Antifungal Constituents of Piper crocatum and Their Activities as Ergosterol Biosynthesis Inhibitors Discovered via In Silico Study Using ADMET and Drug-Likeness Analysis.

Along with the increasing resistance of Candida spp. to some antibiotics, it is necessary to find new antifungal drugs, one of which is from the medicinal plant Red Betel (Piper crocatum). The purpose of this research is to isolate antifungal constituents from P. crocatum and evaluate their activities as ergosterol biosynthesis inhibitors via an in silico study of ADMET and drug-likeness analysis. Two new active compounds 1 and 2 and a known compound 3 were isolated, and their structures were determined using spectroscopic methods, while their bioactivities were evaluated via in vitro and in silico studies, respectively. Antifungal compound 3 was the most active compared to 1 and 2 with zone inhibition values of 14.5, 11.9, and 13.0 mm, respectively, at a concentration of 10% w/v, together with MIC/MFC at 0.31/1.2% w/v. Further in silico study demonstrated that compound 3 had a stronger ΔG than the positive control and compounds 1 and 2 with -11.14, -12.78, -12.00, and -6.89 Kcal/mol against ERG1, ERG2, ERG11, and ERG24, respectively, and also that 3 had the best Ki with 6.8 × 10-3, 4 × 10-4, 1.6 × 10-3, and 8.88 µM. On the other hand, an ADMET analysis of 1-3 met five parameters, while 1 had one violation of Ro5. Based on the research data, the promising antifungal constituents of P. crocatum allow P. crocatum to be proposed as a new antifungal candidate to treat and cure infections due to C. albicans.

Erucic acid derived from rosemary regulates differentiation of mesenchymal stem cells into osteoblasts/adipocytes via suppression of peroxisome proliferator-activated receptor γ transcriptional activity.

Osteoporosis is associated with increase in fat tissue in bone marrow in humans. Mesenchymal stem cells in bone marrow are induced to differentiate into osteoblasts rather than adipocytes by the stimulation of peroxisome proliferator-activated receptor (PPAR) γ antagonists. PPARγ antagonists are expected to be useful to prevent osteoporosis by regulating the lineages of mesenchymal stem cells in bone marrow, as well as the prevention of obesity. In this study, we explored natural components suppressing PPARγ transcriptional activity in rosemary. Separation of active fraction of rosemary extract by repeated high performance liquid chromatograph and PPARγ luciferase reporter assay identified erucic acid, one of the monounsaturated fatty acids, as an active component. Twenty-five-micrometer erucic acid significantly decreased PPARγ luciferase activity and enhanced the differentiation of mouse-delivered C3H10T1/2 cells into osteoblasts rather than adipocytes. Furthermore, 25-µM erucic acid significantly decreased the expression of adipocyte marker genes, while accelerating osteoblast marker genes. In conclusion, erucic acid is a novel natural component derived from rosemary regulating mesenchymal stem cell differentiation via suppression of PPARγ transcriptional activity.