| Daphne genkwa Sieb. et Zucc, one of the medicinal species in Thymelaeaceae, is widely distributed in the provinces of southern China as well as the regions along the Yellow River. This plant has been used as folk medicines for the treatment of various diseases because it contains lots of biologically active constituents, of which the flavonoid is the major bioactive phytochemical. Previous pharmacological researches showed that flavoniods possessed anti-oxidative, anti-tumor, anti-inflammatory, immunomodulatory, analgesic activities. However, the bioactivities of flavoniods from Daphne genkwa have not been reported so for to our knowledge. Moreover, the increasing surveys disclosed that the disturbance on immunity system could be one of the reasons for many diseases, that inflammation and pain were the very universal as two types of clinical symptoms to lots of diseases. Hereby, the immunomodulatory, anti-inflammatory and analgesic effects of the total flavones of radixes of Daphne genkwa were investigated, and the chemical components from the radixes of Daphne genkwa were also analysed in this thesis. The results are as follows:1 Studies on the pharmacology1.1 Modulatory effectsDelayed type hypersensitivity (DTH) of mice was induced by dinitrochlorobenzol (DNCB), and the enhanced and suppressed DTH of mice was developed by cyclophosphamide (CY) at the proper doses respectively for observation on effects to DTH by different doses of the total flavonoids of Daphne genkwa (DTF). Peritoneal macrophages of mice were induced by sodium thioglycolic acid for the assay of impact on interleukin-1 release by different concentration of DTF. The T lymphocytes from spleen and thymus of mice were utilized for examination of effects on proliferation in vivo, the release ofinterleukin-2 by different doses of DTF at different duration of treatment. The immune tolerance of mice was induced by super optimal dose of DNCB for examining effects on subclass of Ts cell in mice by DTF. The results showed that DTF at the proper doses resulted in significant enhancement to DTH in immuno-suppressed mice and obvious reduction to DTH in immuno-enhanced mice, promoted the release of IL-1, enhanced the proliferation of T lymphocytes and release of IL-2 with the manner of dose-dependent in vivo. DTF at the proper doses evidently reduced the immune tolerance of mice induced by super optimal dose of DNCB, whereas the same doses of DTF used in combination with CY behaved significant increase in the immune tolerance.The results hinted the adequate dose of DTF acted not only as enhancing but modulatory agent in cell immunity of mice. The mechanisms for modulation in cell immunity were probably realized that DTF regulated the activation of macrophages, the proliferation of T lymphocytes, the secretion of IL-2 from T lymphocytes and the change of number of Ts cells.1.2 Anti-inflammatory effectsThe in vivo anti-inflammatory activity of DTF against acute and chronic animal test models was assayed. The results indicated that DTF at proper doses produced evident inhibition to histamine-induced vasodilation, Carrageenin-induced and Freund's complete adjuvant-induced (FCA) paw edema. Meanwhile, DTF showed significant reduction to the granuloma formation and significantly enhanced phagocytosis of reticular endothelial system (RES). The mediators induced by Carrageenin and Freud's complete adjuvant were greatly reduced in the inflamed tissue of the rats treated by DTF at used doses. On the other hand, the activity of SOD and CAT were obviously potentiated and the activity of iNOS, the enzyme responsible for synthesis of inflammatory mediator NO, was significantly reduced.The mechanisms for anti-inflammatory activity was realized, at least in part, that DTF inhibited the release of mediators in early stage, such as IL-1B and TNF-a, to prevent the producing of mediators in latter stage, such as PGE2, NO and MDA, enhanced the activity of SOD and CAT to scavenge oxygen free radicals, inhibited the activity of iNOS to reduce the synthesis of... |
PDF Full Text Request