PMID- 23261483 OWN - NLM STAT- MEDLINE DCOM- 20130730 LR - 20131121 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 145 IP - 3 DP - 2013 Feb 13 TI - A herbal formula containing roots of Salvia miltiorrhiza (Danshen) and Pueraria lobata (Gegen) inhibits inflammatory mediators in LPS-stimulated RAW 264.7 macrophages through inhibition of nuclear factor kappaB (NFkappaB) pathway. PG - 776-83 LID - S0378-8741(12)00845-8 [pii] LID - 10.1016/j.jep.2012.12.011 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: The herbal formula DG, containing roots of Salvia miltiorrhiza (Danshen) and Pueraria lobata (Gegen), has long history in treating cardiovascular diseases. It has been shown to be able to reduce intima-media thickening in coronary patients in our previous clinical study. Since intima-media thickening is the hallmark of atherosclerotic disease, the etiology of which is inflammation of the arterial wall, the mechanism underlying the effect of DG may be related to its anti-inflammatory activities. AIM OF STUDY: The present study aims to determine the anti-inflammatory activity of DG and elucidate its underlying mechanisms with regards to its molecular basis of action. MATERIALS AND METHOD: The anti-inflammatory effect of DG was studied by using lipopolysaccharide (LPS)-stimulated activation of nuclear factor kappaB (NFkappaB) pathway and subsequent production of inflammatory mediators, including nitric oxide (NO), prostaglandin E(2) (PGE(2)), interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and macrophage chemotactic protein-1 (MCP-1), in mouse RAW 264.7 macrophages. RESULTS: The present study demonstrated that DG could suppress the production of NO and PGE(2) through the inhibition of iNOS and COX-2 genes. DG could also inhibit the production of IL-1beta, IL-6 and MCP-1, but not TNF-alpha, through the inhibition of respective mRNA expressions. Further investigations showed the inhibitory effect of DG on activation of IKKalpha/beta and degradation of IkappaBalpha, thus preventing nuclear translocation of NFkappaB. All these results suggested the inhibitory effects of DG on the production of inflammatory mediators through the inhibition of the NFkappaB pathway. CONCLUSIONS: The inhibitory effects of DG on the production of inflammatory mediators by LPS-stimulated RAW 264.7 macrophages, are accomplished by inhibiting the nuclear translocation of NFkappaB through inactivating IKKalpha/beta and preventing degradation of IkappaBalpha. CI - Crown Copyright (c) 2012. Published by Elsevier Ireland Ltd. All rights reserved. FAU - Cheung, David Wing-Shing AU - Cheung DW AD - Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong. FAU - Koon, Chi-Man AU - Koon CM FAU - Wat, Elaine AU - Wat E FAU - Ko, Chun-Hay AU - Ko CH FAU - Chan, Judy Yuet-Wa AU - Chan JY FAU - Yew, David Tai-Wai AU - Yew DT FAU - Leung, Ping-Chung AU - Leung PC FAU - Chan, Wai-Yee AU - Chan WY FAU - Lau, Clara Bik-San AU - Lau CB FAU - Fung, Kwok-Pui AU - Fung KP LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121220 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Plant Extracts) RN - 0 (RNA, Messenger) RN - 31C4KY9ESH (Nitric Oxide) 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) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Cell Line MH - Cell Survival/drug effects MH - Cyclooxygenase 2/genetics MH - Cytokines/genetics MH - Inflammation Mediators/*antagonists & inhibitors/metabolism MH - Lipopolysaccharides MH - Macrophages/drug effects/metabolism MH - Mice MH - NF-kappa B/antagonists & inhibitors MH - Nitric Oxide/metabolism MH - Nitric Oxide Synthase Type II/genetics MH - Plant Extracts/*pharmacology MH - Plant Roots MH - *Pueraria MH - RNA, Messenger/metabolism MH - *Salvia miltiorrhiza EDAT- 2012/12/25 06:00 MHDA- 2013/07/31 06:00 CRDT- 2012/12/25 06:00 PHST- 2012/09/19 00:00 [received] PHST- 2012/12/06 00:00 [revised] PHST- 2012/12/07 00:00 [accepted] PHST- 2012/12/25 06:00 [entrez] PHST- 2012/12/25 06:00 [pubmed] PHST- 2013/07/31 06:00 [medline] AID - S0378-8741(12)00845-8 [pii] AID - 10.1016/j.jep.2012.12.011 [doi] PST - ppublish SO - J Ethnopharmacol. 2013 Feb 13;145(3):776-83. doi: 10.1016/j.jep.2012.12.011. Epub 2012 Dec 20.