Inhibition of Tau Hyperphosphorylation by Bletilla striata Extract and Its Active Constituents

Bletilla striata Reichenbach, a member of the Orchidaceae family has traditionally been used for wound healing, hemostasis, and reducing swelling due to its astringent properties. In this study, the 70% ethanol extract of B. striata tubers significantly reduced okadaic acid-induced tau hyperphosphorylation in HT22 cells, as determined by western blot analysis. Tau hyperphosphorylation is considered one of major contributors to Alzheimer&quot disease. The dichloromethane-partitioned fraction of the B. striata extract, which exhibited the strongest activity, was subjected to bioassay-guided isolation using various column chromatography techniques. This process led to the isolation and identification of three compounds: 3,7-dihydroxy-2,4-dimethoxyphenanthrene (1), coelonin (2) and 4-hydroxybenzyl-4,7-dimethoxy-9,10-dihydrophenanthrene-2-ol (3). All three compounds reduced tau hyperphosphorylation in a dose-dependent manner without exhibiting cytotoxicity. Notably, 4-hydroxybenzyl-4,7-dimethoxy-9,10-dihydrophenanthrene-2-ol (3) at 15 μg/mL significantly reduced tau hyperphosphorylation to 60% of the levels observed in the okadaic acid-only treated control group. These results suggest that B. striata extract and its active compounds may offer potential therapeutic benefits against Alzheimer’s disease by inhibiting tau hyperphosphorylation.