Thunbergia alata inhibits inflammatory responses through the inactivation of ERK and STAT3 in macrophages.
Thunbergia alata (Acanthaceae) has been used traditionally to treat various inflammatory diseases such as fever, cough and diarrhea in East African countries including Uganda and Kenya. However, systemic studies elucidating the anti-inflammatory effects and precise mechanisms of action of T. alata have not been conducted, to the best of our knowledge. To address these concerns, we explored the anti-inflammatory effects of a methanol extract of T. alata (MTA) in macrophages. Non-cytotoxic concentrations of MTA (≤300 µg/ml) inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)‑stimulated RAW 264.7 macrophages by transcriptional regulation of inducible NO synthase in a dose-dependent manner. The expression of cyclooxygenase-2, the enzyme responsible for the production of prostaglandin E2, was unchanged by MTA at the mRNA and protein levels. MTA treatment inhibited interleukin (IL)-6 production and decreased the mRNA expression of pro‑inflammatory cytokines, including IL-6 and IL-1β. Tumor necrosis factor-α production and mRNA expression were not regulated by MTA treatment. The decreased production of inflammatory mediators by MTA was followed by the reduced phosphorylation of extracellular signal‑regulated kinase (ERK) and signal transducer and activator of transcription 3 (STAT3). MTA treatment had no effect on activity of other mitogen‑activated protein kinases (MAPKs), p38, c-Jun N-terminal kinase (JNK), and nuclear factor-κB (NF-κB). These results indicate that MTA selectively inhibits the excessive production of inflammatory mediators in LPS-stimulated murine macrophages by reducing the activity of ERK and STAT3, suggesting that MTA plays an important inhibitory role in the modulation of severe inflammation.
Laboratory of Molecular and Pharmacological Cell Biology, College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.
Young-Chang
YC
Cho
Laboratory of Molecular and Pharmacological Cell Biology, College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.
Ye Rang
YR
Kim
Laboratory of Molecular and Pharmacological Cell Biology, College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.
Ba Reum
BR
Kim
Vietnam Academy of Science and Technology (VAST), Hanoi 10307, Vietnam.
Tran The
TT
Bach
Laboratory of Molecular and Pharmacological Cell Biology, College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.
Sayeon
S
Cho
D027901:Acanthaceae / Q000737:chemistry*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D000432:Methanol / Q000737:chemistry; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*
D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010936:Plant Extracts; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases; D048049:Extracellular Signal-Regulated MAP Kinases; D000432:Methanol