Anti-inflammatory Quinoline Alkaloids from the Roots of Waltheria indica .

Sixteen new quinoline alkaloids ( 1a - 7 , 8a , 9 , 10 , 13 - 15 , 17 , and 21 ) and 10 known analogs ( 8b , 11 , 12 , 16 , 18 - 20 , and 22 - 24 ), along with three known cyclopeptide alkaloids ( 25 - 27 ), were isolated from the roots of Waltheria indica . 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 6 , 8a , 9 - 11 , 13 , 21 , and 24 reduced TNF-α-induced NF-κB activity with IC 50 values ranging from 7.1 to 12.1 μM, comparable to the positive control (BAY 11-7082, IC 50 = 9.7 μM). Compounds 6 , 8a , 8b , and 11 showed significant NO-inhibitory activity with IC 50 values ranging from 11.0 to 12.8 μM, being more active than the positive control (l-NMMA, IC 50 = 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 8b [(5 S )-waltherione M, IC 50 11.7 ± 0.8 μM] correlated with inhibition of iNOS mRNA expression. The biological potential of W. indica metabolites supports the traditional use of this plant for the treatment of inflammatory-related disorders.