Anti-osteoclastogenic Effects of Indole Alkaloids Isolated from Barley (Hordeum vulgare Var. Hexastichon) Grass.
Manh Tuan HaPhuong Thao TranHuynh Nguyen Khanh TranOkwha KimYong-Bum KimJeong-Hyung LeeByung Sun MinPublished in: Journal of agricultural and food chemistry (2021)
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 RANKL-induced 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 osteoclast-specific 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.
Keyphrases
- bone loss
- lps induced
- signaling pathway
- high glucose
- diabetic rats
- oxidative stress
- genome wide
- drug induced
- endothelial cells
- adipose tissue
- type diabetes
- gene expression
- metabolic syndrome
- skeletal muscle
- climate change
- postmenopausal women
- replacement therapy
- bone regeneration
- binding protein
- smoking cessation
- risk assessment