Anti-Inflammatory Effects of Hypophyllanthin and Niranthin Through Downregulation of NF-κB/MAPKs/PI3K-Akt Signaling Pathways

Hemavathy Harikrishnan, Ibrahim Jantan, Md Areeful Haque, Kumolosasi Msi Endang

Research output: Contribution to journalArticle

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Abstract

Hypophyllanthin (HYP) and niranthin (NIR) are major lignans in Phyllanthus spp. and have been shown to possess strong anti-inflammatory activity. In this study, we investigated the anti-inflammatory effects and the underlying molecular mechanisms of HYP and NIR in in vitro cellular model of LPS-induced U937 macrophages. The effects of HYP and NIR on the production of prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were measured by using ELISA, Western blot, and qRT-PCR. The expressions of signaling molecules related to nuclear factor-kappa B (NF-κB), mitogen-activated protein kinases (MAPKs), and phosphatidylinositol 3′-kinase-Akt (PI3K-Akt) signaling pathways were examined. The role of NF-κB, MAPKs, and Akt signaling pathways was confirmed by using specific inhibitors (BAY 11-7082, U0126, SB202190, SP600125, and LY294002) mediated suppression of TNF-α and COX-2 production. HYP and NIR significantly inhibited the protein and gene levels of COX-2 as well as the downstream signaling products of PGE2, TNF-α, and IL-1β. HYP and NIR also suppressed the inhibitors of kappa B (IκB), IkB kinases (Ikkα/β), NF-κB phosphorylation, and IκB degradation. HYP suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 while NIR only suppressed JNK and ERK but did not have effect on p38. These results demonstrate that HYP and NIR downregulated COX-2, TNF-α, and IL-1β gene expressions in U937 macrophages by interfering with the activation of NF-κB, MAPKs, and Akt. In conclusion, these lignans have potential to be developed as anti-inflammatory agents targeting the NF-κB, MAPK, and PI3K-Akt pathways.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalInflammation
DOIs
Publication statusAccepted/In press - 9 Feb 2018

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Phosphatidylinositol 3-Kinase
NF-kappa B
Mitogen-Activated Protein Kinases
Anti-Inflammatory Agents
Down-Regulation
Cyclooxygenase 2
Tumor Necrosis Factor-alpha
Interleukin-1
Lignans
Extracellular Signal-Regulated MAP Kinases
Dinoprostone
Phyllanthus
Macrophages
Phosphorylation
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
JNK Mitogen-Activated Protein Kinases
Prostaglandin-Endoperoxide Synthases
niranthin
hypophyllanthin
Phosphotransferases

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Anti-Inflammatory Effects of Hypophyllanthin and Niranthin Through Downregulation of NF-κB/MAPKs/PI3K-Akt Signaling Pathways. / Harikrishnan, Hemavathy; Jantan, Ibrahim; Haque, Md Areeful; Endang, Kumolosasi Msi.

In: Inflammation, 09.02.2018, p. 1-12.

Research output: Contribution to journalArticle

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