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      Discovery of synergistic anti-inflammatory compound combination from herbal formula GuGe FengTong Tablet

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          Abstract

          Multi-components in herbal formulae exert holistic effects in synergistic or additive manners. However, appropriate strategies and supportive evidences are still lacking to uncover the synergistic or additive combinations. The present investigation aimed at seeking a screening strategy to identify the targeted combinations in GuGe FengTong Tablet (GGFTT), an herbal formula. Two compounds, belonging to different chemical classes, were combined with different concentration ratios and their anti-inflammation effects were investigated. The most significant anti-inflammatory combinations were evaluated by combination index (CI) method (additive effect, CI = 1; synergism, CI < 1; antagonism, CI < 1). The modulating effects of candidate combinations on pro-inflammatory cytokines and MAPKs signaling pathway were also detected. Two combinations, “biochanin A + 6-gingerol” (Bio-6G) and “genistein + 6-gingerol” (Gen-6G), showed synergistic effects (CI < 1), and Bio-6G was selected for further study. Compared with single compound, Bio-6G could synergistically inhibit the production of pro-inflammatory cytokines (TNF-α, IL-1 β, and IL-6) and the activation of MAPKs signaling pathway in LPS-stimulated RAW264.7 cells. The combined results showed that Bio-6G was a synergistic anti-inflammatory combination in GGFTT. Our results could provide a useful strategy to screen the synergistic combinations in herbal formulae.

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          Author and article information

          Journal
          CJNM
          Chinese Journal of Natural Medicines
          Elsevier
          1875-5364
          20 September 2018
          : 16
          : 9
          : 683-692
          Affiliations
          1State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China
          Author notes
          *Corresponding authors: LIU E-Hu, Tel/Fax: 86-25-83271379, E-mails: liuehu2011@ 123456163.com ; LI Ping, liping2004@ 123456126.com

          ΔThese authors contributed equally to the work.

          These authors have no conflict of interest to declare.

          Article
          S1875-5364(18)30108-0
          10.1016/S1875-5364(18)30108-0
          Copyright © 2018 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
          Funding
          Funded by: National Science & Technology Pillar Program during the Twelfth Five-year Plan Period
          Award ID: 2012BAI29B07
          Funded by: National Natural Science Foundation of China
          Award ID: 81202898
          Award ID: 81473343
          This work was supported by a project in the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period (No. 2012BAI29B07), the National Natural Science Foundation of China (Nos. 81202898 and 81473343) and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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