Akuammidine

Microfractionation bioactivity-based ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry for the identification of nuclear factor-kappaB inhibitors and beta2 adrenergic receptor agonists in an alkaloidal extract of the folk herb Alstonia scholaris.[Pubmed:23122407]

J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Nov 1;908:98-104.

Traditional Chinese medicines (TCMs) are generally considered complementary or alternative remedies in most Western countries. The constituents of TCMs are hard to define, and their efficacy is difficult to appraise. Thus, the development of suitable methods for evaluating the relationship between bioactivity and the chemical makeup of complex TCM mixtures remains a great challenge. In the present work, the bioactivity-integrated fingerprints of alkaloidal leaf extracts of Alstonia scholaris, a folk medicinal herb for chronic respiratory diseases, were established by ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF). This method was coupled with two dual-luciferase reporter assay systems to show nuclear factor-kappaB (NF-kappaB) inhibition and beta(2) adrenergic receptor (beta(2)AR) activation. Using UPLC-Q/TOF, 18 potential candidates were identified according to unique mass spectrometric fragmentation. After in vitro biological evaluation, several indole alkaloids with anti-inflammatory and anti-asthmatic properties were found, including Akuammidine, (E)-alstoscholarine, and (Z)-alstoscholarine. Compared with conventional fingerprints, the microfractionation based bioactivity-integrated fingerprints that contain both chemical and bioactivity details offer a more comprehensive understanding of the chemical makeup of plant materials. This strategy clearly demonstrated that dual bioactivity-integrated fingerprinting is a powerful tool for the improved screening and identification of potential dual-target lead compounds in complex herbal medicines.

Opioid activity of alkaloids extracted from Picralima nitida (fam. Apocynaceae).[Pubmed:9683021]

Eur J Pharmacol. 1998 May 29;350(1):101-8.

Extracts of the seeds of Picralima nitida (fam. Apocynaceae) have been reported to have opioid analgesic activity. In this investigation, isolated tissue bioassays and radioligand binding assays have been used to determine the opioid activity of five alkaloids--Akuammidine, akuammine, akuammicine, akuammigine and pseudoakuammigine--extracted from the seeds of P. nitida. Akuammidine showed a preference for mu-opioid binding sites with Ki values of 0.6, 2.4 and 8.6 microM at mu-, delta- and kappa-opioid binding sites, respectively. The agonist actions of Akuammidine in the mouse-isolated vas deferens were antagonised by naloxone and the mu-opioid receptor selective antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) confirming an action at mu-opioid receptors. In contrast, akuammine also showed highest affinity for mu-opioid binding sites (Ki 0.5 microM) but was an antagonist at mu-opioid receptors with a pK(B) of 5.7 against the selective mu-opioid receptor agonist [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO). Akuammicine has the highest affinity for kappa-opioid binding sites (Ki 0.2 microM) and was a full agonist at kappa-opioid receptors in the guinea pig ileum preparation but a partial kappa-opioid receptor agonist in the vasa deferentia of the mouse and the rabbit. Akuammigine and pseudoakuammigine showed little or no efficacy in the opioid bioassays. None of the alkaloids had significant activity for opioid receptor-like binding sites (ORL1-binding sites) with Ki values >> 10 microM. These data show that some alkaloids extracted from the medicinal plant P. nitida possess varying degrees of agonist and antagonist activity at opioid receptors but possess neither high affinity nor selectivity for mu-, delta- or kappa-opioid receptors or the ORL1-receptor.