Kudzu Leaf Extract Suppresses the Production of Inducible Nitric Oxide Synthase, Cyclooxygenase-2, Tumor Necrosis Factor-Alpha, and Interleukin-6 via Inhibition of JNK, TBK1 and STAT1 in Inflammatory Macrophages

• Published in: International journal of molecular sciences 2018-05, Vol.19 (5), p.1536
• Main Authors: Eom, Seok Hyun, Jin, So-Jung, Jeong, Hee-Yeong, Song, Youngju, Lim, You Jin, Kim, Jong-In, Lee, Youn-Hyung, Kang, Hee
• Format: Article
• Language: English
• Subjects: Activator protein 1; Animals; Anti-inflammatory agents; c-Jun protein; Cells, Cultured; Constituents; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Cytokines; Enzyme Inhibitors - pharmacology; Flavonoids; Food sources; Herbal medicine; Inflammation; Interferon; Interleukin 6; Interleukin-6 - metabolism; JNK protein; Kaempferol; Leaves; Lipopolysaccharides; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Male; MAP Kinase Kinase 4 - antagonists & inhibitors; MAP Kinase Kinase 4 - metabolism; Mice; Mice, Inbred BALB C; Necrosis; Nitric oxide; Nitric Oxide Synthase Type II - metabolism; Nitric-oxide synthase; Peritoneum; Plant Extracts - pharmacology; Plant Leaves - chemistry; Protein Serine-Threonine Kinases - antagonists & inhibitors; Protein Serine-Threonine Kinases - metabolism; Proteins; Pueraria - chemistry; Pueraria montana lobata; Rodents; Stat1 protein; STAT1 Transcription Factor - antagonists & inhibitors; STAT1 Transcription Factor - metabolism; Transcription activation; Transcription factors; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumors; γ-Interferon
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19051536

Kudzu ( var. (Willd.) Sanjappa & Pradeep) is a perennial leguminous vine, and its root and flower have been used for herbal medicine in Asia for a long time. Most dietary flavonoids are reported to be concentrated in its root, not in its aerial parts including leaves. In this study, we investigated whether kudzu leaf and its major constituent, robinin (kaempferol-3- -robinoside-7- -rhanmoside) possessed anti-inflammatory activity. To test this hypothesis, we used peritoneal macrophages isolated from BALB/c mice and stimulated the cells with lipopolysaccharide (LPS) or LPS plus interferon (IFN)-γ. Compared with kudzu root extract, its leaf extract was more potent in inhibiting the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2, tumor necrosis factor-α, and interleukin-6. Kudzu leaf extract decreased LPS-induced activation of c-Jun N-terminal kinase (JNK) and TANK-binding kinase 1(TBK1) with no effects on nuclear factor-κB and activator protein 1 transcriptional activity. Also, kudzu leaf extract inhibited LPS/IFN-γ-induced signal transducer and activator of transcription 1 (STAT1) activation partly via an altered level of STAT1 expression. Robinin, being present in 0.46% of dry weight of leaf extract, but almost undetected in the root, decreased iNOS protein involving modulation of JNK and STAT1 activation. However, robinin showed no impact on other inflammatory markers. Our data provide evidence that kudzu leaf is an excellent food source of as yet unknown anti-inflammatory constituents.