NMR, LC-MS Characterization of Rydingia michauxii Extracts, Identification of Natural Products Acting as Modulators of LDLR and PCSK9

Abstract

Rydingia michauxii (Briq.) Scheen and V.A.Albert (Lamiaceae) is used in Iranian traditional medicine to treat malaria, diabetes, hyperlipidemia, rheumatism and cardiovascular diseases. NMR and LC-DAD-MSn analyses were used to establish extract composition and phenylethanoid, flavonoid glycosides, lignans, labdane diterpenes and iridoids were identified and quantified. The main constituents were isolated, and structures were elucidated based on NMR, polarimetric and MS measurements. A new natural compound, ent-labda-8(17),13-dien-18-glucopyranosyl ester-15,16-olide is described here. The effects of ent-labda-8(17),13-dien-18-oic acid-15,16-olide (1), ent-labda-8(17),13-dien-18-glucopyranosyl es-ter-15,16-olide (2), antirrhinoside (3), echinacoside (4), verbascoside (5), and apigenin 6,8-di-C-glucoside (6), on the low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9), were studied in the human hepatocarcinoma cell line Huh7. Among the six constituents, (3) showed the strongest induction of the LDLR (3.7 ± 2.2 fold vs. control) and PCSK9 (3.2 ± 1.5 fold vs. control) at a concentration of 50 µM. The in vitro observations indicated a potential lipid lowering activity of (3) with a statin-like mechanism of action.

Ultrasound-Assisted Extraction of Verbascoside from Clerodendrum glandulosum Leaves for Analysis of Antioxidant and Antidiabetic Activities

“…Confirmation by NMR of phenylethanoids (VER) has been reported earlier from Rydingia michauxii extracts . NMR in combination with LC–MS data was adopted to elucidate the structural basis of different classes of polyphenols in case of a metabolomic study .…”

“…NMR analysis of crude extracts for confirming the presence of active polyphenols has been reported previously in several studies. 47 , 48 Zou et al utilized 1 H NMR to characterize the chemical profile of plant extracts of Cistanche deserticola and confirmed VER as one of the active marker compounds. 49 Confirmation by NMR of phenylethanoids (VER) has been reported earlier from Rydingia michauxii extracts.…”

“… 49 Confirmation by NMR of phenylethanoids (VER) has been reported earlier from Rydingia michauxii extracts. 47 NMR in combination with LC–MS data was adopted to elucidate the structural basis of different classes of polyphenols in case of a metabolomic study. 47 1 H and 2D-NMR spectra of crude methanolic extract of Stachys thracica led to the unambiguous assignment of 15 individual compounds including VER.…”

“… 47 NMR in combination with LC–MS data was adopted to elucidate the structural basis of different classes of polyphenols in case of a metabolomic study. 47 1 H and 2D-NMR spectra of crude methanolic extract of Stachys thracica led to the unambiguous assignment of 15 individual compounds including VER. 48 In the present study, principal signals showing the 1 H resonances and principal homonuclear correlations obtained by 2D-COSY spectra have led to the assignment of the different moieties of VER in the ethanol extract on the basis of previously published compound assignments.…”

A Bio-Guided Screening for Antioxidant, Anti-Inflammatory and Hypolipidemic Potential Supported by Non-Targeted Metabolomic Analysis of Crepis spp.

“…NMR and LC-MS analyses can be powerful tools to assess the chemical composition of specialized natural products that occur in complex mixtures. In respect to NMR, such protocols involve a “metabolomic” approach supported by a plethora of previously published papers, displaying the usefulness of both 1D and 2D NMR experiments for compound identification in complex matrix-like plant extracts, and also for comparative and qualitative analysis, as well as several other purposes and applications [ 9 ]. The relevant advantage of this approach is attributed to the unique NMR property of having the same response factor for different classes of metabolites.…”