Auroranes A–G: Polyoxygenated cyclohex(a/e)ne diterpenes from Kaempferia aurora and their anti-inflammatory activity via inhibition of nitric oxide production

Abstract

Kaempferia species have long been used in traditional medicine; however, their diterpenoid constituents remain underexplored, particularly in relation to anti-inflammatory potential. In this work, the chemical constituents and anti-inflammatory properties of Kaempferia aurora were investigated. Seven polyoxygenated cyclohex(a/e)ne diterpene esters, auroranes A–G (3–9), together with their biosynthetic precursors, antiacanthoic acid (1), and antiacanthol (2), were isolated from the rhizomes of K. aurora. Their structures and relative configurations were determined by extensive spectroscopic analyses. The absolute configurations of compounds 6–8 were assigned using NMR-based DP4+ probability calculations in combination with TDDFT-calculated ECD spectra. These compounds represent a structurally rare subclass of diterpenoids within the Zingiberaceae, contributing to the phytochemical diversity of this plant group. All compounds, except for compounds 2 and 3, were evaluated for their inhibitory effects on nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages. Compounds 1, 4–6, 8, and 9 exhibited notable NO inhibitory activity, with IC50 values ranging from 4.82 to 9.00 μM. To explore potential molecular interactions, molecular docking and molecular dynamics simulations were performed, suggesting favorable binding of the active compounds to inducible nitric oxide synthase (iNOS). A preliminary structure–activity relationship (SAR) analysis indicated that the presence of an epoxide ring or a double bond within the cyclohexane ring moiety may contribute to the observed activity. These findings provide a basis for further investigation into the bioactive constituents of K. aurora and may support its value as a potential source of anti-inflammatory agents.