Lobatamunsolides A–C, Norlignans from the Roots of <i>Pueraria lobata </i>and their Nitric Oxide Inhibitory Activities in Macrophages

oleh: Mun Seok Jo, Jae Sik Yu, Joo Chan Lee, Seoyoung Lee, Young-Chang Cho, Hyun-Ju Park, Ki Hyun Kim

Format: Article
Diterbitkan: MDPI AG 2019-11-01

Deskripsi

Phytochemical investigation of the methanol (MeOH) extract of <i>Pueraria lobata </i>roots, known as &#8220;kudzu&#8221;, combined with liquid chromatography/mass spectrometry (LC/MS)-based analysis, resulted in the identification of four norlignans (<b>1</b>&#8722;<b>4</b>), including three new norlignans, lobatamunsolides A&#8722;C (<b>1</b>&#8722;<b>3</b>), and five known isoflavonoids (<b>5</b>&#8722;<b>9</b>). The structures of the new compounds were elucidated by a combination of spectroscopic methods, including 1D and 2D nuclear magnetic resonance (NMR) and high resolution (HR)-electrospray ionization mass spectrometry (ESIMS), and their absolute configurations were determined by chemical reaction and quantum chemical electronic circular dichroism (ECD) calculations. The isolated compounds (<b>1</b>&#8722;<b>9</b>) were evaluated for their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Compound <b>9</b> displayed the strongest NO inhibitory effect and compound <b>2</b> showed a weak effect. The potential mechanism of the effect of compound <b>9</b> was investigated by analysis of its molecular docking on the active site of inducible nitric oxide synthase (iNOS), which showed the potential interactions of compound <b>9</b> with key amino acid residues and the heme cofactor of iNOS. The mechanism as the inhibition of transcriptional iNOS protein expression was confirmed by western blotting experiments.