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). 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-1β, 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.
Subject(s)
Animals , Mice , Anti-Inflammatory Agents , Chemistry , Pharmacology , Drug Compounding , Drug Synergism , Drugs, Chinese Herbal , Chemistry , Pharmacology , Interleukin-1beta , Allergy and Immunology , Macrophages , Allergy and Immunology , NF-kappa B , Allergy and Immunology , Tablets , Chemistry , Pharmacology , Tumor Necrosis Factor-alpha , Allergy and ImmunologyABSTRACT
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). 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-1β, 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.
Subject(s)
Animals , Mice , Anti-Inflammatory Agents , Chemistry , Pharmacology , Drug Compounding , Drug Synergism , Drugs, Chinese Herbal , Chemistry , Pharmacology , Interleukin-1beta , Allergy and Immunology , Macrophages , Allergy and Immunology , NF-kappa B , Allergy and Immunology , Tablets , Chemistry , Pharmacology , Tumor Necrosis Factor-alpha , Allergy and ImmunologyABSTRACT
In the present study, we developed and validated a rapid analytical method using high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (HPLC-Q-TOF/MS) to investigate the metabolic profile of Guge Fengtong tablet (GGFTT), a traditional Chinese medicine. The urine and bile samples were collected with 24 h after oral administration of GGFTT. A total of 34 compounds, including 11 parent compounds and 23 metabolites were unambiguously or tentatively identified. Our results indicated that glucuronidation, oxidation and methylation were the major metabolic pathways of the constituents in GGFTT. In addition, the results of this work also demonstrated the feasibility of HPLC-ESI-Q-TOF/MS for reliable characterization of the in vivo metabolites from herbal preparations.
Subject(s)
Animals , Male , Rats , Administration, Oral , Bile , Chemistry , Metabolism , Chromatography, High Pressure Liquid , Methods , Drugs, Chinese Herbal , Chemistry , Metabolism , Metabolome , Molecular Structure , Rats, Sprague-Dawley , Spectrometry, Mass, Electrospray Ionization , Methods , Tablets , Chemistry , Metabolism , Tandem Mass Spectrometry , Methods , Urine , ChemistryABSTRACT
The present study was designed to characterize the chemical constituents of Guge Fengtong Tablet (GGFTT). Based on the chromatographic retention behavior, fragmentation pathways of chemical components and the published literatures, a diagnostic ion filtering strategy with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (HPLC-ESI-Q-TOF/MS) was established to identify the multiple bioactive constituents of GGFTT. The rapid identification of forty-seven components, including 18 phenolic acids, 8 saponins, 14 gingerol-related compounds, and 7 diarylhepatonoids, was accomplished using this newly developed method. The coupling of HPLC-ESI-Q-TOF/MS with the diagnostic ion filtering strategy was useful and efficient for the in-depth structural elucidation of chemical compounds of GGFTT.