Complexation of Lappaconitine with Glycyrrhizic Acid:  Stability and Reactivity Studies

Abstract

NMR and UV-vis spectroscopy have been used to study the complexation of antiarrhythmic alkaloid lappaconitine with an efficient complexing agent from licorice, glycyrrhizic acid, which is known to profoundly influence the therapeutic activity of the alkaloid in the complex. In MeOH, DMSO, or aqueous solutions, lappaconitine has been shown to form a stable complex with glycyrrhizic acid with 1:1 stoichiometry over a broad concentration range from 1 microM to 300 microM. The stability constant K(11) equals 2.0 x 10(5) M(-1) in aqueous solution. A similar complex of lappaconitine hydrobromide--the pharmaceutical formulation used in the treatment of arrhythmia--is 2 orders of magnitude less stable than pure lappaconitine. A notable decrease in the rate of the photoinduced electron-transfer reaction between lappaconitine in a complex with glycyrrhizic acid and tyrosine allows the suggestion of an explicit interrelation between the suppressed chemical reactivity of the bound alkaloid and the changes of its therapeutic efficiency.

Glycyrrhizic Acid as a Novel Drug Delivery Vector: Synergy of Drug Transport and Efficacy

“…Similar to nifedipine radical anion, radical anion of lappaconitine is unstable and rapidly transforms into reaction products which are not the Na ion channel blockers. Note that the knowledge about short lived paramagnetic intermediates of lappaconitine is very important because of its high toxicity, including phototoxicity [66][67]. There is high probability that the side effects of LA are connected with formation of its paramagnetic forms.…”

Redox reactions of natural alkaloid lappaconitine

“…At the used reactant concentrations the intramo lecular electron transfer occurs in parallel to the intermo lecular reaction with the amino acids and affords another set of products. 24 The first conclusion that follows from a comparison of the CIDNP spectra (see Fig. 9, spectra 2 and 4) is that GA almost completely blocks the radical pathway of the reaction.…”

“…30 The fact that the polariza tion is observed indicates the formation of polarized prod ucts via the radical mechanism. The CIDNP spectrum contains information on the structure of paramagnetic intermediates involved in the reaction.…”

“…24 It was shown that the complex in a 20% aqueous solution of DMSO has the same stability as that in a 20% solution of methanol. At the same time, in pure methanol the stability constant decreased by an order of magnitude.…”

Formulation and evaluation of novel glycyrrhizic acid micelles for transdermal delivery of podophyllotoxin

“…If so, whether could this new POD delivery system attenuate the side effects of POD? It has been reported that GA could form the ''host-guest'' type (Polyakov et al, 2006) with some medicines such as nifedipine (Tolstikova et al, 2010), buspirone (Fomina et al, 2014), carotenoids (Polyakov et al, 2006), simvastatin (Vavilin et al, 2008), and lappaconitine (Polyakov et al, 2005), of which GA is the host while the medicine is the guest. Interestingly, it was demonstrated that applications of GA together with these medicines could strengthen their therapeutic actions (Selyutina et al, 2015) and reduce their side effects.…”