Lotusin A: a novel pyrrole terpenoid hydrid from lotus roots (Nelumbo nucifera Gaertn.).

Nelumbo nucifera Gaertn. has been used as a traditional medicine and food. To date, many unknown constituents have been discovered. Most of the researches on secondary metabolites and their pharmacological properties focus on alkaloid derivatives. In this study, a novel pyrrole terpenoid hydrid, lotusin A (1), and five reported substances, cholestanol (2), stigmast-4-en-3-one (3), quercetin (4), isorhamnetin (5), and norartocarpetin (6), were isolated from the methanol extract of the roots of N. nucifera Gaertn. The structures (1-6) were identified via spectroscopic analyses of NMR (1D and 2D), HR-ESIMS, and comparisons with those previously reported in the literature. Compound 1, a pyrrole terpenoid hydrid, is a unique isolate from plant natural products. Compounds 1 and 2 exhibited inhibitory activity against NO production, while all compounds showed growth inhibition of six bacterial strains. Results indicated that 1 moderately inhibited NO production with an IC50 value of 21.5 µM, but no inhibition of microbial growth was observed at a concentration of 10 µM. Besides, compound 1 exhibited good inhibition of α-glucosidase (IC50 = 18.2 µM); in contrast, this result was not observed for other compounds. From the result of molecular docking data, 1 has good interaction to with both of pro-inflammatory cytokines (iNOS, COX-2, TNF-α, IL-1β, and IL-6); transcription factors (Nrf2 and NF-κB), diabetes enzyme with binding energies of -6.4, -6.4, -5.0, -5.8, -6.1 kcal mol-1; -6.1, -6.6 kcal mol; and -6.4 kcal mol-1, respectively, resulted that 1 is the promising candidate for anti-inflammatory and α-glucosidase inhibition. Moreover, in silico ADMET and toxicity predictions indicated that 1 had favourable safety and pharmacokinetic profiles.