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ARS Home » Pacific West Area » Hilo, Hawaii » Daniel K. Inouye U.S. Pacific Basin Agricultural Research Center » Tropical Plant Genetic Resources and Disease Research » Research » Publications at this Location » Publication #392968
Research Project: Genetic Improvement and Sustainable Production Systems for Sub-tropical and Tropical Crops in the Pacific Basin

Location: Tropical Plant Genetic Resources and Disease Research

Title: Anti-inflammatory quinoline alkaloids from the roots of Waltheria indica

Author
item LIU, FEIFEI - Jiangsu Normal University
item O'DONNELL, TIMOTHY - University Of Hawaii
item PARK, EUN-JUNG - University Of Hawaii
item KOVACS, SASHA - University Of Hawaii
item NAKAMURA, KENZO - University Of Hawaii
item DAVE, ASIM - Long Island University
item LUO, YUHENG - University Of Hawaii
item SUN, RUI - University Of Hawaii
item Wall, Marisa
item WONGWIWATTHANANUKIT, SUPAKIT - University Of Hawaii
item SILVA, DANE KAOHELANI - University Of Hawaii
item WILLIAMS, PHILIP - University Of Hawaii
item PEZZUTO, JOHN - Western New England University
item CHANG, LENG CHEE - University Of Hawaii

Submitted to: Journal of Natural Products
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/20/2022
Publication Date: 2/6/2023
Citation: Liu, F., O'Donnell, T., Park, E., Kovacs, S., Nakamura, K., Dave, A., Luo, Y., Sun, R., Wall, M.M., Wongwiwatthananukit, S., Silva, D., Williams, P., Pezzuto, J., Chang, L. 2023. Anti-inflammatory quinoline alkaloids from the roots of Waltheria indica. Journal of Natural Products. 86(2):276-289. https://doi.org/10.1021/acs.jnatprod.2c00861.
DOI: https://doi.org/10.1021/acs.jnatprod.2c00861

Interpretive Summary: Waltheria indica (also known as ‘uhaloa’) has been used to treat a variety of inflammation-related diseases by Native Hawaiian medicinal practitioners. In this study, we report the structure and anti-inflammatory activities of sixteen new quinoline alkaloids, and ten known analogues, isolated from the roots of Walteria indica. The structure–activity relationship was determined for several of the bioactive quinoline alkaloids, and the biologic potential of these new compounds provide support for the traditional use of this plant for treatment of inflammatory-associated disorders.

Technical Abstract: Sixteen new quinoline alkaloids (1a-7, 8a, 9-10, 13-15, 17 and 21) and ten known analogues (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 nuclear magnetic resonance (NMR), circular dichroism (CD) with extensive computational support, and mass spectroscopic data interpretation. The isolates were evaluated for anti-inflammatory potential based on their ability to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) production and tumor necrosis factor-alpha (TNF-a)-induced nuclear factor kappa B (NF-'B) activity with cell culture models. In the absence of cell growth inhibition, compounds 6, 8a, 9-11, 13, 21 and 24 decreased TNF-a-induced NF-'B activity with IC50 values ranging from 7.1 to 12.1 µM, comparable to the positive control (BAY11-7082 , IC50 = 9.7µM). Compounds 6, 8a, 8b and 11 showed significant NO-inhibitory activity with IC50 values ranging from 11.0 to 12.8 µM, superior to the positive control (L-NMMA, IC50 = 22.7µM). Structure–activity relationships with these quinoline alkaloids indicated that NO inhibitory activity was significantly affected by C-8 substitution. Elevation of inducible nitric oxide synthase (iNOS) by treatment with LPS was inhibited by 8b, and this response correlated with inhibition of iNOS mRNA expression. Further mechanistic studies are required. Nonetheless, the biologic potential of these chemical constituents derived from Waltheria indica provide support for the traditional use of this plant material for the treatment of inflammatory-associated disorders.