Determination of Piperidine Alkaloids from Indian Tobacco (Lobelia inflata) Plants and Plant-Derived Products

Original Article

Austin Biochem. 2017; 2(2): 1014.

Determination of Piperidine Alkaloids from Indian Tobacco (Lobelia inflata) Plants and Plant-Derived Products

St-Pierre A¹, Lajeunesse A1,2 and Desgagné-Penix I1,2*

¹Department of Chemistry, Biochemistry and Physics, Université du Québec à Trois-Rivières, Canada

²Forensic Research Group, Université du Québec à Trois- Rivières, Canada

*Corresponding author: Desgagné-Penix I, Forensic Research Group, Université du Québec à Trois-Rivières, 3351 boul. des Forges, Trois-Rivières, QC, G9A 5H7, Canada

Received: November 15, 2017; Accepted: December 06, 2017; Published: December 13, 2017


Lobelia inflata also known as Indian tobacco is a traditional medicinal plant native to North America. L. inflata contains piperidine alkaloids that constitute a large family of specialized metabolites, many of which are of great interest for their various pharmaceutical activities. To date, no studies have reported on the alkaloid profile of various L. inflata products. This study aims to characterize the chemical composition of L. inflata products using several methods. Efficient Thin-Layer Chromatography (TLC), High-Performance Liquid-Chromatography (HPLC or LC) and LC-tandem Mass Spectrometry (LC-MS/MS) methods were developed for the analysis of piperidine alkaloids from extracts of L. inflata whole plants and from Lobelia-derived natural products including tincture, capsule and tobacco in order to determine the alkaloid profiles of these samples. Several piperidine alkaloids including 8,10-diethyl-lobelionol, norlelobanidine and lobeline were detected and identified from the sample extracts. Tincture did not contain lobeline. Therefore, the Lobelia-derived products have to be selected with caution if intended for pharmaceutical use.

Keywords: Lobelia inflata; Campanulaceae; Indian tobacco; Piperidine alkaloids; High-Performance Liquid Chromatography (HPLC); Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS); Lobeline


Lobelia inflata L. (Indian tobacco, Pukeweed) is a traditional medicinal plant of the Campanulaceae family native to eastern North America including southeast Canada and eastern United States [1,2]. It has long been used by aboriginal Amerindians for medicinal and religious purposes. Nowadays, Indian tobacco and its derived products are used to treat asthma and bronchitis, to repel bugs, and to relieve respiratory and muscular disorders. Lobelia plants produce bioactive piperidine alkaloids, including lobeline, which is used in the treatment of addictions [3,4]. Experimental and clinical research studies on Lobelia piperidine alkaloids have determined that they have many pharmacological properties including stimulant, diuretic, expectorant, antimicrobial and anti-cancer [3-6]. Also it was reported that piperidine alkaloids act on the nicotinic acetylcholine receptors and interact with neurotransmitter transporters such as transporters for dopamine, serotonin and monoamine vesicle transporter [6]. This type of interaction in the central nervous system makes this plant interesting not only for its beneficial effect in the treatment of addiction but also for the treatment of diseases such as Alzheimer’s and Parkinson’s diseases [6,7].

Unlike the abundant literature on the pharmaceutical effects of piperidine alkaloids, information on the biochemistry and metabolic pathways is incomplete. Previous studies using radio-labeled precursors have led to biochemical elucidation of the first reactions [8-10]. However, no gene involved in biosynthesis has been identified or characterized to date. The piperidine alkaloid biosynthesis begins with the formation of the piperidine ring derived from lysine. The first reaction is catalyzed by a Lysine Decarboxylase (LDC) to yield cadaverine (Figure 1). From there, a series of reactions likely involving a deamination, oxidation and imine formation yields the piperidinium cation (Figure 1). Benzoylacetic acid is another proposed precursor necessary for Lobelia alkaloid biosynthesis. It is most likely derived from phenylalanine through the phenylpropanoid pathway. The first reaction involves Phenylalanine Ammonia-Lyase (PAL) to yield cinnamic acid, then hydroxylation and oxidation are required to form the benzoylacetic acid (Figure 1). Lobelia alkaloids present several substitutions at the C2 and C6 positions of the piperidine ring. These substituents vary from a phenyl ring to acetate side chain. Thus, we divided Lobelia alkaloids into three groups. Group I comprises substitutions like formate or acetate side chains including 8-methyl- 10-ethyl-lobelionol and 8,10-diethyl-lobelionol. Group II includes one phenyl substitution such as allosedamine and norlelobanidine whereas group III comprises two phenyl substitutions such as lobeline (Figure 1). It should be noted that the exact sequence of reactions leading to these conversions is not yet known. Figure 1 shows the hypothetical biosynthesis suggesting that L-lysine is the precursor of the central piperidine ring while the side chains are derived from other pathways.