Characterization of Two Structural Forms of Otonecine-Type Pyrrolizidine Alkaloids from Ligularia hodgsonii by NMR Spectroscopy

Abstract

Clivorine (1) and ligularine (2), two hepatotoxic otonecine-type pyrrolizidine alkaloids isolated from Ligularia hodgsonii, an antitussive traditional Chinese medicine, were investigated in CDCl(3) and D(2)O by various NMR techniques to delineate why this type of alkaloid displays uncharacteristic solubility properties by dissolving in both nonpolar organic and aqueous solutions. The results demonstrated that both alkaloids exist in a non-ionized form in CDCl(3), but in an ionized form in D(2)O, suggesting that this unique dual solubility may play a role in the intoxication resultant from consumption of water extracts of herbs, including herbal teas, containing otonecine-type pyrrolizidine alkaloids.

Pyrrolizidine alkaloid profile in a traditional Chinese herbal medicine Chuan Zi Wan (Ligulariae Radix et Rhizoma) by liquid chromatography/electrospray ionization ion trap mass spectrometry

“…Identification of otonecine-type PAs in CZW 3.1.1. 19,21 Compounds 16 Because C-20 is one of three chiral carbons in the necic acid moiety of hodgsonine, which absolute configuration (R/S) was unknown, the two PAs may be the isomers of hodgsonine with different configuration(s) at C-20 for each other. Six compounds corresponding to peak 16, 17, 18, 24, 25 and 27 ( Fig.…”

Deacetylclivorine: A Gender-Selective Metabolite of Clivorine Formed in Female Sprague-Dawley Rat Liver Microsomes

“…Diethyldithiocarbamate, ketoconazole, monocrotaline, phenylmethylsulfonyl fluoride (PMSF), pilocarpine, retrorsine, sulfaphenazole, glutathione (GSH), and all the other chemicals were purchased from Sigma Chemical Co. (St. Louis, MO). Clivorine was isolated from L. hodgsonii Hook in our laboratory by a standard extraction procedure for pyrrolizidine alkaloid (Lin et al, 2000b). The identity of the isolated clivorine was confirmed by UV, infrared, NMR, and mass spectrometry (MS) analysis, and its purity was determined to be higher than 99% by high-performance liquid chromatography (HPLC).…”

“…Two types of PA, namely, retronecine and otonecine, are mainly responsible for the PA-induced hepatotoxicity (Mori et al, 1985;Huxtable, 1989;Buhler et al, 1990;Fu et al, 2004). Clivorine, a representative toxic otonecine-type PA, is present in many Ligularia species and especially exists as a predominant PA in the traditional Chinese medicinal herb Ligularia hodgsonii Hook (Lin et al, 2000b;Xia et al, 2004). Clivorine has been reported to cause hepatotoxicity and carcinogenicity in rodents and a positive mutagenic response in the Ames test in the presence of rat liver homogenates, suggesting the importance of hepatic metabolic activation in its intoxication (Yamanaka et al, 1979;Kuhara et al, 1980;Xia et al, 2004).…”

Eremophilane-type sesquiterpene lactones from Ligularia hodgsonii Hook

“…The roots of L. hodgsonii Hook., used as a traditional herbal medicine, have antibiotic, antiphlogistic and antitumor properties (Xu et al, 2006). In prior reports, sesquiterpenes (Ishizaki et al, 1974(Ishizaki et al, , 1979Liao et al, 2002;Xu et al, 2006Xu et al, , 2009 and pyrrolizidine alkaloids (Lin et al, 2000) were isolated from L. hodgsonii. We investigated the EtOH extract of roots and rhizomes of L. hodgsonii and obtained two new eremophilane-type sesquiterpenes.…”