Kalahe Hewage Iresha Nadeeka Madushani Herath1, Hyo Jin Kim2, Ju Hee Lee3, Jun Geon Je4, Hak-Sun Yu5, You-Jin Jeon6, Hyun Jung Kim7, Youngheun Jee8. 1. Interdisciplinary Graduate Program in Advanced Convergence Technology & Science, Jeju National University, Jeju, 63243, Republic of Korea. Electronic address: madushaniherath001@gmail.com. 2. Department of Food Bioengineering, Jeju National University, 102 JeJudaehakro, Jeju, 63243, Republic of Korea. Electronic address: jyouding@gmail.com. 3. Department of Food Bioengineering, Jeju National University, 102 JeJudaehakro, Jeju, 63243, Republic of Korea. Electronic address: wngml9993@naver.com. 4. Department of Marine Life Science, Jeju National University, Jeju, 63243, Republic of Korea. 5. Department of Parasitology, Pusan National University School of Medicine, Yangsan, Republic of Korea. Electronic address: hsyu@pusan.ac.kr. 6. Department of Marine Life Science, Jeju National University, Jeju, 63243, Republic of Korea. Electronic address: youjin2014@gmail.com. 7. Department of Food Bioengineering, Jeju National University, 102 JeJudaehakro, Jeju, 63243, Republic of Korea. Electronic address: hyunjkim@jejunu.ac.kr. 8. Interdisciplinary Graduate Program in Advanced Convergence Technology & Science, Jeju National University, Jeju, 63243, Republic of Korea; Department of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, Jeju, 63243, Republic of Korea. Electronic address: yhjee@jejunu.ac.kr.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Sargassum horneri (Turner) C. Agardh (S. horneri), an edible brown marine algae, is known to have immunomodulatory effects and has been used in oriental medicine to treat inflammatory diseases. It is well known that ambient particulate matter (PM) is closely related to increased respiratory diseases inducing lung inflammation. AIM: Considering the use of Sargassum horneri in traditional medicine to treat inflammatory diseases, we hypothesized and investigated the use of Sargassum horneri containing polyphenols against PM-induced inflammatory responses. MATERIALS AND METHODS: In this study, we evaluated the impact of PM (majority <2.5 μm in diameter) on deep bronchial penetration ability upon inhalation and a therapeutic approach to mitigate its harmful effects using an ethanol extract of Sargassum horneri, an edible brown algae, containing polyphenols on a type II alveolar epithelial cell line, MLE-12. RESULTS: PM triggered mRNA expression of toll-like receptors (TLRs) TLR2/4/7, and those TLRs were significantly attenuated by Sargassum horneri extract (SHE). SHE further attenuated the phosphorylation of mitogen-activated protein kinase (MAPK) p38, extracellular signal-regulated kinase 1/2 (Erk1/2), and c-Jun NH (2)-terminal kinase (JNK), which were also activated in PM-exposed cells. Altogether, SHE subdued the PM-induced mRNA expression of pro-inflammatory cytokines (interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6) and lung epithelial cell derived-chemokines (IL-8, monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-C motif) ligand 5 (CCL5)). SHE also suppressed the mRNA expression of PM-induced pro-allergic cytokines thymic stromal lymphopoietin (TSLP) and interleukin (IL)-33. Furthermore, we showed that SHE suppressed the MAPK-dependent signaling pathway by attenuating receptor-associated factor (TRAF) 6 activation of proteins MyD88 and TNF. CONCLUSION: Taking all the data together, we suggest that the anti-inflammatory potential of SHE on PM-exposed MLE-12 cells is mediated by the inhibition of PM-triggered downstream signaling along the TLR2/4/7-MyD88-TRAF6 axis of MAPK signaling.
ETHNOPHARMACOLOGICAL RELEVANCE: Sargassum horneri (Turner) C. Agardh (S. horneri), an edible brown marine algae, is known to have immunomodulatory effects and has been used in oriental medicine to treat inflammatory diseases. It is well known that ambient particulate matter (PM) is closely related to increased respiratory diseases inducing lung inflammation. AIM: Considering the use of Sargassum horneri in traditional medicine to treat inflammatory diseases, we hypothesized and investigated the use of Sargassum horneri containing polyphenols against PM-induced inflammatory responses. MATERIALS AND METHODS: In this study, we evaluated the impact of PM (majority <2.5 μm in diameter) on deep bronchial penetration ability upon inhalation and a therapeutic approach to mitigate its harmful effects using an ethanolextract of Sargassum horneri, an edible brown algae, containing polyphenols on a type II alveolar epithelial cell line, MLE-12. RESULTS: PM triggered mRNA expression of toll-like receptors (TLRs) TLR2/4/7, and those TLRs were significantly attenuated by Sargassum horneriextract (SHE). SHE further attenuated the phosphorylation of mitogen-activated protein kinase (MAPK) p38, extracellular signal-regulated kinase 1/2 (Erk1/2), and c-Jun NH (2)-terminal kinase (JNK), which were also activated in PM-exposed cells. Altogether, SHE subdued the PM-induced mRNA expression of pro-inflammatory cytokines (interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6) and lung epithelial cell derived-chemokines (IL-8, monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-C motif) ligand 5 (CCL5)). SHE also suppressed the mRNA expression of PM-induced pro-allergic cytokines thymic stromal lymphopoietin (TSLP) and interleukin (IL)-33. Furthermore, we showed that SHE suppressed the MAPK-dependent signaling pathway by attenuating receptor-associated factor (TRAF) 6 activation of proteins MyD88 and TNF. CONCLUSION: Taking all the data together, we suggest that the anti-inflammatory potential of SHE on PM-exposed MLE-12 cells is mediated by the inhibition of PM-triggered downstream signaling along the TLR2/4/7-MyD88-TRAF6 axis of MAPK signaling.
Authors: Pek Xyen Tan; Krishnapriya Thiyagarasaiyar; Cheng-Yau Tan; You-Jin Jeon; Mohd Shahrul Mohd Nadzir; Yong-Jiang Wu; Liang-Ee Low; Atanas G Atanasov; Long Chiau Ming; Kai Bin Liew; Bey-Hing Goh; Yoon-Yen Yow Journal: Mar Drugs Date: 2021-05-30 Impact factor: 5.118