Coleon U, Isolated from Plectranthus mutabilis Codd., Decreases P-Glycoprotein Activity Due to Mitochondrial Inhibition.

Multidrug resistance in cancer is often mediated by P-glycoprotein. Natural compounds have been suggested as a fourth generation of P-glycoprotein inhibitors. Coleon U, isolated from Plectranthus mutabilis Codd., was reported to modulate P-glycoprotein activity but the underlying mechanism has not yet been revealed. Therefore, the effects of Coleon U on cell viability, proliferation, and cell death induction were studied in a non-small-cell lung carcinoma model comprising sensitive and multidrug-resistant cells with P-glycoprotein overexpression. P-glycoprotein activity and mitochondrial membrane potential were assessed by flow cytometry upon Coleon U, sodium-orthovanadate (an ATPase inhibitor), and verapamil (an ATPase stimulator) treatments. SwissADME was used to identify the pharmacokinetic properties of Coleon U, while P-glycoprotein expression was studied by immunofluorescence. Our results showed that Coleon U is not a P-glycoprotein substrate and is equally efficient in sensitive and multidrug-resistant cancer cells. A decrease in P-glycoprotein activity observed with Coleon U and verapamil after 72 h is antagonized in combination with sodium-orthovanadate. Coleon U induced a pronounced effect on mitochondrial membrane depolarization and showed a tendency to decrease P-glycoprotein expression. In conclusion, Coleon U-delayed effect on the decrease in P-glycoprotein activity is due to P-glycoprotein's functioning dependence on ATP production in mitochondria.

Enhanced Anticancer Activity of Hymenocardia acida Stem Bark Extract Loaded into PLGA Nanoparticles.

Hymenocardia acida (H. acida) is an African well-known shrub recognized for numerous medicinal properties, including its cancer management potential. The advent of nanotechnology in delivering bioactive medicinal plant extract with poor solubility has improved the drug delivery system, for a better therapeutic value of several drugs from natural origins. This study aimed to evaluate the anticancer properties of H. acida using human lung (H460), breast (MCF-7), and colon (HCT 116) cancer cell lines as well as the production, characterization, and cytotoxicity study of H. acida loaded into PLGA nanoparticles. Benchtop models of Saccharomyces cerevisiae and Raniceps ranninus were used for preliminary toxicity evaluation. Notable cytotoxic activity in benchtop models and human cancer cell lines was observed for H. acida crude extract. The PLGA nanoparticles loading H. acida had a size of about 200 nm and an association efficiency of above 60%, making them suitable to be delivered by different routes. The outcomes from this research showed that H. acida has anticancer activity as claimed from an ethnomedical point of view; however, a loss in activity was noted upon encapsulation, due to the sustained release of the drug.

C20-nor-Abietane and Three Abietane Diterpenoids from Plectranthus mutabilis Leaves as P-Glycoprotein Modulators.

In this study, a bioguided fractionation of Plectranthus mutabilis extract was performed by chromatographic methods. It yielded one new nor-abietane diterpene, mutabilol (1), and three known abietanes, coleon-U-quinone (2), 8α,9α-epoxycoleon-U-quinone (3), and coleon U (4). The abietane diterpenoid 5 was also tentatively identified using HPLC-MS/MS. Moreover, the extract profile and quantification of each isolated compound were determined by HPLC-DAD. Compound 4 was the major compound in the extract. Compounds 2-4 were found to be selective toward cancer cell lines and were able to inhibit P-glycoprotein (P-gp) activity in NCI-H460/R cells at longer exposure of 72 h and consequently revert doxorubicin (DOX) resistance in subsequent combined treatment. None of the compounds influenced the P-gp expression in NCI-H460/R cells, while the extract significantly increased it.

Characterization of Kefir Produced in Household Conditions: Physicochemical and Nutritional Profile, and Storage Stability.

Kefir, a traditional fermented food, has numerous health benefits due to its unique chemical composition, which is reflected in its excellent nutritional value. Physicochemical and microbial composition of kefir obtained from fermented milk are influenced by the type of the milk, grain to milk ratio, time and temperature of fermentation, and storage conditions. It is crucial that kefir characteristics are maintained during storage since continuous metabolic activities of residual kefir microbiota may occur. This study aimed to examine the nutritional profile of kefir produced in traditional in use conditions by fermentation of ultra-high temperature pasteurized (UHT) semi-skimmed cow milk using argentinean kefir grains and compare the stability and nutritional compliance of freshly made and refrigerated kefir. Results indicate that kefir produced under home use conditions maintains the expected characteristics with respect to the physicochemical parameters and composition, both after fermentation and after refrigerated storage. This work further contributes to the characterization of this food product that is so widely consumed around the world by focusing on kefir that was produced in a typical household setting.