Anti-inflammatory Quinoline Alkaloids from the Roots of

Sixteen new quinoline alkaloids (-, , , , -, , and ) and 10 known analogs (, , , , -, and -), along with three known cyclopeptide alkaloids (-), were isolated from the roots of . The structures of the new compounds were elucidated by detailed NMR and circular dichroism with computational support and mass spectrometry data interpretation. Anti-inflammatory potential of isolates was evaluated based on inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production and tumor necrosis factor-alpha (TNF-α)-induced nuclear factor kappa B (NF-κB) activity with cell culture models. In the absence of cell growth inhibition, compounds , , -, , , and reduced TNF-α-induced NF-κB activity with IC values ranging from 7.1 to 12.1 μM, comparable to the positive control (BAY 11-7082, IC = 9.7 μM). Compounds , , , and showed significant NO-inhibitory activity with IC values ranging from 11.0 to 12.8 μM, being more active than the positive control (l-NMMA, IC = 22.7 μM). Structure-activity relationships indicated that NO inhibitory activity was significantly affected by C-8 substitution. Inhibition of LPS-induced nitric oxide synthase (iNOS) by [(5)-waltherione M, IC 11.7 ± 0.8 μM] correlated with inhibition of iNOS mRNA expression. The biological potential of metabolites supports the traditional use of this plant for the treatment of inflammatory-related disorders.