PMID- 37121691 OWN - NLM STAT- MEDLINE DCOM- 20230502 LR - 20230502 IS - 1347-5215 (Electronic) IS - 0918-6158 (Linking) VI - 46 IP - 5 DP - 2023 TI - Anti-inflammatory Activity of Gegen Decoction and Its Modulatory Mechanism on the NF-kappaB and MAPK Signaling Pathways. PG - 647-654 LID - 10.1248/bpb.b22-00632 [doi] AB - Gegen Decoction as anti-inflammatory medicine is used in clinic widespread, however the specific anti-inflammatory molecular mechanism of Gegen Decoction is still unclear. The purpose was to study the anti-inflammatory activity of Gegen Decoction in vivo and to research its anti-inflammatory molecular mechanism. The content of main essential components in Gegen Decoction were determined by HPLC method. The anti-inflammatory activity of Gegen Decoction was confirmed through in vivo animal experiments. Furthermore, RAW 264.7 cells were stimulated by lipopolysaccharides to induce inflammatory reaction, the modulatory effect of Gegen Decoction on the activation process of mitogen-activated protein kinases and nuclear factor-kappaB signaling pathways was investigated. The content of puerarin was the highest among all the index components. Gegen Decoction inhibited carrageenan-induced paw edema in rats and xylene-induced ear swelling in mice. Gegen Decoction had no obvious toxicity against RAW 264.7 cells at the concentrations of 10-40 mg/mL; significantly inhibited the release of nitric oxide, prostaglandin E(2), tumor necrosis factor-alpha and interleukin-6; down-regulated the high expression of inflammatory proteins inducible nitric oxide synthase and cyclooxygenase-2. It inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs)/extracellular regulated protein kinases (ERK)/c-Jun N-terminal kinase (JNK), the degradation of nuclear factor-kappaB (NF-kappaB)/inhibitor of NF-kappaB-alpha (IkappaB-alpha) and the nuclear translocation of NF-kappaB/p65 into nucleus. Gegen Decoction exerts significant anti-inflammatory activity, mainly by blocking the activation of both MAPKs and NF-kappaB pathway. FAU - Gao, Yinhe AU - Gao Y AD - Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University. FAU - Zhang, Yonggang AU - Zhang Y AD - Weifang Hospital of Traditional Chinese Medicine. FAU - Zhang, Qingran AU - Zhang Q AD - Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University. FAU - Song, Wenting AU - Song W AD - Weifang Hospital of Traditional Chinese Medicine. FAU - Xu, Hui AU - Xu H AD - Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University. FAU - Chen, Daquan AU - Chen D AD - Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University. FAU - Zhao, Feng AU - Zhao F AD - Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University. LA - eng PT - Journal Article PL - Japan TA - Biol Pharm Bull JT - Biological & pharmaceutical bulletin JID - 9311984 RN - 0 (NF-kappa B) RN - 0 (kakkon-to) RN - 0 (Anti-Inflammatory Agents) RN - 0 (I-kappa B Proteins) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - 0 (Lipopolysaccharides) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.14.99.1 (Cyclooxygenase 2) SB - IM MH - Rats MH - Mice MH - Animals MH - *NF-kappa B/metabolism MH - *Anti-Inflammatory Agents/pharmacology/therapeutic use MH - I-kappa B Proteins/metabolism MH - Mitogen-Activated Protein Kinases/metabolism MH - Signal Transduction MH - Nitric Oxide Synthase Type II/metabolism MH - Lipopolysaccharides/pharmacology MH - Nitric Oxide/metabolism MH - Cyclooxygenase 2/metabolism OTO - NOTNLM OT - Gegen Decoction OT - anti-inflammatory OT - mechanism OT - mitogen-activated protein kinase (MAPK) OT - nuclear factor-kappaB (NF-kappaB) EDAT- 2023/05/01 00:42 MHDA- 2023/05/02 06:42 CRDT- 2023/04/30 21:23 PHST- 2023/05/02 06:42 [medline] PHST- 2023/05/01 00:42 [pubmed] PHST- 2023/04/30 21:23 [entrez] AID - 10.1248/bpb.b22-00632 [doi] PST - ppublish SO - Biol Pharm Bull. 2023;46(5):647-654. doi: 10.1248/bpb.b22-00632.