Metacytofilin has potent anti-malarial activity.

Metacytofilin (MCF) was isolated from the fungus Metarhizium sp. TA2759. Although MCF possesses anti-Toxoplasma activity, the effects of this compound against other parasites are unknown. Here, we evaluated the in vitro anti-malarial activity of MCF against the 3D7 strain and the chloroquine-resistant K1 strain of Plasmodium falciparum. The half maximal inhibitory concentrations (IC50) of MCF against the 3D7 and K-1 strains following culture for 48 h were 666 nM and 605 nM, respectively. Artemisinin was more potent than MCF against both strains (3D7 IC50: 17.4 nM; K-1 IC50: 18.3 nM), while chloroquine was ineffective against the chloroquine-resistant strain (3D7 IC50: 39.1 nM; K-1 IC50: 1.62 µM). MCF affected the ring stage of the parasites, resulting in their death as shown by spots within red blood cells. MCF also inhibited parasite growth following culture for 72 h (3D7 IC50, 285 nM). Four optical isomers of cyclo[Leu-Phe]-diketopiperazine derivatives with modified methoxy and/or hydroxyl groups lost anti-malarial activity, suggesting that the spatial positions of the methoxy and hydroxyl groups in MCF play an important role in its anti-malarial effects. Together, these data suggest that MCF may represent a promising lead compound for treatment of drug-resistant malarial parasites.

Astragalus root induces ovarian ß­oxidation and suppresses estrogen­dependent uterine proliferation.

Continuous estrogen stimulation in the uterus has been known to cause excess proliferation of the functional layer of endometrium, resulting in endometrial hyperplasia and leading to infertility. Estrogens can modulate other nuclear receptor signaling pathways, such as peroxisome proliferator­activated receptors (PPARs). Astragalus root (AsR) has exhibited strong PPARα agonistic activity. Female Imprinting Control Region mice were fed a powder diet that included 5% AsR hot water extract or 0.1% bezafibrate as a positive control for 56 days to investigate AsR effects on the reproductive tract, ovary and uterus. AsR resulted in upregulation of the expression of uterine and ovarian PPARα mRNA by 2.5­fold, and 1.5­fold, respectively, compared with controls. AsR significantly increased ovarian expression levels of mitochondrial 2,4­dienoyl­CoA reductase (mDECR), an auxiliary enzyme involved in ß­oxidation. AsR­fed mice also exhibited a significant increase in blood estradiol levels and tended to have higher ovary weight. AsR resulted in significantly decreased uterine weight and mDECR expression levels. It has been reported that a PPARα agonist suppresses the development of estrogen­dependent endometrial hyperplasia. These findings raise the possibility that AsR suppresses estrogen­dependent endometrial hyperplasia and ovarian dysfunction leading to infertility.