Novel Sesquiterpenoids with Renoprotective Activities from the Fruits of Alpinae oxyphylla as Potent TGF-β1/Smads Phosphorylation Inhibitors.

The fruit of Alpinia oxyphylla Miq is an important food spice in southern China and has been used in the treatment of kidney disorders for centuries. In order to discover the natural products with potent renoprotective activities in A. oxyphylla and provide some references for its usage, systematic phytochemical studies were carried out and 24 new diverse sesquiterpenoids, including seven guaiane sesquiterpenoids ( 1 - 7 ), 10 eudesmane sesquiterpenoids ( 9 - 13 , 18 , 19 , and 21 - 23 ), six cadinane sesquiterpenoids ( 31 - 35 and 38 ), and an eremophilane sesquiterpenoid ( 40 ), along with 24 known analogues were isolated and elucidated by analysis of spectroscopic data and quantum-chemical calculations. Biological evaluation showed that 6 sesquiterpenoids could significantly inhibit the expression of extracellular matrix components, α-SMA in TGF-β1 induced kidney proximal tubular cells (NRK-52e) at low concentrations, and 9 sesquiterpenoids could also downregulate fibronectin and collagen I in a concentration-dependent manner, showing their potential in renal fibrosis. Further action mechanism study displayed that TGF-β1/Smads pathway might be involved in the antifibrotic effects of active sesquiterpenoids 15 and 43 . These studies suggest that A. oxyphylla may have a potential to serve as a functional food in preventing renal fibrosis-associated diseases.