PMID- 27660010 OWN - NLM STAT- MEDLINE DCOM- 20170515 LR - 20170912 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 192 DP - 2016 Nov 4 TI - Therapeutic effect of Mahaenggamseok-tang on neutrophilic lung inflammation is associated with NF-kappaB suppression and Nrf2 activation. PG - 486-495 LID - S0378-8741(16)30895-9 [pii] LID - 10.1016/j.jep.2016.09.040 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Mahaenggamseok-tang (MHGST), an herbal formula in traditional Asian medicine, has been used to treat patients with various pulmonary diseases including common cold and influenza. However, the potential therapeutic effect of MHGST on acute lung injury (ALI), a leading cause of death worldwide, and the anti-inflammatory mechanisms of MHGST remained less understood. MATERIALS AND METHODS: The methanol extract of MHGST was prepared and fingerprinted by HPLC. For the induction of ALI, C57BL/6 mice (n=5/group) received a single intraperitoneal (i.p.) injection of LPS. Referring to the dose for patients, two different amounts of MHGST were delivered in an aerosol to mouse lungs via trachea 2h after the i.p. LPS administration. Lung histology, bronchoalveolar lavage fluid, myeloperoxidase (MPO) activity, and the expression of inflammatory and Nrf2-dependent genes were analyzed to determine the effect of MHGST on lung inflammation. For mechanistic studies, western blotting and semi-quantitative RT-PCR were conducted using RAW 264.7 cells. RESULTS: When administered 2h after the onset of ALI, MHGST relieved lung pathology characteristic to ALI, with decreases of neutrophil infiltration and MPO activity. While suppressing the expression of inflammatory genes, MHGST increased the expression of Nrf2-dependent genes in ALI mouse lungs. Concordantly, MHGST activated Nrf2 activity while suppressing NF-kappaB in RAW 264.7 cells. CONCLUSION: MHGST suppressed neutrophilic lung inflammation, a hallmark of ALI, which was associated with the activation of anti-inflammatory Nrf2 and the suppression of pro-inflammatory NF-kappaB. Our results suggest that MHGST has a therapeutic potential against ALI. CI - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved. FAU - Kim, Kyun Ha AU - Kim KH AD - School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea. FAU - Lee, Ji Yeon AU - Lee JY AD - School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea. FAU - Kwun, Min Jung AU - Kwun MJ AD - School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea. FAU - Choi, Jun-Young AU - Choi JY AD - Department of Internal Medicine, Korean Medicine Hospital, Pusan National University, Yangsan 50612, Republic of Korea. FAU - Han, Chang Woo AU - Han CW AD - Department of Internal Medicine, Korean Medicine Hospital, Pusan National University, Yangsan 50612, Republic of Korea. FAU - Ha, Ki-Tae AU - Ha KT AD - School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea. FAU - Jeong, Seung-Il AU - Jeong SI AD - Jeonju Biomaterials Institute, Jeonju 561-360, Republic of Korea. FAU - Jeong, Han-Sol AU - Jeong HS AD - School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea. Electronic address: jhsol33@pusan.ac.kr. FAU - Joo, Myungsoo AU - Joo M AD - School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea. Electronic address: mjoo@pusan.ac.kr. LA - eng PT - Journal Article DEP - 20160920 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Inflammation Mediators) RN - 0 (Lipopolysaccharides) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NF-kappa B) RN - 0 (Nfe2l2 protein, mouse) RN - 0 (mahaenggamseok-tang) RN - EC 1.11.1.7 (Peroxidase) SB - IM MH - Acute Lung Injury/chemically induced/metabolism/pathology/*prevention & control MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Bronchoalveolar Lavage Fluid/chemistry MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Down-Regulation MH - Drugs, Chinese Herbal/*pharmacology MH - Inflammation Mediators/metabolism MH - Lipopolysaccharides MH - Lung/*drug effects/metabolism/pathology MH - Macrophages/drug effects/metabolism MH - Mice MH - Mice, Inbred C57BL MH - NF-E2-Related Factor 2/*metabolism MH - NF-kappa B/*metabolism MH - Neutrophil Infiltration/*drug effects MH - Peroxidase/metabolism MH - Pneumonia/chemically induced/metabolism/pathology/*prevention & control MH - RAW 264.7 Cells MH - Signal Transduction/drug effects OTO - NOTNLM OT - Acute lung injury OT - Anti-inflammation OT - Mahaenggamseok-tang OT - NF-kappaB OT - Nrf2 OT - Therapeutic effect EDAT- 2016/09/24 06:00 MHDA- 2017/05/16 06:00 CRDT- 2016/09/24 06:00 PHST- 2016/03/17 00:00 [received] PHST- 2016/09/06 00:00 [revised] PHST- 2016/09/18 00:00 [accepted] PHST- 2016/09/24 06:00 [pubmed] PHST- 2017/05/16 06:00 [medline] PHST- 2016/09/24 06:00 [entrez] AID - S0378-8741(16)30895-9 [pii] AID - 10.1016/j.jep.2016.09.040 [doi] PST - ppublish SO - J Ethnopharmacol. 2016 Nov 4;192:486-495. doi: 10.1016/j.jep.2016.09.040. Epub 2016 Sep 20.