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Open AccessArticle

Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells

1
Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
2
Graduate School, Chiang Mai University, Chiang Mai 50200, Thailand
3
Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
4
Research Center of Pharmaceutical Nanotechnology, Chiang Mai University, Chiang Mai 50200, Thailand
5
Institute of Molecular Biosciences, Mahidol University, Salaya, Nakorn Pathom 73170, Thailand
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(4), 1355; https://doi.org/10.3390/ijms21041355
Received: 27 January 2020 / Revised: 13 February 2020 / Accepted: 14 February 2020 / Published: 17 February 2020
Artocarpus lakoocha Roxb. (AL) has been known for its high content of stilbenoids, especially oxyresveratrol. AL has been used in Thai traditional medicine for centuries. However, the role of AL in regulating inflammation has not been elucidated. Here we investigated the molecular mechanisms underlying the anti-inflammation of AL ethanolic extract in RAW 264.7 murine macrophage cell line. The HPLC results revealed that this plant was rich in oxyresveratrol, and AL ethanolic extract exhibited anti-inflammatory properties. In particular, AL extract decreased lipopolysaccharide (LPS)-mediated production and secretion of cytokines and chemokine, including IL-6, TNF-α, and MCP-1. Consistently, the extract inhibited the production of nitric oxide (NO) in the supernatants of LPS-stimulated cells. Data from the immunofluorescence study showed that AL extract suppressed nuclear translocation of nuclear factor-kappa B (NF-κB) upon LPS induction. Results from Western blot analysis further confirmed that AL extract strongly prevented the LPS-induced degradation of IκB which is normally required for the activation of NF-κB. The protein expression of iNOS and COX-2 in response to LPS stimulation was significantly decreased with the presence of AL extract. AL extract was found to play an anti-inflammatory role, in part through inhibiting LPS-induced activation of Akt. The extract had negligible impact on the activation of mitogen-activated protein kinase (MAPK) pathways. Specifically, incubation of cells with the extract for only 3 h demonstrated the rapid action of AL extract on inhibiting the phosphorylation of Akt, but not ERK1/2. Longer exposure (24 h) to AL extract was required to mildly reduce the phosphorylation of ERK1/2, p38, and JNK MAPKs. These results indicate that AL extract manipulates its anti-inflammatory effects mainly through blocking the PI3K/Akt and NF-κB signal transduction pathways. Collectively, we believe that AL could be a potential alternative agent for alleviating excessive inflammation in many inflammation-associated diseases. View Full-Text
Keywords: anti-inflammation; macrophage cells; Artocarpus lakoocha; Akt activation; inflammatory cytokines anti-inflammation; macrophage cells; Artocarpus lakoocha; Akt activation; inflammatory cytokines
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MDPI and ACS Style

Hankittichai, P.; Buacheen, P.; Pitchakarn, P.; Na Takuathung, M.; Wikan, N.; Smith, D.R.; Potikanond, S.; Nimlamool, W. Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells. Int. J. Mol. Sci. 2020, 21, 1355. https://doi.org/10.3390/ijms21041355

AMA Style

Hankittichai P, Buacheen P, Pitchakarn P, Na Takuathung M, Wikan N, Smith DR, Potikanond S, Nimlamool W. Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells. International Journal of Molecular Sciences. 2020; 21(4):1355. https://doi.org/10.3390/ijms21041355

Chicago/Turabian Style

Hankittichai, Phateep; Buacheen, Pensiri; Pitchakarn, Pornsiri; Na Takuathung, Mingkwan; Wikan, Nitwara; Smith, Duncan R.; Potikanond, Saranyapin; Nimlamool, Wutigri. 2020. "Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells" Int. J. Mol. Sci. 21, no. 4: 1355. https://doi.org/10.3390/ijms21041355

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