4.7 Article

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

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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 69, 期 44, 页码 12994-13005

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.1c04337

关键词

Hordeum vulgare var. hexastichon; barley grass; indole alkaloids; osteoclastogenesis; RANKL; NFATc1

资金

  1. National Research Foundation of Korea (NRF) - Ministry of Science and ICT, Korea [NRF-2021R1A2C2011940]

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The alkaloid fraction of barley grass significantly inhibited osteoclast formation and protected bones. Compound 5 in particular showed strong suppression of osteoclast formation and related signaling pathways, making it a potential candidate for treating osteolytic bone diseases.
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-kappa B 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.

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