The cytotoxic activity of five alkaloids, namely 4,5-dioxo-dehydrocrebanine (1), dehydrocrebanine (2), crebanine (3), oxostephanine (4), and thailandine (5) isolated from the tuber and leaves of Stephania venosa (Blume) Spreng was investigated. Thailandine showed the strongest activity against lung carcinoma cells (A549) (IC50 of 0.30 µg/mL) with very low cytotoxicity against normal embryonic lung cells (MRC-5). Thailandine also demonstrated strong activity against Plasmodium falciparum, K1 strain (IC50 of 20 ng/mL), and Mycobacterium tuberculosis H(37)Ra (MIC of 6.25 µg/mL) as well as gram-positive bacteria such as Streptococcus pneumoniae and Staphylococcus aureus. Oxostephanine exhibited strong activity against breast cancer (BC) and acute lymphoblastic leukemia cells (MOLT-3) with an IC50 of 0.24 and 0.71 µg/mL, respectively, and exhibited very low cytotoxicity against MRC-5 cells. Dehydrocrebanine demonstrated strong activity against promyelocytic leukemia cells (HL-60) with an IC50 of 2.14 µg/mL whereas crebanine showed weak activity against cancer cell lines. However, both of them showed cytotoxicity against MRC-5 cells.

Cereulide and valinomycin are both 36-membered cyclic depsipeptides with 12 stereogenic centers that have a very similar sequence of cyclo [-D-O-Leu-D-Ala-L-O-Val-L-Val-]3 and cyclo [-D-O-Val-D-Val-L-O-Ala-L-Val-]3, respectively. Cereulide is an emetic toxin produced by Bacillus cereus through an unusual non-ribosomal peptide synthesis (NRPS), whereas valinomycin, produced by Streptomyces fulvissimus, is a known antibiotic drug. Both compounds are known as K+-ion-selective ionophores and cause a potassium-dependent drop in the transmembrane potential of mitochondria, arising from the uptake of a K+-ion-charged ionophore complex. Such compounds may affect mitochondrial function. In the three-dimensional structure of cereulide and valinomycin, cereulide has a vertical and horizontal mirror-image-like structure as is the case in valinomycin. The only difference is the side chains which are linked to a similar framework. Through the current 1H NMR spectroscopy and metal-complexation studies, we found that cereulide had a higher complexation ability to metal ions compared to valinomycin. Cereulide exhibited the K+-ion-selective ionophore property at a lower concentration than valinomycin. X-ray crystallographic analyses of the cereulide and valinomycin H+ form were compared, and revealed that the higher structures of both compounds also showed similarity in the crystal structures. The structure of cereulide-H+ form was found to be in agreement with the structure obtained by a combination of NMR spectroscopy and molecular-mechanics calculations, which afforded reasonable dihedral angles at the local-minimum-energy conformation of the cereulide-K+-ion complex.

A controlled release system of Plai (Zingiber cassumunar Roxb.) oil based on electrospun poly(lactic) acid (PLA) nanofiber mat was successfully developed. The physicochemical properties of the nanofibers loaded with select amounts of oil (15%, 20%, and 30% wt) were characterized using various techniques, including a morphological study using scanning electron microscopy (SEM), structural determination using Fourier transform infrared spectrometry (FTIR) and x-ray diffraction (XRD), as well as thermal properties study using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The loading content and the entrapment efficiency of Plai oil within the fiber mats were evaluated and were found to be remarkably high, ensuring that PLA was an appropriate material for Plai oil loading. The ability of the nanofiber mats to release (E)-1-(3,4dimethoxyphenyl) butadiene (DMPBD) was also examined and the fiber mats showed controlled release characteristics. As the nanofiber mats have particularly high specific surface area with fully accessible and interconnected pore structures, a liquid medium with active ingredients will not be trapped in blind pores but can be fully released out of the fiber matrix. Furthermore, in vitro skin permeation of the active compound as well as a skin irritation were assessed using reconstructed human epidermis (EpiSkin TM ). It was found that DMPBD could efficiently penetrate through the skin model. Moreover, the nanofiber mats containing Plai oil also showed no skin irritation, indicating them as promising prototypes for medical applications.

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