroscopic methods. Mushroom tyrosinase enzyme inhibition of extracts, fractions and pure compounds obtained from P. mahaleb kernels were investigated and structure-activity relationship revealed. According to a detailed, comprehensive and validated LC-MS/MS technique analysis, vanilic acid (41.407 mg/g), protocatechuic acid (8.992 mg/g) and ferulic acid (4.962 mg/g) in the kernel ethylacetate fraction; quinic acid (14.183 mg/g), fumaric acid (8.349 mg/g) and aconitic acid (5.574 mg/g) were found as major phenolic compounds in the water fraction. The correlation of trace element copper content in extracts and fractions with mushroom enzyme activity was determined. By examining the enzyme kinetics of the compounds with effective cinnamic acid derivatives, inhibition types and enzyme binding constants K(i) were calculated. Compounds 1,3 and 5 exhibited high noncompetitive tyrosinase inhibitory activity against L-tyrosine substrates, with IC(50) values of 0.22, 0.31 and 0.37 mM respectively. In addition compounds 1, 3 and 5 showed dose-dependent inhibitory effects on intracellular tyrosinase and melanin levels in alpha-melanocyte-stimulating hormone (alpha-MSH)-induced B16F10 melanoma cells. CONCLUSIONS: Potent tyrosinase inhibitory compounds and extracts of P. mahaleb kernels suggest that it could be a new, non-toxic and inexpensive resource for the cosmeceutical industry and in skin diseases associated with hyperpigmentation.

Methoxyisoflavan derivative from Trigonella stellata inhibited quorum sensing and virulence factors of Pseudomonas aeruginosa.[Pubmed:35798919]

World J Microbiol Biotechnol. 2022 Jul 8;38(9):156.

The number of deaths caused by multidrug-resistant Pseudomonas aeruginosa has risen in the recent decade. The development of quorum sensing inhibition (QSI) is a promising approach for controlling Pseudomonas infection. Therefore, this study mainly aimed to investigate how a plant-source material inhibits QSI to produce an antipathogenic effect for fighting microbial infections. The QSI effect of Trigonella stellata was assessed by using Chromobacterium violaceum ATCC 12472 reporter strain. Trigonella stellata exhibited high QSI activity, and an ethanolic extract of T. stellata was prepared for phytochemical isolation of the most active QSI compound. Nine pure compounds were isolated and identified as kaempferitrin (1), soyasaponin I (2), beta-sitosterol-3-O-glucoside (3), Dihydromelilotoside (4), astrasikokioside I (5), methyl Dihydromelilotoside (6), (3R, 4S)-4, 2', 4'-trihydroxy-7-methoxy-4'-O-beta-D-glucopyranosylisoflavan (7), (3S, 4R)-4, 2', 4'-trihydroxy-7-methoxyisoflavan (8, TMF), and (+)-D-pinitol (9). These compounds were screened against C. violaceum ATCC 12472, and TMF exhibited a potent QSI. The effect of TMF at sub-minimum inhibitory concentrations (MICs) was assessed against P. aeruginosa virulence factors, including biofilm, pyocyanin formation protease and hemolysin activity. TMF induced significant elimination of QS-associated virulence behavior. In addition, TMF at sub-MICs significantly reduced the relative expression of lasI, lasR, rhlI, and rhlR compared with that in untreated cells. Furthermore, molecular docking was performed to predict structural basis of the QSI activity of TMF. The study demonstrated the importance of T. stellata as a signal modulator and inhibitor of P. aeruginosa pathogenesis.

Bioactivity-Guided Isolation of Potential Antidiabetic and Antihyperlipidemic Compounds from Trigonella stellata.[Pubmed:29676912]

J Nat Prod. 2018 May 25;81(5):1154-1161.

The in vitro antidiabetic and antihyperlipidemic activities of an alcoholic extract of Trigonella stellata were evaluated in terms of the activation of PPAR(alpha) and PPAR(gamma) in human hepatoma (HepG2) cells. The extract was investigated phytochemically, aiming at the isolation of the most active compounds to be used as a platform for drug discovery. Three new isoflavans, (3 S,4 R)-4,2',4'-trihydroxy)-7-methoxyisoflavan (1), (3 R,4 S)-4,2',4'-trihydroxy-7-methoxy-4'- O-beta-d-glucopyranosylisoflavan (2), and (2 S,3 R,4 R)-4,2',4'-trihydroxy-2,7-dimethoxyisoflavan (3), were isolated and characterized along with the five known compounds p-hydroxybenzoic acid (4), 7,4'-dihydroxyflavone (5), Dihydromelilotoside (6), quercetin-3,7- O-alpha-l-dirhamnoside (7), and soyasaponin I (8). The structures of 1-3 were elucidated using various spectroscopic techniques including HRESIMS and 1D and 2D NMR. The absolute stereochemistry of the new isoflavans (1-3) was determined using both experimental and calculated electronic circular dichroism as well as DP4 calculations. The isolated compounds were tested for their PPAR(alpha) and PPAR(gamma) activation effects in HepG2 cells.

Evaluation of in vitro antiprotozoal activity of Ajuga laxmannii and its secondary metabolites.[Pubmed:26734766]

Pharm Biol. 2016 Sep;54(9):1808-14.

Context Some Ajuga L. (Lamiaceae) species are traditionally used for the treatment of malaria, as well as fever, which is a common symptom of many parasitic diseases. Objective In the continuation of our studies on the identification of antiprotozoal secondary metabolites of Turkish Lamiaceae species, we have investigated the aerial parts of Ajuga laxmannii. Materials and methods The aerial parts of A. laxmannii were extracted with MeOH. The H2O subextract was subjected to polyamide, C18-MPLC and SiO2 CCs to yield eight metabolites. The structures of the isolates were elucidated by NMR spectroscopy and MS analyses. The extract, subextracts as well as the isolates were tested for their in vitro antiprotozoal activities against Plasmodium falciparum, Trypanasoma brucei rhodesiense, T. cruzi and Leishmania donovani at concentrations of 90-0.123 mug/mL. Results Two iridoid glycosides harpagide (1) and 8-O-acetylharpagide (2), three o-coumaric acid derivatives cis-melilotoside (3), trans-melilotoside (4) and Dihydromelilotoside (5), two phenylethanoid glycosides verbascoside (6) and galactosylmartynoside (7) and a flavone-C-glycoside, isoorientin (8) were isolated. Many compounds showed moderate to good antiparasitic activity, with isoorientin (8) displaying the most significant antimalarial potential (an IC50 value of 9.7 mug/mL). Discussion and conclusion This is the first report on the antiprotozoal evaluation of A. laxmannii extracts and isolates. Furthermore, isoorientin and Dihydromelilotoside are being reported for the first time from the genus Ajuga.

High-performance liquid chromatography-diode array detection/electrospray ionization mass spectrometry for the simultaneous analysis of cis-, trans- and dihydro-2-glucosyloxycinnamic acid derivatives from Dendrobium medicinal plants.[Pubmed:17497625]

Rapid Commun Mass Spectrom. 2007;21(12):1833-40.

Sensitive, selective and reliable high-performance liquid chromatography (HPLC)-diode array detection (DAD)/electrospray ionization multi-stage mass spectrometry (ESI-MSn) methods have been developed for the characterization of nine 2-glucosyloxycinnamic acid derivatives and quantitative analysis of three of the major 2-glucosyloxycinnamic acids, cis-melilotoside, trans-melilotoside and Dihydromelilotoside, present in Dendrobium medicinal plants. The identities of the latter three major 2-glucosyloxycinnamic acids were confirmed by comparing their retention times, UV and mass spectra with those of the reference standards. The characteristic ESI-MSn fragmentation patterns of the remaining six 2-glucosyloxycinnamic acid derivatives, which are similar to the three major compounds, have allowed the putative elucidation of their structures. The concentrations of the cis-, trans- and Dihydromelilotosides were simultaneously determined by HPLC/ESI-MS2 using the multiple reaction monitoring (MRM) mode in extracts of Dendrobium species. The method was validated with respect to the overall intra- and inter-day variation (RSD less than 8%) and the limits of quantification for the cis-, trans- and Dihydromelilotosides were 0.09, 0.09 and 0.01 microg/mL, respectively.

Bio-guided isolation of antioxidants from the stems of Dendrobium aurantiacum var. denneanum.[Pubmed:17421059]

Phytother Res. 2007 Jul;21(7):696-8.

Bio-guided fractionation of the stems of Dendrobium aurantiacum var. denneanum using a 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging assay, led to the isolation of three 2-glucosyloxycinnamic acid derivates, namely, cis-melilotoside, trans-melilotoside and Dihydromelilotoside, respectively. Their structures were elucidated through the analysis of uni- and bi-dimensional NMR, UV, IR and MS data. All these three compounds were first reported from the genus Dendrobium and exhibited potent antioxidant activities.

[Glycosides from Mussaenda arcuata Lam. ex Poiret leaves].[Pubmed:2088163]

Ann Pharm Fr. 1990;48(5):273-7.

Fractionation of the methanolic extract of Mussaenda arcuata leaves resulted in the isolation of four flavonoid glycosides and of two phenylpropanoid derivatives. The flavonoids were identified as astragalin 2, isoquercitrin 3, kaempferol-3-O-beta-D-rutinoside 5 and rutin 6 and the two phenylpropanoid derivatives as melilotoside 4 and Dihydromelilotoside 1. This latter compound is a novel natural product. The structures of compounds 1-6 have been elucidated on the basis of their spectral data and of those of their acetyl derivatives.