New Lignans with Different Degrees of Polymerization from Alpinia galanga : Their Chiral Resolution, Anti-Inflammatory Activity, and Mechanism

Alpinia galanga (greater galangal) is a famous spice widely cultivated in Asia. To investigate its anti-inflammatory constituents, 16 new lignans (1–16) were isolated from its fruits. Their structures, including absolute configurations, were elucidated by extensive spectroscopic data and quantum chemical calculations. Anti-inflammatory screening revealed that four dilignans (4–7) and one monolignan (15) significantly inhibited NO production in LPS-stimulated RAW264.7 macrophages, with IC50 values of 3.8–6.9 μM. Notably, alpigalangin D (4a) with an IC50 value of 3.9 μM, was 32-fold more potent than indomethacin. Mechanistic study demonstrated that 4 targets AKT1 to inhibit the TNF signaling pathway, suppressing phosphorylation of NF-κB, p38, and JNK, and downregulating Tnfα, Il1β, Il6, Ccl2, and iNOS expression. This study disclosed alpigalangin D (4) as a promising anti-inflammatory lead showing multisuppression on the AKT1/TNF signaling axis. The fruits of A. galaga are rich in lignans, which may collectively contribute to its anti-inflammatory properties.