Anti-osteoclastogenic Effects of Indole Alkaloids Isolated from Barley (Hordeum vulgareVar.Hexastichon) Grass

Abstract

As part of our continuous program to identify new potential candidates for controlling osteolytic bone diseases from natural products, the alkaloid fraction of barley (Hordeum vulgare var. hexastichon) grass (HVA) significantly inhibited RANKLinduced osteoclast formation and protected mice from LPS-induced bone loss. A phytochemical investigation of HVA afforded nine indole alkaloids, including one new compound [hordeumin A (1)] and eight known analogues (2−9). Of them, four (1, 2, 4, and 5) were anti-osteoclastogenic compounds. Of these four, compound 5 significantly suppressed RANKL-induced osteoclast formation, actin ring formation, and bone resorption in a concentration-dependent manner. It also suppressed the RANKL-induced NF-κB and MAPK signaling pathways and the activation of c-Fos and NFATc1. Compound 5 also reduced the expression levels of osteoclastspecific marker genes, including TRAP, CtsK, DC-STAMP, OSCAR, and MMP9. Our findings suggest that HVA and its alkaloid constituents could be valuable candidates for the prevention and treatment of osteolytic bone diseases.

Natural products in crop protection: thiosemicarbazone derivatives of 3‐acetyl‐N‐benzylindoles as antifungal agents and their mechanism of action

“…1) occurs in the oil of jasmine, cloves and coal tar, and also exists widely as a putrefaction product from animals' intestines 10,11 . Indole and its derivatives exhibited a variety of biological properties, including anti‐cancer, 12 anti‐bacterial, 13 anti‐osteoclastogenic, 14 anti‐influenza, 15 and anti‐Alzheimer's disease activities 16 . Recently, structural modification and antifungal activities of indole and its derivatives have been reported continually 17–19 .…”