The Pharmacological Activities of (−)-Anonaine

Several species of Magnoliaceae and Annonaceae are used in Traditional Chinese Medicine. (−)-Anonaine, isolated from several species of Magnoliaceae and Annonaceae, presents antiplasmodial, antibacterial, antifungal, antioxidation, anticancer, antidepression, and vasorelaxant activity. This article provides an overview of the pharmacological functions of (−)-anonaine.


Introduction
Various constituents of Michelia alba (Magnoliaceae) are used for medical purposes. In our research, we have identified a series of compounds from Michelia alba, including (−)-anonaine ( Figure 1A) [1], an aporphine (isoquinoline) alkaloid also isolated from other plants (Table 1) with interesting and varied biological and pharmacological activities, including vasorelaxant, antibacterial, antifungal, antioxidative, anticancer and antidepressant effects, as summarized in Table 1  . In this article, we will focus on describing the pharmacological mechanisms of action of (−)-anonaine.

Anticancer Activity
There are three different mechanisms by which a cell commits suicide by apoptosis. One is initiated by signals arising within the cells. The second is triggered by death activators binding to receptors at the cell surface. The third is triggered by reactive oxygen species (ROS).

Antioxidative Activity
Oxidative stress is an imbalance of prooxidants and antioxidants in the organism. The oxidative stress can contribute to inflammation, heart disease, hypertension, various neurodegenerative diseases, and cancers. Anti-oxidative capacity of anonaine has been studied as a potential inhibitor of lipid peroxidation stimulated by Fe 2+ /cysteine in rat liver microsomal fractions [25]. The antioxidation activity of anonaine was also evaulated monitoring inhibition of microsomal lipid peroxidation induced by Fe 2+ /ascorbate, CCl 4 /NADPH or Fe 3+ ADP/NADPH [21]. However, one study demonstrated that anonaine increased deoxyribose degradation by generated hydroxyl radical. This effect was determined by thiobarbituric acid method in the incubation medium Fe 3+ -EDTA and H 2 O 2 [22].

Antiparasitic Activity and Antimicrobial Activity
Plasmodium falciparum is the cause of malaria, a life-threatening disease for thousands of years all around the World, particularly in Africa. The drug resistance is reducing the therapeutic efficiency for the treatment malarial and parasite. The in vitro antiplasmodial activity of (−)-anonaine was examined [5,32]. One study has reported that (−)-anonaine has antiplasmodial activity against both chloroquine sensitive D10 strain (IC 50 values of 25.9 ± 0.2 μM) and chloroquine resistant D12 strain of Plasmodium falciparum (IC 50 values of 19.6 ± 1.1 μM) with low cytotoxicity in a Chinese Hamster Ovarian cell line (CHO) [5]. Another study indicated that (−)-anonaine has antiplasmodial activity by in vitro radiometric Plasmodium falciparum growth inhibition assay (IC 50 values of 7 ± 2 μM) [32].

Conclusions
With the current information, it is evident that anonaine has interesting pharmacological functions, including vasorelaxant, antbacterial, antifungal, antioxidative, anticancer and antidepressant effects. In addition, one approved U.S. patent reports that anonaine also has utility in the prevention and treatment of gastrointestinal dyskinetic diseases (US patent number US7198804) [33]. However, there is lack of correlation between in vitro and in vivo studies on the effects of anonaine Toxicity studies are missing too. For this reason, extensive pharmacological, chemical experiments and metabolism studies should be undertaken. Last but not least, this article aims to provide useful information about anonaine for researchers in this field.