Leonurenones A–C: Labdane diterpenes from Leonotis leonurus

Abstract

Labdanes, leonurenones A–C, two known labdanes, luteolin 7-O-β-glucoside and luteolin were isolated and characterized from a commercial source of Leonotis leonurus. Genetic methods allowed for identification of the plant material. The leonurenones contain an uncommon α,β-unsaturated enone moiety in ring B, and leonurenones A and B were evaluated in a competitive inhibition assay at the GABA A neuroreceptor site.

“Wild cannabis”: A review of the traditional use and phytochemistry of Leonotis leonurus

“…However, repeated chromatography of an acetone extract of the same plant afforded Leonurenone C (3), 9,13:15,16-diepoxylabdane-6β,15α-diol (14), previously reported by Naidoo (2011) a year earlier, and nepetaefolin (4) ( Table 2 and figure 5) which was also found in Leonotis nepetifolia (He et al, 2012).…”

“…A second compound, a quinone, isolated from the methanol extract, but not identified, protected 75% and 87.5% of the experimental animals (mice) from PTZ induced seizures or significantly delayed seizure onset at doses of 200 mg/kg and 400 mg/kg respectively. Moreover, He et al (2012) also investigated the anticonvulsant effect by screening an aqueous extract of L. leonurus (1 g/mL) in a binding assay at the GABAA site and an inhibition of 81% was reported. However, two compounds isolated in the study, Leonurenone A and B, were reported to be inactive at this receptor which indicates that these compounds are not in themselves responsible for the anticonvulsant activity via this mechanism.…”

“…Also reported from phytochemical investigations of different extracts of the plant including ethanol, acetone or aqueous extracts, are an iridoid glycoside and phenolic compounds, primarily of the flavonoid category (He et al, 2012). (Connolly and Hill, 1991).…”

“…These reports however remain anecdotal and are yet to be substantiated, despite claims on internet websites that the plant contains the alkaloid, leonurine. Continuing research reports yielded many other compounds from L. leonurus, but leonurine (20) (Table 3), which is a mildly psychoactive guanidino alkaloid, was documented only to have been isolated from related species (He et al, 2012). Kuchta et al, in 2012 confirmed that no leonurine (20) could be detected in the aerial parts of L. leonurus using a newly developed sensitive and highly reproducible novel RP-HPLC analytical method.…”

“…However, He et al (2012) reported the presence of nepetaefolin (4) in L. leonurus for the first time in 2012. Von Dreele et al (1975) also proposed that the absolute configurations of Leonurenone A (1), and 9,13:15,16-diepoxylabdane-6β,15α-diol (epimeric mixture of (14)) were in agreement with the absolute configurations of other known labdanes given the concomitant occurrence of Leonurenone A (1), 9,13:15,16-diepoxylabdane-6β,15α-diol (epimeric mixture of (14)) and nepetaefolin (4) for which the crystal structure had been previously reported (Von Dreele et al,1975).…”