Anti-inflammatory potential of Patrineolignan B isolated from Patrinia scabra in LPS-stimulated macrophages via inhibition of NF-κB, AP-1, and JAK/STAT pathways

• Published in: International immunopharmacology 2020-09, Vol.86, p.106726-106726, Article 106726
• Main Authors: Lee, Hwi-Ho, Jang, Eungyeong, Kang, Shin-Young, Shin, Ji-Sun, Han, Hee-Soo, Kim, Tae-Woo, Lee, Da Hye, Lee, Jang-Hoon, Jang, Dae Sik, Lee, Kyung-Tae
• Format: Article
• Language: English
• Subjects: Activator protein 1; Animals; Anti-inflammatory agents; Anti-Inflammatory Agents - pharmacology; AP-1; Aquatic plants; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Cytokines; Cytokines - metabolism; Cytotoxicity; Dinoprostone - metabolism; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Inflammation; Inflammation - chemically induced; Inflammation - drug therapy; Inflammation Mediators - metabolism; Interleukin 6; JAK/STAT; Janus kinase; Janus Kinases - metabolism; JNK Mitogen-Activated Protein Kinases - metabolism; Kinases; Lignans; Lignans - pharmacology; Lipopolysaccharides; Lipopolysaccharides - toxicity; Macrophages; Macrophages - drug effects; Mice; Molecular modelling; NF-kappa B p50 Subunit - metabolism; NF-κB; NF-κB protein; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - metabolism; Nitric-oxide synthase; Patrineolignan B; Patrinia - chemistry; Phosphorylation; Prostaglandin E2; RAW 264.7 Cells; RAW 264.7 macrophages; Rhizomes; Signal transduction; Signal Transduction - drug effects; Signaling; STAT Transcription Factors - metabolism; Stat1 protein; Transcription activation; Transcription Factor AP-1 - metabolism; Transcription factors; Transducers; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2020.106726

•Patrineolignan B (PB) exhibits anti-inflammatory potency through interfering with the NF-κB, AP-1, and JAK/STAT signaling pathway in LPS-stimulated macrophages.•Patrineolignan B (PB) shows potential as an active compound against inflammation-related diseases. Patrineolignan B (PB), a lignan compound isolated from the radix and rhizomes of Patrinia scabra, was previously reported to possess a strong tumor-specific cytotoxic activity and beneficial effects on nitric oxide (NO) levels in macrophages induced by lipopolysaccharide (LPS). In this study, we assessed the effects of PB on LPS-induced inflammation in RAW 264.7 cells and clarified its molecular mechanisms. PB reversed LPS-induced increase in NO levels and prostaglandin E2 (PGE2) production, as well as inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and mRNA levels in macrophages. Besides, PB prevented the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 in a concentration-dependent manner. The regulatory effects of PB on LPS-induced inflammatory mediators and overproduction of pro-inflammatory cytokines were shown to depend partly on the suppression of nuclear factor kappa B (NF-κB)-mediated transcription and AP-1 activation regulated by a c-Jun amino-terminal kinase (JNK) and extracellular signal-regulated kinases (ERK). Its anti-inflammatory activity was also mediated by regulating the phosphorylation of Janus kinase (JAK)/signal transducers and activators of transcription 1/3 (STAT1/3) signaling pathway. Taken together, our results suggest that PB exhibits anti-inflammatory potency through interfering with the NF-κB, AP-1, and JAK/STAT signaling pathway in LPS-stimulated macrophages.