Tubulin polymerization-stimulating activity of Ganoderma triterpenoids.

Tubulin polymerization is an important target for anticancer therapies. Even though the potential of Ganoderma triterpenoids against various cancer targets had been well documented, studies on their tubulin polymerization-stimulating activity are scarce. This study was conducted to evaluate the effect of Ganoderma triterpenoids on tubulin polymerization. A total of twenty-four compounds were investigated using an in vitro tubulin polymerization assay. Results showed that most of the studied triterpenoids exhibited microtuble-stabilizing activity to different degrees. Among the investigated compounds, ganoderic acid T-Q, ganoderiol F, ganoderic acid S, ganodermanontriol and ganoderic acid TR were found to have the highest activities. A structure-activity relationship (SAR) analysis was performed. Extensive investigation of the SAR suggests the favorable structural features for the tubulin polymerization-stimulating activity of lanostane triterpenes. These findings would be helpful for further studies on the potential mechanisms of the anticancer activity of Ganoderma triterpenoids and give some indications on the design of tubulin-targeting anticancer agents.

Potent angiotensin-converting enzyme inhibitory tripeptides identified by a computer-based approach.

Currently, peptides and peptidomimetics are the main focus in attempts to identify inhibitors of angiotensin-converting enzyme (ACE), the dipeptidyl carboxypeptidase that causes blood vessels to constrict and blood pressure to increase. This study was conducted to identify the most potent ACE-inhibitory tripeptides with a proline C-terminus, using a novel three-step (tautomerization-docking-ADME simulation) virtual screening process and in vitro assays. Sixteen candidates were identified, and their IC50 values ranged from 5.6 to 274.4µM. ACE inhibition activity for 14 of the 16 tripeptides was reported for the first time. We also found that changing from the L-form to the D-form of the amino acid at the amino and carboxyl termini resulted in a decrease of inhibition, but a greater decrease was observed for C-terminal changes. With low IC50 values and high-predicted bioavailability, the peptides identified by our protocol are comparable in terms of ACE-inhibition to those derived from costly and time-consuming wet screening. Our in vitro and docking results showed that the configuration of the C-terminus is a critical parameter contributing to the inhibitory activity of tripeptides with proline at this position. These findings will contribute to the use of simulation tools for rational drug design, especially for ACE inhibitors.

Wild Mushrooms in Nepal: Some Potential Candidates as Antioxidant and ACE-Inhibition Sources.

Twenty-nine mushrooms collected in the mountainous areas of Nepal were analyzed for antioxidant activity by different methods, including Folin-Ciocalteu, ORAC, ABTS, and DPPH assays. Intracellular H2O2-scavenging activity was also performed on HaCaT cells. The results showed that phenolic compounds are the main antioxidant of the mushrooms. Among studied samples, Inonotus andersonii, and Phellinus gilvus exhibited very high antioxidant activity with the phenolic contents up to 310.8 and 258.7 mg GAE/g extracts, respectively. The H2O2-scavenging assay on cells also revealed the potential of these mushrooms in the prevention of oxidative stress. In term of ACE-inhibition, results showed that Phlebia tremellosa would be a novel and promising candidate for antihypertensive studies. This mushroom exhibited even higher in vitro ACE-inhibition activity than Ganoderma lingzhi, with the IC50 values of the two mushrooms being 32 µ g/mL and 2 µ g/mL, respectively. This is the first time biological activities of mushrooms collected in Nepal were reported. Information from this study should be a valuable reference for future studies on antioxidant and ACE-inhibitory activities of mushrooms.