PMID- 36985786 OWN - NLM STAT- MEDLINE DCOM- 20230330 LR - 20230331 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 28 IP - 6 DP - 2023 Mar 20 TI - Ethanol Extract of Rosa laevigata Michx. Fruit Inhibits Inflammatory Responses through NF-kappaB/MAPK Signaling Pathways via AMPK Activation in RAW 264.7 Macrophages. LID - 10.3390/molecules28062813 [doi] LID - 2813 AB - The fruit of Rosa laevigata Michx. (FR), a traditional Chinese herb utilized for the treatment of a variety diseases, has notably diverse pharmacological activities including hepatoprotective, anti-oxidant, and anti-inflammatory effects. Despite ongoing research on illustrating the underlying anti-inflammatory mechanism of FR, the principal mechanism remained inadequately understood. In this study, we investigated in depth the molecular mechanism of the anti-inflammatory actions of the ethanol extract of FR (EFR) and its potential targets using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro. We showed that EFR effectively ameliorated the overproduction of inflammatory mediators and cytokines, as well as the expression of related genes. It was further demonstrated that LPS-induced activation of nuclear factor kappa B (NF-kappaB) and mitogen-activated protein kinases (MAPKs) were significantly inhibited by pretreatment with EFR, accompanied by a concomitant decrease in the nuclear translocation of the p65 subunit of NF-kappaB and activator protein 1 (AP-1). In addition, EFR pretreatment potently prevented LPS-induced decreased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK). Our data also revealed that the activation of AMPK and subsequent inhibition of the mammalian target of the rapamycin (mTOR) signaling pathway was probably responsible for the inhibitory effect of EFR on LPS-induced inflammatory responses, evidenced by reverse changes observed under the condition of AMPK inactivation following co-treatment with the AMPK-specific inhibitor Compound C. Finally, the main components with an anti-inflammatory effect in EFR were identified as madecassic acid, ellagic acid, quinic acid, and procyanidin C1 by LC-MS and testified based on the inhibition of NO production and inflammatory mediator expression. Taken together, our results indicated that EFR was able to ameliorate inflammatory responses via the suppression of MAPKs/NF-kappaB signaling pathways following AMPK activation, suggesting the therapeutic potential of EFR for inflammatory diseases. FAU - Wu, Hongtan AU - Wu H AD - Department of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China. AD - Engineering Research Center of Natural Cosmeceuticals, College of Fujian Province, Xiamen 361023, China. FAU - Lin, Tingting AU - Lin T AD - Department of Pharmacy, Xiamen Medical College, Xiamen 361023, China. FAU - Chen, Yupei AU - Chen Y AD - Department of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China. AD - Engineering Research Center of Natural Cosmeceuticals, College of Fujian Province, Xiamen 361023, China. FAU - Chen, Fangfang AU - Chen F AD - Department of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China. AD - Engineering Research Center of Natural Cosmeceuticals, College of Fujian Province, Xiamen 361023, China. FAU - Zhang, Shudi AU - Zhang S AD - Department of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China. AD - Engineering Research Center of Natural Cosmeceuticals, College of Fujian Province, Xiamen 361023, China. FAU - Pang, Haiyue AU - Pang H AD - Department of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China. AD - Engineering Research Center of Natural Cosmeceuticals, College of Fujian Province, Xiamen 361023, China. FAU - Huang, Lisen AU - Huang L AD - Department of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China. AD - Engineering Research Center of Natural Cosmeceuticals, College of Fujian Province, Xiamen 361023, China. FAU - Yu, Chihli AU - Yu C AD - Department of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China. AD - Engineering Research Center of Natural Cosmeceuticals, College of Fujian Province, Xiamen 361023, China. FAU - Wang, Gueyhorng AU - Wang G AD - Department of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China. AD - Engineering Research Center of Natural Cosmeceuticals, College of Fujian Province, Xiamen 361023, China. FAU - Wu, Chun AU - Wu C AD - Department of Clinical Medicine, Xiamen Medical College, Xiamen 361023, China. LA - eng GR - 2021J01342/Fujian Provincial Department of Science and Technology/ GR - HXJB-16/Xiamen Medical College/ PT - Journal Article DEP - 20230320 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (NF-kappa B) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - 0 (Lipopolysaccharides) RN - 0 (Anti-Inflammatory Agents) RN - 31C4KY9ESH (Nitric Oxide) SB - IM MH - Animals MH - Mice MH - *NF-kappa B/metabolism MH - AMP-Activated Protein Kinases/metabolism MH - *Rosa/metabolism MH - Lipopolysaccharides/pharmacology MH - Fruit/metabolism MH - Macrophages MH - Signal Transduction MH - Anti-Inflammatory Agents/therapeutic use MH - RAW 264.7 Cells MH - Nitric Oxide/metabolism MH - Mammals/metabolism PMC - PMC10054580 OTO - NOTNLM OT - AMPK/MAPK/NF-kappaB cascade OT - EFR OT - LPS OT - anti-inflammatory COIS- The authors declare no conflict of interest. EDAT- 2023/03/30 06:00 MHDA- 2023/03/30 06:11 PMCR- 2023/03/20 CRDT- 2023/03/29 01:57 PHST- 2023/03/04 00:00 [received] PHST- 2023/03/13 00:00 [revised] PHST- 2023/03/16 00:00 [accepted] PHST- 2023/03/30 06:11 [medline] PHST- 2023/03/29 01:57 [entrez] PHST- 2023/03/30 06:00 [pubmed] PHST- 2023/03/20 00:00 [pmc-release] AID - molecules28062813 [pii] AID - molecules-28-02813 [pii] AID - 10.3390/molecules28062813 [doi] PST - epublish SO - Molecules. 2023 Mar 20;28(6):2813. doi: 10.3390/molecules28062813.