New patchoulol- and guaiane-type sesquiterpenoids from Sanguisorba officinalis with anti-melanogenic activity.

Twelve new sesquiterpenoids, sanguisorbaols A-L (1-12), along with twenty-five known compounds (13-37), were isolated from the roots of Sanguisorba officinalis. Structures were determined through comprehensive analysis of HRESIMS, 1D and 2D NMR spectroscopic data, ECD and NMR calculations, and X-ray crystallographic analysis. Among them, compounds 1-6 were identified as new patchoulol-type sesquiterpenoids bearing hydroxyl groups at different positions, the further structural elucidation revealed that compounds 5 and 6 are nor-patchoulol-type sesquiterpenoids due to the absence of the C-11 carbon atom. Compounds 7-11 were characterized as guaiane-type sesquiterpenoids incorporating a [5,7]-bicyclic framework, among which 7 and 8 constitute a pair of C-11 epimers. Notably, compound 12 possesses a rare bicyclo[4.3.1]decane core scaffold. All the patchoulol-type sesquiterpenoids reported here were obtained for the first time from the genus Sanguisorba, and a plausible biosynthetic pathway was proposed. Furthermore, the anti-melanogenic bioactivity of all isolates was assessed using IBMX-stimulated B16F10 melanoma cells. Compounds 3-5, 8-10, 12-14, 17, 19, 21, 22, 25-27, 29, 31, 32 and 34 demonstrated significant inhibitory activity against melanogenesis at concentrations ranging from 6.25 to 50 μM. These results highlighted the potential of S. officinalis as a natural anti-melanogenesis agent for skin-whitening or for the treatment of hyperpigmentation disorders.