HPLC‐ESI‐MS/MS of brain neurotransmitter modulator lobeline and related piperidine alkaloids in Lobelia inflata L

Abstract

There is a renewed interest in lobelia alkaloids because of their activity on the central nervous system. Lobeline, the most active of them, a nicotinic receptor ligand and neurotransmitter transporter inhibitor, is a candidate pharmacotherapy for metamphetamine abuse. In the present work, high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry in positive ion mode was used for investigating the alkaloid profile in Lobelia inflata L. Chromatographic separations were achieved on a Gemini C6-phenyl reversed-phase column providing good peak shape and improved selectivity. Being mostly 2,6-disubstituted piperidines, lobelia alkaloids presented abundant [M + H](+) ions with typical fragmentation. Identification was possible from a few specific ions, especially those resulting from excision of one of the substituents. Based on fragmentation pattern of lobeline as reference compound, 52 alkaloids were identified in the aqueous methanolic extract of L. inflata in contrast to the previously known some 20. Structural variability of these alkaloids identified arises basically from their substituents which can be phenyl-2-ketoethyl- or phenyl-2-hydroxyethyl units as well as their methyl-, ethyl- or propyl- homologues attached in different combinations. Several propyl homologue lobelia alkaloids and five hydroxypiperidine derivatives were found in the plant at the first time. In addition to 8-O-esters of 2-monosubstituted piperidine alkaloids previously reported by us in L. inflata, a 3-hydroxy-3-phenylpropanoic acid ester of hydroxyallosedamine ring-substituted was also identified as a new natural product. High-performance liquid chromatography-electrospray ionization tandem mass spectrometry can be successfully applied to Lobeliacae plant samples in the routine screening for new and known bioactive constituents, quality control of the crude drug, lobelia herba, alkaloid production studies, breeding and chemotaxonomy.

Targeted and untargeted profiling of alkaloids in herbal extracts using online solid‐phase extraction and high‐resolution mass spectrometry (Q‐Orbitrap)

“…Fig. (a) and (b) shows the MS fragmentation profiles of ALKs that were not previously documented in literature …”

“…1(a) and (b) shows the MS fragmentation profiles of ALKs that were not previously documented in literature. [43][44][45][46][47] Table 3 shows accurate masses of the selected precursor ion and fragments, and the normalised collision energy of the detected targeted (N = 35) and untargeted (49) ALKs.…”

Chemical Profiling of Lobelia chinensis with High-Performance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry (HPLC/Q-TOF MS) Reveals Absence of Lobeline in the Herb

“…In the TIC chromatogram of L. chinensis in positive ionization mode, Peaks 1−10, 12 and 13 were assigned as piperidine alkaloids. According to the reported fragmentation behaviors of 2,6-disubstituted N -methylpiperidine alkaloids where cleaving α to N is preferred, the cleavage of one side chain, or both side chains with hydrogen transfer to leave singly or doubly unsaturated N -methylpiperidine, or the cleavage of N -methyl group is the characteristic behavior of 2,6-disubstituted N -methylpiperidine alkaloids in their MS/MS spectra [10,21,22].…”

The Phytochemistry of Cherokee Aromatic Medicinal Plants

“…Lobelia inflata L. Campanu-laceae Indian tobacco root poultice used on pains; root/leaf poultice used on ringworm, insect bites root, leaves [15] Hairy root culture: diacetylene triol lobetyol + glucosides lobetyolin and lobetyolinin [303] Aerial parts: piperidine alkaloids (lobeline, lobelanine, norlobeline, norlobelanine, lobelanidine, norallosedamine, 8-ethyl-10-phenylnorlobelionol, 8-ethyl-10-phenyllobelionol) [304] Aerial parts: piperidine alkaloids (8,10-diethyllobelidione, 8,10-diethyllobelidione, 8-ethyl-10-phenyl-norlobelionol, 8-ethyl-10-phenyl-dehydrolobelionol, 8-ethyl-10-phenyl-dehydrolobelionol, lobeline, lobelidine, lobelanine) [305] Lobelia siphilitica L. Campanu-laceae Great blue lobelia root infusion for worms; leaf infusion for colds, fever root, leaves [15] Aerial parts: piperidine alkaloids (lobeline, cis-8,10-diphenyllobelidiol, Aerial parts: flavone glucuronides (7-O-β-D-glucuronides of apigenin, acacetin, and luteolin as well as the methyl ester of apigenin 7-O-β-D-glucuronide) [307] Magnolia acuminata (L.) Magnoli-aceae Cucumber magnolia bark infusion for toothache bark [15] Root bark: lignans (calopiptin, galgravin, veraguensin, and acuminatin) [308] Root bark: alkaloids (anolobine, N-methyllidcarpine methiodide, N,N -dimethyl-2,11,-dihydro-1,10-dimethoxyaporphine iodide), lignans (calopiptin, galgravin, veraguensin, acuminatin), sesquiterpene lactone (costunolide), sterol (β-sitosterol) [309] Leaves: alkaloids (asimilobine, liriodenine, norarmepavine, roemerine, armepavine, magnocurarine, magnoflorine) [310] Menispermum canadense L. Menisperm-aceae Common moonseed root used for skin diseases root [15] Roots: alkaloid dauricine [311] Aerial parts: alkaloid acutumine [312] Roots: alkaloids (acutumine, acutumidine, dauricine, daurinoline, N -desmethyldauricine, magnoflorine, N,N-dimethyllindcarpine, dehydrocheilanthifoline) [312] Monarda didyma L. Lamiaceae Scarlet beebalm infusion abortifacient; poultice for colds, headache leaves Several essential oil chemotypes are known [15] Floral EO: sabinene (5.0%), γ-terpinene (5.3%), p-cymene (11.0%), linalool (64.5%) [313] Leaf EO: linalool (74.2%), bornyl acetate (5.7%), germacrene D (5.3%) [313] Commercial EO (Pam innov, Le Chaffaut-Saint-Jurson, Provence, France): geraniol (89.5%) [314] Leaf EO: δ-3-carene (4.5%), p-cymene (10.5%), γ-terpinene (9.3%), thymol (57.3%); EO showed antifungal and DPPH radical inhibitory activities [315] Leaf EO: γ-terpinene (7.0%), α-terpinene ( Roots: gallic acid (antifungal) [326] Roots: 6-...…”