Dereplication‐guided isolation of a new indole alkaloid triglycoside from the hooks of Uncaria rhynchophylla by LC with ion trap time‐of‐flight MS

Abstract

Uncaria rhynchophylla (Gou-Teng) as the monarch herb of many formulae (Fufang), e.g. "Tian-Ma-Gou-Teng-Yin," "Ling-Jiao-Gou-Teng-Yin," and "Yi-Gan-San", is a famous traditional Chinese medicine documented in the Chinese pharmacopoeia for mental and cardiovascular diseases. In the traditional Chinese medicine system, only the hook-bearing stems are used as the crude materials for Gou-Teng, and the hooks are always considered more effective than the stems. Focusing on the mono-herb and its active constituents from combinatorial formulae is the core idea of reductionism of traditional Chinese medicine theory. Detailed liquid chromatography with mass spectrometry analysis on the hooks of U. rhynchophylla was performed to profile the chemical constituents based on tandem mass spectrometry fragmentation and UV absorption. Under the guidance of liquid chromatography with ion trap/time-of-flight mass spectrometry, one new indole alkaloid triglycoside (1), together with five known compounds 2-6 as the main constituents, were isolated from the hooks of U. rhynchophylla by various column chromatography methods. Compound 1 showed moderate activity on MT and MT melatonin receptors with agonistic rates of 79.6 and 46.3% at the concentration of 1 mM. This dereplication strategy can be equally applicable to rapidly disclose the active constituents of other Chinese herbs through targeted purification.

The Potentials of Uncariae Ramulus Cum Uncis for the Treatment of Migraine: Targeting CGRP in the Trigeminovascular System

“…In addition, Zhang et al reported that the extracts of different UR species also displayed agonistic effects on melatonin receptors [ 99 ]. Several new alkaloids isolated from UR show agonistic activities on both MT1 and MT2 melatonin receptors [ 100 , 101 ]. The increase in melatonin signaling by these UR components may confer inhibitory signal to the active trigeminal nerve and further suppress the abnormal release of CGRP.…”

UFLC-PDA-MS/MS Profiling of Seven Uncaria Species Integrated with Melatonin/5-Hydroxytryptamine Receptors Agonistic Assay

“…Indole alkaloids are the characteristic constituents in Uncaria plants with high response in positive mode MS. In this investigation, a number of 35 indole alkaloids were described and divided into six subclasses including cadambine-type (19, 21, 23, 26, 47), vinsosamide-type (15), D-seco-type (18, 25, 33, 38, 44, 50), corynoxine-type (11,20 , 22, 24, 27, 28, 31, 32, 34, 35, 36, 37, 42), corynantheintype (40, 43, 45, 48, 51, 53, 55, 57), and ajmalicine-type (39,54). In accordance with the previous investigation [17], D-seco alkaloids commonly generated the characteristic fragmentation ions ascribed to the loss of 17 Da (NH 3 ) in the MS 2 experiment; the indole and oxindole alkaloids could be differentiated from their respective maximal UV absorptions around 280 nm (indole) or 240 nm (oxindole); the numbers and types of glycosyl moieties were determined by the mass defects between the parent and fragment ions.…”

“…In the positive MS 2 experiment, the sequential losses of three glycosyl moieties (C 6 H 10 O 5 , 162 Da) suggested the presence of three glucosyl in the structure. Finally, this compound was isolated under the guidance of LCMS analysis, and identified to be 2′-O-[β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranosyl]-11hydroxyvincosamide based on rigid 1D and 2D NMR spectroscopic data [20].…”

“…Bioassay for agonistic activities on melatonin and 5-hydroxytryptamine receptors was performed in accordance with the previous reports [20,45]. In brief, HEK293 cells stably expressing human melatonin (MT 1 and MT 2 ) and 5-hydroxytryptamine (5-HT 1A and 5-HT 2C ) receptors were maintained in DMEM containing 10% FBS.…”

Triterpenoids from Uncaria rhynchophylla and Their PTP1B Inhibitory Activity

“…Alkaloids, triterpenoids, flavonoids and organic acids are the main constituents in U. rhynchophylla [8]. Our previous study disclosed that different parts of U. rhynchophylla could be well differentiated by their chemical profiles [9], from which two pairs of dimeric isoechinulin-type alkaloids [10], two flavanols [11], and one indole alkaloid triglycoside [12] with antidepressant potency were isolated under the guidance of bioassay. As a comparison, the antidiabetic constituents of U. rhynchophylla have been little investigated.…”