Chemical constituents of Roscoea humeana: their anti-inflammatory and GLP-1 secretagogic activity

Plants of the genus Roscoea have been widely utilized in traditional Chinese and Tibetan medicine for a variety of therapeutic purposes. However, the chemical constituents of Roscoea humeana remained unexplored to date. In this first phytochemical investigation of R. humeana, twelve compounds were isolated, including two previously undescribed fatty acid monoglycerides, roscohumeanols A and B (1-2), one previously undescribed labdane diterpenoid glycoside, roscohumeanol C (5), and one previously undescribed diarylheptanoid glycoside, roscohumeanol D (7). Their structures were elucidated through comprehensive spectroscopic analysis (HRESIMS, 1D and 2D NMR, ECD) combined with quantum chemical calculation and chemical methods. Among the isolates, four compounds (1, 3, 7 and 8) exhibited anti-inflammatory activity in LPS-stimulated RAW264.7 cells. Notably, 15,16-triol(3S)-3-hydroxy-1,7-bis(4-hydroxyphenyl)-6E-hepten-5-one (8) significantly inhibited NO production with an IC₅₀ value of 4.21 ± 0.21 μM. Network pharmacology and molecular docking simulations suggested that MAPK3 and PPARG are the potential targets of 8 mediating anti-inflammatory effects. Moreover, (12Z,14R)-labda-8(17),12-diene-14,15,16-triol (6) demonstrated concentration-dependent GLP-1 secretagogic activity with promotion rates ranging from 90.6% to 573.4%. Mechanistic study revealed that its activity is closely associated with the PLC-Gq-Ca²⁺-CaMKII signaling cascade, independent of the Gα pathway. This study discloses fatty acid-monoglycerides, diarylheptanoids and labdane diterpenoids as the key constituents in R. humeana, as well as their anti-inflammatory and GLP-1 promoting activities and the underlying mechanisms.