Anti-Neuroinflammatory ent-Kaurane Diterpenoids from Pteris multifida Roots
Jung Wha Kim1, Ji Yeon Seo2, Won Keun Oh3
1College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul 08826, Korea. jkim11@snu.ac.kr.
Abstract:
Activated microglia are known to be a major source of cellular neuroinflammation which causes various neurodegenerative diseases, including Alzheimer's disease. In our continuing efforts to search for new bioactive phytochemicals against neuroinflammatory diseases, the 80% methanolic extract of Pteris multifida (Pteridaceae) roots was found to exhibit significant NO inhibitory activity in lipopolysaccharide (LPS)-activated BV-2 microglia cells. Three new ent-kaurane diterpenoids, pterokaurane M₁ 2-O-β-d-glucopyranoside (4), 2β,16α-dihydroxy-ent-kaurane 2,16-di-O-β-d-glucopyranoside (10), and 2β,16α,17-trihydroxy-ent-kaurane 2-O-β-d-glucopyranoside (12), were isolated along with nine other known compounds from P. multifida roots. The chemical structures of the new compounds were determined by 1D- and 2D-NMR, HR-ESI-MS, and CD spectroscopic data analysis. Among the isolates, compounds 1 and 7 significantly inhibited NO production in LPS-stimulated BV-2 cells reducing the expression of the cyclooxygenase-2 (COX-2) protein and the level of pro-inflammatory mediators such as prostaglandin E₂ (PGE₂), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. These results suggest that ent-kaurane diterpenes from P. multifida could be potential lead compounds that act as anti-neuroinflammatory agents.
Insights
Researchers identified new compounds from Pteris multifida roots that reduce neuroinflammation. These ent-kaurane diterpenes show potential as anti-neuroinflammatory agents by inhibiting nitric oxide (NO) production in microglia cells.
Area of Science:
- Natural Product Chemistry
- Neuroscience
- Pharmacology
Background:
- Activated microglia are a key source of neuroinflammation, contributing to neurodegenerative diseases like Alzheimer's.
- Phytochemicals are being investigated for their potential to combat neuroinflammation.
Purpose of the Study:
- To isolate and identify bioactive compounds from Pteris multifida roots with anti-neuroinflammatory properties.
- To evaluate the inhibitory effects of these compounds on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated microglia.
Main Methods:
- Extraction of Pteris multifida roots using 80% methanol.
- Isolation and structural elucidation of compounds using NMR, HR-ESI-MS, and CD spectroscopy.
- Assessment of NO inhibitory activity in LPS-activated BV-2 microglia cells.
Main Results:
- Three new ent-kaurane diterpenoids and nine known compounds were isolated.
- Compounds 1 and 7 significantly inhibited NO production in LPS-stimulated BV-2 cells.
- These active compounds reduced the expression of cyclooxygenase-2 (COX-2) and pro-inflammatory mediators (PGE₂, TNF-α, IL-1β, IL-6).
Conclusions:
- Ent-kaurane diterpenes from Pteris multifida roots possess significant anti-neuroinflammatory activity.
- These compounds may serve as potential lead compounds for developing novel therapeutic agents against neuroinflammatory diseases.
