| Gancaofuzi decoction was first included in Treatise on Cold-induced Febrile Diseases, which was written by Zhang Zhongjing, including Fuzi(Heishunpian), Gancao, Baizhu, and Guizhi. Gancaofuzi decoction has the function of dispelling wind and dampness, warming and activating meridian, warming yang and benefiting qi, which has been used for the treatment of wind dampness over a long period of time. In this study heishunpian and its couplet medicines, alkaloids and its compatibility with other chemical components was used to study pharmacodynamics and metabolism to make sure the prescription drugs and chemical compositions of pharmacodynamics and mechanism analysis of chemical components in the treatment of rheumatism.The hot plate test and acetic acid writhing method were adopted in the experiment to investigate the analgesic effect. Heishunpian has a significant inhibitory effect on pain. Gancao, Guizhi and Baizhu could enhance its effect, especially Gancao. Alkaloids also have a significant inhibitory effect on pain, flavonoids could enhance its effect significantly. The results showed that the main analgesic drugs of Gancaofuzi decoction were Heishunpian and Gancao and the main chemical composition were alkaloids and flavonoids.The anti-inflammatory effect of the drugs was observed in mice with the swelling of paw induced by carrageenin and rats with adjuvant-induced arthritis. Heishunpian and alkaloids in "Gancaofuzi Decoction" have a better effect on acute anti-inflammatory than chronic anti-inflammatory. The compatibility of Heishunpian and Gancao has a very good anti-inflammatory effect. However the compatibility of Heishunpian and Baizhu or Guizhi has a better acute anti-inflammatory effect. Flavonoids and saponins could enhance the anti-inflammatory effect of alkaloids. The acute anti-inflammatory effect of alkaloids can be enhanced when alkaloids mixed with flavonoids. However the combination of alkaloids and saponins has a good effect on chronic inflammation. But three chemical components are mixed with each other exert the best anti-inflammatory effect. The results showed that the main antiinflammatory drug of Gancaofuzi decoction were Gancao and the main chemical composition were flavonoids and saponins.The murine macrophage cell line RAW264.7 as cellular model was used to study the immunoregulative effect of the drugs. The drug of Heishunpian and the chemical composition of alkaloids in "Gancaofuzi Decoction" played an important role in immunosuppressive effect. Gancao and Guizhi could enhance the immunosuppressive effect of Heihunpian, while Baizhu could reduce its immunosuppressive effects. Flavonoids could enhance the immunosuppressive effect of alkaloids, while saponins could reduce its immunosuppressive effects. The results showed that the main immunosuppressive effects drugs of Gancaofuzi decoction were Gancao Heishunpian and Guizhi, and the main chemical composition were flavonoids and alkaloids.A urinary metabonomics method based on the UPLC-Q-TOF-MS had been established to investigate potential biomarkers of secondary inflammation in adjuvant-induced arthritis rats and the therapeutic effects of Gancaofuzi decoction. Multivariate statistical approaches, such as PCA and OPLS-DA were used to distinguish groups and find potential biomarkers. 26 potential biomarkers were identified including Kynurenic acid, uric acid, 4-pyridoxic acid, citric acid, phenylalanine, creatinine, etc. which revealed that Tryptophan metabolism, phenylalanine metabolism, taurine and taurine metabolism, TCA cycle and vitamin B6 metabolism and other metabolic pathways were disturbed in adjuvant-induced arthritis rats. These potential biomarkers changes showed that the treatment of adjuvant arthritis by alkaloids, flavonoids and saponins in Gancaofuzi decoction on mainly through the regulation of amino acid metabolism, energy metabolism and intestinal flora metabolism. |
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