PMID- 28577049 OWN - NLM STAT- MEDLINE DCOM- 20180509 LR - 20211204 IS - 1432-1912 (Electronic) IS - 0028-1298 (Linking) VI - 390 IP - 8 DP - 2017 Aug TI - Eburicoic acid from Laetiporus sulphureus (Bull.:Fr.) Murrill attenuates inflammatory responses through inhibiting LPS-induced activation of PI3K/Akt/mTOR/NF-kappaB pathways in RAW264.7 cells. PG - 845-856 LID - 10.1007/s00210-017-1382-3 [doi] AB - Excessive activation of macrophages has been implicated in various types of inflammatory injury. Suppression of macrophage activation would have therapeutic benefits, leading to the alleviation of the progression of inflammatory diseases. Eburicoic acid (EA) is one of main bioactive components isolated from Laetiporus sulphureus (Bull.:Fr.) Murrill. In our previous study, we found that EA possessed anti-inflammatory activities. However, the cellular and molecular mechanisms underlying its anti-inflammatory activities remain to be poorly understood. The present study aimed to further evaluate its effect on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 macrophage cells. We investigated the anti-inflammatory effect by modulating LPS-induced activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/nuclear transcription factor-kappaB (NF-kappaB) pathway in RAW264.7 cells. The results showed that EA caused no obvious cytotoxicity, and its suitable concentrations on RAW264.7 cells were in the range from 0.02 to 0.08 muM. EA significantly inhibited the releases of inflammatory mediators, nitrite oxide (NO) and prostaglandin E2 (PGE(2)); suppressed mRNA and protein expression levels of inducible nitrite oxide synthase (iNOS) and cyclooxygenase-2 COX-2 and pro-inflammatory cytokine TNF-alpha, IL-6, and IL-1beta; and reduced levels of phosphorylated PI3K, Akt, mTOR, and NF-kappaBp65 in LPS-induced RAW264.7 cells in dose- and time-dependent manners. These aforementioned results indicated that EA executed anti-inflammatory effect on LPS-induced RAW264.7 cells, and this effect might be achieved via suppressing the PI3K/Akt/mTOR/NF-kappaB signaling pathway and inhibiting the LPS-induced productions of inflammatory mediators and pro-inflammatory cytokines. FAU - Wang, Junzhi AU - Wang J AD - Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Science, China Three Gorges University, Yichang, Hubei, 443002, China. AD - Hubei Research Institute of Tujia Medicine, China Three Gorges University, Yichang, Hubei, China. FAU - Zhang, Pan AU - Zhang P AD - Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Science, China Three Gorges University, Yichang, Hubei, 443002, China. FAU - He, Haibo AU - He H AD - Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Science, China Three Gorges University, Yichang, Hubei, 443002, China. hehaibo252219@163.com. AD - Hubei Research Institute of Tujia Medicine, China Three Gorges University, Yichang, Hubei, China. hehaibo252219@163.com. FAU - Se, Xinxin AU - Se X AD - Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Science, China Three Gorges University, Yichang, Hubei, 443002, China. FAU - Sun, Wenjun AU - Sun W AD - Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Science, China Three Gorges University, Yichang, Hubei, 443002, China. FAU - Chen, Beiyan AU - Chen B AD - Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Science, China Three Gorges University, Yichang, Hubei, 443002, China. FAU - Zhang, Lin AU - Zhang L AD - Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Science, China Three Gorges University, Yichang, Hubei, 443002, China. FAU - Yan, Ximing AU - Yan X AD - Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Science, China Three Gorges University, Yichang, Hubei, 443002, China. FAU - Zou, Kun AU - Zou K AD - Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Science, China Three Gorges University, Yichang, Hubei, 443002, China. AD - Hubei Research Institute of Tujia Medicine, China Three Gorges University, Yichang, Hubei, China. LA - eng PT - Journal Article DEP - 20170602 PL - Germany TA - Naunyn Schmiedebergs Arch Pharmacol JT - Naunyn-Schmiedeberg's archives of pharmacology JID - 0326264 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (Transcription Factor RelA) RN - 1J05Z83K3M (Lanosterol) RN - 31C4KY9ESH (Nitric Oxide) RN - 560-66-7 (eburicoic acid) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, mouse) RN - EC 1.14.99.- (Ptgs2 protein, mouse) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Cell Survival/drug effects MH - Cyclooxygenase 2/genetics MH - Cytokines/genetics/metabolism MH - Dinoprostone/metabolism MH - Lanosterol/*analogs & derivatives/pharmacology MH - Lipopolysaccharides MH - Mice MH - Nitric Oxide/metabolism MH - Nitric Oxide Synthase Type II/genetics MH - Phosphatidylinositol 3-Kinase/*metabolism MH - Polyporales MH - Proto-Oncogene Proteins c-akt/*metabolism MH - RAW 264.7 Cells MH - Signal Transduction MH - TOR Serine-Threonine Kinases/*metabolism MH - Transcription Factor RelA/*metabolism OTO - NOTNLM OT - Eburicoic acid OT - Inflammatory mediators OT - PI3K/Akt/mTOR/NF-kappaB signaling pathway OT - Pro-inflammatory cytokines OT - RAW264.7 cells EDAT- 2017/06/04 06:00 MHDA- 2018/05/10 06:00 CRDT- 2017/06/04 06:00 PHST- 2016/12/08 00:00 [received] PHST- 2017/05/17 00:00 [accepted] PHST- 2017/06/04 06:00 [pubmed] PHST- 2018/05/10 06:00 [medline] PHST- 2017/06/04 06:00 [entrez] AID - 10.1007/s00210-017-1382-3 [pii] AID - 10.1007/s00210-017-1382-3 [doi] PST - ppublish SO - Naunyn Schmiedebergs Arch Pharmacol. 2017 Aug;390(8):845-856. doi: 10.1007/s00210-017-1382-3. Epub 2017 Jun 2.